Perioperative Management of Patients with Rheumatic Disease

Brian F. Mandell Editor

Perioperative Management of Patients with Rheumatic Disease Editor Brian F. Mandell, M.D., Ph.D Department of Rheumatologic and Immunologic Disease Cleveland Clinic Cleveland, OH, USA

ISBN 978-1-4614-2202-0 ISBN 978-1-4614-2203-7 (eBook) DOI 10.1007/978-1-4614-2203-7 Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2012940198

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Springer is part of Springer Science+Business Media (www.springer.com) Preface

Perioperative care of the patient with a multisystem infl ammatory (rheumatic) disease has become increasingly complex. Patients are often receiving mul- tiple medications, are at least intermittently profoundly immunosuppressed, and may have signi fi cant organ dysfunction. At the same time, perioperative medicine has evolved almost into its own subspecialty. Physicians who have expertise in managing patients with rheumatic disease infrequently spend signi fi cant amount of their time also managing patients undergoing surgical procedures, and the reverse is equally true. Hence, there is the need for a reference source offering some guidance on the management of these patients in the perioperative setting. Despite the burgeoning literature on the medical management of the surgi- cal patient, scant data have been generated regarding patients with complex rheumatic disease. Prospective trials do not generally include these patients, and retrospective reviews are few and relatively small. Thus, textbooks and review articles in this clinical area have been by necessity limited to expert opinion, and none have extensively focused on the special clinical problems that are emphasized in this text. The authors of this text have collectively done yeoman’s work in putting together a set of unique chapters which I hope that you will fi nd both readable and useful. Many of the authors when approached to write these chapters voiced concern that there were little data, let alone strong evidence, to dictate their management suggestions. My standard reply was, “Exactly; that’s why this book should be written, and why you should provide your experience based opinion.” For many of the clinical scenarios discussed in this book, it is not likely that there will ever be strong evidence to guide us in making the decisions that must, nonetheless, be made. Evidence is referenced and commented upon when available, but as editor, I pushed the authors to provide you with their best opinion (based on their extensive personal experience that few clinicians have had the opportunity to share) when high-level evidence does not exist. Our goal is to provide at least a semipaved path for rheumatologists, who infrequently manage surgical problems, and medical consultants, who only seldom encounter patients with these rheumatic diseases, to tread as they care for these patients in the periop- erative period. We all recognize that “truth” in medicine is a fl uid concept, but at the time of this writing, these contents re fl ect the best we can do.

v vi Preface

On a personal note, I warmly acknowledge my former partners at the University of Pennsylvania, Michael Baime and Eliot Nierman, superb gen- eral internists, who kindled my interest in medical consultation and tolerated and supported my efforts as a rheumatologist trying to learn the nuances of perioperative medicine.

Cleveland, OH, USA Brian F. Mandell Contents

1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases ...... 1 John E. Tetzlaff 2 Perioperative Pain Management and Orthopedic Surgery ...... 23 John E. Tetzlaff 3 Autologous Blood Transfusion ...... 41 Ajay Kumar 4 Venous Thromboembolism Prophylaxis in the Patient with Rheumatic Diseases Undergoing Orthopedic Surgery ...... 45 Taki Galanis and Geno J. Merli 5 Preoperative Cardiovascular Risk Assessment ...... 57 C. Ronald MacKenzie and Michael K. Urban 6 Management of Medications in Patients with Rheumatic Diseases During the Perioperative Period ...... 71 Gregory C. Gardner 7 Prophylactic Antibiotic Use in Patients with Rheumatic Diseases ...... 87 Lucileia Teixeira 8 Perioperative Management of Antiphospholipid Antibody Positive Patients During Noncardiac Surgeries ...... 91 Katherine H. Saunders and Doruk Erkan 9 Perioperative Management of Anticoagulation in the Patient with the Antiphospholipid Syndrome in Cardiac Surgery and Cardiac Interventions ...... 109 John R. Bartholomew

vii viii Contents

10 Perioperative Management of the Patient with Immune Thrombocytopenic Purpura De Novo and the Thrombocytopenia of Antiphospholipid Antibody Syndrome ...... 129 Raja S. Bobba and Mark A. Crowther 11 Perioperative Management of the Patient with Pulmonary Hypertension ...... 137 Adriano R. Tonelli, Omar A. Minai, and Raed A. Dweik 12 Perioperative Management of the Neutropenic Rheumatologic Patient ...... 155 Leonard J. Horwitz 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension, or End-Stage Renal Disease ...... 165 James F. Simon and Joseph V. Nally 14 Systemic Lupus Erythematosus ...... 183 Elena Katzap and Richard A. Furie 15 Scleroderma and Raynaud Phenomenon ...... 193 Corey M. Hat fi eld and Richard M. Silver 16 Perioperative Management of the Patient with Idiopathic In fl ammatory Myopathy ...... 201 Rohit Aggarwal and Chester V. Oddis 17 Perioperative Management of Patients with Rheumatoid Arthritis ...... 209 Lisa L. Schroeder and Mary Chester M. Wasko 18 Perioperative Management of the Patient with Takayasu’s Arteritis ...... 221 Patrick Liang 19 Medical Issues in Osteoporotic Hip Fractures ...... 233 Christopher M. Whinney 20 Total Joint Arthroplasty in the Patient with Connective Tissue Disease ...... 243 C. Ronald MacKenzie and Edwin P. Su 21 Postoperative Fever and Infection in Immunosuppressed Patients ...... 253 David van Duin 22 Diagnosis and Management of Prosthetic Joint Infection ...... 261 Steven K. Schmitt Contents ix

23 Perioperative Gout and Pseudogout ...... 271 Brian F. Mandell 24 Perioperative Myocardial Infarction ...... 277 Benico Barzilai 25 Cervical Spine Stabilization ...... 285 Christopher A. Iannotti and Gordon R. Bell 26 Laminectomy ...... 297 Fernando Techy and Gordon R. Bell 27 Vertebral Augmentation ...... 303 Fernando Techy and R. Douglas Orr 28 Shoulder Arthroplasty ...... 313 Jason D. Doppelt and Joseph P. Iannotti 29 Carpal Tunnel Surgery ...... 319 Peter J. Evans and Ngozi I. Mogekwu 30 Metacarpophalangeal Arthroplasty ...... 323 Peter J. Evans and Ngozi I. Mogekwu 31 Total Hip Arthroplasty in Rheumatic Disease and Associated In fl ammatory Arthropathies ...... 327 David M. Joyce and Michael J. Joyce 32 Total Knee Arthroplasty in Rheumatoid Disease and Other Associated In fl ammatory Arthropathies ...... 341 David M. Joyce and Michael J. Joyce 33 Knee Arthroscopy ...... 353 James S. Williams 34 Surgery for Avascular Necrosis of the Femoral Head ...... 361 Peter J. Brooks 35 Laparoscopic Splenectomy ...... 367 R. Matthew Walsh 36 Lung Biopsy ...... 373 Sudish C. Murthy 37 Renal Transplantation ...... 377 David A. Goldfarb and Natarajan Sezhian 38 Lung Decortication ...... 385 Sudish C. Murthy 39 Lung Transplantation ...... 389 Marie M. Budev x Contents

40 Comanagement Models for the Patient with Joint Disease ...... 397 Preethi Patel and Christopher M. Whinney

Index ...... 403 Contributors

Rohit Aggarwal , M.D., M.S. Instructor , UPMC Arthritis and Autoimmunity Clinic, Assistant Professor of Medicine, Division of Rheumatology and Clinical Immunology , University of Pittsburgh , Pittsburgh , PA , USA John R. Bartholomew , M.D., F.A.C.C. Section Head Ð Vascular Medicine, Department of Cardiovascular Medicine , Cleveland Clinic , Cleveland , OH , USA Benico Barzilai , M.D. Section Head , Clinical Cardiology, Department of Cardiovascular Medicine , Cleveland Clinic Foundation , Cleveland , OH , USA Gordon R. Bell , M.D. Director, Center for Spine Health , Cleveland Clinic , Cleveland , OH , USA Raja S. Bobba , M.D., B.Sc., M.Sc. Clinician Educator , Department of Internal Medicine , McMaster University , Hamilton , ON , Canada Peter J. Brooks , M.D., F.R.C.S(C). Chief of Surgery , Department of Orthopaedic Surgery , Cleveland Clinic , Cleveland , OH , USA Marie M. Budev , D.o., M.P.H., F.C.C.P. Medical Director , Lung Transplantation and Heart Lung Transplantation, The Respiratory Institute , Cleveland Clinic , Cleveland , OH , USA Mark A. Crowther , M.D., M.Sc., F.R.C.P.C. Professor, Academic Division Director, Chief of Laboratory Medicine Department of Medicine, Hematology and Thromboembolism and Pathology and Molecular Medicine , McMaster University, St Joseph’s Healthcare and Hamilton Health Sciences , Hamilton , ON , Canada Jason D. Doppelt , M.D. Fellow, Department of Orthopaedic Surgery , Cleveland Clinic , Cleveland , OH , USA David van Duin , M.D., Ph.D. Department of Infectious Disease , Cleveland Clinic , Cleveland , OH , USA Raed A. Dweik , M.D. Director , Pulmonary Vascular Program, Department of Pulmonary, Allergy, Critical Care Medicine , Cleveland Clinic Foundation , Cleveland , OH , USA

xi xii Contributors

Doruk Erkan , M.D. Associate Physician-Scientist, The Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, Weill Medical College of Cornell University, New York , NY , USA Peter J. Evans , M.D., Ph.D., F.R.C.S.C. Director , Hand and Upper Extremity Center, Orthopaedic and Rheumatologic Institute , Cleveland Clinic Foundation , Cleveland , OH , USA Richard A. Furie , M.D. Division of Rheumatology and Allergy-Clinical Immunology , North Shore Ð LIJ Health System , Lake Success , NY , USA Taki Galanis , M.D. Physician, Jefferson Vascular Center, Department of Surgery , Thomas Jefferson University Hospital , Philadelphia , PA , USA Gregory C. Gardner , M.D., F.A.C.P. Gilliland-Henderson Professor of Medicine, Adjunct Professor of Orthopaedics and Sports Medicine and Rehabilitation Medicine , Division of Rheumatology , University of Washington , Seattle , WA , USA David A. Goldfarb , M.D. Surgical Director, Renal Transplantation Program, Glickman Urological and Kidney Institute, Department of Urology , Cleveland Clinic Foundation , Cleveland , OH , USA Corey M. Hat fi eld , D.O. Instructor , Division of Rheumatology and Immunology , Medical University of South Carolina , Charleston , SC , USA Leonard J. Horwitz , M.D. Staff Physician, Department of Hematology and Blood Disorders , Taussig Cancer Institute of the Cleveland Clinic Foundation , Cleveland , OH , USA Christopher A. Iannotti , M.D., Ph.D. Spine Surgery Fellow , Center for Spine Health , Cleveland Clinic , Cleveland , OH , USA Joseph P. Iannotti , M.D. Chairman, Maynard Madden Professor, Orthopaedic and Rheumatologic Institute , Cleveland Clinic , Cleveland , OH , USA David M. Joyce , M.D. Orthopaedist, Department of Orthopaedic Surgery , Cleveland Clinic , Cleveland , OH , USA Michael J. Joyce , M.D. Staff Orthopaedist, Orthopaedic Trauma Section, Department of Orthopaedic Surgery , Cleveland Clinic , Cleveland , OH , USA Elena Katzap , D.O. Fellow, Division of Rheumatology , North Shore University Hospital , Lake Success , NY , USA Ajay Kumar , M.D., F.A.C.P., S.F.H.M. Chief, Division of Hospital Medicine, Hartford Hospital, Hartford , CT , USA Patrick Liang , M.D. Associate Professor, Rheumatology Division , University of Sherbrooke , Sherbrooke , QC , Canada C. Ronald MacKenzie , M.D. Associate Attending Physician, Department of Rheumatology Ð Medicine , Hospital for Special Surgery , New York , NY , USA Contributors xiii

Brian F. Mandell , M.D., Ph.D., F.A.C.R., M.A.C.P. Professor and Chairman of Medicine, Department of Rheumatic and Immunologic Disease , Cleveland Clinic , Cleveland , OH , USA Geno J. Merli , M.D. Senior Vice President and Chief Medical Of fi cer , Jefferson Vascular Center, Department of Surgery , Thomas Jefferson University Hospital , Philadelphia , PA , USA Omar A. Minai , M.D., F.C.C.P, D.A.B.S.M. Staff Physician , Department of Pulmonary, Allergy, Critical Care Medicine , Cleveland Clinic , Cleveland , OH , USA Ngozi I. Mogekwu , M.D. Fellow , Hand and Upper Extremity Center, Orthopaedic and Rheumatologic Institute , Cleveland Clinic Foundation , Cleveland , OH , USA Sudish C. Murthy , M.D., Ph.D. Surgical Director, Professional Staff Center of Major Airway Disease, Department of Thoracic and Cardiovascular Surgery , Cleveland Clinic Foundation , Cleveland , OH , USA Joseph V. Nally , M.D. Staff Physician , Department of Nephrology and Hypertension , Cleveland Clinic Foundation , Cleveland , OH , USA Chester V. Oddis , M.D. Professor of Medicine, Director , Fellowship Training Program, Division of Rheumatology and Clinical Immunology , University of Pittsburgh School of Medicine , Pittsburgh , PA , USA R. Douglas Orr , M.D., F.R.C.S.C. Attending Staff , Neuroscience Institute, Cleveland Clinic , Cleveland , OH , USA Preethi Patel , M.D. Staff , Department of Hospital Medicine , Cleveland Clinic Foundation , Cleveland , OH , USA Katherine H. Saunders , M.D. Medical Student (4th year) Weil Medical College of Cornell University , New York-Presbyterian Hospital, New York , NY , USA Steven K. Schmitt , M.D. Staff Physician , Department of Infectious Disease , Cleveland Clinic Foundation , Cleveland , OH , USA Lisa L. Schroeder , M.D. Chief Medical Resident , Internal Medicine , Rheumatology, Geisinger Medical Center , Danville , PA , USA Natarajan Sezhian , M.B.B.S., F.R.C.S (Urol) Clinical Fellow , Glickman Urological and Kidney Institute , Cleveland Clinic Foundation , Cleveland , OH , USA James F. Simon , M.D. Staff Physician , Department of Nephrology and Hypertension , Cleveland Clinic Foundation , Cleveland , OH , USA Richard M. Silver , M.D. Division of Rheumatology and Immunology, Medical University of South Carolina , Charleston , SC , USA Edwin P. Su , M.D. Attending Orthopaedic Surgeon , Adult Reconstruction and Joint Replacement Service , Hospital for Special Surgery , New York , NY , USA xiv Contributors

Fernando Techy , M.D. Spine Surgery Fellow , Neurological Institute, Center for Spine Health , Cleveland Clinic , Cleveland , OH , USA Lucileia Teixeira , M.D., M.S. Staff Physician , Department of Infectious Diseases , Cleveland Clinic , Cleveland , OH , USA John E. Tetzlaff , M.D. Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University , Cleveland , OH , USA Adriano R. Tonelli , M.D. Staff , Department of Pulmonary, Allergy, Critical Care Medicine , Cleveland Clinic , Cleveland , OH , USA Michael K. Urban , M.D., Ph.D. Director, Associate Professor of Clinical Anesthesia , Department of Anesthesia , Hospital for Special Surgery, Weil Medical College of Cornell University , New York , NY , USA R. Matthew Walsh , M.D., F.A.C.S. Chairman , Department of General Surgery , Cleveland Clinic Foundation , Cleveland , OH , USA Mary Chester M. Wasko , M.D., M.Sc. Rheumatologist , Lupus Center of Excellence, Internal Medicine , West Penn/Allegheny Health System , Pittsburgh , PA , USA Christopher M. Whinney , M.D., F.A.C.P., F.H.M. Interim Chairman , Department of Hospital Medicine , Cleveland Clinic Foundation , Cleveland , OH , USA James S. Williams , M.D. Orthopaedic Surgeon , Department of Orthopaedics , Orthopaedic and Rheumatologic Institute , Euclid , OH , USA Anesthetic Issues for Orthopedic Surgery in Patients with 1 Rheumatoid Diseases

John E. Tetzlaff

Introduction Preanesthetic Preparation for the Patient with Rheumatoid Arthritis (Ra) Patients with rheumatoid diseases present complex management issues in the perioperative period The generalized reduction of tissue stability pres- because of the pathophysiologic consequences of ents positioning risks [ 1 ] . The skin is extremely these diseases and other comorbidities. The anes- thin and has reduced resistance to shear stress in thesia team is being increasingly required to deter- RA patients on chronic steroids and/or cytotoxic mine the suitability of patients for operative drugs [2, 3 ]. Minor pressure or aggressive removal procedures. Extremes of age, surgical complexity, of adhesive tape can be associated with full- and coexisting illness place surgeons in the position thickness skin loss. Frequent cycling of auto- of seeking “medical clearance” from the anesthesia mated blood pressure measurement devices can team for an increasing number of patients, emergent cause skin damage. Adhesive liquids, such as and elective. A systematic approach to optimizing benzoin, applied to the skin to increase the adhe- these patients would appear rational. The criteria for sion of dressings or tape, need to be carefully elective surgery that need to be established by each considered and removed with extreme caution, group are issues of preoperative screening, labora- possibly even with liquid adhesive remover. Bed tory evaluation, work-up of known coexisting dis- surfaces need to be soft and positioning aides ease, and a systematic approach to high-risk patients. (bean bags, kidney rests) must be applied with The sequelae of rheumatoid arthritis create risk of skin injury in mind. Prone positioning pathophysiologic changes that direct impact on devices which disperse the area of body contact, anesthetic practice. This is especially true for the as opposed to placing it over small areas, are patient with cervical spine instability—the anesthe- potential good choices. Fracture table attachment siologist is obligated to decide whether airway man- points must disperse the shear force at attachment agement is required, and if so, the technique to sites over as large an area as possible. accomplish this task should be performed without The treatment of RA can present preoperative endangering the spinal cord. This creates a variety issues for the anesthesiologist. Patients on of issues for the anesthetic management of patients chronic steroid therapy may have adrenal sup- with rheumatic diseases. pression and should be given stress dose steroids. Steroid-induced reduction in bone density can create a risk for bone fracture and should be  J. E. Tetzlaff , M.D. ( ) considered during positioning for surgery [4 ] . Cleveland Clinic Lerner College of Medicine of Case Western Reserve University , Cleveland , OH , USA The emotional consequences of the disease can e-mail: [email protected] cause depression, and these patients may be

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 1 DOI 10.1007/978-1-4614-2203-7_1, © Springer Science+Business Media, LLC 2013 2 J.E. Tetzlaff treated with chronic antidepressant therapy, ization may be the only possible approach. including tricyclic antidepressants and monoam- Exacerbation of the laryngeal symptoms has ine oxidase inhibitors (MAOIs). These drugs are been reported with the use of laryngeal mask air- known to interfere with catecholamine activity way (LMA) for airway management during and cause exaggerated hypertension in repose to anesthesia [ 13 ] , with the need for tracheostomy sympathetic stimulation or indirect-acting vaso- [14, 15 ] . When combined, the dif fi culty with pressors. The consensus is against preoperative laryngoscopy due to decreased range of motion withdrawal of these drugs [5– 8] , because of seri- and the dif fi culty with direct visualization of the ous consequences from exacerbation of depres- larynx can present with an extremely dif fi cult sion and the ability to treat hemodynamic airway. There is increasing use of video laryn- changes without withdrawing these drugs. If goscopy to manage the rheumatoid airway. MAOI therapy is not stopped, meperidine is con- Instability based on incompetence of structural traindicated to avoid the rare but serious hyper- elements of the cervical spine is a serious anes- pyrexic coma. If hypotension occurs during thetic consideration. When synovial destruction anesthesia, the fi rst response should be fl uid creates incompetence of the transverse ligament, therapy and followed by titration of direct acting C1–C2 instability can occur [ 16 ] . While instabil- vasopressors (such as phenylephrine). ity can develop at almost any level of the cervical spine due to destruction of synovial articulation, the most likely site is the weakening of the Rheumatoid Arthritis and Airway fi xation (transverse ligament) of the axis of C2 to Management the ventral side of C1 [ 17, 18] or erosion of the base of the axis [ 19 ] . In either case, dorsal trans- Due to the existence of synovial joints at a variety location of C2 on C1 places the spinal cord at risk of locations, the management of the airway in [ 20, 21] . Less common, upward movement of the rheumatoid patients is the most common and odontoid toward the brain stem can also occur serious perioperative issue. The cervical spine, with erosion of the base of the odontoid [ 19 ] . temporomandibular joints (TMJ), and the aryte- C1–C2 instability can be pain-free [22 ] , but it can noid bodies can have degenerative changes. The also present with radiculopathy, long-tract signs, lack of mobility of the neck can be the primary or even severe myelopathy [ 23 ] in patients with presentation. When this is combined with normal or limited range of motion of the neck. decreased mouth opening due to TMJ involve- Some patients even have a clunking sensation ment, suspicion of a complex airway is greater. with certain types of movement, which represents Less obvious but equally challenging can be acute subluxation of the cranium and C1 onto C2. the results of rheumatoid disease on the larynx Some patients will report long-tract signs with itself. Since the joints are synovial, rheumatoid certain types of movement, especially neck exten- disease can lead to degeneration. Cricoarytenoid sion. Neck extension is most likely to elicit neu- arthritis in RA patients can present with severe rological signs since this induces dorsal dysfunction of the larynx, including stridor [ 9 ] , subluxation of C2, encroaching on the spinal cord requiring urgent tracheostomy [10 ] . With vari- [ 24, 25 ] . The optimum position for the neck able attack of synovial destruction of mobile depends on what type of instability is present, elements of the larynx, the result can be an angu- and is different for vertical atlantoaxial instability lated laryngeal opening due to unilateral (AAIS) compared to the more common horizon- arytenoid changes [11 ] , causing alteration of tal AAIS [26 ] . Fluoroscopic guidance has been the endolarynx [12 ] . Direct visualization of the used for optimum position for airway manage- larynx can be diffi cult and may require special ment in RA patients [27 ] . maneuvers to rotate the opening into view. In a In many cases, instability of the neck is known small percentage of cases, fi ber-optic visual- in advance, especially in those patients who 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 3

present for elective or urgent stabilization. When instability, even awake intubation by itself may early instability is identi fi ed, it is assumed that not be totally safe, and prior mechanical stabili- progression will occur. Documentation with zation of the neck may be necessary. forced fl exion–extension neck X-rays is important prior to anesthesia [28 ] , unless surgical fusion has been con fi rmed. Conventional airway manage- When Is Regional Anesthesia ment involves extension of the cervical spine, and the Correct Choice for the Patient trauma to spinal cord is a risk [29 ] . Simple lateral with Rheumatoid Arthritis? fi lms are not adequate, since instability may only present with movement. Even in patients with Regional anesthesia is often the best choice for prior surgical fusion of C2 to occiput, fl exion– orthopedic surgery, with the majority of proce- extension views can identify a fusion dependent dures suitable to some regional anesthetic tech- solely on the wires, which could be disrupted dur- nique for surgical anesthesia and/or postoperative ing airway management. Incompetence of the analgesia. In the patient with RA, other issues base of the odontoid is detected with open mouth, must be considered including airway management, A–P X-ray of the neck. dif fi culty with performing regional anesthesia, The preoperative dilemma occurs when the failure of regional anesthesia (5–10% of attempts), rheumatoid patient without known instability positioning issues, and chronic pain. presents for elective surgery with no prior X-rays of the neck. While the patient may be asymptom- atic, the incidence of silent C-spine instability is Patient Selection common [22 ] . Orthopedic surgeons accustomed to dealing with RA and reconstructive surgery The emotional suitability of a patient for regional may be aware of the reports of neurological injury anesthesia can be dif fi cult to evaluate. Most from airway management in patients with cervi- patients fi rst present to an anesthesia provider cal spine instability. Some centers will require after they have been diagnosed with a surgical fl exion–extension fi lms for elective surgery. If condition and have accepted a surgical procedure. presented with rheumatoid patients with unknown The patient is often emotionally fi xed on telling cervical spine stability, the starting point is to all his physicians and nurses what the patient evaluate the airway to determine if intubation can thinks that they want to hear. In addition, in some be performed without gross spine manipulation. patients with chronic disease, there can be denial. Several factors determine the urgency for fl exion– A realistic presentation of the experience of extension X-rays of the neck. The length of time surgery during regional anesthesia is mandatory. from the onset of symptoms is one, since the inci- Some patients will refuse regional anesthesia at dence of instability increases with time. Another this point, because of the sounds of the operating is the other criteria for airway management. If the room during orthopedic surgery, which can be mouth opens well, thyromental distance is normal, terrifying. These patients are easy to identify, and and the physical exam of the oropharynx is normal, it is a mistake to offer these patients regional the urgency to require neck fi lms is reduced. If anesthesia. Other less-than-ideal candidates for not, either X-ray evaluation or awake fi ber-optic regional anesthesia are not as easy to detect. They intubation will be indicated [ 30 ] . When insta- may talk about fear or express reservation about bility is known, the X-rays must be repeated at being awake in the operating room. Regional intervals, and the consensus is 3 years. When anesthesia requires the use of needles, and those neurological fi ndings are present, especially with patients with extreme aversion to needles may motion of the neck, an MRI to identify cord not be able to cooperate with placement of a compression or nerve root impingement should block even if they would be able to tolerate the be considered important. In cases of extreme operative procedure awake. 4 J.E. Tetzlaff

Various medical conditions also make patients factors that could cause either block failure or less-than-ideal candidates for regional anesthe- possible complications. sia. Patients with various psychiatric diseases can be poor candidates for regional anesthesia. Schizophrenic patients with altered perception of Infection reality should not be offered regional anesthesia. Depressed patients are often not suited to be Even without predisposing conditions, any awake in the operating room. Manic depressive regional anesthetic technique can result in an disorders can be associated with acute psychosis infection at the site of injection. In the case of or unruly behavior during regional anesthesia. central blocks, meningitis and epidural abscess Patients with a variety of severe neuroses, espe- are serious complications. There is consensus cially claustrophobia, can be extremely diffi cult that a regional anesthetic should not be attempted to manage in the operating room awake. Patients under most situations when the patient has signs with advanced Alzheimer’s disease, organic brain of systemic infection. Sepsis is an absolute con- syndrome, and dementia cannot understand the traindication to regional anesthesia. It is also felt frightening sounds of the operating room and to be dangerous to attempt a regional block if the often cannot tolerate being awake during surgery. skin at the site of injection is in fl amed or infected. If the patient does not speak the principal language Genital herpes can present as a fi nding at preop- in use in the operating room and if a member of erative examination. The second and subsequent the anesthesia team is not fl uent in that language, recurrence of this disease is not a problem for regional anesthesia without supplemental general regional anesthesia, but the fi rst evidence of anesthesia is probably not wise. infection (primary herpes) is often associated There will be surgical procedures that even the with viremia, which is a contraindication to most motivated adult cannot tolerate. Orthopedic regional anesthesia. Localized infection at sites surgery requires patient positioning which can distant to the site of the potential block should become extremely uncomfortable after a period of not be an issue for regional anesthesia. Chronic time. The lateral decubitus position is an example, osteomyelitis is a common indication for ortho- particularly for some patients with painful arthritis pedic surgery. In most instances, there will be no of many joints. Even if surgical anesthesia is excel- evidence of bacteremia, and a block will be a rea- lent, the gradual movement that will result from sonable choice, although the symptoms of bacte- restlessness after several hours can require either remia must be sought to avoid performing a excessive sedation or become disruptive to the regional technique in the early stage of sepsis. surgical activity. Procedures which require fi eld Pelvic infections represent a dilemma when con- avoidance, such as shoulder surgery, require the sidering a central block. The confl uence of lym- patient to be almost completely covered by the sur- phatic drainage from the pelvis and the epidural gical drapes for considerable periods of time and space make placing a needle, with the potential may not be tolerated awake by every patient, espe- new nidus for infection, problematic. How this cially one with claustrophobia. applies to the geriatric orthopedic patient with hip fracture and newly diagnosed urinary tract infection is not as clear. For sure, if regional anes- Patient Factors that Infl uence thesia is considered, systemic signs of sepsis or the Anesthetic Choice pyelonephritis must be absent.

In addition to those things that are done to evalu- ate all patients for suitability for anesthesia, there Neurological Disease are some additional steps when considering the possibility of regional anesthesia. Correct prean- There is consensus about the deleterious effects of esthesia preparation requires identi fi cation of local anesthetics on nervous system tissue where 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 5 there is active demyelination. Central demyelina- should not be automatically excluded from the tion includes diseases like amyotrophic lateral possibility of regional anesthesia but rather should sclerosis (ALS), Guillain Barré syndrome, and be further evaluated for objective indicators of a others. In any of these situations, the choice of defect in the coagulation cascade. A platelet count regional anesthesia would be unwise. An area with is required if there is a concern about coagula- less of a consensus is the patient with a peripheral tion, and regional anesthesia will generally not be neuropathy (e.g., diabetic neuropathy). These chosen if the platelet count is less than 100,000. patients often have other end-organ disease which Prothrombin time (PT/INR) and activated partial makes them ideal candidates for regional tech- thromboplastin time (aPTT) are reliable indica- niques. Even though the mechanism for the neu- tors of normal function of the intrinsic and ropathy is known, and thought to be unaffected by extrinsic pathways of coagulation. The incidence the action of local anesthetics, the medicolegal of false-positive results for these tests is higher issue of progression of the neuropathy makes some in the rheumatoid patient population because anesthetists reluctant to use regional anesthesia. of circulating lupus anticoagulants and others. There are potential issues with the choice of a Fortunately, if these tests are done enough in central block in the patient with previous stroke. advance, the elevated PT and aPTT panels can be An old stroke, especially an embolic event, should obtained and the pathologist can identify the not represent an issue for the choice of any cause of a false positive and allow the selection of regional technique. And just as clearly, if a patient regional anesthesia. Any signifi cant abnormal requires urgent surgery in the period immediately results should be assumed to be related to either after a hemorrhagic stroke, the choice of a central anticoagulants (heparin, Coumadin), excessive block with either intentional dural puncture (spi- use of antiplatelet drugs (aspirin, nonsteroidal nal anesthesia) or the risk of large dural puncture anti-infl ammatory drugs—NSAIDS), or severe (epidural, caudal) is probably unwise. The gray hepatic parenchymal dysfunction. If the cause is zone, of course, is the time interval between acute aspirin, the acetylation of platelets is irreversible, and chronic. Risk/benefi t analysis and documen- and the effects not resolved until a new genera- tation is mandatory. Because there are alterna- tion of platelets generated by the patient’s bone tives, if there is a doubt about a stroke being marrow at about 2 weeks. Signs of platelet dys- recent, the practical choice will invariably be to function include excessive bleeding from small choose general anesthesia. For the same reasons, skin cuts, easy bruising (visually obvious), hema- central blocks are not reasonable for any patient turia, or blood with tooth brushing in the absence with potential increased intracranial pressure. of periodontal disease. In the absence of a posi- tive clinical history, it may be reasonable to pro- ceed without further investigation. If there is a Coagulopathy doubt, the best clinical indicator or intact platelet function is platelet aggregation testing, limited Creation of compressive hematoma or neural by availability, the time required to get the results, ischemia is the potential result of an attempted and the unclear relationship between the result block in a patient with therapeutic anticoagula- and bleeding risk. The potent antiplatelet drugs tion or a coagulopathy. While the routine screen- (e.g., clopidogrel) used for cardiovascular dis- ing of the coagulation of healthy patients is not eases required extended withdrawal (5–7 days) indicated, the practitioner of regional anesthesia prior to regional anesthesia. The thienopyridine must seek history, symptoms, or signs at physical class, including ticlopidine and clopidogrel, irre- exam which suggest any defect in coagulation. versibly prevent ADP-induced platelet aggrega- The history of prolonged bleeding from simple tion with a high potency. The plasma half-life of cuts of the skin, easy bruising, ingestion of any of both drugs is long and clopidogrel must be dis- the antiplatelet drugs, or prior history of surgical continued 5–7 days and ticlopidine 10–14 days bleeding diathesis should be sought. The patient before normal platelet activity can be assumed. 6 J.E. Tetzlaff

The glycoprotein IIb/IIIa receptor antagonists surgery, the dermatomes involved, and the (abciximab, epti fi batide, tiro fi ban) interfere with expected duration is mandatory. In orthopedic platelet aggregation and prevent platelet surgery, the probability of vigorous activity and fi brinogen and platelet–platelet interaction in a physical manipulation of the patient is likely. reversible manner. Normal platelet function can- Many lower extremity procedures involve the lat- not be assumed until 8 h (eptifi batide, tirofi ban) eral position and subsequently require toleration up to 48 h (abciximab). Epidural hematoma has of considerable physical movement. Use of the been reported after neuraxial block in patients fracture table with traction and forced abduction receiving thienopyridine derivatives. The IIb/IIIA of the legs creates considerable physical stress drugs are new enough that the absence of reports for the awake patient, even if a functioning of bleeding complications with regional anesthesia regional anesthetic is working. Prolonged inter- cannot be extrapolated to safety of central block vals in the lateral position can be poorly toler- within the therapeutic window of these drugs. ated, especially if the patient is af fl icted with the Required therapy to prevent or treat embolic total body aches and pains often found in rheu- disease can present issues for the choice of matoid patients. The potential for major blood regional anesthesia. Deep venous thrombosis loss can also represent a relative contraindication (DVT) can be a major source of postoperative to regional anesthesia, especially central blockade morbidity after orthopedic surgery, as the cause with the concomitant sympathectomy. of pulmonary embolism (PE). Prophylaxis of DVT can include low dose anticoagulation with antiplatelet drugs, Coumadin, or low molecular Anesthetic Selection for Joint weight heparin. In the case of prophylaxis, the Replacement Patients coagulation cascade is most often not altered. However, with “mini-dose heparin,” a fi xed per- Prior history of deep venous thrombosis or centage of patients will have abnormal coagula- pulmonary embolism mandates DVT prophy- tion lab tests. It is more dif fi cult with low laxis [ 30 ] , which in fl uences the anesthetic choice. molecular weight heparin, where the monitoring The prophylactic bene fi t of regional anesthesia, of PT and aPTT does not reveal the impact on the particularly epidural anesthesia extended into the coagulation cascade. If there is a clinically docu- postoperative period, should be considered in this mented embolism, and urgent surgery is indi- evaluation [ 31] . If Coumadin or subcutaneous cated, stopping anticoagulation must be a joint heparin is selected for preoperative DVT prophy- choice of the surgeon and the anesthesia team. laxis, coagulation must be evaluated prior to Often, the acute treatment will be heparin with- regional anesthesia. Certain indications for total drawal for 4 h, followed by coagulation testing. joint replacement are known to be associated Resumption of heparin will be decided by the with greater bleeding, and intravenous access and surgeon when the surgical bleeding is stable in monitoring plans altered accordingly. This is less the postoperative period. Rarely, an indication to of an issue for knee replacement, which is per- use regional anesthesia will be so strong that formed with a pneumatic tourniquet. Joints that active reversal of anticoagulation will be per- have been previously infected, and are being formed with blood component therapy (fresh operated on after resolution of the infection, are frozen plasma, cryoprecipitate, vitamin K). known to bleed more than previously unoperated joints. Paget’s disease, renal cell metastatic dis- ease, and metastatic disease of the bone are Implications of the Specifi c known to be associated with more bleeding. Surgical Procedure Revision of an existing joint, particularly one secured with methyl methacrylate, is known to be After patient selection, preparation, and premedi- associated with much more blood loss than pri- cation, the surgical procedure in fl uences the out- mary joint replacement due to the bleeding caused come of the anesthetic. Knowing the type of by cutting through scar tissue and removal of 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 7 methyl methacrylate, which is deeply interdigi- work suggests that regional anesthesia may tated with the bone. Sickle cell disease and other reduce the incidence of superfi cial wound infec- hemoglobinopathies may require that even total tion in the perioperative period. There may be knee replacement be done without pneumatic more urinary retention with regional anesthesia tourniquet to avoid acute sickle cell crisis. This compared to general anesthesia [42 ] although will require more plans for transfusion, since the less with spinal compared to epidural [54 ] . blood loss will be much greater and the hemoglo- When there is serious coexisting disease, the binopathy can become more symptomatic if choices of anesthesia are more focused. In the severe anemia is allowed to occur. RA patient with serious pulmonary compromise, some anesthesiologists would prefer to avoid instrumenting the airway and select a regional Total Hip Replacement anesthetic. On the other hand, a high regional anesthetic may signifi cantly impair ventilation The anesthetic care of the patient for total hip and be poorly tolerated. Spinal and epidural tech- replacement is dictated by the health of the patient, niques must be designed to have a solid block patient preference, knowledge of the duration of below the level of T8. With severe cardiac dis- the procedure for the surgeon in question, and the ease, there is a similar divergence of opinions anticipated blood loss. The patient with isolated about the ef fi cacy of regional anesthesia. Those arthritis damage of one hip can have any possible who advocate regional anesthesia would argue anesthetic technique including spinal, epidural, that with adequate intravascular volume, sym- and general anesthesia. Knowledge of the average pathectomy improves the function of the left ven- operating time for the surgeon will help to select tricle and decreases oxygen demand and may the agent for spinal anesthesia and determine suppress the metabolic changes secondary to the whether one shot spinal anesthesia is appropriate. stress response to surgery [55 ] . Those who would Since the surgical procedure is done either lateral select general anesthesia argue that a controlled or semi-lateral, it is important to avoid regional general anesthetic is associated with less hemo- techniques which either fail or resolve during the dynamic alteration than a central block with procedure while the patient is in the lateral decu- chemical sympathectomy. This is an important bitus position, since induction of general anes- issue because perioperative myocardial ischemia thesia in the lateral position can be diffi cult. related to hemodynamic instability is common in The patient should be informed about the patients at risk in the postoperative period after choices of anesthetic plans and allowed to par- total hip replacement [56 ] . ticipate in the decision. They need to know the The total hip patient with diffi cult airway possible advantages of a regional technique, from rheumatoid disease or other arthritis of the including reduced blood loss [ 32– 37 ] due to cervical spine (e.g., ankylosing spondylitis) pres- decreased blood pressure and local vasodilation ents a similar situation with discordant choices [38– 40 ] , less risk of transfusion, and a lower inci- advocated by different anesthesiologists. On the dence of deep venous thrombosis [33, 41– 46 ] one hand, due to the lateral position and the related to improved fi brinolysis [ 47 ] or improved potential diffi culty with airway management, fl ow in the venous microcirculation [ 48 ] . There is one group would prefer to control the airway less postoperative confusion [49 ] , although this prior to anesthetic induction with awake intuba- effect cannot be demonstrated at 3 months postop tion. Alternatively, some anesthesiologists would [50, 51] . Hypotensive epidural anesthesia may select a regional anesthetic, to avoid having to improve the quality of the interface between manipulate a diffi cult airway, using a regional methyl methacrylate and bone compared to gen- technique likely to result in a dense, long-acting, eral anesthesia, determined radiographically [48 ] . low regional block. It is important to verify a Regional anesthesia may improve neutrophil complete regional block prior to turning the activity [52 ] but not cell-mediated immunity [ 53 ] patient from the supine position. When general compared to general anesthesia, and preliminary anesthesia is selected as the primary anesthetic, 8 J.E. Tetzlaff provision must be made for movement to lateral during the transition from soft solid to biological from supine. Positioning injuries must be cement, the amount of heat liberated is tolerable avoided, the brachial plexus must be protected to human tissue. from compression on the dependent side, and the The interaction of this process with the con- airway must be secured so that accidental extu- duct of anesthesia depends on the site used, the bation is very unlikely. Pressure injuries to the method applied, and the physiological state of the dependent side of the face and special senses patient. The hemodynamically active part of the must be also considered carefully, in particular, cement is the monomer, which is a very potent, the eye and ear. direct vasodilator and a potent stimulus for Unlike other types of surgery, estimates of degranulation of mast cell with release of hista- blood loss with hip surgery require attention, mine [ 63– 66 ] . Other vasoactive substances since the surgical fi eld is large. The typical pri- released with mast cell degranulation [67 ] have mary total hip replacement is associated with an myocardial depressant properties. The combina- average blood loss of 500–1,000 ml, with more tion of vasodilation and degranulation of mast possible if technical issues are encountered. cells can cause signifi cant hemodynamic instabil- Steady loss onto the drapes, the use of irrigation, ity. If the patient is also hypovolemic or has and the partial soakage of sponges make the esti- diminished cardiac reserves from cardiovascular mation best performed by the primary anesthe- comorbidity, the effect can be further exagger- tist. When general anesthesia is used, the blood ated. If the patient is intravascularly contracted loss will be related to control of the blood pressure from preoperative treatment of hypertension with [57, 58 ] and reduced with deliberate hypotension diuretics, or has reduced ability to create the [37, 59– 61] , as it is during epidural anesthesia refl ex tachycardia from beta-blocker therapy, the with lower blood pressure [41, 62 ] . reaction can also be exaggerated. The early use of methyl methacrylate was associated with severe reactions including cardiac Methyl Methacrylate (MMA) arrest and death [68– 70 ] . As the mechanism became understood, the impact of the monomer Methyl methacrylate (MMA) had an important was reduced by later application of the cement in role in early development of joint arthroplasty. It the polymerization process, when less of the was necessary to fi nd a substance which would monomer was still present. More refi ned manu- evolve from a liquid to a very dense solid over a facture of the cement improved the quality, with short period of time, would interdigitate into more uniform, early polymerization which elimi- bone, and would not create enough heat to be nates much of the monomer sooner. The anesthe- destructive to human tissue. Methyl methacrylate sia team prepares for potential reactions by can be used in a manner that accomplishes all of lightening general anesthesia, maintaining the these objectives. The key to the utility of this blood volume and being prepared to immediately compound is a catalyzed polymerization of a treat any hemodynamic deterioration. There small molecule (the monomer) into a huge multi- would be more vigilance when the cement was chain polymer which is a very dense, solid sub- used at a site not isolated from the circulation with stance. The monomer is a liquid. When added to pneumatic tourniquet or when the surgeon’s plans the powdered, small-chain polymer, the process called for the use of a large amount of the cement of polymerization is accelerated. This is apparent or placement of the cement under pressure [71, by the distinct smell, which accompanies the 72] , either of which will increase the potential for change from a watery liquid, to a doughy liquid blood levels of the monomer. Pressures above when it is used by the surgeons, to a solid as 300 mmHg during cement pressurization and dense as cortical bone within 10–15 min depend- femoral stem insertion have been recorded within ing on the size of the batch and the amount of the femoral canal [ 71 ] . When pressurization is catalyst added. While the reaction is exothermic, important or unavoidable, small holes drilled 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 9

distally or a venting tube within the medullary hip revision surgeons can accomplish revision of canal [72, 73 ] will relieve the internal pressure both components of a total hip with cement and decrease the amount of driving force on the removal under the time constraint of a one-shot cement into the circulation, at the expense of sub- spinal anesthetic, even with agents such as bupi- jecting the bone to increased risk of fracture. vacaine or tetracaine with epinephrine. The use A less frequent event occurs when pressuriza- of epidural anesthesia is reasonable, as long as tion of the cement causing embolization of fat the patient is capable of tolerating prolonged [ 74, 75 ] , marrow, or air [67, 70, 75– 78 ] . This will intervals in the lateral position. The amount of present as abrupt hemodynamic deterioration, monitoring necessary is dependent on the indica- hypoxemia, and decreased carbon dioxide produc- tion for revision, the presence of cement, and tion from dead-space ventilation [ 73 ] . Sudden knowledge of the skill level of the surgeon. cardiac arrest can result from high volume, pres- Placement of an arterial catheter for continuous surized cement use, especially in the femoral canal blood pressure monitoring and blood gas sam- [79 ] . Gross embolization of particles may occur pling is often selected. Adequate venous access during almost every endoprosthesis insertion into is mandatory with a minimum of two sites large the femur. The raw, open sinuses after bone cement enough for rapid infusion of blood. The coexist- removal [74 ] during revision of total hip arthro- ing health of the patient and the expected blood plasty may be ideally suited for methyl methacry- loss will determine whether central venous access late reaction due to easy access into the circulation or occasionally, pulmonary artery catheter place- for the monomer as well as embolized particles. ment is indicated. When embolization is gross, deterioration can be The degree of blood loss anticipated requires related to mechanical obstruction of the right preparation for massive transfusion. Most revision ventricular outfl ow, pulmonary hypertension, and/ total hip procedures are associated with a blood or acute ischemia from coronary embolization. loss of at least 1,000 ml, and this is considerably increased when the revision involves a hip that has been secured with methyl methacrylate. In all but Revision Total Hip Arthroplasty infected cases, cell salvage devices can be used. Washed, packed cells can be returned to the patient, The revision of a total hip is invariably more and the amount of heterologous transfusion dif fi cult than the initial placement for the sur- decreased. Once heavy blood loss is encountered, geon. This is especially true with cemented total baseline coagulation studies should be obtained so hip, because the methyl methacrylate must be that later it is possible to compare the baseline PT, removed so that a new cemented or porous-coated INR, aPTT, platelet count, and fi brinogen levels to non-cemented femoral component has a chance those measured during massive transfusion. When to get solid purchase and not develop early loos- the volume replaced approaches the original blood ening. Younger patients will be more likely to volume, dilutional coagulopathy becomes likely, receive a non-cemented revision to preserve bone especially considering the use of crystalloid and stock for the longer expected life duration and non-blood colloid. The most likely defect is a low harder work applied to the extremity. From the platelet count, although dilutional de fi ciency of anesthetic perspective, the case can be assumed the labile clotting factors (V, VIII) and decreased to be long and potentially very bloody. If the revi- fi brinogen levels are possible. Accurate diagnosis sion is being performed for a fractured femur or of the defect in coagulation dictates appropriate pelvic protrusion of the acetabulum, the amount treatment—platelet for low platelet count, fresh of reconstruction that will be necessary will be frozen plasma for elevated PT/PTT, and cryopre- great, and the anticipated time and blood loss will cipitate for fi brinogen defects. When cell salvage be even greater. is used with heparin as the anticoagulant, most but The anesthetic technique selected must allow not all of the heparin is removed with washing, prolonged duration of the surgery. Only the best and the possibility of systemic heparinization must 10 J.E. Tetzlaff be evaluated. Activated clotting time is the most suture placement for reapproximation of tissues accurate assessment of heparinization effects, and will generate severe pain. the antidote is protamine. When cell salvage After satisfactory postoperative analgesia is devices use citrate as the anticoagulant, combined achieved, it is important to verify the integrity of with the citrate in banked blood, there can be a the sciatic nerve and detect dislocation of the new magnifi ed effect of citrate decreasing the ionized hip joint during emergence from anesthesia. The calcium level and subsequently decreased perfor- sciatic nerve is just posterior (dorsal) to where mance of the myocardium and hypotension requir- the majority of the dissection has occurred and ing treatment with calcium chloride. demonstration of intact motor function from Intraoperatively, the approach to the hip joint below the knee is mandatory. Any evidence of can be much more dif fi cult due to scarring. During defi cit may require radiological confi rmation of cement removal, blood loss from raw bone sur- correct placement of components and absence of faces can be profuse and continuous, and fracture dislocation. The possibility of compressive hema- is a potential adverse event, which greatly increases toma could even be an indication to return to the bleeding and time due to the need for repair of operating room under rare circumstances. Routine the fracture of the femur with wires, cables, or radiological exam of the pelvis (AP view) is stan- plates. Due to loss of bone from the loosening and dard procedure in the recovery room for many secondary osteoporosis, custom, long-stem pros- joint surgeons, since the undetected dislocation is thesis are necessary in some cases, requiring the more dif fi cult to reduce once postoperative tissue use of more cement and reaming of the femur. swelling has occurred. As stated earlier, the potential for systemic absorp- Some total hip replacement procedures will tion of the monomer of methyl methacrylate is involve the placement of a gravity or vacuum- greater during diffi cult hip revision, potentially assisted drainage device. Even though the magni fi ed by acute anemia and/or hypovolemia. placement of the prosthesis greatly decreases subsequent blood loss, the drains can be expected to accumulate a signifi cant amount of blood from Recovery Issues After Total Hip soft tissue bleeding. The majority of this loss will Replacement occur in the early recovery period, where as much as 500–800 cc can be lost and replaced with crys- The fi rst procedure-specifi c issue during recovery talloid, colloid, and potential transfusion. With after total hip replacement is pain control. When the increasing trend toward less transfusion in the regional anesthesia has been selected, the acute operating room, there will be more patients taken postoperative analgesia should not be an issue. to recovery room with the issue of whether to This is especially the case when the regional anes- transfuse blood or not being unresolved. The thetic is extended into the recovery phase, when indications for transfusion will be serial determi- local anesthetic and/or narcotic can be started in nations of hematocrit and vital signs—particularly the operating room, prior to the fi rst onset of pain. pulse and blood pressure—considered in the If regional anesthesia is not part of the immediate context of the amount of ongoing loss. postoperative pain control plan, some provision Early prevention of deep venous thrombosis for parenteral analgesia should be part of the anes- starts in the postanesthesia care unit. Pneumatic thetic plan. If the anesthetic technique includes stocking will often be placed. Regional anesthe- signifi cant narcotics, this can be suffi cient until sia can be continued via continuous infusion. the patient is conscious enough to identify the Once the perioperative bleeding decreases, some need for more pain relief. If the general anesthetic surgical services will initiate DVT prophylaxis technique is more focused on the inhalation with low molecular weight heparin or oral agents, it is important to provide some form of Coumadin therapy, knowing the lag time to thera- parenteral analgesic for emergence. The amount peutic effect and anticipation of no infl uence on of soft tissue dissection, osteotomy, and deep acute bleeding during this lag period. 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 11

After the numbness associated with a long Total Knee Replacement pneumatic tourniquet has resolved, there will be considerable pain due to the large arthrotomy and Total knee replacement can be performed with the large surface area for osteotomy. any anesthetic technique for the lower extremity, including general anesthesia, spinal anesthesia, epidural anesthesia, and femoral–sciatic leg Recovery Room Issues After Total block. The choice of regional anesthesia is logis- Knee Replacement tically easier with the total knee compared to the total hip replacement since the patient remains in The majority of blood loss after total knee the supine position throughout the surgery and replacement will occur in the early postoperative conversion to general anesthesia is not further period, and hypovolemia can occur. Drains may complicated by dif fi cult access to the airway. be in place and the amount can be identifi ed eas- Because of the use of a pneumatic tourniquet, the ily. When drains are not used, occult blood loss intraoperative blood loss during total knee must be considered. The report on arrival to replacement is unusually minimal (although this recovery of small estimated blood loss in the is not true of the recovery period, as will be operating room can decrease the vigilance about de fi ned below). The use of pneumatic tourniquet acute blood loss until hemodynamic instability is an additional stimulus for the patient, which again raises the issue. This does not mean that may require increasing doses of general anesthesia premature transfusion in the operating room is and in the awake patient under regional anesthe- indicated, since transfusion of the awake patient sia can result in tourniquet pain. Prior experience in the recovery room is probably safer because of with severe tourniquet pain may leave the patient the symptoms of transfusion reaction are easier unwilling to accept another regional anesthetic. to detect compared to transfusion in the operating While the femoral–sciatic leg block is a good room, where sedation and/or general anesthesia anesthetic for total knee replacement, the large can delay the identi fi cation of a major reaction. total doses of local anesthetic required, combined Veri fi cation of circulatory and neurological with the time involved, make this an infrequent integrity is also an issue after total knee replace- choice. Use of a femoral nerve block combined ment. The popliteal artery and vein and the sciatic with a catheter insertion into the sheath around nerve—both tibial and peroneal branches—could the femoral nerve will provide a component of be injured. Veri fi cation of the integrity of circula- intraoperative anesthesia and excellent postoper- tion will prevent ischemic injury to the leg, and ative pain control. Spinal anesthesia is a good the verifi cation of neurological integrity will choice for the majority of primary total knee prevent the permanent damage associated with replacements with long-acting local anesthetics compressive hematoma in the area of a peripheral being selected. For complex revision knee nerve. Since the incidence of deep venous throm- replacement, it is possible that a single shot spi- bosis is so high of total knee replacement (48– nal anesthetic might not last long enough and an 64%), prophylaxis is a priority in the early epidural anesthetic preferred. The epidural offers recovery after total knee replacement. the additional advantage of being continued into the postoperative period for postoperative anal- gesia and prevention, with signi fi cant reduction Is There a Difference Between of deep venous thrombosis being an additional Regional and General Anesthesia for advantage. Combined Spinal/Epidural anesthe- Lower Extremity Joint Replacement? sia is an increasingly popular option which includes the best of both the spinal and epidural Complications related to thromboembolism are options. General anesthesia can be selected, and the leading cause of mortality and morbidity after like total hip replacement, it should be designed elective lower extremity total joint replacement. with a postoperative pain control plan in mind. There is considerable evidence that anesthetic 12 J.E. Tetzlaff choice infl uences the incidence of thromboembo- hematoma related to indwelling epidural cathe- lic complications after total joint replacement. ters, use of LMWH, and removal of the epidural Several of the best reports are from Jan Modig catheter [87, 88] . In response to this cluster of et al. in Sweden. When they compared general reports of epidural hematoma, current recom- and epidural anesthesia for total hip replacement, mendations [89 ] are that regional anesthesia not popliteal, femoral, and combined calf-thigh clot be used for 12 h after a single dose of LMWH, was decreased, as was the incidence of pulmo- that indwelling epidural catheters not be main- nary embolism (PE) [ 80, 81 ] . They investigated tained if LMWH is planned, and that epidural the advantage for epidural anesthesia in other catheters not be removed until 8–12 h after the work, using venous plethysmography and demon- last dose of LMWH. More detailed conservative strated considerably better calf blood fl ow with guidelines for regional anesthesia and LMWH epidural anesthesia compared to general anes- have been published by the American Society of thesia [ 82 ] . In another report, they randomized to Regional Anesthesia [90 ] . general anesthesia versus epidural, extended Results of numerous studies suggest that lower epidural analgesia into the postoperative period, extremity joint replacement is associated with and investigated each patient with venogram and decreased perioperative blood loss when regional lung scan [ 38 ] . They concluded that epidural anesthesia is selected compared to general anes- anesthesia provides signifi cant prophylaxis thesia. Modig et al. [ 81, 82 ] found signi fi cantly against DVT and PE. Thorburn et al. [39 ] looked decreased EBL with epidural anesthesia for total at spinal versus general anesthesia (without ran- hip replacement compared to general anesthesia domization) for total hip replacement and found and attributed the difference to the sympathetic reduced DVT by venogram with SAB versus block and dependent drainage of blood away general anesthesia (29% vs. 53%). Covert et al. from the wound. Thornburn et al. [ 39 ] found [83 ] looked at regional (CLE or SAB) versus reduced EBL with spinal anesthesia for elective general anesthesia for total hip replacement and total hip replacement and found a reduction in found reduced DVT in the regional group. heterologous transfusion in the SAB group. McQueen et al. [42 ] looked at mixed group of Covert et al. [ 83] found reduced EBL with total hip and total knee replacements randomly regional anesthesia (SAB and Epidural), com- assigned to either general or epidural anesthesia pared to general anesthesia for total hip replace- and found decreased DVT in the epidural group. ment in geriatric patients. Chin et al. [ 32 ] looked Although unrelated to joint surgery, Rosenfeld at EBL for total hip replacement for epidural ver- [84 ] identi fi ed improved peripheral blood fl ow sus general anesthesia and found reduced EBL during epidural anesthesia compared to general and transfusion in the epidural group. anesthesia for peripheral vascular surgery with Based on the in fl uence of regional anesthesia the additional advantage of improved platelet on DVT and EBL, there has been interest in the function and fi brinolysis in the epidural group. in fl uence of anesthetic technique on coagulation Yet another issue with total joint replacement, during the perioperative period. Modig et al. [ 82 ] anesthetic choice and outcome is related to the suggested that general anesthesia for total hip consequences of chemical DVT prophylaxis with replacement resulted in decreased fi brinolysis, low molecular weight heparin (LMWH). Initial which did not occur when epidural anesthesia. reports found improved DVT prophylaxis with Rosenfeld [ 84] looked at this issue after vascular LMWH, independent of anesthetic choice [ 85, surgery and found improved fi brinolysis, more 86 ] . There were no neurological complications in normal platelet activity, and decreased endothe- this series which included a subset who were lial cell activity with epidural anesthesia com- given LMWH preoperatively; although there pared to general anesthesia. In contrast, when were no neurological complications, there was a Sharrock et al. [91 ] looked at a small series of high rate of wound hematoma (0.5%). Subsequent patients for total knee replacement, he found no reports have revealed case reports of epidural difference between general anesthesia and 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 13

epidural anesthesia for speci fi c components of increased urinary retention after elective total hip coagulation including tissue plasmogen activator replacement and total knee replacement after epi- (TPA), TPA antigen, fi brinopeptide, D dimer, or dural anesthesia compared to general anesthesia. thrombin–antithrombin complex. The signifi cance of these reports must be consid- The in fl uence of anesthetic technique on acute ered in the context of the report of Petersen et al. and subacute mental status after elective joint [ 95] who found a signifi cant increase in urinary replacement has been studied. Covert et al. [ 83 ] tract infection when urinary retention occurred. looked at regional (SAB and CLE) versus general There is some question whether regional anesthesia for elective total hip replacement and anesthesia interferes with the diagnosis or con- found signifi cantly increased levels of confusion tributes to peripheral nerve injury after lower during hospitalization in the general anesthesia extremity joint replacement. Horlocker et al. group. The occurrence of more hypoxemia in the [ 96 ] looked at the incidence of peroneal nerve general anesthesia group during the fi rst 7 days palsy after total knee replacement. Although may have contributed to confusion. Davis et al. there was no signifi cant difference in the inci- [92 ] looked at mental status of hip fracture repair dence between regional and general anesthesia, after discharge and found no difference based on the diagnosis was delayed when epidural analge- anesthetic technique, but overall mortality sia was extended into the postoperative period increased with pre-injury confusion or dementia. with high concentration local anesthetics. A case When Nielson et al. [ 50 ] looked at geriatric patients report by Strecker et al. [ 97] describes a case after total knee replacement, they found no differ- where epidural analgesia may have concealed ence in cognitive function at 3 months between early signs of a lower extremity compartment patients given general or spinal anesthesia. syndrome until massive necrosis had occurred. There is some indirect evidence that anesthetic When a similar event occurred in the PACU dur- technique infl uences the risk of infectious com- ing analgesia via lumbar epidural catheter with plications after lower extremity joint replace- 0.125% bupivacaine and fentanyl, the pain of an ment. Regional anesthesia decreases perioperative impending compartment syndrome related to blood transfusion, and this may in fl uence post- prolonged lithotomy position was not masked, operative infection, since heterologous transfu- fasciotomy was performed, and the outcome was sion seems to increase the rate of infection. excellent [ 98 ] . Fernandez et al. [ 93 ] looked at 376 patients for total knee replacement or major spine surgery and found increased infectious complications in Fat Embolism Syndrome patients who received heterologous transfusion. Murphy et al. [94 ] looked at elective total hip There are numerous occasions when there is a replacement and found an almost tenfold increase possibility of encountering fat embolism during in postoperative infection in those patients who trauma surgery, reconstructive orthopedic proce- received heterologous blood. Neither of these dures, and in the care of patients with long bone studies involved either randomization or control fractures. The fat embolism syndrome (FES), for anesthetic technique, but both speculate with hypoxia, pulmonary hypertension, and sec- that heterologous transfusion impairs the host ondary pulmonary vascular obstruction and sys- immune system. temic embolization, is less frequent, although Neuraxial regional anesthesia is known to associated with 10–20% mortality [ 99, 100 ] . interfere with voiding re fl exes and cause urinary Microscopic fat embolism has been shown to retention. However, general anesthesia also inter- occur during most operative procedures on feres with the refl ex to void. Thorburn et al. [ 39 ] long bones done without pneumatic tourniquet found equivalence in this issue by comparing and after most long bone fractures [ 101 ] . general anesthesia and SAB after elective total Subclinical fat embolism accompanies intra- hip replacement. McQueen et al. [ 42 ] found medullary manipulation of long bones, as in rod 14 J.E. Tetzlaff placement and reaming for endoprosthesis. occur, tubular necrosis from clogging is the When microscopic fat embolism occurs, the mechanism [72, 115 ] . majority of cases remain subclinical. The central nervous system signs of fat embo- FES is more serious and, fortunately, much lism are thought to occur from the passage of more uncommon. The majority (<90%) occur venous fat particles through the lung and into the after blunt trauma, associated with fractures systemic side, where accumulation produces CNS [101– 104 ] . One report of high-speed skiing acci- events [ 116] . A patent foramen ovale or intrapul- dents reports as many as 23% with evidence of monary arteriovenous shunts bypass the pulmo- serious fat embolism clinically [105 ] . With large nary fi ltration system and contribute macroscopic bone fractures, FES is thought to occur in 1–2% fat particles into the CNS [117 ] . Activation of of cases, with as much as 5% with pelvic frac- lipases can cause cell damage which releases tures [106 ] . The common occurrence of hypox- various vasoactive substances, which contribute emia after geriatric hip fracture may be related to directly to increase CNS damage. If a CNS injury a high incidence of fat embolism syndrome [ 107– is the cause of mortality during FES, the lesion is 109 ] . Less than 1% of total hip replacement cases most often in the brain stem [115 ] . The pulmo- are associated with a clinical event consistent nary damage with FES can cause hypoxemia, with FES, marrow embolism, or some synergy which can cause or accentuate CNS injury. with a methyl methacrylate event. Transesophageal The hemodynamic consequences of FES are echocardiography revealed a high probability related to the effect of fat accumulation in the pul- (14/24) of fat embolism during femoral rodding, monary vasculature and the evolution of reactive but the clinical correlation with FES is unclear pulmonary hypertension. The gradual accumulation [110 ] . There is decreasing probability with total of fat leads to pulmonary capillary obstruction. knee replacement, proximal humeral replace- There is acutely increased work for the right ment, and other major arthroplasty. There may be heart. The fi rst effect is acute right ventricular an age association with FES, with decrease in the strain, followed by decreased right-sided cardiac very young [ 111, 112] and an increase in the very output, which forces a decrease in the left ven- old [112 ] . tricular cardiac output. Hypoxemia from decreased The most widely accepted theory for the origin pulmonary blood fl ow and poor systemic perfu- of the fat embolism syndrome is mechanical. There sion are the endpoints when severe hemodynamic must be injury to adipose tissue, injury to blood compromise occurs [118 ] . Embolization of fat to vessels, and tissue conditions forcing fat into the the coronary arteries, with acute myocardial isch- circulation [99 ] . The full-blown fat embolism syn- emia has been reported [115 ] . drome has cutaneous, central nervous system, pul- The pulmonary consequences of FES are monary, and hemodynamic consequences that are related to the cardiovascular effects. Pulmonary obvious [113 ] . The cutaneous manifestations are a hypertension [64 ] with decreased pulmonary result of deposit of fat particles as well as activa- blood fl ow will lead to decreased systemic oxy- tion of anti-cellular enzymes that lead to capillary genation, especially if systemic cardiac output damage and leakage. There will be cutaneous decreases. Decreased availability of pulmonary petechiae over the chest, neck, trunk, and back in capillaries due to fat obstruction will cause more than 50% of cases [ 114 ] . Analogous events increased dead-space ventilation [119, 120 ] . The in the eye lead to capillary leakage, which results response within the capillary–alveolar bed will in retinal exudates, visible as “cotton-wool” [ 115 ] lead to local injury from infl ammation. The acti- exudates. In the event that renal biopsy or patho- vation of lipase will lead to breakdown of the logical exam occurs concurrently, or at autopsy, embolic fat, but it will also lead to destruction of there can be evidence of systemic embolization to type II pneumocytes directly and by the increased the kidney, although the incidence of renal injury presence of free fatty acids [121, 122 ] . Although during FES is uncommon. When renal failure does there is normal production of lipase in the 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 15

pulmonary capillary bed, the presence of greatly specifi c parts of the brain, seizure activity can increased levels of fat will accelerate produc- evolve with poor prognosis. Coma can evolve tion. This leads to increased production of free from ischemia, hypoxia, as well as embolization fatty acids, which is cytotoxic to pulmonary to key areas in the brain stem. Elevated tempera- capillaries. This will induce microthrombi ture as a nonspeci fi c CNS sign of FES has been involving lipids, platelets, and fi brin. The end reported [127 ] . result is pulmonary capillary damage, which Disseminated intravascular coagulation (DIC) further contributes to hypoxemia. The most can result from both the consumption of proco- common cause of death related to FES is respi- agulants as well as the activation of microscopic ratory failure [123 ] . coagulation from the interaction of free fatty Early clinical changes indicative of fat embo- acids with cell membranes and the adherence of lism syndrome (FES) include altered level of platelets and fi brin within the pulmonary circula- consciousness, tachypnea, dyspnea, elevated tion. An early indication of possible DIC is an temperature without other cause, and tachycardia. unexplained drop in the platelet count or the With the universal availability of pulse oximetry, fi brin level [126– 128 ] . the detection of early hypoxemia should be an There are no specifi c laboratory tests that early warning sign. An arterial oxygen tension absolutely con fi rm the diagnosis of FES. There is of less than 60 mmHg by itself should indicate general agreement that an unexplained PaO2 possible FES [124, 125] . Evolution of the pulmo- below 60 mm Hg unexplained by other pathology nary signs can include wheezing, pleuritic chest is highly suggestive of FES [ 126 ] . Serial blood pain and increasing hemoptysis, or copious secre- gas determinations that demonstrate progressive tions consistent with non-cardiogenic pulmonary hypoxemia are further confi rmation. Progressive edema. By the time that the clinical signs of FES decrease in the platelet count is another potential are apparent, the PaO2 is usually below con fi rmatory sign. Decreased hematocrit is 70 mmHg. Bilateral clinical fi ndings to ausculta- reported with either loss of red cells into tissues tion can be associated with bilateral in fi ltrates at with capillary leak or volume shifts into the blood chest X-ray, although the radiographic changes volume [ 126 ] . Fat globules in the sputum, serum, are a relatively late fi nding. Concurrent with or urine occur in a large number of subclinical changes in respiration, there should be examina- cases of fat embolism and, therefore, may be too tion for cutaneous signs of FES, and this can be sensitive to use as an indicator of serious FES, further confi rmed with retinal exam if “cotton- although the presence of these positive fi ndings wool” exudates are found. after an acute clinical episode can be used as Cardiovascular changes depend on the stage of confi rmatory evidence. A majority of patients evolution. An early fi nding can be a nonspecifi c with FES develop diffuse, bilateral in fi ltrates on tachycardia, possibly associated with some ven- chest X-ray, although this almost invariably tricular ectopy. Another early fi nding can be right occurs after clinical signs of hypoxemia have heart EKG changes such as axis change and ST–T been apparent for some time. These radiographic wave changes [126 ] . Concomitant with the devel- changes are said to resemble the radiographic opment of pulmonary hypertension will be a changes associated with adult respiratory distress hyperdynamic state on the systemic side. If there syndrome (ARDS) and, unlike vascular emboli, is hypoxemia and cyanosis, it is expected that are usually bilateral. In patients with A-a O2 gra- there may be concurrent hypotension, if the dients greater than 100 mm Hg, there is a high obstruction to right ventricular ejection results in probability of severe FES. Bronchial lavage has signifi cantly decreased left-sided fi lling pressure. been reported as diagnostic and therapeutic in Early CNS signs of FES include anxiety, severe cases [129 ] . Another unusual diagnostic apprehension, disorientation, diminished affect, approach uses somatosensory-evoked potentials lethargy, and unconsciousness. With extreme or brain stem-evoked potentials for sever CNS amounts of embolization, or embolization to injury [ 130 ] . 16 J.E. Tetzlaff

of fractures, reaming of a medullary canal, and High-Risk Surgical Procedures for FES lack of immobilization of a long bone fracture [144, 145 ] . The most serious sequelae of FES There are a variety of orthopedic surgical proce- are related to cardiovascular collapse and major dures known to be associated with a high risk of CNS injury, and the most important treatment FES. Surgery for multiple fractures is one of measures are designed to decrease the impact these situations [124, 131 ] . Total joint replace- of these changes. The cardiovascular system ment is another area where there have been a should be assumed to be in a state of acute, large number of reports of embolization of fat but right heart failure. The fi rst step is the support much less FES. Fat embolism associated with of the circulation, with aggressive volume sup- femoral stem insertion and the use of methyl port. It may become diffi cult to judge volume methacrylate has been associated with severe status without the use of full invasive hemody- hypotension and right heart failure [ 65, 66, 70, namic monitoring. Use of central venous pres- 73, 75, 78, 130, 132– 134 ] . This has also been sure monitoring should be considered at reported with total hip replacement without the minimum, and in light of the potential for severe use of cement [ 135 ] . The hypotension related pulmonary hypertension and decreasing cardiac to fat embolism during total hip insertion may be output, pulmonary artery (PA) catheterization related to massive release of tissue thrombo- should be instituted at an early point in the plastin [79 ] . Macroscopic fat was recovered from management. The aggressive support of intra- the brachial artery and femoral vein during vascular volume from left-sided fi lling pressures femoral reaming and stem insertion for total hip can more accurately guide the timing for insti- replacement [136 ] . Massive coronary artery fat tution of inotropic support of the cardiac out- was recovered at autopsy after cardiac arrest put. There is also an indication for early PA during cement insertion for total hip replacement catheter placement to manage the need for posi- [137 ] . Although the incidence is lower due to the tive end-expiratory ventilatory pressure (PEEP) use of pneumatic tourniquet, there have been which, at the high levels, will interfere with reports of FES associated with total knee cardiac output by decreasing fi lling pressures replacement [ 69, 72, 138– 141 ] . Femoral reaming from increased mean intrathoracic pressure. [136 ] , femoral shaft osteotomy [ 142 ] , and even The optimum level of PEEP may not be toler- intraosseous injection [ 143 ] have been associated ated hemodynamically without vasodilators or with FES. even selective pulmonary vasodilators to deal During key moments of arthroplasty, such as with the extreme pulmonary hypertension and reaming of the femur and insertion of endopros- inadequate pulmonary blood fl ow. thesis, with or without methyl methacrylate, Since the lesion involves in fl ammatory injury changes in heart rate, blood pressure, end-tidal to the lung and other tissue, there may be a ratio- oxygen levels as well as wave form should sug- nale for the use of high-dose steroids [99, 146– gest potential embolization of fat. Signs of right 149 ] . The CNS injuries unfortunately have ventricular strain or myocardial ischemia should limited treatment options beyond reducing the be sought with multi-lead EKG monitoring. circulation of fat and avoiding either hypoxemia Arterial blood gas determinations to quantify the or CNS ischemia from hypotension. When there degree of hypoxemia detected with pulse oxime- is cerebral edema and increased intracranial pres- try can be important. Abrupt drops in the blood sure [150 ] , cerebral perfusion pressure is also pressure can be associated with acute obstruction decreased by the increased intrathoracic pressure of ventricular out fl ow or abrupt drops in left- from the use of PEEP. In the presence of evolving sided fi lling from preload loss. CNS changes, there is a stronger indication for The fi rst step in the treatment of fat embo- the use of steroid therapy. Aggressive treatment lism is to minimize those factors that are con- of increased ICP would also be warranted, with tributing to the process, such as manipulation diuresis and hyperventilation. 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 17

Support of the pulmonary system will be key matoid arthritis and systemic lupus erythematosus. to the survival of the patient with severe FES. J Rheumatol. 2001;28:624–6. 10. Kumai Y, Murakami D, Masuda M, Yumoto E. The patients are often previously very healthy Arytenoid adduction to treat impaired adduction of and have sustained a profound, acute insult. If the vocal fold due to rheumatoid arthritis. Auris supportive measures are successful in sustaining Nasus Larynx. 2007;34:545–8. the patient without major morbidity, the potential 11. Hamdan AL, El-Khatib M, Dagher W, Othman I. Laryngeal involvement in rheumatoid arthritis. for healing of the injury and return to normal Middle Eastern J Anesth. 2007;19:335–44. function is high. The principal objective is ade- 12. Bayar N, Kara SA, Keles I, Koc C, Altinok D, Orkun quate oxygenation of the tissues, particularly the S. Cricoarytenoiditis in rheumatoid arthritis: radio- myocardium, the CNS, and other end organs. logic and clinical study. J Otolaryngol. 2003;12: 373–8. Optimum support of the cardiac output is impor- 13. Miyanohara T, Igarashi T, Suzuki H, Hiranayashi Y, tant, as is adjustment of ventilation to achieve the Seo N. Aggravation of laryngeal rheumatoid arthritis best possible oxygen delivery to the tissues, with after use of a laryngeal mask airway. J Clin the lowest possible inspired oxygen concentra- Rheumatol. 2006;12:142–4. 14. Takakura K, Hirakawa S, Kudo K, Kitano T, Noguchi tion to avoid high oxygen injury to the pulmonary T. Cricoarytenoid arthritis diagnosed after tracheos- parenchyma. This is where optimum PEEP, ade- tomy in a rheumatoid arthritis patient. Masui. quate cardiac output, and the proper sedation of 2005;54:690–3. the patient and ventilation mode are important. 15. Hayashi I, Komeichi Y, Morinaga N, Mizoguchi H, Takakuwa R, Fujiwara M. A case of severe laryngeal High inspired pressures due to patient agitation edema which occurred before removal of a laryngeal will further injure the already damaged pulmo- mask airway. Masui. 2004;53:679–81. nary system. 16. Crellin RQ, Maccabe JJ, Hamilton EBD. Severe sub- luxation of the cervical spine in rheumatoid arthritis. J Bone Joint Surg. 1993;52B:244–51. 17. Mathews JA. Atlanto-axial subluxation in rheuma- References toid arthritis: a 5-year follow-up study. Ann Rheum Dis. 1974;33:526–31. 1. MacKenzie CR, Sharrock NE. Perioperative medical 18. Rana NA, Hancock DO, Taylor AR, Hill AGS. considerations in patients with rheumatoid arthritis. Atlanto-axial subluxation in rheumatoid arthritis. Rheum Dis Clin North Am. 1998;24:1–10. J Bone Joint Surg. 1973;55B:458–70. 2. Pieringer H, Stuby U, Biesenbach G. The place of 19. Rana NA, Hancock DO, Taylor AR, Hill AGS. methotrexate perioperatively in elective orthopedic Upward translocation of the dens in rheumatoid surgeries in patients with rheumatoid arthritis. Clin arthritis. J Bone Joint Surg. 1973;55B:471–7. Rheumatol. 2008;27:1217–20. 20. Stevens JE, Cartlidge NEF, Saunders M, Stevens J, 3. Bridges SL, Moreland LW. Perioperative use of Appleby A, Hall M, Shaw DA. Atlanto-axial sublux- methotrexate in patients with rheumatoid arthritis ation and cervical myelopathy rheumatoid arthritis. undergoing orthopedic surgery. Rheum Dis Clin J Med. 1971;40:391–408. North Am. 1997;23:981–93. 21. Mayer JW, Messner RP, Kaplan RJ. Brain stem 4. Lisowska B, Rutkowska-Sak L, Maldyk P, Cwiek R. compression in rheumatoid arthritis. JAMA. Anaesthesiological problems in patients with rheu- 1976;236:1094–5. matoid arthritis undergoing orthopaedic surgeries. 22. Neva MH, Hakkinen A, Makinen H, Hannonen P, Clin Rheumatol. 2008;27:553–6. Kauppi M, Sokka T. High prevalence of asymptom- 5. Stack CG, Rogers P, Linter SPK. Monoamine oxi- atic cervical spine subluxation in patients with rheu- dase inhibitors and anesthesia: a review. Br J Anaesth. matoid arthritis waiting for orthopaedic surgery. Ann 1988;60:222–7. Rhem Dis. 2006;65:884–8. 6. Sides CA. Hypertension during anesthesia with 23. Whaley K, Dick WC. Fatal subaxial dislocation of monoamine oxidase inhibitors. Anaesthesia. 1987; cervical spine in rheumatoid arthritis. Br Med J. 42:633–5. 1968;2:31. 7. El-Ganzouri AR, Ivankovich AD, Braverman B, 24. Takenaka I, Urakami Y, Aoyama K, Terada T, McCarthy R. Monoamine oxidase inhibitors: should Ishimura H, Iwagaki T, Kadoya T. Severe subluxation they be discounted preoperatively? Anesth Analg. in the sniffi ng position in a rheumatoid patient with 1985;64:592–6. anterior atlantoaxial subluxation. Anesthesiology. 8. Wells DG, Bjorksten AR. Monamine oxidase inhibi- 2004;101:1235–7. tors revisited. Can J Anaesth. 1989;36:64–74. 25. Takenaka I, Aoyama K, Iwagaki T, Ishimura H, 9. Nanke Y, Kotake S, Yonemoto K, Hara M, Hasegawa Tanenaka Y, Kadoya T. Fluoroscopic observation of M, Kamatani N. Cricoarytenoid arthritis with rheu- the occipitoatlantoaxial complex during intubation 18 J.E. Tetzlaff

attempt in a rheumatoid patient with severe atlanto- sia in total hip or knee arthroplasty patients. axial subluxation. Anesthesiology. 2009;111:917–9. Orthopedics. 1992;w69–73. 26. Macarthur A, Kleiman S. Rheumatoid cervical joint 43. Hoek JA, Henny CP, Knipscheer HC, ten Cate H, disease- a challenge to the anaesthetist. Can J Nurmohamed MT, ten Cate JW. The effect of differ- Anaesth. 1993;40:154–9. ent anaesthetic techniques on the incidence of throm- 27. Tokunaga D, Hase H, Makiamai Y, Hojo T, Ikoma K, bosis following total hip replacement. Thromb Hatta Y, Ishida M, Sessler DI, Mizobe T, Kubo T. Haemost. 1991;65:122–5. Atlantoaxial subluxation in different intraoperative 44. Wille-Jorgensen P, Christensen SW, Bjerg-Nielsen head positions in patients with rheumatoid arthritis. A, Stadeager C, Kjaer L. Prevention of thromboem- Anesthesiology. 2006;104:675–9. bolism following elective hip surgery. The value of 28. Kwek TK, Lew TW, Thoo FL. The role of preopera- regional anesthesia and graded compression stock- tive cervical spine x-rays in rheumatoid arthritis. ings. Clin Orthop. 1989;247:163–7. Anaesth Intensive Care. 1008;26:636–41. 45. Davis FM, Laurenson VG, Gillespie WJ, Wells JE, 29. Hakala P, Randell T. Intubation dif fi culties in patients Foate J, Newman E. Deep vein thrombosis following with rheumatoid arthritis. A retrospective analysis. total hip replacement. A comparison between spinal Acta Anaesthesiol Scand. 1998;42:195–8. and general anesthesia. J Bone Joint Surg. 1989;71B: 30. Stulberg BN, Insall JN, Williams GW, Ghelman B. 181–5. Deep-vein thrombosis following total knee replace- 46. Davis FM, Laurenson VG, Gillespie WJ, Foatye J, ment. J Bone Joint Surg. 1984;66:194–201. Seagar AD. Leg blood fl ow during hip replacement 31. Jorgensen LN, Rasmussen LS, Nielsen PT, Leffers under spinal or general anaesthesia. Anaesth A, Albrecht-Beste E. Antithrombotic effi cacy of Intensive Care. 1989;17:136–43. continuous extradural analgesia after knee replace- 47. Donadoni R, Baele G, Duvulder J, Rolly G. ment. Br J Anaesth. 1991;66:8–12. Coagulation and fi brinolytic parameters in patients 32. Chin SP, Abou-Madi MN, Eurin B, Witvoet J, undergoing total hip replacement: infl uence of anes- Montagne J. Blood loss in total hip replacement: thetic technique. Acta Anaesthesiol Scand. 1989;33: extradural vs phenoperidine analgesia. Br J Anaesth. 588–92. 1982;54:491–4. 48. Ranawat CS, Beaver WB, Sharrock NE, Maynard 33. Sculco TP, Ranawat C. The use of spinal anesthesia MJ, Urquhart B, Schneider R. Effect of hypotensive for total hip-replacement arthroplasty. J Bone Joint epidural anesthesia on acetabular cement-bone Surg. 1975;57A:173–7. fi xation in total hip arthroplasty. J Bone Joint Surg. 34. Keith I. Anesthesia and blood loss in total hip 1991;73B:779–82. replacement. Anaesthesia. 1977;32:444–50. 49. Hole A, Terjesen T, Breivik H. Epidural versus gen- 35. Wakamatsu M, Ono K, Katoh H, Furuta M, Kondo eral anaesthesia for total hip arthroplasty in elderly U, Yamamoto T. Effect of combined spinal and epi- patients. Acta Anaesthesiol Scand. 1980;24:279–87. dural anesthesia on blood loss during total hip 50. Nielson WR, Gelb AW, Casey JE, Penny FJ, replacement. Masui. 1993;42:56–9. Merchant RN, Manninen PH. Long-term cognitive 36. Maruyama M, Takei H, Takei T, Kitagawa E. Factors and social sequelae of general versus regional anes- that infl uence intraoperative blood loss during total thesia during arthroplasty in the elderly. hip replacement. Masui. 1992;41:1180–2. Anesthesiology. 1990;73:1103–9. 37. Rosberg B, Fredin H, Gustafson C. Anesthetic tech- 51. Riis J, Lomholt B, Haxold O, Kehler H, Valentin N, niques and surgical blood loss in total hip arthro- Danielsen U, Dyrberg V. Immediate and long-term plasty. Acta Anaesthesiol Scand. 1982;26:189–93. mental recovery from general versus epidural anes- 38. Modig J. Bene fi cial effects on intraoperative and thesia in elderly patients. Acta Anaesthesiol Scand. postoperative blood loss in total hip replacement 1983;27:44–9. when performed under lumbar epidural anesthe- 52. Erksine R, Janicki PK, Ellis P, James MF. sia- an explanatory study. Acta Chir Scand. Neutrophils from patients undergoing hip surgery 1989;550:95–100. exhibit enhanced movement under spinal anesthesia 39. Thorburn J. Subarachnoid blockade and total hip compared to general anesthesia. Can J Anaesth. replacement. Br J Anaesth. 1985;57:290–3. 1992;39:899–904. 40. Modig J. Benefi cial effects on intraoperative and post- 53. Salo M, Nissila M. Cell-mediated and humoral operative blood loss in total hip replacement when immune response to total hip replacement under spi- performed under lumbar epidural anesthesia- an nal or general anesthesia. Acta Anaesthesiol Scand. explanatory study. Acta Chir Scand. 1989;55:95–100. 1990;34:241–8. 41. Sharrock NE, Haas SB, Hargett MJ, Urquhart B, 54. Davis S, Erksine R, James MF. A comparison of spi- Insall JN, Scuderi G. Effects of epidural anesthesia nal and epidural anaesthesia for hip arthroplasty. on the incidence of deep-vein thrombosis after Can J Anaesth. 1992;39:551–4. total knee arthroplasty. J Bone Joint Surg. 1991; 55. Davis FM, Laurensen VG, Lewis J, Wells JE, 73A:502–6. Gillespie WJ. Metabolic response to total hip arthro- 42. McQueen DA, Kelly HK, Wright TF. A comparison plasty under hypobaric subarachnoid or general of epidural and non-epidural anesthesia and analge- anesthesia. Br J Anaesth. 1987;59:725–9. 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 19

56. Marsch SC, Schaefer HG, Skarvan K, Castelli I, 71. Tronzo RG, Kallos T, Wyche MQ. Evaluation of Scheidegger D. Perioperative myocardial ischemia intramedullary pressure when methylmethacrylate is in patients undergoing elective hip arthroplasty dur- inserted in total hip arthroplasty. J Bone Joint Surg. ing lumbar regional anesthesia. Anesthesiology. 1974;54:714–8. 1992;76:518–27. 72. Jones RH. Physiologic emboli changes observed 57. Amaranath L, Cascorbi H, Singh-Amaranath AV, during total hip replacement arthroplasty. Clin Frankmann DB. Relation of anesthesia to total hip Orthop. 1975;112:192–200. replacement and control of operative blood loss. 73. Kallos T. Impaired arterial oxygenation associated Anesth Analg. 1975;54:641–8. with the use of bone cement in the femoral shaft. 58. Yukioka H, Asada K, Fujimora M, Shimazu A. Anesthesiology. 1975;42:210–6. Prostaglandin E1 as a hypotensive drug during gen- 74. Modig J, Busch C, Olerud S, Saldeen T. Pulmonary eral anesthesia for total hip replacement. J Clin microembolism during orthopedic intramedullary Anesth. 1993;5:310–4. trauma. Acta Anaesthesiol Scand. 1974;18: 59. Barbier-Bohm G, Desmonts JM, Couderc E, Moulin 133–43. D, Prokocimer P, Oliver H. Comparative effects of 75. Alexander JP. Clinical considerations in anaesthesia induced hypotension and normovolemic haemodilu- for hip arthroplasty. Anaesthesia. 1978;33:748–51. tion on blood loss in total hip arthroplasty. Br J 76. Michel R. Air embolism in hip surgery. Anaesthesia. Anaesth. 1980;52:1039–43. 1980;35:858–62. 60. Qvist TF, Skovsted P, Bredgaard-Sorensen M. 77. Andersen KH. Air aspirated from the venous sys- Moderate hypotensive anesthesia for reduction of tem during total hip replacement. Anaesthesia. blood loss during total hip replacement. Acta 1983;38:1175–8. Anaesthesiol Scand. 1982;26:351–3. 78. Newens AF, Volz RG. Severe hypotension during 61. Thompson GE, Miller RD, Stevens WC, Murray prosthetic hip surgery with acrylic bone cement. WR. Hypotensive anesthesia for total hip arthro- Anesthesiology. 1972;36:298–300. plasty. A study of blood loss and organ function. 79. Modig J, Malmberg P. Pulmonary and circulatory Anesthesiology. 1978;48:91–6. reactions during total hip replacement. Acta 62. Sharrock NE, Mineo R, Urquhart B, Salvati EA. Anaesthesiol Scand. 1975;19:219–37. The effect of two levels of hypotension on intraop- 80. Modig J, Borg T, Karlstrom G, Maripuu E, Sahlstedt erative blood loss during total hip arthroplasty per- B. Thromboembolism after total hip replacement: formed under lumbar epidural anesthesia. Anesth role of epidural and general anesthesia. Anesth Analg. 1993;76:580–4. Analg. 1983;62:174–80. 63. Safwat AM, Dror A. Pulmonary capillary leak asso- 81. Modig J, Malmberg P, Karlstrom G. Effect of epidural ciated with methylmethacrylate during general anes- versus general anaesthesia on calf blood fl ow. Acta thesia. Clin Orthop. 1982;168:59–63. Anaesthesiol Scand. 1980;24:305–9. 64. Byrick RJ, Wong PY, Mullen JB, Wigglesworth DF. 82. Modig J, Maripuu E, Sahlstedt B. Thromboembolism Ibuprofen pretreatment does not prevent hemody- following total hip replacement: a prospective inves- namic instability after cemented arthroplasty in tigation of 94 patients with emphasis on the ef fi cacy dogs. Anesth Analg. 1992;75:515–22. of lumbar epidural anesthesia in prophylaxis. Reg 65. Cohen CA, Smith TC. The intraoperative hazard of Anesth. 1986;11:72–9. acrylic bone cement: report of a case. Anesthesiology. 83. Covert CR, Fox GS. Anaesthesia for hip surgery in 1971;35:547–9. the elderly. Can J Anaesth. 1989;36:311–9. 66. Peebles DJ, Ellis RJ, Slide SD, Simpson BR. 84. Rosenfeld BA. Bene fi ts of regional anesthesia on Cardiovascular effects of methylmethacrylate thromboembolic complications following surgery. cement. Br Med J. 1972;1:349–51. Reg Anesth. 1996;21:9–12. 67. Modig J, Busch C, Olerud S, Saldeen T, Waernbaum 85. Wolf H. Experience with regional anesthesia in G. Arterial hypotension and hypoxemia during total patients receiving low molecular weight heparins. hip replacement: the importance of thromboelastic Semin Thromb Hemost. 1993;19:152–4. products, fat embolism and acrylic monomers. Acta 86. Bergovist D, Lindblad B, Matzsch T. Risk of com- Anaesthesiol Scand. 1975;19:28–43. bining low molecular weight heparin for thrombo- 68. Learned DW, Hantler CB. Lethal progression of prophylaxis and epidural or spinal anesthesia. Semin heart block after prosthesis cementing with methyl- Thromb Hemost. 1993;19:147–9. methacrylate. Anesthesiology. 1992;77:1044–6. 87. Horlocker TT, Heit JA. Low molecular weight hepa- 69. Byrick RJ, Forbes D, Waddell JP. A monitored car- rin: biochemistry, pharmacology, perioperative pro- diovascular collapse during cemented total knee phylaxis regimens, and guidelines for regional replacement. Anesthesiology. 1986;65:213–6. anesthetic management. Anesth Analg. 1997;85: 70. Egbert R, von Hundelshausen B, Gradinger R, Hipp 874–85. E, Kolb E. Heart arrest in implantation of a cemented 88. Choquet O, Krivosic-Horber R, Delecroix M, Huriau total hip endoprosthesis under spinal anesthesia–a M, Pruvo JP. Spinal subarachnoid haematoma after case report. Anasthesie Intensivther Notfallmed. spinal anaesthesia and low molecular weight hepa- 1989;24:118–20. rin. Ann Fr Anesth Reanim. 1993;12:428–30. 20 J.E. Tetzlaff

89. VandePol C. Exoxaparin and epidural analgesia. evaluation in 92 fracture patients. Crit Care Med. Anesthesiology. 1996;85:432–4. 1990;18:42–6. 90. Horlocker TT, Wedel DJ, Rowlingson JC, Enneking 107. Pallak R, Meyers RAM. Early diagnosis of fat embo- FK, Kopp SL, Benzon HT, Brown DL, Heit JA, lism syndrome. J Trauma. 1978;18:121–3. Mulroy MF, Rosenquist RW, Tryba M, Yuan CS. 108. Gurd AR. Fat embolism: a guide to diagnosis. Regional anesthesia in the patient receiving anti- J Bone Joint Surg. 1970;52:732–7. thrombotic or thrombolytic therapy. Reg Anesth 109. McKenzie PJ, Wishart HY, Dewar KMS, Gray I, Pain Med. 2010;35:64–101. Smith G. Comparison of the effects of spinal anaes- 91. Sharrock NE, Go G. Fibrinolytic activity following thesia and general anaesthesia on postoperative oxy- total knee arthroplasty under epidural or general genation and perioperative mortality. Br J Anaesth. anesthesia. Reg Anesth. 1992;17:94. 1980;52:49–53. 92. Davis FM, Woolner DF, Frampton C, Wilkinson A, 110. Pell AC, Christie J, Keating JF, Sutherland GR. The Grant A, Harrison RT, Roberts MTS, Thadaka R. detection of fat embolism by transoesophageal Prospective, multi-centre trial of mortality following echocardiography during reamed intramedullary general or spinal anaesthesia for hip fracture surgery nailing. A study of 24 patients with femoral and tib- in the elderly. Br J Anaesth. 1987;59:1080–8. ial fractures. J Bone Joint Surg Br. 1993;75:921–5. 93. Fernandez MC, Gottlieb M, Menitove JE. Blood 111. Pollack Jr CV, Pender ES. Fat emboli syndrome. transfusion and postoperative infection in orthopedic J Emerg Med. 1992;10:705–11. patients. Transfusion. 1992;32:318–22. 112. Pender ES, Pollack Jr CV, Evans OB. Fat embolism 94. Murphy P, Heal JM, Blumberg N. Infection or sus- syndrome in a child with muscular dystrophy. J Emerg pected infection after hip replacement surgery with Med. 1992;10:705–11. autologous or homologous blood transfusions. 113. Carr JB, Hansen ST. Fulminant fat embolism. Transfusion. 1991;31:212–7. Orthopedics. 1990;13:258–61. 95. Petersen MS, Collins DN, Selakovich WG, 114. Kaplan RP, Grant JN, Kaufman AJ. Dermatologic Finkbeiner AE. Postoperative urinary retention asso- features of the fat embolism syndrome. Cutis. 1986; ciated with total hip and total knee arthroplasties. 38:52–5. Clin Orthop Relat Res. 1991;269:102–8. 115. Sevitt S. The signi fi cance and pathology of fat embo- 96. Horlocker TT, Cabanela ME, Wedel DJ. Does post- lism. Ann Clin Res. 1977;9:173–80. operative epidural analgesia increase the risk of per- 116. Jacobson DM, Terrence CF, Reinmuth OM. The neu- oneal nerve palsy after total knee arthroplasty? rologic manifestations of fat embolism. Neurology. Anesth Analg. 1994;79:495–500. 1986;36:847–51. 97. Strecker WB, Wood MB, Bieber EJ. Compartment 117. Pell AC, Hughes D, Keating J, Christie J, Busuttil A, syndrome masked by epidural anesthesia for postop- Sutherland GR. Brief report: fulminating fat embo- erative pain. J Bone Joint Surg. 1986;68A:1447–8. lism syndrome caused by paradoxical embolism 98. Beerle BJ, Rose RJ. Lower extremity compartment through a patent foreman ovale. N Engl J Med. syndrome from prolonged lithotomy position not 1993;329:926–9. masked by epidural bupivacaine and fentanyl. Reg 118. Reid CB, Hill DA. Acute cor pulmonale and death Anesth. 1993;18:189–90. due to massive fat embolism. Aust N Z J Surg. 99. Ashbaugh DG, Petty TL. The use of corticosteroids 1992;62:320–2. in the treatment of respiratory failure associated with 119. Moser KM. Diagnostic measures in pulmonary massive fat embolism. Surg Gynecol Obstet. embolism. Basics of RD. 1975;3:57–9. 1966;60:493–500. 120. Galdermans D, Coolen D, Neetens I, Bultinck J, Parizel 100. Peltier LF. Fat embolism: a perspective. Clin Orthop. G. Pulmonary fat embolism presenting as chronic 1988;232:263–70. respiratory failure. Eur Respir J. 1989;2:185–7. 101. Wheelwright EF, Byrick RJ, Wigglesworth DF, Kay 121. Batra P. The fat embolism syndrome. J Thorac JC, Wong PY, Mullen JB, Waddell JP. Hypotension Imaging. 1987;2:12–7. during cemented arthroplasty. Relationship to car- 122. Schnaid E, Lamprey JM, Viljoen MJ, Joffe BI, Seftel diac output and fat embolism. J Bone Joint Surg Br. HC. The early biochemical and hormonal pro fi le of 1993;75:715–23. patients with long bone fractures at risk of fat embo- 102. Robert JH, Hoffmeyer P, Broquet PE, Cerutti P, lism syndrome. J Trauma. 1987;27:309–11. Vasey H. Fat embolism syndrome. Orthop Rev. 123. Van Besouw JP, Hinds CJ. Fat embolism syndrome. 1993;22:567–71. Br J Hosp Med. 1989;42:304–11. 103. Fulde GW, Harrison P. Fat embolism–a review. Arch 124. Benoit PR, Hampson LG, Burgess JH. Value of arte- Emerg Med. 1991;8:233–9. rial hypoxemia in the diagnosis of fat embolism syn- 104. Levy D. The fat embolism syndrome. A review. Clin drome. Ann Surg. 1972;175:128–37. Orthop. 1990;261:281–6. 125. Chan KM, Tham KT, Chiu HS, Chow YN, Leung 105. Ganong RB. Fat emboli syndrome in isolated fractures PC. Post-traumatic fat embolism–its clinical and of the tibia and femur. Clin Orthop. 1993;291:208–14. subclinical presentations. J Trauma. 1984;24:45–9. 106. Fabian TC, Hoots AV, Stanford DS, Patterson CR, 126. Wright BD. Diagnostic features of fat embolism- Mangiante EC. Fat embolism syndrome: prospective results in six cases. Anesthesiology. 1971;34:290–4. 1 Anesthetic Issues for Orthopedic Surgery in Patients with Rheumatoid Diseases 21

127. ten Duis HJ, Nijsten MW, Klasen HJ, Binnendijk B. 139. Caillouette JT, Anzel SH. Fat embolism syndrome Fat embolism in patients with an isolated fracture of following the intramedullary alignment guide in the femoral shaft. J Trauma. 1988;28:383–90. total knee arthroplasty. Clin Orthop. 1990;251: 128. Bradford DS, Forster RR, Nossel HL. Coagulation 198–9. alterations, hypoxemia and fat embolism in fracture 140. Dorr LD, Merkel C, Mellman MF, Klein I. Fat patients. J Trauma. 1970;10:307–21. emboli in bilateral total knee arthroplasty. Predictive 129. Chastre J, Fagon JY, Soler P, Fichelle A, Dombret factors for neurologic manifestations. Clin Orthop. MC, Huten D, Hance AJ, Gilbert C. Bronchoalveolar 1989;248:112–9. lavage for rapid diagnosis of the fat embolism syn- 141. Orsini EC, Richards RR, Mullen JM. Fatal fat embo- drome in trauma patients. Ann Intern Med. lism during cemented total knee arthroplasty: a case 1990;113:583–8. report. Can J Surg. 1986;29:385–6. 130. Morioka T, Yagi H. Brain function in patients with 142. Edwards KJ, Cummings RJ. Fat embolism as a com- cerebral fat embolism evaluated using somatosen- plication of closed femoral shortening. J Pediatr sory and brain-stem auditory evoked potentials. Orthop. 1992;12:542–3. J Neurol. 1989;236:415–7. 143. Orlowski JP, Julius CJ, Petras RE, Porembka DT, 131. O’Toole DP, Gilroy D, Baili IM. Fulminant fat Gallagher JM. The safety of intraosseous infusions: embolism associated with closed fracture reduction. risks of fat and bone marrow emboli to the lungs. Ulster Med J. 1986;55:86–8. Ann Emerg Med. 1989;18:1062–7. 132. Maxeiner H. Fatal intraoperative lung fat embolism 144. Pazell JA, Peltier LF. Experience with sixty-three in endoprosthesis of the hip joint. Beitr Gerichtl patients with fat embolism. Surg Gynecol Obstet. Med. 1989;47:415–27. 1972;135:77–80. 133. Noguchi T, Iwasaka H, Hayano Y, Miyamoto M, 145. Peltier LF. Fat embolism. A perspective. Clin Orthop. Oda S, Taniguchi K, Honda N, Honda Y. Effects of 1989;232:263–70. acrylic bone cement following total hip replacement. 146. Putterman C. Corticosteroids in fat embolism syn- Masui. 1986;35:1727–31. drome: treatment and prevention. Harefuah. 134. Hagley SR, Lee FC, Blumbergs PC. Fat embolism 1991;120:596–8. syndrome with total hip replacement. Med J Aust. 147. Byrick RJ, Mullen JB, Wong PY, Wigglesworth D, 1986;145:541–3. Kay JC. Corticosteroids do not inhibit acute pulmo- 135. Watson JT, Stulberg BN. Fat embolism associated nary response to fat embolism. Can J Anaesth. with cementing of femoral stems designed for press- 1990;37:130. fi t application. J Arthroplasty. 1989;4:133–7. 148. Kallenbach J, Lewis M, Zaltzman M, Feldman C, 136. Renne J, Wuthier R, House E, Cancro JC, Hoaglund Orford A, Zwi S. ‘Low-dose’ corticosteroid prophy- FT. Fat macroglobulemia caused by fractures or total laxis against fat embolism. J Trauma. 1987;27: hip replacement. J Bone Joint Surg. 1978;65A:613–8. 1173–6. 137. Camann WR, Sacks GM, Schools AG, Heggeness ST, 149. Lindeque BG, Schoeman HS, Dommisse GF, Reilly DT, Concepcion M. Nearly fatal cardiovascular Boeyens MC, Vlok AL. Fat embolism and the fat collapse during total hip replacement: probable coro- embolism syndrome. A double-blind therapeutic nary arterial embolism. Anesth Analg. 1991;72:245–8. study. J Bone Joint Surg Br. 1987;69:128–31. 138. Monto RR, Garcia J, Callaghan JJ. Fatal fat embo- 150. Meeke RI, Fitzpatrick GJ, Phelan DM. Cerebral lism following total condylar knee arthroplasty. oedema and the fat embolism syndrome. Intensive J Arthroplasty. 1990;5:291–9. Care Med. 1987;13:291–2. Perioperative Pain Management and Orthopedic Surgery 2

John E. Tetzlaff

prevent effective pulmonary toilet, and can be Introduction related to postoperative pulmonary complications. Poorly treated postoperative pain may increase Given the nature of orthopedic surgery, moderate the incidence of deep venous thrombosis and to severe pain should be anticipated with almost pulmonary embolism. every major procedure. To achieve a reasonable Not only are the strategies for acute pain control degree of patient satisfaction, a well-designed being investigated, but considerable work has plan to control acute pain should be a part of every focused on the mechanisms of acute pain and procedure. Ideally, the plan should be presented timing of analgesia administration. The peaks to patients before they go to the operating room and valleys of pain control and sedation that so that they will understand their role in the plan occur with traditional, on-demand opiate treat- and can participate fully. This approach assures ment has been compared to PCA approaches, and the patient that some intervention to deal with the pain scores in the PCA patients are more level acute pain will be implemented before excruciating over time, with the same or lower total doses of pain is felt. This approach is reinforced by opiates [1 ] . Other work has demonstrated that patients, who hear from the lay press that excellent combinations of analgesic strategies, including control of pain is possible and should be consid- interventions prior to surgery (“preemptive anal- ered in selecting physicians and health-care gesia”) can improve pain control [2 ] , reduce facilities. length of hospital stay [3 ] , and decrease the cost Beyond patient satisfaction, evidence is of lower extremity joint replacement [4 ] . increasing that poorly controlled acute pain may Many of the advances in perioperative pain be associated with the development of postopera- control have evolved from an increased under- tive complications and that excellent analgesia standing of the mechanism of acute pain. The may improve the outcome after surgery. Acute anatomy, physiology, and pharmacology of acute pain has adverse hemodynamic consequences, pain signaling translate directly into strategies for such as hypertension, tachycardia, and increased acute pain control. tissue oxygen demand, which in patients with cardiac or pulmonary disease can cause myocardial ischemia. Acute pain can decrease ventilation, Mechanisms of Acute Pain

Tissue injury causes the emotional experience of  J. E. Tetzlaff , M.D. ( ) acute pain for the patient when traumatic inter- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cle veland , OH , USA ventions (e.g., surgery) activate nociceptors, e-mail: [email protected] which code the stimuli as a pattern of neural

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 23 DOI 10.1007/978-1-4614-2203-7_2, © Springer Science+Business Media, LLC 2013 24 J.E. Tetzlaff impulses for conduction by the small A-delta and ing in a change in the biochemistry around the C fi bers (slow conducting) of the peripheral dorsal horn cells, decreasing receptor threshold nerves to the central nervous system. Tissue required to create nociceptive transmission injury causes release of intracellular mediators decreases and enlarging the receptor fi eld [ 10 ] . (bradykinin, serotonin, substance P, histamine) This sustained, self-propagating depolarization and which increase the sensitivity of peripheral creates central hypersensitivity [11 ] and is also receptors. The combination of edema, vasodilata- called “wind-up” [ 12 ] . The progression from tion, and the direct effects of tissue-injury media- peripheral to central hypersensitivity and maxi- tors further activates mechanical receptors. The mally nociceptive transmission leads to the net increase of nociceptive activity that results is hyperacute phase of early postoperative pain. referred to as peripheral hypersensitivity [5 ] , and The signals from the dorsal horn synapse with the gradually increasing transmission from receptor cells, cross to the opposite side at the peripheral nociceptors is termed hyperalgesia. same level or within 1–2 segments, and enter Evidence from work with experimental arthritis the lateral spinothalamic tract. They ascend into in the cat knee joint has revealed that silent recep- the thalamus, where some synapse directly with tors are recruited to take on a nociceptive func- the somatosensory cortex to produce acute sensation tion in response to tissue injury and infl ammation and some synapse in the brainstem reticular [6 ] . At wound sites not within joints, peripheral formation, where they participate in the downward hypersensitivity results in similar recruitment of pathways that modulate nociceptive transmis- previously “silent” receptors in the tissues sur- sion. These synapses also project into the lim- rounding the wound site [ 7 ] . Normal mechanical bic brain, creating the emotional aspects of stimulation, such as light touch or gentle move- pain perception. ment, causes these receptors to send nociceptive signals, resulting in pain disproportionate to the stimulus. The Physiology of Pain in Orthopedic As peripheral nociceptive signals approach Patients the spinal cord, they move ventrolateral to syn- apse in the gray matter of the dorsal horn. These A unique aspect of orthopedic surgery is that large synapses contain numerous neurotransmitters, amounts of tissue injury messengers are released including gamma aminobutyric acid, glutaminic via manipulation of fractures, osteotomy, or ream- acid, substance P, somatostatin, vasoactive intes- ing the medullary canal of long bones. The pro- tinal peptide, and cholecystokinin octapeptide [8 ] pensity to peripheral and central hypersensitivity which facilitate transmission rostral through the is great, and the probability of hyperacute pain is spinothalamic tracts cephalad toward the thala- high. The need for analgesia is obvious. mus. There are also descending pathways that inhibit nociceptive transmission via neurotrans- mitters including norepinephrine, serotonin, and Therapeutic Options the encephalins. Much of the analgesic effect of for Postoperative Analgesia systemic opiates occurs by activation of these descending control paths [9 ] . Nonsteroidal Anti-Infl ammatory Drugs Nociceptive transmission is modulated by the rate of transmission. The initial tissue injury The role of NSAIDs postoperative analgesia lies within a surgical wound creates a limited number in the ability to interfere with the peripheral of nociceptive signals, which reach the dorsal production of some tissue-injury mediators [13 ] . column. When sustained tissue injury creates A decrease in production of eicosanoid precursors peripheral hypersensitivity, signaling greatly of prostaglandins from arachidonic acid decreases increases. As the number of signals increases, the amount of these mediators, which are mainly there is accumulation of neurotransmitter, result- prostaglandin derivatives. This decreases nocice- 2 Perioperative Pain Management and Orthopedic Surgery 25 ptive transmission by decreasing peripheral sensi- patients, when morphine does not achieve the tization. Also, some evidence shows that parenteral level of analgesia desired. The synthetic opioids, NSAIDs act directly on the central nervous sys- such as fentanyl and sufentanil, are more potent tem by blocking excessive secretion of dorsal with a more rapid onset and shorter half-life. horn excitatory transmitters, preventing central Their advantage is a rapid onset with fewer side hypersensitization. Experimental evidence shows effects (itching and urinary retention), although that parenteral NSAIDs and central opioids act the short duration makes the continuous adminis- synergistically [ 14 ] . NSAIDs can act as an adjunct tration by pump or a PCA device mandatory. to opioids (“opioid-sparing”) or as a substitute The use of opiate agonist–antagonist agents, sole analgesic for procedures associated with mild such as nalbuphine, in orthopedic patients has to moderate postoperative pain [ 15] . The new, been limited by upper limit to the amount of anal- selective NSAIDs in the COX-2 class have similar gesia that can be obtained which is often too low ef fi cacy with less impact on the gastrointestinal to achieve adequate pain control after major tract and no impact on platelet function [16– 18 ] . orthopedic surgery. In addition, opiate agonist– NSAIDs have a limited threshold for analgesia antagonist agents should be used with caution in and are not usually effective as a sole analgesic patient dependent on opiates to avoid triggering after major orthopedic surgery. They may be better withdrawal. suited to be part of a multimodal analgesic plan. Preoperative use of NSAIDs has been associated with increased bleeding in the perioperative Peripheral Nerve Blocks period. Another limitation of NSAID use is the small decrease in renal blood fl ow, which should Postoperative analgesia can be induced if the route be clinically silent except in those patients with from the site of surgical injury to the spinal cord is limited renal reserves or who are hypovolemic. interrupted with local anesthetics injected [2 ] via The potential for inducing acute renal failure peripheral nerve block, fi eld block, or wound limits the use of NSAIDs for postoperative anal- infi ltration. Upper and lower extremity peripheral gesia in patients with chronic renal insuffi ciency. nerve block with a catheter can accomplish this objective for a large percentage of extremity pro- cedures [19, 20] . Peripheral nerve block with low- Parenteral Opioids concentration local anesthetics via catheter virtually silences nociceptive transmission and Classic pain control with on-demand parenteral has the added benefi t of reducing infl ammation at opiates has been the standard for treatment of the wound site [ 21, 22 ] . For those cases where postoperative pain. Morphine is the best known catheter placement is not applicable or technically agent and readily lends itself to both parenteral possible, single-shot interruption of nociceptive and on-demand PCA delivery. Primary side transmission with long-acting local anesthetics, effects are dose-dependent respiratory depres- such as bupivacaine or ropivacaine, is a good sion, followed by nausea, itching, and urinary alternative. It is rapidly becoming a consensus retention. Meperidine is a comparable agent, with that peripheral nerve blocks, especially via cathe- PCA use being limited by the accumulation of a ter infusion, are the single best approach to post- metabolic product, normeperidine, which can operative analgesia for orthopedic patients. cause seizures. As a result, there is very little use There is evidence that injection of local anes- of meperidine in PCA devices. Meperidine must thetic into joint spaces [ 23] , before or after intra- be avoided in patients taking MAO inhibitors, articular surgery, decreases or eliminates which have had a role in the treatment of rheuma- postoperative pain. The pain relief achieved is toid patients in the past, because of the concern reported in some instances to greatly outlast the for hyperpyrexic coma. Dilaudid has become a duration of action of the agent injected, especially favorite alternative to morphine for hospital if combined with intra-articular morphine [ 24 ] . 26 J.E. Tetzlaff

In addition, when epinephrine is used for its vaso- constrictive bene fi ts, the adrenergic agent has Preemptive Analgesia been observed to increase the analgesic quality of and Orthopedic Patients the intra-articular injections [ 25 ] .Some of the enthusiasm for intra-articular injection has been Observations of reduced postoperative pain in reduced by preliminary information that impli- orthopedic patients who had received pain medi- cates intra-articular local anesthetics with chon- cine prior to surgery led to speculation about the drolysis in the setting of shoulder surgery [26 ] . concept of preemptive analgesia. One of the early reports was from McQuay [32 ] in trauma surgery. If patients received an opiate premedication, their Central Blocks interval to fi rst request for pain medicine postop- eratively was signi fi cantly prolonged and the Neuraxial blocks for surgical anesthesia can also total opiate required in the fi rst 24 h was reduced. achieve postoperative pain control depending on This preventative effect of opiate premedication the solution injected. With spinal anesthesia via was also reported after elective lumbar spine surgery local anesthetic, the effect is limited with the res- [ 33] . Almost 50% of the patients who received an olution of the block. When epidural anesthesia is opiate premedication required no parenteral opiates extended into the postoperative period with low- within the fi rst 24 h after surgery. A preemp- concentration local anesthetics, excellent analgesia tive effect was also reported by Taivainen [ 34 ] can be achieved. Although epidural local in trauma surgery patients who were given anesthetics provide good pain control with an parenteral indomethacin starting in the emer- acceptable side-effect profi le, hypotension in gency room, although there was some additional hypovolemic patients, orthostasis, and urinary postoperative bleeding. The pain of iliac crest retention can occur. bone graft harvest was signifi cantly reduced by Use of adjuncts to centrally administered pre-incisional in fi ltration of the site [35 ] . This local anesthetics can improve their analgesic reduction in pain extended as far as 24 h after a profi le or allow a lower concentration of local single injection. anesthetic to be added. These include opiates and adrenergic agonists such as clonidine and epinephrine. Synergistic mechanisms at the Approaches to Analgesia for Specifi c spinal cord level [27, 28 ] may make the local Orthopedic Procedures anesthetic–opiate combination ideal. Other agents that interfere with hypersensitivity, Different orthopedic procedures create unique wind-up, and cephalad transmission of nocice- postoperative analgesia requirements. It is useful ption have potential roles as neuraxial analge- to consider the approaches to analgesia for indi- sics, including ketorolac [ 13] , ketamine [ 29 ] , vidual types of orthopedic surgery. calcium [ 30 ] , calcium channel antagonists [ 31 ] , GABA inhibitors, serotonin antagonists, and others. Because nociceptive transmission Shoulder Surgery involves a number of steps, involving a variety of neurotransmitters, combinations of agonists The majority of the clinical reports of pain con- and antagonists at receptor sites have great trol after shoulder surgery involve supraclavicu- potential as an analgesic strategy, and the con- lar or interscalene block, either by injection of a cept of “multimodal analgesia” has been evalu- long-acting local anesthetic or the placement of a ated [ 2, 31] . An attractive possibility is that the catheter [36 ] . The ease of single injection inter- doses of the individual agents could be reduced, scalene block is in contrast with some of the tech- thereby decreasing the incidence of side effects nical issues with catheter placement. Tuominen from each [ 27, 28 ] . [ 37 ] described the technique, noting the technical 2 Perioperative Pain Management and Orthopedic Surgery 27 diffi culty of placing and maintaining a catheter in patient, CNS toxicity in four, and catheter failure the neck. Haasio [ 38 ] reported minimal need for in 5/40 patients in his series [ 51 ] . Placement of the supplemental opiates after shoulder surgery with catheters during general anesthesia is discouraged an interscalene catheter, although 10% of the because the patient cannot report paresthesia patients experienced at least mild CNS signs of during catheter insertion, which increases the risk local anesthetic toxicity. The use of continuous of neurological injury, even though being unaware interscalene block resulted in severe bupivacaine during the procedure is attractive from the patient cardiac toxicity in a case reported by Tuominen satisfaction standpoint [52 ] . [39 ] involving the migration of the catheter into Less common approaches to analgesia for an artery several days after placement. With shoulder surgery include fl uoroscopic-guided, improved catheter placement techniques using proximal axillary catheter placement [53 ] and ultrasound, the effi cacy of interscalene cathe- intra-articular injection or infusion of local anes- ters for postoperative pain control has been thetics [54– 56] . The initial enthusiasm with established [ 40– 42] . When compared to PCA intra-articular and subacromial placement of local morphine, an interscalene catheter with patient- anesthetics has been dampened by subsequent controlled infusion option provided superior reports that dispute the ef fi cacy [57– 59 ], and omi- analgesia with reduced side effects [ 43 ] . The nous early reports of chondrolysis with continuous same benefi t can be achieved with ambulatory intra-articular infusion of bupivacaine, thought to patients when an interscalene catheter and a be related to direct cytotoxicity [26 ] . disposable local anesthetic delivery device are The consensus for pain control after major compared to parenteral opiates in the PACU and shoulder surgery focuses on peripheral nerve block oral narcotics at home [ 44, 45 ] . The techniques via catheter technique, either via the supraclavicu- for patient-controlled interscalene anesthesia have lar or interscalene route. In centers without an acute been studied, and it was reported that a continuous pain service, single-shot interscalene block with infusion combined with patient-controlled doses low-concentration bupivacaine or ropivacaine (to improved the quality of analgesia after shoulder minimize motor block) is a reasonable alternative. surgery compared to the patient-controlled doses without the basal infusion [46 ] . The safety of interscalene catheters and continuous infusion Hip Fracture of 0.25% bupivacaine has been established by showing plasma levels well below toxic levels up The majority of data about pain control after repair to 52 h after the start of the infusion [47 ] . of hip fracture centers around neuraxial blocks. There have been more reports of technical Although intrathecal opiates have been tried, the dif fi culties with the placement and maintenance of high incidence of delayed respiratory depression in interscalene catheters than with any other periph- the advanced geriatric patient has decreased the eral catheter technique. Tuominen reported 6 cath- enthusiasm for this technique. Continuous infusion eter failures and one pump failure among 24 via epidural catheter with low-concentration local patients [37 ] . Use of an epidural needle and cath- anesthetic has demonstrated effi cacy. Very low eter to perform the interscalene technique may doses of intrathecal morphine have provided good improve this failure rate [ 48 ] . Continuous intersca- analgesia with acceptable safety in controlled lene block will maintain the decreased function of circumstances (regular monitoring of respiration, the diaphragm due to ipsilateral phrenic nerve continuous pulse oximetry) [60 ] .Various peri- block [48, 49] and can be associated with decreased pheral blocks have also demonstrated positive ventilatory function [50 ] . Even reduction of the impact on postoperative analgesia, including the concentration of the bupivacaine to 0.125% or psoas compartment block [61, 62 ] and the fascia further reduction with the addition of fentanyl did iliaca compartment block [63 ] . Hood [64 ] reported not decrease this potential adverse effect [50 ] . signifi cant reduction of pain within the fi rst 24 h Haasio reported ventilatory compromise in one after hip fracture repair under general anesthesia 28 J.E. Tetzlaff when a femoral 3 in 1 block (femoral, obturator, pain relief in the study group. Intrathecal lateral femoral cutaneous nerves) was compared morphine also provided profound, long-lasting to intraoperative parenteral opiates. Coad [65 ] analgesia in the report of Ross [ 72 ] . They caution found even greater opiate sparing when the femoral that although the doses they used (0–0.5 mg) did block was performed prior to incision for hip not result in any respiratory depression which fracture repair. required treatment, a signi fi cant number had at The consensus for postoperative analgesia least one interval where respiration decreased after hip fracture surgery is not clear. In centers below 12/min at the 6–18 h interval after injection. with an acute pain service, an epidural catheter, Intrathecal 0.4 mg of morphine injected by the perhaps as a part of a combined spinal/epidural surgeon provided excellent analgesia with reason- anesthetic is preferred. In centers without an able safety in a controlled protocol [ 73 ] . Bernard acute pain service, the intraoperative anesthetic is [ 74 ] also found delayed respiratory depression often spinal anesthesia with postoperative anal- with intrathecal morphine after scoliosis surgery gesia with intravenous opiate via PCA device. and suggested that intravenous analgesia with a combination of fentanyl and clonidine provided equivalent analgesia with no delayed respiratory Spine Surgery depression. Rectal [ 75 ] and intravenous [ 76 ] indometha- Pain control after elective spine surgery has been cin provided supplemental but not total analgesia extensively studies, with application of local after lumbar disc surgery without bleeding or anesthetics and opiates into the epidural space gastrointestinal side effects. Preoperative intrave- and the subarachnoid space, as well as parenteral nous naproxen [ 77 ] increased the interval to fi rst use of NSAIDs. Milligan [ 66 ] found that treatment of pain after lumbar laminectomy and injection of 10 ml of 0.5% bupivacaine into the decreased the total analgesics required for up to erector spinae muscles and wound edges increased 24 h. A meta-analysis established that NSAIDs the time interval to fi rst request of pain medica- were an effective adjunct to parenteral opiates for tion, decreased total morphine for the fi rst 24 h, postoperative pain control after major spine sur- and decreased the average pain scores. Otto [67 ] gery [78 ] . Lavyne [79 ] found no analgesic effect used 0.25% bupivacaine in the epidural space via from 40 mg of epidural methylprednisolone, a catheter placed by the surgeon during the surgical applied at the conclusion of surgery. procedure and eliminated the need for analgesics For simple elective lumbar spine surgery, on- in the majority of patients during the fi rst 24 h. demand analgesia is suffi cient. For major spine When compared to parenteral opiates, patient- reconstruction, the use of epidural analgesia, controlled epidural analgesia for major spine either by direct in fi ltration or preferably by a surgery was superior [68 ] . catheter inserted via the surgical fi eld, would be a Neuraxial opiate use for pain control after consensus choice. The most common agent spine surgery has also been extensively studied. would be a dilute local anesthetic such as bupiva- Joshi [69 ] compared PCA fentanyl to epidural caine, unless the dura was violated, in which case fentanyl via a catheter placed by the surgeon and opiate may be selected. found improved pain scores in the epidural fentanyl group. Bourke [ 70 ] compared morphine (3 mg) applied directly by the surgeon into the epidural Total Joint Replacement space to intramuscular morphine (3 mg) and demonstrated signi fi cantly improved analgesia Pain control after total hip and total knee replace- with epidural application, with no major compli- ment has been reported with central blocks, cations and comparable minor side effects (itching). peripheral nerve blocks, and a variety of paren- Waikakul [71 ] compared directly applied epidural teral supplements to conventional opiate treat- morphine to saline and found 15 h of complete ment. Epidural analgesia has the traditional role 2 Perioperative Pain Management and Orthopedic Surgery 29 as the gold standard for postoperative analgesia distribution during the fi rst 24 h after surgery. after lower extremity joint replacement. Epidural Edwards [91 ] compared a femoral nerve catheter morphine provided superior pain control com- combined with PCA morphine to PCA morphine pared to PCA morphine in the report of Weller alone and achieved superior pain control with the [80 ] , but there were more side effects, including catheter, using less morphine. When compared to pruritus which required treatment and decreased PCA morphine, and epidural analgesia, femoral ventilation, which did not require treatment in nerve catheter achieved equivalent analgesia, any patient. McQueen [ 81 ] also found superior excellent success rate, and signi fi cantly reduced pain control with epidural analgesia compared side-effect pro fi le [92 ] . Both continuous infusion with on-demand IM/IV morphine, with an and patient-controlled doses were compared; both increase in minor side effects including pruritus achieved excellent analgesia, with reduced total and urinary retention which required extended dose in the patient-controlled group [93 ] . Three- urinary catheterization. Modig [ 82 ] compared in-one block has also been reported as an approach epidural morphine to epidural bupivacaine, to pain control after total hip replacement [ 94, 95 ] . fi nding improved pain control in the morphine Reduction in opiate use was found with incom- group, but serious side effects, including respira- plete analgesia and signi fi cant motor block. tory depression which required treatment with NSAIDs have been used as a part of pain con- naloxone. Badner [83 ] found excellent analgesia trol after total joint replacement but not as sole with lumbar epidural fentanyl which was not analgesic. When used after surgery, they compli- improved by addition of low-dose bupivacaine. ment opiate analgesia [ 96, 97 ] . When given prior Slow-release compounds of morphine applied to the conclusion of surgery, the opiate sparing epidurally have provided up to 48 h of excellent effect also occurs, with improved analgesia [98, analgesia after hip replacement with an excellent 99] . The concern after joint replacement with side-effect pro fi le [84 ] . bleeding and hematoma has caused some concern Intrathecal morphine in low doses has been about the use of NSAIDs prior to surgery because reported to provide excellent analgesia with a of the effect on platelet function. Using selective long duration and no side effects [ 85 ] . Drakeford COX-2 agents eliminates this concern because [86 ] found equivalent analgesia with intrathecal they have no impact on platelet function. Laitinen Dilaudid and morphine, both providing complete [ 100] found no change in bleeding time or clini- pain control for as much as 24 h. Low-dose cal bleeding with NSAIDs use prior to total hip intrathecal morphine (0.2 mg) provide analgesia replacement. Other parenteral interventions have equivalent to continuous infusion of fentanyl via demonstrated additive analgesia with opiates, microcatheter, with less urinary retention and including clonidine [ 101 ] and metoclopramide comparable analgesia for 18 h postoperatively [ 102 ] , presumably by interfering with the periph- [ 87] . Intrathecal diamorphine (heroin) has been eral or central mechanisms of hypersensitivity. studied in Europe, with a longer duration of anal- Because of the ease of placement of a femoral gesia compared to morphine with equivalent nerve catheter, it is also easy to achieve lumbar side-effect pro fi le [88 ] . plexus block continuously, using proximal Femoral nerve block, the femoral nerve sheath advancement of the catheter to achieve “3-in-1” approach, and the psoas compartment approach block and analgesia. Lumbar plexus block has to lumbar plexus block have been used for pain demonstrated improved analgesia after knee control after total knee and total hip replacement. replacement [91 ] . Very low concentrations of bupi- Serpell [89 ] placed a catheter in the femoral nerve vacaine provide excellent analgesia with proximal sheath and achieved signifi cant (not complete) lumbar plexus catheters, thereby reducing risks of analgesia with infusion of 0.5% bupivacaine, local anesthetic toxicity [ 103 ] . Although the pre- with an ipsilateral motor block. Hirst [90 ] found sumption is that these catheters follow the femoral less ef fi cacy with femoral block alone for total nerve proximally to its origin at the lumbar plexus, knee replacement because of pain of the sciatic there is contradictory evidence by Capdevila that a 30 J.E. Tetzlaff minority do so, and the balance that are effective A clinical study of intra-articular pain control are located under the fascia iliaca [ 104 ] . Catheter was reported by Stein [24 ] . The dose was very placement in this space has provided excellent small (1 mg) and provided complete pain relief analgesia after total hip replacement [105 ] . for up to 18 h after arthroscopic surgery of the The consensus for pain control after total hip knee. Other reports found similar excellent anal- replacement considered will focus on the indwell- gesia with intra-articular local anesthetic and/or ing epidural catheter. Unfortunately, the consid- opiate [119– 122 ] Pain control after anterior cru- erations for deep venous thrombosis (DVT) ciate ligament reconstruction has also been eval- prophylaxis put practical limits on the length of uated. With non-arthroscopic ACL repair, time that the catheter can be maintained, and for intra-articular morphine was signifi cantly better routine cases, PCA opiates are selected for pain than saline administered at the conclusion of sur- control when spinal anesthesia resolved. For revi- gery [123, 124 ] . Joshi [125 ] found that morphine sion, there is more enthusiasm for maintaining an provided intra-articular analgesia which was not epidural catheter until postoperative day one increased by the addition of bupivacaine. This because the pain is more signi fi cant because of was the same conclusion of Cepeda [ 126 ] with more surgical dissection. For pain control after very large dose of morphine (10 mg). The issues knee replacement, epidural catheters have the with evidence of chondrolysis with intra-articular same limitations as with total hip and actually infusion of local anesthetics have reduced the more since the risk of DVT is greater. The use of enthusiasm with intra-articular analgesia in the spinal anesthesia for surgery and postoperative knee joint beyond single injections. analgesia via femoral nerve catheter is rapidly The consensus for analgesia after reconstruc- becoming the consensus choice at medical centers tive knee surgery has been in fl uenced by the with an acute pain service. Single-shot femoral movement toward same-day discharge. Peripheral nerve block with low-concentration bupivacaine nerve block remains the gold standard, although remains an option where an acute pain service is catheters for home infusion are rapidly expand- not available, with PCA opiate available when ing in centers with an acute pain service capable the femoral nerve analgesia resolves. of the home monitoring necessary for safety.

Knee Surgery Complications of Regional Anesthesia for Pain Control Epidural analgesia provides excellent pain con- trol and pain-free range of motion after open Anticoagulant Drugs ACL repair [ 106] . The addition of epidural cloni- dine to epidural morphine did not improve the The incidence of spontaneous epidural hematoma pain control after open meniscectomy [ 107 ] . unrelated to regional anesthesia in hospitalized Femoral nerve block via catheter technique pro- patients is estimated between 1 in 200,000 admis- vided excellent pain control, although proximal sions and 1 in 300, 000 admissions. The association motor block was common [108, 109 ] . Femoral of epidural hematoma with spinal and epidural nerve block by single shot provided excellent anesthesia is almost as low, except when anticoagu- pain control in the report of Goranson [ 110 ] . lants are involved. The risk of epidural hematoma Femoral nerve block performed prior to surgery associated with low molecular weight heparin reduced the need for postoperative opiate by 80% (LMWH) is now well known. Initial reports with [111 ] . NSAIDs were more effective when given LMWH use after total joint surgery identifi ed no prior to surgery than postoperatively [ 112– 116 ] . complications related to anesthetic interventions, The impact of ketorolac on platelet function was including spinal anesthesia and indwelling epidural not clinically signi fi cant during spinal [117 ] or catheters. Subsequent reports have revealed case general anesthesia [118 ] . reports of epidural hematoma related to indwelling 2 Perioperative Pain Management and Orthopedic Surgery 31 epidural catheters and removal of the epidural cath- Allergy eter in patients receiving LMWH. In response to this cluster of reports of epidural hematoma, the As with any chemical, there is a fi nite possibility of FDA, the American Society of Regional Anesthesia, allergy to any local anesthetic. Fortunately, the inci- and the manufacturer have jointly issued recom- dence of true allergy to local anesthetics is exceed- mendations that regional anesthesia not be used ingly uncommon [127 ] , and a majority of the events after LMWH, that indwelling epidural catheters not are actually something else. Many patients have had be maintained if LMWH was planned, and that epi- an adrenergic response to epinephrine added to dural catheters not be removed until 8–12 h after the local anesthetics in an unmonitored setting. [128 ] . last dose of LMWH. Parenteral response to vascular uptake of the local Experience has demonstrated the safety of anesthetic or an added opiate could also be mistaken regional anesthesia in patients taking some of the for allergy. Preservatives have been added to local antiplatelet drugs. Low-dose aspirin (60 mg daily) anesthetics for extended clinical storage or for mul- was shown to be safe in a high-risk obstetric popula- tiuse vials. Methylparaben is an example of a pre- tion who received epidural anesthesia. Several large servative with allergy potential, being chemically reports in the non-obstetric population including related to wax products found very commonly in regional anesthesia for surgery and chronic patient the cosmetic industry [ 129 ] . When true allergy management formed the same conclusion. There occurs to local anesthetics, it is more common have been two epidural hematomas associated with among the ester agents because of the metabolite, the thienopyridine class of antiplatelet drugs. para-aminobenzoic acid (PABA) [130 ] . Allergy Although no cases have been reported, the risk testing for local anesthetics can be frustrating. should be considered equivalent or higher in patients Strongly positive and negative patch tests or intrad- receiving drugs in IIb/IIIa class. ermal tests can be helpful. What is less satisfying If regional anesthesia is chosen for an antico- are the equivocal tests which can occur as often as agulated patient, the vigilance for bleeding com- 30% of the time [131 ] . plications must increase. If technical diffi culty occurs during neuraxial block placement, or if blood is aspirated through the needle or catheter, Infection the risk of epidural hematoma is increased and vigilance should be increased. The block must be Since all regional anesthesia involves needles and allowed to resolve in the early postoperative puncture of the skin, there is always a possibility period to verify neurological integrity. If epidural for infectious complications. Most regional anes- analgesia is planned into recovery, a low concen- thesia is performed using sterile technique. Despite tration of local anesthetic must be selected to precautions, superfi cial infection at the skin punc- allow for monitoring of motor and sensory integ- ture sites is possible [132 ] . It may be slightly more rity in the pelvis and lower extremities. If the likely in the immune-compromised patient or if a block does not regress or if new neurological hematoma follows block placement. signs are noted, this must be assumed to be a sign Controversy exists about whether to perform of epidural hematoma. Other signs of epidural various regional anesthetic procedures when hematoma include increasing, sharp back pain, or there is evidence of infection elsewhere in the long-tract signs (paresthesia). The work-up for body. The concern is infection at the site of the suspected epidural hematoma is MRI (or CT scan block. There is very little argument about sepsis if there is metal in the spine). Decompression is or infection at the site of the block being an abso- usually associated with a good neurological out- lute contraindication [133, 134 ] . When there is come if it occurs within 8–12 h of the fi rst signs localized infection elsewhere, such as an infected of neurological change. Conversely, after joint, most regional anesthetic techniques would 18–24 h, the probability of any neurological be reasonable as long as there are no systemic recovery is very low. signs of infection. 32 J.E. Tetzlaff

More serious and fortunately very uncommon Incremental dosing, test doses, and continuous are deep infections such as epidural abscess and vigilance during and immediately after injection meningitis. These complications can occur at a are important components of seizure prevention. considerable time interval after the block or during If signs of CNS toxicity (cranial nerve paresthe- indwelling catheter use. Aseptic meningitis can sia, such as numbness and tingling around the occur as a result of chemicals (e.g., Betadine) or mouth, ringing in the ears, etc.) are detected, powder (surgical gloves) being introduced into the injection can be halted, and administration of subarachnoid space. The presentation of fever, benzodiazepines or barbiturates to raise the sei- nuchal rigidity, and meningeal irritation is undistin- zure threshold may halt the evolution from CNS guished from bacterial meningitis except by CSF excitation to seizures. The most common choice analysis. The most common bacterial meningitis is midazolam, titrated to a level of slurred speech after dural puncture involves staph, E. coli, or without respiratory depression. Pseudomonas. The typical presentation is 24–48 h If local anesthetic-induced seizure activity after neuraxial instrumentation, although this can occurs, treatment is focused on maintaining the be delayed/confused by surgical use of antibiotics. airway and eliminating the seizure. Depending Epidural abscess formation presents with back on the total CNS levels, the seizure can be very pain, fever, and elevated white count several days brief or sustained. Even with the largest intra- after instrumentation. Diagnosis is con fi rmed by vascular injections, seizure duration for more MRI evidence of an epidural mass and the pre- than a few minutes should be very uncommon sence of neurological signs or de fi cits. Epidural if treatment is prompt and effective. At the fi rst abscess can also develop during indwelling epi- sign of CNS toxicity, supplemental oxygen dural catheter use although the incidence is very should be provided. The most common cause low. The exception is prolonged catheter use in of morbidity with local anesthetic-induced sei- patients with debilitating disease such as cancer, zures is related to cerebral hypoxia. The oxygen which can impair the immune system and increase demand of the CNS is increased by the uncon- the incidence of epidural abscess to >5%. Whether trolled electrical activity that causes the seizure. this applies to chronic rheumatoid patients taking The supply to the CNS is decreased by the huge immunosuppressants is unknown. oxygen demand of the skeletal muscle mani- festations of the seizure and the embarrassment of ventilation from uncontrolled movement. Seizure Activity This defi nes the goals of treatment. Controlled ventilation, and often endotracheal intubation, All local anesthetics are capable of causing sei- will optimize ventilation. Large doses of anti- zure activity. Factors which in fl uence the inci- epileptic agents such as methohexital or mida- dence of seizures with local anesthetic zolam will decrease or eliminate electrical administration include the total dose, use of seizure activity within the brain. When succi- vasoconstrictors, route of administration, and nylcholine is given to facilitate intubation, the the occurrence of direct intravascular injection. skeletal muscle manifestations also cease. The total dose of an agent is determined by the When an induction agent and succiny lcholine volume needed to achieve a complete block, the are given, combined with intubation and opti- concentration required, and the intrinsic toxicity mum oxygenation/ventilation, the seizure will of the agent. Use of vasoconstrictors will most often have resolved before recovery from decrease the amount of local anesthetic absorbed the hypnosis of the induction agent. Effective into the bloodstream and the rate of uptake. oxygenation/ventilation is a vital part of the Both decrease the CNS toxicity of a given dose management of local anesthetic toxicity of local anesthetics. because hypoxia, hypercarbia, and acidosis A major part of the treatment of local anes- potentiate the CNS and cardiac toxicity of local thetic-induced seizure activity is prevention. anesthetics. 2 Perioperative Pain Management and Orthopedic Surgery 33

Vascular Injury from total sympathectomy. With high spinal anesthesia (above T-4), vasodilatation from sym- Because of the proximity of neural structures to pathetic denervation decreases preload, cardiac blood vessels, the performance of regional anes- sympathetic denervation decreases heart rate, thesia can result in injury to blood vessels. and the combination decreases blood pressure. Hematoma can occur, which can be cosmetically Hypotension will induce apnea and uncon- unappealing, a potential site for infection or com- sciousness by CNS effects. Management pression injury to surrounding structures. The involves controlled ventilation support of the technique of the block, type of needle, and pres- circulation and continuous monitoring until ence/absence of anticoagulants/coagulopathy resolution. The duration will depend on the agent. in fl uence the risk of blood vessel injury. High epidurals will have a similar impact, but Ischemia from vasospasm , added vasocon- local anesthetic stops at the foramen magnum, strictors, or mechanical compromise of poorly and consciousness may be maintained if blood collateralized or end arteries can occur. Injury or pressure is maintained. The onset of sympathetic vasospasm of the anterior spinal artery can result block during high epidural anesthesia is slower, in ischemic injury to the anterior spinal cord. and as a result, the hemodynamic and ventilatory This rare occurrence can result in a cauda equina changes are less abrupt. syndrome. Epinephrine is generally thought to Post-dural puncture headache (PDPH) is a be contraindicated in blocks of the fi ngers, toes, neurological complication of spinal/epidural ear lobes, and external genitalia because of the anesthesia. The persistent leakage of CSF causes risk of ischemia in tissue with end-arterial blood downward shift of the brain, traction on the blood supply. Regional techniques, such as transarterial vessels, and a vascular-mediated headache. The injection which violates blood vessels intention- incidence of PDPH is related to age, gender of the ally, may be less ideal in patients with any of the patient, and size of the needle used. Conservative generalized vasculitis diseases, like Raynaud’s treatment includes volume expansion, analgesics, disease. stool softeners, and bed rest. Most PDPH will Compressive hematoma can be a serious con- resolve with conservative therapy within 72 h. sequence of blood vessel injury. Compressive Intravenous caffeine sodium benzoate is an inter- ischemia of the brachial plexus and epidural mediate therapy. Defi nitive therapy is accom- hematoma are examples. Any neuraxial block plished with epidural blood patch. which does not resolve in the expected time inter- Neural tissue injury is a serious potential val, or any block which resolves and later appears adverse outcome of any regional technique. to have returned, must be considered to have a Persistent paresthesia, peripheral nerve damage, possible compressive hematoma as the cause plexus injury, or spinal nerve/cord can be a conse- [135 ] . The investigation of choice to detect quence of a procedure where needles are inten- compressive hematoma is MRI or CAT scan if tionally placed percutaneously near nerves. metal interferes with obtaining MRI. Intentional or unintentional elicitation of par- esthesia has been associated with post-procedure nerve injury, although a causal association has not Neurological Injury been established. Blunt bevel needles, gentle manipulation of the needle, and an absolute refusal There are a variety of neurological complica- to inject during a severe paresthesia are important tions of regional anesthesia. The incidence is technical issues. Whether block techniques— most determined by the type of block and tech- transarterial, nerve stimulator, perivascular— nique used to perform the block. With central infl uence nerve injury remains controversial. blocks, the local anesthetic spreading cephalad There is an increasing consensus that ultrasound- can cause a total spinal anesthetic with uncon- guided regional anesthesia has reduced the risk of sciousness, apnea, and hemodynamic instability nerve injury during block performance. 34 J.E. Tetzlaff

Conclusion References

Acute pain is a common characteristic of the 1. Lutz LJ, Lamer TJ. Management of postoperative postoperative period after orthopedic surgery. pain: review of current techniques and methods. Mayo Clin Proc. 1990;65:584–96. Approaches to control such pain have changed 2. Hebl JR, Dilger JA, Byer DE, Kopp SL, Stevens SR, in response to an improved understanding of Pagnano MW, Hanssen AD, Horlocker TT. A pre- the neuroanatomy of acute pain and from emptive multimodal pathway featuring peripheral patient requests for better analgesia. The clini- nerve block improves perioperative outcomes after major orthopedic surgery. Reg Anesth Pain Med. cal behavior of peripheral receptors is better 2008;33:510–7. understood, as is their role in the postoperative 3. Duellman TJ, Gaf fi gan C, Milbrandt JC, Allan DG. cycle of pain in which pain leads to increasing Multi-modal, pre-emptive analgesia decreases the tissue sensitivity, muscle spasms, edema, and length of hospital stay following total joint arthro- plasty. Orthopedics. 2009;32:1–5. perpetuation of the pain. These peripheral 4. Duncan CM, Long KH, Warner DO, Hebl JR. The changes can be prevented with physical and economic implications of a multimodal analgesic pharmacologic interventions. The role of the regimen for patients undergoing major orthopedic spinal cord and the plasticity of dorsal column surgery. Reg Anesth Pain Med. 2009;34:301–7. 5. LaMotte RH. Neurophysiological mechanisms of receptors in acute pain have been established, cutaneous secondary hyperalgesia in the primate. In: with acute pain causing increased sensitivity Willis WD, editor. Hyperalgesia and allodynia. New and increased rates of nociceptive transmis- York: Raven Press; 1992. p. 175–85. sion. Prevention of these changes has estab- 6. Schaible HG, Schmidt RF. Direct observation of sensitization of articular afferents during experi- lished advantages in pain control. The overall mental arthritis. In: Proceedings of the Vth world link between acute pain and the creation of fur- congress on pain. Amsterdam: Elsevier; 1988. ther pain has led to the concept of pain preven- p. 44–50. tion, “preemptive analgesia,” with analgesic 7. Kinnman E, Aldskogius H, Wiesenfeld-Hallin Z, Johansson O. Expansion of sensory innervation after choices applied before surgery to prevent or peripheral nerve injury. In: Proceedings of the Vth signi fi cantly decrease acute pain. With agents world congress on pain. Elsevier; 1988. p. 277–82. available that can act at many sites, such as the 8. Wilcox GL. Excitatory neurotransmitters and pain. receptors, peripheral nerves, the spinal cord, In: Proceedings of the Vth world congress on pain. Boston: Elsevier; 1988. p. 97–117. and in the brainstem, synergism can be 9. Kendig JJ. Spinal cord as a site of anesthetic action. achieved. Multimodal preemptive analgesia is Anesthesiology. 1993;79:1161–2. the basis for the increasingly common use of 10. Yamamoto T, Shimoyama N, Mizuguchi T. Role of multiple agents to achieve pain control [ 136]. the injury discharge in the development of thermal hyperesthesia after sciatic nerve constriction injury Using agents that can be delivered continu- in the rat. Anesthesiology. 1993;79:993–1002. ously, especially those that can be controlled 11. Katz J, Kavanagh BP, Sandler AN, et al. Preemptive by the patients themselves, has increased analgesia. Clinical evidence of neuroplasticity con- patient satisfaction and improved the quality tributing to postoperative pain. Anesthesiology. 1992;77:439–46. of analgesia achieved. 12. Woolf CJ, Chong MS. Preemptive analgesia- treat- Future directions involve identifying speci fi c ing postoperative pain by preventing the establish- antagonists to the substances released by tissue ment of central sensitization. Anesth Analg. 1993;77: injury and identifying antagonists to nociceptive 362–79. 13. Malmberg AB, Yaksh TL. Pharmacology of the spi- neurotransmitters or, alternatively, selective ago- nal action of ketorolac, morphine, ST-91, U50488H, nists of inhibitory nociceptive pathways. and L-PIA on the formalin test and an isobolographic Treatment strategies may involve substances analysis of the NSAID interaction. Anesthesiology. placed within the wound site, in the pathway of 1993;79:270–81. 14. Munro HM, Walton SR, Malviya S, Merkel S, peripheral transmission, or at sites within the Voepel-Lewis T, Loder RT, Farley FA. Low-dose CNS. The goal should be a “pain-free” postoper- ketorolac improves analgesia and reduces morphine ative period. requirements following posterior spinal fusion in adolescents. Can J Anaesth. 2002;49:461–6. 2 Perioperative Pain Management and Orthopedic Surgery 35

15. Rosenow DE, Alberchtsen M, Stolke D. A compari- on postoperative pain and wound hyperalgesia. son of patient-controlled analgesia with lornoxicam Anesth Analg. 1994;78:205–9. versus morphine in patients undergoing lumbar disc 30. Sugiyama K, Muteki T. Local anesthetics depress surgery. Anesth Analg. 1998;86:1045–50. the calcium current of rat sensory neurons in culture. 16. Fenton C, Keating GM, Wagstaff AJ. Valdecoxib. Anesthesiology. 1994;80:1369–78. A review of its use in the management of osteoarthri- 31. Omote K, Sonoda H, Kawamata M, Iwasaki H, tis, rheumatoid arthritis, dysmenorrhoea and acute Namiki A. Potentiation of antinociceptive effects of pain. Drug. 2004;64:1231–61. morphine by calcium channel blockers at the level of 17. Bannwarth B, Berenbaum F. Clinical pharmacology the spinal cord. Anesthesiology. 1993;79:746–52. of lumiracoxib, a second-generation cyclooxygenase 32. McQuay HJ, Carroll D, Moore RA. Postoperative 2 selective inhibitor. Expert Opin Investig Drugs. pain- the effect of opiate premedication and local 2005;14:521–33. anesthetic blocks. Pain. 1988;33:291–5. 18. Weaver AL. Refecoxib: clinical pharmacology and 33. Kiss IE, Kilian M. Does opiate premedication clinical experience. Clin Ther. 2001;23:1323–38. infl uence postoperative analgesia? A prospective 19. Capdevilla X, Pirat P, Bringuier S, Gaertner E, study. Pain. 1992;48:157–8. Singelyn F, Bernard N, Choquet O, Bouaziz H, 34. Taivainen T, Hiller A, Rosenberg PH, Neuvonen P. Bonnet F. Continuous peripheral nerve blocks in The effect of continuous indomethacin infusion on hospital wards after orthopedic surgery. Anesthesio- bleeding time and postoperative pain in patients logy. 2005;103:1035–45. undergoing emergency surgery of the lower extremi- 20. Capdevilla X, Dadure C, Bringuier S, Bernard N, ties. Acta Anaesthesiol Scand. 1989;33:58–60. Biboulet P, Gaertner E, Macaire P. Effect of patient 35. Todd BD, Reed SC. The use of bupivacaine to relieve controlled perineural analgesia on rehabilitation and pain at iliac graft donor sites. Int Orthop. 1991; pain after ambulatory orthopedic surgery. 15:53–5. Anesthesiology. 2006;105:566–73. 36. Fredrickson MJ, Krishnan S, Chen CY. Postoperative 21. Bagry H, de la Cuadra JC, Asenjo JF, Bracco D, analgesia for shoulder surgery: a critical appraisal Carli F. Effect of continuous peripheral nerve block and review of current techniques. Anaesthesia. on the in fl ammatory response in knee arthroplasty. 2010;65:547–8. Reg Anesth Pain Med. 2008;33:17–23. 37. Tuominen M, Haasio J, Hekali R, Rosenberg PH. 22. Martin F, Martinez V, Mazoit JX, Bouhassira D, Continuous interscalene brachial plexus block: clini- Cherif K, Gentili E, Pirou P, Chauvin M, Fletcher cal effi cacy, technical problems and bupivacaine D. Antiin fl ammatory effect of peripheral nerve plasma concentrations. Acta Anaesthesiol Scand. blocks after knee surgery. Anesthesiology. 2008; 1989;33:84–8. 109:484–90. 38. Haasio J, Tuominen M, Rosenberg PH. Continuous 23. De Andres J, Bellver J, Barrera L, Febre E, Bolinches interscalene brachial plexus block during and after R. A comparative study of analgesia after knee sur- shoulder surgery. Ann Chir Gynaecol. 1990;79: gery with intraarticular bupivacaine, intraarticular 103–7. morphine and lumbar plexus block. Anesth Analg. 39. Tuominen MK, Pere P, Rosenberg PH. Unintentional 1994;77:727–30. arterial catheterization and bupivacaine toxicity 24. Stein C, Comisel K, Haimerl E, et al. Analgesic associated with continuous interscalene brachial effects of intraarticular morphine after arthroscopic plexus block. Anesthesiology. 1991;75:356–8. knee surgery. N Engl J Med. 1991;325:1123–6. 40. Goebel S, Stehle J, Schwemmer U, Reppenhagen S, 25. Tetzlaff JE, Dilger JA, Abate J, Parker RD. Rath B, Gohlke F. Interscalene brachial plexus block Preoperative intra-articular morphine and bupiva- for open-shoulder surgery: a randomized, double- caine for pain control after outpatient arthroscopic blind, placebo-controlled trial between single-shot anterior cruciate ligament reconstruction. Reg and patient-controlled catheter system. Arch Orthop Anesth Pain Med. 1999;34:220–4. Trauma Surg. 2010;130:533–40. 26. Gomoli AH, Yanke AB, Kang RW, Chubinskaya S, 41. Mariano ER, Llolan VJ, Ilfeld BM. Interscalene Williams JM, Bach BR, Cole BJ. Lon-tern effects of perineural catheter placement using an ultrasound- bupivacaine on cartilage in a rabbit shoulder model. guided posterior approach. Reg Anesth Pain Med. Am J Sports Med. 2009;37:72–7. 2009;34:60–3. 27. Solomon RE, Gebhart GF. Synergistic antinocicep- 42. Fredrickson MJ, Ball CM, Dalgleish AJ, Stewart tive interactions among drugs administered to the AW, Short TG. A prospective randomized compari- spinal cord. Anesth Analg. 1994;78:1164–72. son of ultrasound and neurostimulation as needle 28. Wang C, Chakrabarti MK, Whitwam JG. Speci fi c endpoint for interscalene catheter placement. Anesth enhancement by fentanyl of the effects of intrathecal Analg. 2009;108:1695–700. bupivacaine on nociceptive afferent but not on sym- 43. Borgeat A, Schappi B, Biasca N, Gerber C. Patient- pathetic efferent pathways in dogs. Anesthesiology. controlled analgesia after major shoulder surgery. 1993;79:766–73. Anesthesiology. 1997;87:1343–7. 29. Tverskoy M, Oz Y, Isakson A, Finger J, Bradley EL, 44. Klein SM, Grant SA, Greengrass RA, et al. Kissin I. Pre-emptive effect of fentanyl and ketamine Interscalene brachial plexus block with a continuous 36 J.E. Tetzlaff

catheter insertion system and a disposable pump. 58. Beaudet V, Willaims SR, Tetreault P, Perrault MA. Anesth Analg. 2000;91:473–8. Perioperative interscalene block versus intra-articu- 45. Ilfeld BM, Morey TE, Wright TW, Chidgey LK, lar injection of local anesthetics for postoperative Enneking FK. Continuous interscalene brachial analgesia in shoulder surgery. Reg Anesth Pain Med. plexus block for postoperative pain control at home: 2008;33:134–8. a randomized, double-blinded, placebo-controlled 59. Coghlan JA, Forbes A, McKenzie D, Bell SN, study. Anesth Analg. 2003;96:1089–95. Buchbinder R. Effi cacy of subacromial ropivacaine 46. Singelyn FJ, Seguy S, Gouveneur JM. Interscalene infusion for rotator cuff surgery. A randomized trial. brachial plexus analgesia after open shoulder sur- J Bone Joint Surg. 2009;91:1558–67. gery: continuous versus patient-controlled infusion. 60. Yamashita K, Fukasaki M, Ando Y, Tanabe T, Terao Anesth Analg. 1999;89:1216–20. Y, Sumikawa K. Postoperative analgesia with mini- 47. Kirkpatrick AF, Bednarczyklr LR, Hime GW, et al. dose intrathecal morphine for bipolar hip prosthesis in Bupivacaine blood levels during continuous inter- extremely elderly patients. J Anesth. 2009;23:504–7. scalene block. Anesthesiology. 1985;62:65–7. 61. Ben-David B, Lee E, Croitori M. Psoas block for 48. Boezaart AP, de Beer JF, du Toit C, van Rooyen K. surgical repair of hip fracture: a case report and A new technique of continuous interscalene nerve description of a catheter technique. Anesth Analg. block. Can J Anaesth. 1999;46:275–81. 1990;71:298–301. 49. Borgeat A, Perschak H, bird P, Hodler J, Gerber C. 62. Chudinov A, Berkenstadt H, Salai M, Cahana A, Patient-controlled interscalene analgesia with ropiv- Perel A. Continuous psoas compartment block for acaine 0.2% versus patient-controlled intravenous anesthesia and perioperative analgesia in patients analgesia after major shoulder surgery. Anesthesio- with hip fractures. Reg Anesth Pain Med. 1999;24: logy. 2000;92:102–8. 563–8. 50. Pere P. The effect of continuous interscalene brachial 63. Foss NB, Kristensen BB, Bundgaard M, Bak M, plexus block with 0.125% bupivacaine plus fentanyl Heiring C, Virkelyst C, Hougaard S, Kehlet H. Fascia on diaphragmatic motility and ventilatory function. iliaca compartment blockade for acute pain control Reg Anesth. 1993;18:93–7. in hip fracture patients. Anesthesiology. 2007;106: 51. Haasio J, Tuominen M, Rosenberg PH. Continuous 773–8. interscalene plexus block during and after shoulder 64. Hood G, Edbrooke DL, Gerrish SP. Postoperative surgery. Ann Surg Gynecol. 1990;79:103–7. analgesia after triple nerve block for fracture of the 52. Coleman MM, Chan VWS. Continuous intersca- femur. Anaesthesia. 1991;46:138–40. lene brachial plexus block. Can J Anaesth. 1999; 65. Coad NR. Post-operative analgesia following femo- 46:209–14. ral-neck surgery- a comparison between 3 in 1 femo- 53. Reuben SS, Steinberg RB. Continuous shoulder ral nerve block and lateral cutaneous nerve block. analgesia via an indwelling axillary brachial plexus Eur J Anesthesiol. 1991;8:287–90. catheter. J Clin Anesth. 2000;12:472–5. 66. Milligan KR, Macafee AL, Fogarty DJ, Wallace 54. Fontana C, DiDonato A, DiGiacomjo G, Constanti RGH, Ramsey P. Intraoperative bupivacaine dimin- A, DeVita A, Lancia F, Caricati A. Postoperative ishes pain after lumbar diskectomy. J Bone Joint analgesia for arthroscopic shoulder surgery: a pro- Surg (British). 1993;75B:769–71. spective randomized controlled study of intraarticu- 67. Otto S, Dietz C, Kuleszynski P, Hopf CH, Stanton- lar, subacromial injection, interscalene brachial Hicks M, Dick W. Postoperative Analgesie bei spondy- plexus block, and intraarticular plus subacromial lodesen mittels intraoperative gelegtem periduralka- injection effi cacy. Eur J Anaesthesiol. 2009;26: theter. Anaesthesist. 1991;40:235–7. 689–93. 68. Cata JP, Noguera EM, Parke E, Ebrahim Z, Kurz A, 55. Axelsson K, Gupta A, Johanzon E, Berg E, Ekback G, Kalfas I, Masha E, Farag E. Patient controlled epidu- Rawal N, Enstrom P, Nordensson U. Intraarticular ral analgesia (PCEA) for postoperative pain control injection of ketorolac, morphine and ropivacaine, after lumbar spine surgery. J Neurosurg Anesthesiol. combined with intraarticular patient-controlled anal- 2008;20:256–60. gesia for pain relief after shoulder surgery: a rando- 69. Joshi GP, McCarroll SM, O’Rourke K. Postoperative mized, double-blind study. Anesth Analg. 2008;106: analgesia after lumbar laminectomy: epidural fenta- 328–33. nyl infusion versus patient-controlled intravenous 56. Bus fi eld BT, Lee GH, Carillo M, Ortega R, Kharrazi morphine. Anesth Analg. 1995;80:511–4. FD. Subacromial pain pump use with arthroscopic 70. Bourke DL, Spatz E, Motara R, Ordia JI, Reed J, shoulder surgery: a short-term prospective study of Hlavacek JM. Epidural opioids during laminectomy complications in 583 patients. J Shoulder Elbow surgery for postoperative pain. J Clin Anesth. Surg. 2008;17:860–2. 1992;4:277–81. 57. Ciccone WJ, Busey TD, Weinstein DM, Walden DL, 71. Waikakul W, Chumniprasas K. Direct epidural mor- Elias JJ. Assessment of pain provided by intersca- phine during lumbar diskectomy for postoperative lene regional block and infusion pump after analgesia. J Med Assoc Thai. 1992;75:428–33. arthroscopic shoulder surgery. Arthroscopy. 2008;24: 72. Ross DA, Drasner K, Weinstein PR, Flaherty JF, 14–9. Barbaro NM. Use of intrathecally administered 2 Perioperative Pain Management and Orthopedic Surgery 37

morphine in the treatment of postoperative pain after with intrathecal morphine infusion or bolus for post- lumbar spinal surgery: a prospective, double-blind, pla- operative pain relief after total hip arthroplasty. cebo-controlled study. Neurosurgery. 1991;28:700–4. Anesth Analg. 1993;77:126–30. 73. Ziegeler S, Feritsch E, Baurer C, Mencke T, Muller 88. Milligan KR, Fogarty DJ. The characteristics of BL, Soltesz S, Silomon M. Therapeutic effect of analgesic requirements following subarachnoid intrathecal morphine after posterior interbody fusion diamorphine in patients undergoing total hip replace- surgery: a prospective, double-blind, randomized ment. Reg Anesth. 1993;18:114–7. study. Spine. 2008;33:2379–86. 89. Serpell MG, Millar FA, Thompson MF. Comparison 74. Bernard JM, Hommeril JL, Legendre MP, Passuti N, of lumbar plexus block versus conventional opioid Pinaud M. Spinal or systemic analgesia after exten- analgesia after total knee replacement. Anaesthesia. sive spinal surgery: comparison between intrathecal 1991;46:275–7. morphine and intravenous fentanyl plus clonidine. 90. Hirst GC, Scott SA, Dust WN, Cassidy JD, Yip RW. J Clin Anesth. 1993;5:231–6. Femoral nerve block; single injection versus contin- 75. McGlew IC, Angliss DB, Gee GJ, Rutherford A, uous infusion for total knee arthroplasty. Reg Anesth. Wood ATA. A comparison of rectal indomethacin 1996;21:292–7. with placebo for pain relief following spinal surgery. 91. Edwards ND, Wright EM. Continuous low-dose Anaesth Intensive Care. 1991;19:40–5. 3-in-1 nerve blockade for postoperative pain relief 76. Nissen I, Jensen KA, Ohrstrom JK. Indomethacin in after total knee replacement. Anesth Analg. the management of postoperative pain. Br J Anaesth. 1992;75:265–7. 1992;69:304–6. 92. Singelyn FJ, Gouverneur JA. Postoperative analge- 77. Coli A, Lari S, Vigano E, Perin S, Lari F. Valutazione sia after total hip arthroplasty: IV PCA with mor- dell’effi cacia dei FANS nella prevenzione del dolore phine, patient-controlled epidural analgesia or postoperatorio. Minerva Anestesiol. 1993;59:531–5. continuous “3-in-1” block. J Clin Anesth. 1999;11: 78. Jirattanaphocal K, Jung S. Nonsteroidal antiin- 550–4. fl ammatory drugs for postoperative pain management 93. Singelyn FJ, Gouverneur JA. Extended “three-in after lumbar spine surgery: a meta-analysis of ran- one” block after total knee arthroplasty: continuous domized controlled trials. J Neurosurg Spine. versus patient-controlled technique. Anesth Analg. 2008;9:22–31. 2000;91:176–80. 79. Lavyne MH, Bilsky MH. Epidural steroids, postop- 94. Uhrbrand B, Toftgaard Jensen T, Klitgaard Bendixen erative morbidity and recovery in patients undergo- D, Flemming Hartmann-Andersen J. Perioperative ing microsurgical lumbar diskectomy. J Neurosurg. analgesia by 3-in-one block in total hip arthroplasty 1992;77:90–5. prospective randomized blind study. Acta Orthop 80. Weller R, Rosenblum M, Conard P, Gross JB. Belg. 1992;58:417–9. Comparison of epidural and patient-controlled intra- 95. Striebel HW, Wilker E. Postoperative schmerzthera- venous morphine following joint replacement sur- pie nach totalendoprothetischen operationen an der gery. Can J Anaesth. 1991;38:582–6. hufte mittels kontinuierlicher 3-in-1 blockade. 81. McQueen DA, Kelley HK, Wright TF. A comparison Anasthesiol Intensivmed Notfallmed Schmerzther. of epidural and non-epidural anesthesia and analge- 1993;28:168–73. sia in total hip and total knee arthroplasty patients. 96. Serpell MG, Thomson MF. Comparison of piroxi- Orthopedics. 1992;15:169–73. cam with placebo in the management of pain after 82. Modig J, Paalzow L. A comparison of epidural mor- total hip replacement. Br J Anaesth. 1989;63: phine and epidural bupivacaine for postoperative 354–6. pain relief. Acta Anaesth Scand. 1981;25:437–41. 97. Laitinen J, Nuutinen L. Intravenous diclofenac cou- 83. Badner NH, Reimer EJ, Komar WE, Moote CA. pled with PCA fentanyl for pain relief after total hip Low-dose bupivacaine does not improve postopera- replacement. Anesthesiology. 1992;76:194–8. tive epidural fentanyl analgesia in orthopedic 98. Claeys MA, Camu F, Maes V. Prophylactic diclofenac patients. Anesth Analg. 1991;72:337–41. infusions in major orthopedic surgery: effects on 84. Martin G, Hamrtmannsgruber M, Riley E, Manvelian analgesia and acute phase proteins. Acta Anaesthesiol G. Single-dose extended-release epidural morphine Scand. 1992;36:270–5. for pain after hip arthroplasty. J Opioid Manag. 99. Anderson SK, Shaikh BA. Diclofenac in combina- 2006;2:209–18. tion with opiate infusion after joint replacement sur- 85. Schaer H, Baasch K, Prochacka K. Intrathekales gery. Anesth Intensive Care. 1991;19:535–8. morphin fur postoperativen schmerz. Anaesthetist. 100. Laitinen J, Nuutinen LS, Puranen J, Ranta P, 1992;41:689–93. Salomaki T. Effect of a non-steroidal anti- 86. Drakeford MK, Pettine KA, Brookshire L, Ebert F. in fl ammatory drug, diclofenac, on haemostasis in Spinal narcotics for postoperative analgesia in patients undergoing total hip replacement. Acta total joint arthroplasty. J Bone Joint Surg. 1991; Anaesthesiol Scand. 1992;36:486–9. 73A:424–8. 101. Grace D, Bunting H, Milligan KR, Fee JPH. 87. Niemi L, Pitkanen MT, Tuominen MK, Rosenberg Postoperative analgesia after co-administration of PH. Comparison of intrathecal fentanyl infusion clonidine and morphine by the intrathecal route in 38 J.E. Tetzlaff

patients undergoing hip replacement. Anesth Analg. 115. Pederson P, Nielsen KD, Jensen PE. The ef fi cacy of 1995;80:86–91. na-naproxen after diagnostic and therapeutic arthros- 102. Kandler D, Lisander B. Analgesic action of metoclo- copy of the knee joint. Arthroscopy. 1993;9:170–3. pramide in prosthetic hip surgery. Acta Anaesthesiol 116. Rasmussen S, Thomsen S, Madsen SN, Rasmussen Scand. 1993;37:49–53. PJS, Simonsen OH. The clinical effect of naproxen 103. Anker-Moller E, Spangsberg N, Dahl JB, Christensen sodium after arthroscopy of the knee: a randomized, EF, Schultz P, Carlsson P. Continuous blockade of double blind, prospective study. Arthroscopy. the lumbar plexus after knee surgery: a comparison 1993;9:375–80. of the plasma concentrations and analgesic effect of 117. Thwaites BK, Nigus DB, Bouska GW, Mongan PD, bupivacaine 0.250% and 0.125%. Acta Anaesthesiol Ayala EF, Merrill GA. Intravenous ketorolac Scand. 1990;34:468–72. tromethamine worsens platelet function during knee 104. Capdevilla X, Macaire P, Dadure C, et al. Continuous arthroscopy under spinal anesthesia. Anesth Analg. psoas compartment block for postoperative analge- 1996;82:1176–81. sia after hip arthroplasty: new landmarks, technical 118. Thwaites BK, Nigus DB, Bouska GW, Mongan PD, guidelines and clinical evaluation. Anesth Analg. Ayala EF, Merrill GA. Intravenous ketoroloc 2002;94:1606–13. tromethamine does not worsen platelet function dur- 105. Williams DP, Longo SR, Cronin AJ. Continuous ing knee arthroscopy under general anesthesia. lumbar plexus analgesia via the fascia iliaca com- Anesth Analg. 1995;81:119–24. partment after total hip arthroplasty. Am J 119. Khoury GF, Chen ACN, Garland DE, Stein C. Anesthesiol. 1998;25:177–80. Intraarticular morphine, bupivacaine, and morphine/ 106. Solheim E, Strand T. Postoperative pain after ante- bupivacaine for pain control after knee videoarthros- rior cruciate ligament reconstruction using a trans- copy. Anesthesiology. 1992;77:263–6. ligamentous approach. Am J Sports Med. 1993;21: 120. Allen GC, St. Amand MA, Lui ACP, Johnson CH, 507–9. Lindsay MP. Post-arthroscopy analgesia with intraar- 107. Van Essen EJ, Bovill JG, Ploeger EJ. Extradural clo- ticular bupivacaine/morphine. Anesthesiology. nidine does not potentiate analgesia produced by 1993;79:475–80. extradural morphine after meniscectomy. Br J 121. Gyrn JP, Olsen KS, Appelquist E, Chraemmer- Anaesth. 1991;66:237–41. Jorgensen B, Duus B, Berner Hansen L. Intra- 108. Anker-Moller E, Spangberg N, Dahl JB, Christensen articular bupivacaine plus adrenaline for arthroscopic EF, Schultz P, Carlsson P. Continuous blockade of surgery of the knee. Acta Anaesthesiol Scand. the lumbar plexus after knee surgery: a comparison 1992;36:643–6. of the plasma concentrations and analgesic effect of 122. White AP, Laurent S, Wilkinson DJ. Intra-articular bupivacaine 0.250% and 0.125%. Acta Anaesthesiol and subcutaneous prilocaine with adrenaline for pain Scand. 1990;34:468–72. relief in day case arthroscopy of the knee joint. Ann 109. Schultz P, Anker-Moller E, Dahl JB, Christensen EF, R Coll Surg. 1990;72:350–2. Spangberg N, Fauno P. Postoperative pain treatment 123. Joshi GP, McSwiney M, Hurson BJ, McCarroll after open knee surgery: continuous lumbar plexus SM, O’Rourke P. Effects of intraarticular mor- block with bupivacaine versus epidural morphine. phine on analgesic requirements after anterior Reg Anesth. 1991;16:34–7. cruciate ligament repair. Reg Anesth. 110. Goranson BD, Lang S, Cassidy JD, Dust WN, 1993;18:254–7. McKerrell J. A comparison of three regional anes- 124. Joshi GP, McCarroll SM, Brady OH, Hurson BJ, thesia techniques for outpatient knee arthroscopy. Walsh G. Intra-articular morphine for pain relief Can J Anaesth. 1997;44:371–6. after anterior cruciate ligament repair. Br J Anesth. 111. Ringrose NH, Cross MJ. Femoral nerve block 1993;70:87–8. in knee joint surgery. Am J Sports Med. 1984; 125. Joshi GP, O’Brien TM, McCarroll Sm, Lenane P. 12:398–402. Intraarticular injection following arthroscopy. 112. Code WE, Yip RW, Erooney ME, Browne PM, Hertz Anesth Analg. 1993;76:333–6. T. Preoperative naproxen sodium reduces postopera- 126. Cepeda MS, Uribe C, Betancourt J, Rugeles J, tive pain following arthroscopic knee surgery. Can J Carr DB. Pain relief after knee arthroscopy: Anaesth. 1994;41:98–101. intraarticular morphine, intraarticular bupiva- 113. McGuire DA, Sanders K, Hendricks SD. Comparison caine or subcutaneous morphine? Reg Anesth. of ketorolac and opioid analgesics in postoperative 1997;22:233–8. ACL outpatient pain control. Arthroscopy. 127. Adriani J, Zepernick R. Allergic reactions to local 1993;9:653–61. anesthetics. South Med J. 1981;74:694–703. 114. Laitinen J, Nuutinen L, Kiiskila EL, Freudenthal Y, 128. Assem ESK, Punnia-Moorthy A. Allergy to local Ranta P, Karvonen J. Comparison of intravenous anaesthetics: an approach to de fi nitive diagnosis. Br diclofenac, indomethacin and oxycodone as post- Dent J. 1988;164:44–7. operative analgesics in patients undergoing knee sur- 129. Crampton RS. Methylparaben in lidocaine. JAMA. gery. Eur J Anesthesiol. 1992;9:29–34. 1968;205:803. 2 Perioperative Pain Management and Orthopedic Surgery 39

130. Caro I. Contact allergy/photo allergy to glyceryl PABA 134. Berman RS, Eisele JH. Bacteremia, spinal anesthe- and benzocaine. Contact Dermatitis. 1978;4:381–2. sia, and development of meningitis. Anesthesiology. 131. Bircher AJ, Messmer SL, Surber C, Ru fl i T. Delayed- 1978;48:376–7. type hypersensitivity to subcutaneous lidocaine with 135. Owens EL, Kasten GW, Hessel EA. Spinal suba- tolerance to articaine: con fi rmation by in vivo and rachnoid hematoma after lumbar puncture and hepa- in vitro tests. Contact Dermatitis. 1996;34:387–9. rinization: a case report, review of the literature, and 132. Du Pen SL, Petersen DG, et al. Infection during discussion of anesthetic implications. Anesth Analg. chronic epidural catheterization. Anesthesiology. 1986;65:1201–7. 1990;73:905–9. 136. Kehlet H, Dahl JB. The value of “multi-modal” or 133. Carp H, Bailey S. The association between meningi- “balanced analgesia” in postoperative pain treat- tis and dural puncture in bacteremic rats. ment. Anesth Analg. 1993;77:1048–56. Anesthesiology. 1992;76:739–42. Autologous Blood Transfusion 3 Ajay Kumar

blood may not always be available. The potential Introduction complications of allogeneic transfusion that can be eliminated or minimized when autologous Autologous blood transfusion (ABT) is the col- blood is administered include acute and delayed lection and reinfusion of the patient’s own blood hemolytic reactions, alloimmunization, allergic or blood components. Autologous donation is and febrile reactions, and transfusion-transmitted used in preparation surgery with the idea of infectious diseases. avoiding allogeneic blood use. Allogeneic blood, Directed donations—blood donated by a friend on the other hand, is collected from someone or family member for a designated patient—are other than the patient. not as safe as the patient’s own blood and must not The use of autologous blood donation be considered equivalent to autologous donations. increased in the late 1980s and early 1990s due to Since most planned surgical procedures are concerns about the transmission of infectious dis- not associated with suf fi cient blood loss to result eases such as HIV [1– 7 ] . in transfusion, autologous blood techniques are Despite reduction of the risk of transmitting not appropriate for all patients. The transfusion viruses such as the human immunode fi ciency virus experience of patients who have undergone simi- (HIV) or hepatitis B or C (HCV)via allogeneic lar procedures can serve as a guide. If transfusion transfusion [1, 2 ] , autologous blood transfusion is likely for a planned surgical procedure, several remains safer than allogeneic blood transfusion and types of autologous transfusion can be used either appropriate for properly selected patients. Exclusive alone or in combination: or supplemental use of autologous blood can Preoperative autologous blood donation eliminate or reduce many adverse effects of trans- (PABD) fusion in planned procedures associated with Intraoperative blood salvage signi fi cant blood loss. Postoperative blood salvage Autologous transfusion also helps to conserve Acute normovolemic hemodilution (ANH) blood resources. Patients with rare blood pheno- types or alloantibodies may bene fi t from autolo- gous transfusion because compatible allogeneic PABD

Preoperative autologous blood donation is a pro-  A. Kumar , M.D., F.A.C.P., S.F.H.M. ( ) cess of blood collection at least up to 72 h prior to Division of Hospital Medicine , Hartford Hospital , Hartford , CT , USA surgery and transfusing it back to patient after e-mail: [email protected] surgery. The blood donation can begin several

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 41 DOI 10.1007/978-1-4614-2203-7_3, © Springer Science+Business Media, LLC 2013 42 A. Kumar weeks in advance not exceeding 42 days prior to require transfusion, such as cholecystectomy, surgery with the assumptions that patient either herniorrhaphy, vaginal hysterectomy, and uncom- recovers the lost hemoglobin with active hemopoi- plicated obstetric delivery. esis. When a patient donates blood preopera- tively, it is expected that he or she will produce additional red blood cells between the time of Indications for PABD blood donation(s) and the day of the surgery. However, there is little stimulus for reticulocyto- PABD should be considered in patients with Hgb sis until the patient’s hematocrit drops below >11 g/dl and the: 30%. In orthopedic surgeries wherein preopera- – Likelihood of transfusion is more than 10% tive donation requires hematocrit to be in the – Elective surgery can be scheduled at least sev- upper 30s in order to donate, the hematocrit sel- eral weeks in advance and the procedure is dom decreases suffi ciently to produce a one for which blood is usually serologically hematopoietic response that will generate addi- matched tional red blood cells. Therefore, it has been – Patients with bleeding tendency (but who are found that most patients who donate blood pre- not currently anemic or bleeding) operatively are relatively anemic on the day of – Patients with alloantibodies where allogeneic surgery and, as a result of their PABD, have an blood may be in short supply increased chance of requiring at least the transfu- sion of their autologous blood if not additional allogeneic blood [8– 11 ] . Contraindications to PABD PABD is utilized in some orthopedic surgeries including hip and knee replacements and major Evidence of infection and risk of bacteremia spine surgeries. Elective surgery to correct aortic stenosis Unstable angina Active seizure disorder Patient Selection Myocardial infarction or cerebrovascular accident within 6 months of donation The standard of the American Association of Patients with signi fi cant cardiac or pulmonary Blood Banks requires that the donor–patient disease who have not yet been consid- hemoglobin level be no less than 11.0 g/dl or ered optimized for surgery by their treat- hematocrit 33% before each donation. The candi- ing physician dates for PABD are stable patients scheduled for High-grade left main coronary artery disease surgical procedures in which transfusion is likely; Cyanotic heart disease if the procedure involves minimal blood loss, Uncontrolled hypertension then PABD should not be used. In selected patient subgroups, preoperative collection of autologous blood can signifi cantly Risks reduce exposure to allogeneic blood. Preoperative autologous collections should be considered for PABD is not without risks including misidentifi cation patients likely to receive transfusion in proce- of patients or units, bacterial contamination of dures such as major orthopedic procedures, stored units, and volume overload. ABO incom- vascular surgery, cardiac or thoracic surgery, patibility risks are not reduced with PABD, and it and radical prostatectomy; the most common can make patient anemic in perioperative period surgical procedures for which autologous blood which in turn may increase the risk for transfu- is predonated are total joint replacements [ 12 ] . sion. The process is generally safe, but the blood Autologous blood should not be collected for donation leads to one serious complication in procedures that seldom (less than 10% of cases) 16,783 donations compared to donation for allo- 3 Autologous Blood Transfusion 43 geneic use where complication rate is much less Cost in approximately 200,000 donations. The most common complications were vasovagal symp- The costs associated with collection are higher toms, but 12% had angina suf fi cient to require than those associated with the collection of allo- hospitalization [11 ] . Vasovagal reactions most geneic blood. Since the autologous blood is not frequently involve pallor, dizziness or lighthead- screened as strictly as blood collected for alloge- edness, and/or profuse perspiration associated neic use including testing for bloodborne patho- with transient hypotension, hyperventilation, and/ gens or donor risk factors, it cannot be transfused or bradycardia, although on rare occasions, such to another patient and must be discarded if not reactions may involve loss of consciousness with utilized for donor–patient. The rate of discard has or without seizure activity. The loss of blood ranged anywhere from 5% to 38%, but several reduces the overall intravascular volume in the hospitals have reported the rate as high as 50% vessels which can lead to a transient reduction in [ 13, 18– 21] . The 0.64 million units of autologous blood pressure and which may result in mild vas- blood collected in 1997 generated a cost to the ovagal reactions. Vasovagal reactions occur dur- society of approximately $103 million. However, ing or immediately after PABD in 2–5% of all two thirds (0.42 million units) of collected units patients [9, 10, 13– 15 ] . were actually transfused of the autologous blood were actually transfused, which indicates about one third (0.22 million units) of collected blood Erythropoietin and PABD for autologous use were discarded. The economic impact of this wastage to the consumer in 1997 Erythropoietin use in elective noncardiac and was estimated to be about $36 million [22 ] . nonvascular surgery is approved in the United Poor cost-effectiveness and increased waste States. Recently, FDA issued warning about the have led some to question the practice of PABD increased risk perioperative VTE with use of program [23 ] . stimulating agents. Erythropoietin is not approved for use in PABD setting, and its use should be discouraged given the risk and cost associated References with the treatment regime. However, in Japan and the UK, the erythropoietin is approved for 1. Wallace EL, Surgenor DM, Hao HS, An J, Chapman use with PABD. It is important to recognize the RH, Churchill WH. Collection and transfusion of existing evidence supporting its use. In the non-PAD blood and blood components in the United States, 1989. Transfusion. 1993;33(2):139–44. setting, erythropoietin can be used to improve 2. Wallace EL, Churchill WH, Surgenor DM, Cho GS, preoperative hemoglobin level. Regimes for McGurk S. Collection and transfusion of blood and erythropoietin can be daily or weekly: 300 U kg21 blood components in the United States, 1994. daily subcutaneously for 14 days beginning Transfusion. 1998;38(7):625–36. 3. Surgenor DM, Wallace EL, Hao SH, Chapman 10 days preoperatively or 600 U kg21 subcutane- RH. Collection and transfusion of blood in the ously three times weekly and on the day of surgery United States, 1982–1988. N Engl J Med. 1990; [16 ] .Both regimens are of proven benefi t and 322(23):1646–51. seem equivalent in safety and ef fi cacy. 4. Comprehensive report on blood collectionb and trans- fusion in the Unites States in 1999.Bethesda: National Erythropoietin use along with PAD has also Blood Data Resource Center; 2001. been shown to boost hemoglobin level, but its cost-effectiveness is questionable. With recent safety, issues surrounding the use of erythropoi- Ref Type: Generic etin including increased risk of venous throm- boembolic events must be considered prior to its 5. Toy PT, Strauss RG, Stehling LC, et al. Predeposited use, especially in patients where postoperative autologous blood for elective surgery. A national mul- VTE prophylaxis is suboptimal [ 17 ] . ticenter study. N Engl J Med. 1987;316(9):517–20. 44 A. Kumar

6. Report on blood collection and transfusion in the 15. Bose WJ. The potential use of human recombinant United States in 1997.Bethesda:National Blood Data erythropoietin in orthopedic surgery. Orthopedics. Resource Center; 2001. 1996;19(4):325–8. 16. Goldberg MA, McCutchen JW, Jove M, et al. A safety and ef fi cacy comparison study of two dosing regi- mens of epoetin alfa in patients undergoing major Ref Type: Generic orthopedic surgery. Am J Orthop (Belle Mead NJ). 1996;25(8):544–52. 7. Goodnough LT, Brecher ME, Kanter MH, AuBuchon 17. http://www.fda.gov/drugs/drugsafety/postmarketdrug JP. Transfusion medicine. First of two parts–blood safetyinformationforpatientsandproviders/ucm transfusion. N Engl J Med. 1999;340(6):438–47. 109375.htm . 8. Mayer MN, de Montalembert M, Audat F, et al. 18. Sculco TP, Gallina J. Blood management experience: Autologous blood donation for elective surgery relationship between autologous blood donation and in children weighing 8–25 kg. Vox Sang. 1996; transfusion in orthopedic surgery. Orthopedics. 70(4):224–8. 1999;22(1 Suppl):s129–34. 9. Toy PT, Kerr K. Preoperative autologous blood dona- 19. Bernstein LH, Coles M, Viner N. Bridgeport hospi- tion. AACN Clin Issues. 1996;7(2):221–8. tal autologous blood donation experience from 1992 10. Gandini G, Franchini M, Bertuzzo D, et al. Preoperative to 1996. Yale J Biol Med. 1995;68(5–6):207–13. autologous blood donation by 1073 elderly patients 20. Nydegger U. Enhanced ef fi cacy of autologous blood undergoing elective surgery: a safe and effective prac- donation with epoetin alfa. Semin Hematol. 1996;33(2 tice. Transfusion. 1999;39(2):174–8. Suppl 2):39–40. 11. Tremper KK. TRansfusion controversies and manage- 21. Santrach P. Autologous transfusion for total-hip ment alternatives. 10-18-1997. American Society of arthroplasty. 11-6-1999. AABB Annual Meeting. Anesthsiologists.

Ref Type: Generic Ref Type: Generic 22. The ANH Online Bulletin:Bulletin No.14. 12-3-1999. 12. Bierbaum BE, Callaghan JJ, Galante JO, Rubash HE, Tooms RE, Welch RB. An analysis of blood manage- ment in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am. 1999;81(1):2–10. Ref Type: Generic 13. Van der Weyden MB, Hart JA, Flux M, Dargaville RM, Magrin G. Preoperative autologous blood 23. Etchason J, Petz L, Keeler E, et al. The cost effective- donation. Linkage of the public and private hospital ness of preoperative autologous blood donations. sectors. Med J Aust. 1993;158(5):302–4. N Engl J Med. 1995;332(11):719–24. 14. Domen RE. Preoperative autologous blood donation: clinical, economic, and ethical issues. Cleve Clin J Med. 1996;63(5):295–300. Venous Thromboembolism Prophylaxis in the Patient with 4 Rheumatic Diseases Undergoing Orthopedic Surgery

Taki Galanis and Geno J. Merli

Introduction Etiology of Deep Vein Thrombosis

Patients with degenerative joint diseases, rheuma- Stasis, intimal injury, and hypercoagulability are toid arthritis, or other rheumatic disorders will the three major factors that contribute to the frequently undergo either hip or knee replacement development of postoperative thromboembolic procedures, knee arthroscopy, or spine surgeries events [2 ] . In this section, each of these areas are as part of their disease treatment. It is important reviewed as they pertain to total hip replacement for the medical consultant to be familiar with the (THR), hip fracture surgery (FH), total knee incidence of venous thromboembolic events and replacement (TKR), elective spine surgery, and the modalities to prevent these complications in knee arthroscopy. the postoperative period. Overall, patients with The supine position on the operating room rheumatologic diseases undergoing orthopedic table, the anatomic positioning of the extremity surgery have the same high risk of deep vein for the surgical procedure, and the effect of anes- thrombosis (DVT) and pulmonary embolism (PE) thesia all contribute to stasis during surgery. The if venous thromboembolism (VTE) prophylaxis is supine position on the operating table has been not applied [ 1 ] . Such a high rate of thrombosis shown by venographic contrast studies to result requires not only preoperative VTE risk assess- in a decreased venous return [3, 4 ] . Second, the ment but also the application of appropriate VTE anatomic positioning of the extremity for the best prophylaxis. In this chapter, the etiology of VTE surgical access to the joint impairs adequate along with its risk assessment and preventative venous drainage during the procedure [ 5 ] . In modalities will be reviewed. TKR and knee arthroscopy, a thigh tourniquet infl ated to 450–500 mm Hg and maintained for 80–90 min is used to obtain a bloodless fi eld. In addition, the knee is fl exed 90° to obtain appro- priate alignment for placement of the prosthesis. In THR and HF, fl exion and adduction of the hip is required for better anatomic access to the sur- gical fi eld. This positioning has been shown to T. Galanis , M.D. • G. J. Merli , M.D. (*) impair venous return [ 5] . Third, general or spinal Jefferson Vascular Center, Department of Surgery , anesthesia causes peripheral venous vasodilata- Thomas Jefferson University Hospital , Philadelphia , PA , USA tion, which also contributes to the overall stasis e-mail: [email protected] during the operative procedure [6– 8 ] .

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 45 DOI 10.1007/978-1-4614-2203-7_4, © Springer Science+Business Media, LLC 2013 46 T. Galanis and G.J. Merli

The second contributing factor, intimal injury, according to the type of surgery, mobility, and may result from anatomic positioning and exces- individual risk factors [ 19 ] . The individual risk sive vasodilatation from anesthesia. The fl exion factors are as follows: surgery, trauma (major and adduction of the hip has been shown to com- trauma or lower extremity injury), immobility press the femoral vein during surgery. (lower extremity paresis), cancer (active or Intraoperative venographic studies provide clear occult), cancer therapy (hormonal, chemother- evidence of distortion of the femoral vein during apy, angiogenesis inhibitors, or radiotherapy), certain phases of total hip replacement [ 5, 9, 10 ] . venous compression (tumor, hematoma, arte- The tourniqueting of the proximal thigh and rial abnormality), previous DVT or PE, increas- fl exion of the knee during total knee replacement ing age, pregnancy and the postpartum period, and knee arthroscopy also compress the underly- estrogen-containing oral contraceptives or hor- ing venous structures. These types of prolonged mone replacement therapy, selective estrogen positions may result in damage to the delicate receptor modulators, erythropoiesis-stimulat- venous endothelium. Anesthesia, on the other ing agents, acute medical illness, in fl ammatory hand, may cause excess vasodilatation and bowel disease, nephritic syndrome, myelopro- endothelial damage [ 11– 14 ] . Both anatomic liferative disorders, paroxysmal nocturnal positioning and excessive vasodilation produce hemoglobinuria, obesity, central venous cathe- a nidus for clot formation secondary to the dam- ter, and inherited thrombophilia [ 19] . The aged endothelium. patient can be classi fi ed as being at low, mod- The third factor is hypercoagulability, for erate, or high risk for the development of VTE. which there has been documentation in a number Low-risk patients are those who are mobile and of orthopedic procedures. Antithrombin III has are having minor surgery. The DVT risk in been shown to be decreased for 3–5 days follow- Table 4.1 is based on a venographic DVT end- ing total hip and knee surgery [ 15 ] . This decrease point. Medical patients who are fully ambula- causes an impaired modulation of the clotting tory are also considered to be at low risk. The cascade at the Factor Xa and IIa level, with an approximate DVT risk without thrombopro- increased propensity toward thrombus formation. phylaxis is less than 10% in patients assigned More recently, the fi brinolytic system has been to the low-risk category. Moderate-risk patients evaluated by the measurement of tissue plasmi- are those undergoing general, open gynecologic, nogen activator (t-PA) and plasminogen activator or urologic surgery. The approximate incidence inhibitor one (PAI-1) levels preoperatively and of DVT risk without thromboprophylaxis in postoperatively [16 ] . A shutdown of the this group is 10–40%. The high-risk group fi brinolytic system as evidenced by an alteration includes patients having hip or knee replace- of t-PA and PAI-1 levels has been demonstrated ment, fractured hip surgery, major trauma, and in a number of surgical studies [17 ] . It seems that acute spinal cord injury. The DVT risk without an increased preoperative level of PAI-1 is indic- thromboprophylaxis in this category is between ative of an increased risk for the development of 40% and 80%. thrombosis in patients undergoing orthopedic Another approach to risk assessment is the surgery [18 ] . Coupled with stasis and intimal Caprini Risk Assessment Model [ 21 ] (Fig. 4.1 ). injury, there is a greater risk for DVT and pulmo- This method consists of a list of exposing risk nary embolism (PE) in this patient population. factors (genetic and clinical characteristics), each with an assigned relative risk score. The scores are summed to produce a cumulative Risk Factor Assessment score which is used to classify the patient into 1 through 4 risk levels and determines the As outlined in Table 4.1 , the American College type and duration of VTE prophylaxis. This of Chest Physicians advocates a single approach risk assessment tool was validated by Bahl to VTE risk assessment by assigning risk et al. [ 22 ] . 4 Venous Thromboembolism Prophylaxis in the Patient with Rheumatic Diseases… 47

Table 4.1 Classi fi cation of the risk of postoperative venous thrombosis and pulmonary embolism Approx DVT risk Level of risk no prophylaxis Prophylaxis options High risk 40–80% Total hip or knee arthroplasty LMWH, fondaparinux, warfarin Hip fracture Major trauma Spinal cord injury High VTE risk plus high bleeding risk Intermittent pneumatic compression Moderate risk 10–40% Most general, open gynecologic or urologic surgery LMWH, fondaparinux, UFH patients, medical patients (bed rest or sick) (BID/TID) Moderate VTE risk plus high bleeding risk Intermittent pneumatic compression Low risk <10% Minor surgery in mobile patients, No speci fi c thromboprophylaxis Medical patients who are fully mobile Early and aggressive ambulation Modi fi ed from [19 ] , with permission from the American College of Chest Physicians

lism occurs in 0.1–2.0% in this patient group VTE Prophylaxis in Orthopedic [ 19] . Low molecular weight heparin, fonda- Surgery parinux, and warfarin are currently the pharma- cologic agents of choice for DVT prophylaxis Prophylaxis for VTE in the orthopedic surgery according to the ACCP. Warfarin may be admin- group has been strongly advocated by the American istered at 5 mg on the evening of surgery and the College of Chest Physicians’ (ACCP) Consensus dose adjusted for a goal INR of 2–3 which is Conference on Antithrombotic Therapy 2008 [ 20 ] . achieved in approximately 4–5 days. Enoxaparin Joint replacement procedures, hip fracture repair, is administered subcutaneously at 30 mg every and elective spine surgery comprise the predomi- 12 h beginning 12 h after the procedure. Dalteparin nant procedures performed in patients with degen- is given 2,500 IU subcutaneously 4–8 h postop- erative joint disease or rheumatoid arthritis eratively followed by 5,000 IU every 24 h. (Table 4.2 ). In these types of surgeries, DVT may Fondaparinux 2.5 mg is given subcutaneously 6 h occur as an isolated proximal, proximal and distal, postoperatively and then every 24 h. The afore- or isolated distal thrombosis. The incidence of mentioned injectable medications are contraindi- fatal pulmonary embolism in total joint replace- cated in patients with severe renal insuf fi ciency, ment patients who have not had prophylaxis has and dose adjustments may be necessary, depend- been reported to be to 5% [19 ] . This high inci- ing on the creatinine clearance. External pneu- dence of fatal pulmonary embolism is not an matic compression has become a frequently used acceptable outcome in patients undergoing these adjunctive prophylactic measure in orthopedic procedures. In order to understand the approach to surgery. This mechanical prophylaxis does not prophylaxis, joint replacement procedures, frac- increase the risk of perioperative bleeding and tured hip repair, spinal surgery, and knee arthros- has been shown to be effective in reducing DVT copy are reviewed (Table 4.3 ). but is recommended as an adjuvant therapy for The overall incidence of DVT in total hip prophylaxis [20 ] . Aspirin is a new addition for replacement (THR) is approximately 42–57% VTE prophylaxis inTHR. whereas the incidence of proximal DVT has The incidence of total DVT in hip fracture ranged from 18% to 36%. Fatal pulmonary embo- (FH) patients is between 46% and 60% with 48 T. Galanis and G.J. Merli

Fig. 4.1 Venous thromboembolism risk factor assessment 4 Venous Thromboembolism Prophylaxis in the Patient with Rheumatic Diseases… 49

Table 4.2 VTE Prevalence after total Procedure Total DVT (%) Pulmonary embolism hip and knee arthroplasty and hip Total hip replacement 42–57 0.9–28% fracture and elective spine surgery without DVT/PE prophylaxis Total knee replacement 41–85 1.5–10% Hip fracture 46–60 3–11% Elective spine surgery 1.09 0.06% Knee arthroscopy 3.1–17.9 Not known Modi fi ed from [ 19] , with permission from the American College of Chest Physicians

Table 4.3 Recommended VTE prophylaxis Procedure LMWH Vitamin K antagonist THR* Dalteparin 2500 IU, SC, 4–8 h postop then 5,000 IU, Warfarin 5 mg evening of surgery SC, Q12 h then adjust INR to 2–3 Enoxaparin 30 mg, SC, 12 h postop then 30 mg, SC, Q12 h (CrCl < 30 cc/ml: 30 mg, SC, Q24 h) Fondaparinux 2.5 mg, SC, 6 h postop then 2.5 mg, SC, Q24 h TKA* Enoxaparin 30 mg, SC, 12 h postop then 30 mg, SC, Warfarin 5 mg, evening of surgery Q12 h (CrCl < 30 cc/ml: 30 mg, SC, Q24 h) then adjust INR to 2–3 Fondaparinux 2.5 mg, SC, 6 h postop then 2.5 mg, SC, Q24 h Hip fracture Fondaparinux 2.5 mg, SC, 6 h postop then 2.5 mg, Warfarin 5 mg, evening of surgery Q24 h then adjust INR to 2–3 Dalteparin 2500 IU, SC, 4–8 h postop then 5000 IU, SC, Q24 h Enoxaparin 30 mg, SC, 12 h postoperative then 30 mg, SC, Q12 h Elective spine No thromboembolic risk factorsa Surgery Early and frequent ambulation Thromboembolic risk factors UFH 5,000 IU, Q8 or 12 h Enoxaparin 40 mg, SC, 24 h postop then 40 mg, SC, Q24 h Dalteparin 5000 IU, 24 h postop then 5,000 IU, SC, Q24 h Fondaparinux 2.5 mg, 24 h postop then 2.5 mg, Q24 h Multiple thromboembolic risk factors IPC plus UFH 5,000 IU, Q8 or 12 h Enoxaparin 40 mg, SC, 24 h postop then 40 mg, SC, Q24 h Dalteparin 5000 IU, 24 h postop then 5,000 IU, SC, Q24 h Fondaparinux 2.5 mg, 24 h postop then 2.5 mg, Q24 h Knee arthroscopy No thromboembolic risk factors Early mobilization Thromboembolic risk factors Enoxaparin 40 mg, Qday Dalteparin 5,000 IU, SC, Qday a Spine surgery thromboembolic risk factors: advanced age, malignancy, neurologic de fi cit, previous VTE, anterior spinal approach. *I do not believe this an appropriate prophylaxis for HF and do not use it for THA or TKA. 50 T. Galanis and G.J. Merli

23–30% of thrombotic events located proximally charide: start 12–24 h postoperative, once daily [19 ] . The fatal PE rate is 0.3–7.5% [ 19 ] . By dosing for 7–12 days, warfarin: start the night extrapolation of the data from total hip replace- before or night of surgery, adjust dose to INR < 2.0, ment, low molecular weight heparin, fonda- treat for 2–6 weeks), (3) standard risk for pulmo- parinux, and warfarin as described above should nary embolism and elevated risk for major bleed- be routinely used as DVT prophylaxis [20 ] . ing (ASA 325 mg once daily × 2 then 81 mg daily External pneumatic compression sleeves may be for 6 weeks, warfarin: start the night before or used alone if the bleeding risk is very high or in night of surgery, adjust dose to INR < 2.0, treat combination with pharmacologic prophylaxis in for 2–6 weeks or no pharmacologic prophylaxis this patient group. and use mechanical methods), and (4) elevated The overall incidence of venographic DVT in risk for pulmonary embolism and elevated risk total knee replacement (TKR) has been reported to for major bleeding (ASA: 325 mg once daily × 2 be 41–85% whereas the incidence of proximal then 81 mg daily for 6 weeks, warfarin: start the DVT has ranged from 5% to 22% [ 20 ] . Fatal PE night before or night of surgery, adjust dose to has occurred in 0.1–1.7% of these patients [ 18 ] . INR < 2.0, treat for 2–6 weeks or no pharmaco- This high rate is attributed to the procedure and logic prophylaxis and use mechanical methods). tourniquet application. Low molecular weight hep- All the above methods are applied to total hip or arin, fondaparinux, and warfarin as described above total knee replacement surgeries. have been recommended as the most effective pro- phylaxis for DVT prevention [ 20 ] . External pneu- matic compression sleeves are the most effective Extended Prophylaxis in Joint nonpharmacologic modality; however, they must Replacement Surgery be worn continuously to provide the physiologic effect of reducing stasis [ 20 ] . Aspirin is a new addi- Duration of risk for the development of DVT fol- tion for VTE prophylaxis in TKA. lowing joint replacement surgery is an important In contrast to the above recommendations, the issue. This problem has been created by the dra- American Academy of Orthopaedic Surgeons matic reduction in the length of stay following (AAOS) has based venous thromboembolism these procedures which often results in the early prophylaxis on the risk of pulmonary embolism discontinuation of VTE prophylaxis. In a large and major bleeding [ 23 ] . This is in contrast to the epidemiologic study, the incidence of symptom- American College of Chest Physicians guidelines atic venous thromboembolic events over 4 weeks which use the surrogate marker of venography as was 2.7% in THR and 2.1% in TKR [24 ] . Hull the effi cacy of VTE prophylaxis. In the AAOS et al., in a systematic review and a meta-analysis guideline, patients are strati fi ed into four major by Eikelboom et al., demonstrated a signi fi cant groups with their respective pharmacologic pro- decrease in the rates of both total and proximal phylaxis. The following are the four categories DVT with extended use of low molecular weight and their respective prophylaxis regimens: (1) heparins [25, 26] . The benefi t of warfarin at an standard risk for pulmonary embolism and major INR of 2–3 for extended VTE prophylaxis in bleeding (ASA 325 mg once daily × 2 then 81 mg joint replacement surgery was demonstrated by daily for 6 weeks, LMWH: start 12–24 h postop- Prandoni et al. VTE occurred in 5.1% of patients erative, once daily dosing for 7–12 days, penta- who stopped warfarin at hospital discharge and in saccharide: start 12–24 h postoperative, once 0.5% of those who continued warfarin [ 27 ] . This daily dosing for 7–12 days, warfarin: start the was a relative risk reduction of 9.4 (95% CI 1.2– night before or night of surgery, adjust dose to 73.5). The ACCP recommends extended VTE INR < 2.0, treat for 2–6 weeks), (2) elevated risk prophylaxis up to 35 days after joint replacement for pulmonary embolism and standard risk for surgery with either low molecular weight hepa- major bleeding (LMWH: start 12–24 h postoper- rins, a pentasaccharide or warfarin (INR 2–3) ative, once daily dosing for 7–12 days, pentasac- [20 ] . The American Academy of Orthopaedic 4 Venous Thromboembolism Prophylaxis in the Patient with Rheumatic Diseases… 51

Surgeons recommends extended prophylaxis mended. The presence of risk factors such as with either aspirin 81 mg once daily for 6 weeks advanced age, malignancy, neurologic defi cit, or warfarin at an INR of < 2 for 6 weeks [23 ] . previous VTE, and an anterior surgical approach in spine surgery warrants the use of unfraction- ated heparin, low molecular weight heparin, or Elective Spine Surgery intermittent pneumatic compression with consid- eration to use gradient elastic stockings as an Recently, Sansone et al. performed a meta-analy- alternative measure. Due to a paucity of data, sis and univariate logistic regression assessment fondaparinux is not recommended as a prophy- of studies which enrolled only spine surgery lactic option. It is recommended to combine patients who had objective diagnostic studies for intermittent pneumatic compression sleeves with DVT/PE [ 28 ] (Table 4.3 ). The overall prevalence unfractionated heparin or low molecular weight of DVT was 1.09% (95% CI 0.54–1.64%), and heparin in patients with multiple risk factors. the prevalence of PE was 0.06% (95% CI 0.01– 0.12%). In this meta-analysis, it was noted that the mean time to the diagnosis of venous throm- Knee Arthroscopy boembolic was 8 days (range 1–16 days). The ACCP recommendations for VTE prophylaxis in The incidence of VTE in patients who undergo this patient population are not as concrete as for knee arthroscopy is lower than in patients who have the other orthopedic surgeries [ 19 ] . This is joint replacement procedures [29– 32 ] (Table 4.3 ). primarily a result of the diversity of both the type In the unprophylaxed patient population, prospec- of spine surgeries and patient populations studied. tive observational studies using compression ultra- There is also a paucity of clinical trials in this sound or venography have shown a total DVT rate patient population. The ACCP highlighted the which has ranged from 3.1% to 17.9% whereas the following as possible risk factors for VTE in spine incidence of proximal DVT has ranged from 0% to surgery: increased age, previous VTE, anterior 4.9% [31 ] . Clinical trials comparing pharmaco- surgical approach, malignancy, a prolonged pro- logic prophylaxis with a low molecular weight cedure, and reduced preoperative or postoperative heparin (LMWH) to either placebo or compression mobility. Another consideration in elective spine stockings have shown a decreased DVT rate with surgery and VTE prevalence is the spine location pharmacologic intervention [ 33– 36 ] . The bene fi t of surgery and the indication for the spine proce- of pharmacologic prophylaxis, however, appears to dure. In the meta-analysis mentioned above, the be predominantly confi ned to reducing the rate of prevalence of DVT for patients undergoing cervi- distal DVT. Because of this, the ACCP does not cal procedures was 1.3% and was identical to the recommend the routine use of pharmacologic pro- prevalence in patients undergoing thoracolumbar phylaxis unless the patient has additional risk fac- surgery [28 ] . The etiologies for elective spinal tors for VTE [18 ] . This recommendation, however, surgery and the associated prevalence of DVT should be interpreted with caution in patients who were as follows: spinal deformity (0.9%), degen- have rheumatic or degenerative diseases for several erative spine disease (1.4%), and 0.3% in those reasons. The patient populations in the aforemen- with spinal tumors, infection, pseudoarthrosis, tioned observational studies were mostly young intraspinal hematoma, syrinx, and arteriovenous men with mean ages that ranged from 38 to 46 fi stula. Univariate analysis revealed that neither [29– 32] . In addition, some of the clinical trials the operation level nor the diagnosis signi fi cantly investigating the effectiveness of pharmacologic affected the prevalence of DVT. prophylaxis excluded patients with a prior history The ACCP recommendations for spine sur- of VTE or those who had multiple risk factors for gery are based on risk factors [ 19 ] . For patients VTE [33– 36 ] . These trials also primarily studied having elective spine surgery and no thromboem- young male participants. Patients with rheumatic bolic risk factors, early ambulation is recom- or degenerative diseases may differ in age and sex 52 T. Galanis and G.J. Merli as well as in ambulatory and comorbidity status. undergoing hip or knee arthroplasty. The pri- For these reasons, an individualized VTE risk mary ef fi cacy outcome for these trials was a assessment should take place both prior to and after composite of asymptomatic and symptomatic the procedure to determine the most appropriate deep vein thrombosis, nonfatal pulmonary embo- prophylactic regimen for the patient. lism, and death from any cause during treatment [ 40– 42 ] . In ADVANCE 1, which involved 3,195 patients, a 10–14-day course of apixaban was Clinical Trials on New Oral compared to a similar duration of enoxaparin Anticoagulants: VTE Prophylaxis (30 mg twice daily) [ 40 ] . Apixaban had ef fi cacy for Joint Replacement Surgery similar to enoxaparin with total event rates of 9.0% and 8.8%, respectively [ 40] . Major bleed- In the above paragraphs, we have reviewed war- ing rates were 0.7% with apixaban and 1.4% farin, unfractionated heparin, low molecular with enoxaparin ( P = 0.05) [40 ] . The ADVANCE weight heparin, a pentasaccharide, and aspirin as 2 trial, which included 3,057 patients, compared the anticoagulants for preventing VTE in ortho- the same apixaban regimen with an equal dura- pedic surgery. Recently, three new oral anticoag- tion of treatment with enoxaparin at a dose of ulants have been developed and evaluated in the 40 mg once daily [ 41 ] . In this trial, apixaban prevention of thromboembolic disease in joint signifi cantly reduced total event rates compared replacement surgery. These agents directly act on with enoxaparin (15.1% and 24.4%, respectively; Factor IIa or Factor Xa, do not require monitor- P < 0.0001) and was associated with a trend for ing, have a broad therapeutic window, have low less major bleeding (0.6% and 0.9% respec- patient variability, and display minimal drug or tively; P = 0.3) [41 ] . The ADVANCE 3 trial dietary interactions [ 37 ] . The purpose of this sec- treated 5,407 total hip arthroplasty patients for tion is to review the pharmacology and clinical 32–38 days with apixaban 2.5 mg twice daily trial experience in joint replacement surgery with versus enoxaparin 40 mg once daily [42 ] . the three new oral anticoagulants apixaban, dab- Apixaban (1.4%) was superior to enoxaparin igatran, and rivaroxaban. Dabigatran and rivar- (3.9%) for the primary outcome [ 42] . Major oxaban are approved for DVT/PE prophylaxis in bleeding rates were the same in apixaban (0.8%) joint replacement surgery in Europe and Canada. and enoxaparin (0.7%) group [ 42] . Apixaban is Apixaban has not yet been approved for this not approved for VTE prophylaxis in Europe, patient population. Canada, and the United States.

Apixaban Rivaroxaban

Apixaban is a selective, reversible, direct inhibi- Rivaroxaban is a selective, reversible direct inhib- tor of Factor Xa. The half-life of this drug is itor of Factor Xa. The time to maximum plasma 8–15 h [38 ] . This agent is metabolized by concentration is 30 min to 3 h. Rivaroxaban’s CYP3A4 in the CYP450 system, and the route of half-life has been reported to be 3–9 h [ 43, 44 ] . elimination is 30% renal and 70% fecal [ 38 ] . Concomitant food intake only marginally Apixaban has not been reported to have any food increased rivaroxaban’s bioavailability in healthy interactions. In healthy volunteers, aPTT and subjects [45 ] . Rivaroxaban prolongs the pro- modifi ed PT were dose dependently prolonged thrombin time (INR) with the sensitivity depen- and correlated with the determined plasma con- dent on the reagent being used. Factor Xa centrations of apixaban [ 39 ] . There are no speci fi c inhibition may be a more appropriate surrogate reversing agents for this medication. marker for evaluating the plasma concentration of Three phase III studies compared apixaban rivaroxaban. There are no speci fi c reversing 2.5 mg twice daily with enoxaparin in patients agents for this medication. 4 Venous Thromboembolism Prophylaxis in the Patient with Rheumatic Diseases… 53

The four RECORD trials evaluated the ef fi cacy revealed a small but signifi cant increase in major and safety of rivaroxaban compared with enox- plus clinically relevant nonmajor bleeding with aparin in over 12,000 patients undergoing hip or rivaroxaban. On the basis of these results, knee arthroplasty [ 46– 49] . The dose of rivaroxaban rivaroxaban is approved in Europe and Canada in all four RECORD trials was 10 mg once daily for the prevention of VTE in patients undergoing started 6–8 h after wound closure. The European- elective hip or knee arthroplasty. approved dose of enoxaparin (40 mg once daily with the fi rst dose given in the evening before sur- gery) was used as the comparator in the fi rst three Dabigatran RECORD trials, whereas the North American- approved dose of enoxaparin (30 mg twice daily Dabigatran etexilate is the prodrug of dabigatran starting 12–24 h after surgery) was the comparator that selectively and reversibly inhibits both free and in the RECORD 4 trial [ 46– 49 ] . The primary clot-bound thrombin by binding to the active site of effi cacy outcome (total event rate) in all of the trials the thrombin molecule. Its half-life is about 12 h. In was the composite of deep vein thrombosis (either human studies, over 90–95% of systemically avail- symptomatic or detected by bilateral venography if able dabigatran was eliminated unchanged via the patient was asymptomatic), nonfatal pulmonary renal excretion with the remaining 5–10% excreted embolism, or death from any cause. in bile [50 ] . A unique aspect of this drug is that it is In the RECORD 1 trial, which included 4,541 neither metabolized by nor induced or inhibited by patients undergoing hip arthroplasty, a 31–39- the cytochrome P450 drug-metabolizing enzymes. day course of rivaroxaban signifi cantly reduced Because this drug exhibits low plasma protein the total event rate compared with an equal dura- binding (35%), it is a dialyzable agent with few tion of treatment with enoxaparin (1.1% and displacement interactions to affect its pharmacody- 3.7%, respectively; P < 0.001) [ 46 ] . In the namics [51 ] . The aPTT may serve as a qualitative RECORD 2 trial involving 2,509 patients under- test because it is less sensitive at supratherapeutic going total hip arthroplasty, a 31–39-day course concentrations of dabigatran. There are no specifi c of rivaroxaban signi fi cantly reduced the total reversing agents for dabigatran. event rate compared with a 10–14-day course of Based on results from phase II studies, two enoxaparin followed by 21–25 days of placebo doses of dabigatran were investigated in the phase (2.0% and 9.3%, respectively; P < 0.0001) [ 46 ] . III trials for thromboprophylaxis after hip or knee The RECORD 3 trial included 2,531 patients arthroplasty: 220 or 150 mg (both given once undergoing knee arthroplasty [ 48 ] . A 10–14-day daily) which was initiated at half the usual dose course of treatment with rivaroxaban signifi cantly on the fi rst day. The European-approved dose of reduced the total event rate compared with an enoxaparin (40 mg once daily with the fi rst dose equal duration of treatment with enoxaparin given in the evening before surgery) was used as (9.6% and 18.9%, respectively, P < 0.001) [ 48 ] . the comparator in the RE-MODEL study (total Finally, in the RECORD 4 trial involving 3,148 knee replacement), RE-NOVATE (total hip patients undergoing knee arthroplasty, a 10–14- arthroplasty), and RE-NOVATE II (total hip day course of treatment with rivaroxaban replacement) [52– 54 ] . The North American- signi fi cantly reduced the total event rate com- approved dose of enoxaparin (30 mg twice daily pared with an equal duration of enoxaparin at the starting 12–24 h after surgery) was the compara- higher 30 mg twice-daily dose (6.9% and 10.1%, tor in the RE-MOBILIZE study after total knee respectively; P < 0.012) [ 49 ] . In both the replacement [55 ] . In all four trials, the primary RECORD 2 and 3 trials, rivaroxaban signifi cantly ef fi cacy end point (total event rate) was a com- reduced the incidence of symptomatic VTE com- posite of venographically detected or symptom- pared with enoxaparin [ 47, 48 ] . Rivaroxaban did atic DVT, nonfatal PE, and all-cause mortality. not increase major bleeding in any of the trials, In the RE-MODEL trial involving 2,076 but a pooled analysis of the four RECORD trials patients undergoing knee arthroplasty, 6–10 days 54 T. Galanis and G.J. Merli of either dose of dabigatran etexilate had ef fi cacy replacement procedures and spine surgery will similar to that of enoxaparin (dabigatran 220 mg, increase. Unique to this surgical group is the prev- 36.4%; dabigatran 150 mg, 40.5%; enoxaparin, alence of postoperative venous thromboembolic 37.7%). The incidence of major bleeding did not events which has been defi ned in the body of this differ signi fi cantly among the three groups (1.5%, chapter. This high incidence of thromboembolic 1.3%, and 1.3%, respectively) [52 ] . In the disease mandates appropriate preoperative throm- RE-NOVATE trial involving 3,494 patients under- boembolic risk assessment and the application of going hip arthroplasty, treatment with either dose venous preventive measures. The new oral antico- of dabigatran etexilate for 28–35 days had effi cacy agulants have the potential to play a signi fi cant similar to that of enoxaparin (dabigatran 220 mg, role in this patient population. The studies pre- 6.0%; dabigatran 150 mg, 8.6%; enoxaparin, sented above in joint replacement surgery demon- 6.7%). The incidence of major bleeding did not strated the effi cacy and safety of these new oral differ signifi cantly among the three groups (2.0%, agents (direct Xa inhibitors apixaban and rivar- 1.3%, and 1.6%, respectively) [53 ] . In the oxaban; direct IIa inhibitor dabigatran) in prevent- RE-MOBILIZE study of 2,615 patients undergo- ing venous thromboembolism. These new agents ing knee arthroplasty, treatment with either dose will soon be approved in the United States. of dabigatran etexilate for 12–15 days was statisti- cally inferior to a similar duration of treatment with enoxaparin (dabigatran 220 mg, 31%; dab- igatran 150 mg, 34%; enoxaparin, 25%) [55 ] . The References incidence of major bleeding did not differ signifi cantly among the three groups (0.6%, 0.6%, 1. Pedersen AB, Sorensen HT, Mehnart F, et al. Risk fac- tors for venous thromboembolism in patients undergoing and 1.4%, respectively) [55 ] . The RE-NOVATE II total hip replacement and receiving routine thrombopro- study evaluated 2,055 patients undergoing total phylaxis. J Bone Joint Surg Am. 2010;92:2156–64. hip arthroplasty treated with dabigatran 220 mg 2. Sevitt S. Pathology and pathogenesis of deep vein once daily versus enoxaparin 40 mg once daily thrombosis. In: Bergan J, Yao J, editors. Venous Problems. Chicago: Year Book; 1976. p. 257–69. for 28–35 days [54 ] . Dabigatran (7.7%) was not 3. Nicolaides A, Kakkar V, Renney J. Soleal sinuses and inferior to enoxaparin (8.8%) for the primary out- stasis. Br J Surg. 1970;57:307. come [54 ] . The incidence of major bleeding did 4. Nicolaides A, Kakkar V, Field E, et al. Venous stasis not differ signi fi cantly among the two groups and deep vein thrombosis. Br J Surg. 1972;59:713–6. 5. Stamatakis J, Kakkar V, Sagar S, et al. Femoral vein throm- (1.4% dabigatran, 0.9% enoxaparin) [ 54 ] . bosis and total hip replacement. BMJ. 1977;2:223–5. Dabigatran etexilate is approved in Europe 6. Clark C, Cotton L. Blood fl ow in deep veins of the legs: and Canada for VTE prevention after elective hip recording technique and evaluation of method to increase or knee arthroplasty. The 220-mg dose of dabiga- fl ow during operation. Br J Surg. 1968;55:211–4. 7. Lindstrom B, Ahlman H, Jonsson O, et al. In fl uence tran etexilate is recommended for the majority of of anesthesia on blood fl ow to the calves during sur- patients, whereas the 150-mg dose is reserved for gery. Acta Anesthesiol Scand. 1984;28:201–3. patients also taking amiodarone and for those at 8. Lindstrom B, Ahlman H, Jonsson O, et al. Blood fl ow higher risk for bleeding, such as patients older in the calves during surgery. Acta Chir Scand. 1977;143:335–9. than 75 years or with a creatinine clearance 9. Johnson R, Carmichael J, Almond H, et al. Deep <50 mL/min. venous thrombosis following Charnley arthroplasty. Clin Orthop. 1978;132:24–30. 10. Planes A, Vochelle N, Fagola M. Total hip replace- ment and deep vein thrombosis: a venographic and Conclusion and Clinical necropsy study. J Bone Joint Surg Br. 1990;72:9–13. Considerations 11. Comerota A, Stewart G, Alburger P, et al. Operative venodilation: a previously unsuspected factor in the Because of the innovations in treating rheumatic cause of postoperative deep vein thrombosis. Surgery. 1989;106:301–9. diseases, the population over the age of 65 is 12. Schaub P, Lynch P, Stewart G. The response of canine increasing in this country. The frequency of joint veins to three types of abdominal surgery: a scanning 4 Venous Thromboembolism Prophylaxis in the Patient with Rheumatic Diseases… 55

and transmission electron microscope study. Surgery. thromboembolic disease following elective spine sur- 1978;83:411–22. gery. J Bone Joint Surg. 2010;92:304–13. 13. Stewart G, Schaub R, Niewiarowske S. Products of 29. Ettema HB. Low incidence of venographically tissue injury: their induction of venous endothelial detected deep vein thrombosis after knee arthroscopy damage and blood cell adhesion in the dog. Arch without thromboprophylaxis: a prospective cohort Pathol Lab Med. 1980;104:409–13. study. J Thromb Haemost. 2006;4:1411–4. 14. Stewart G, Alburger P, Stone E, et al. Total hip replace- 30. Hoppener MR. Low incidence of deep vein thrombo- ment induces injury to remote veins in a canine model. sis after knee arthroscopy without thromboprophy- J Bone Joint Surg Am. 1983;65:97–102. laxis: a prospective cohort study of 335 patients. Acta 15. Gitel S, Salvanti E, Wessler S, et al. The effect of total Orthop. 2006;77(5):767–71. hip replacement and general surgery on antithrombo- 31. Moreno, Hugo Armando Rodriguez. Risk of deep tin III in relation to venous thrombosis. J Bone Joint vein thrombosis in patients undergoing knee arthros- Surg Am. 1979;61:653–6. copy. Curr Orthop Pract. 2009;20(6):665–8. 16. Eriksson B, Eriksson E, Erika G, et al. Thrombosis 32. Ilahi OA. Deep venous thrombosis after knee arthros- after hip replacement: relationship to the fi brinolytic copy: a meta-analysis. Arthrosc J Arthrosc Relat Surg. system. Acta Orthop Scand. 1989;60:159–63. 2005;21(6):727–30. 17. Kluft C, Verheijen J, Jie A, et al. The postoperative 33. Camporese G. Low-molecular-weight heparin ver- fi brinolytic shutdown: a rapidly reverting acute phase sus compression stockings for thromboprophylaxis pattern for the fast acting inhibitor of tissue-type plas- after knee arthroscopy. Ann Intern Med. 2008;149: minogen activator after trauma. Scand J Clin Lab 73–82. Invest. 1985;45:605–10. 34. Wirth T. Prevention of venous thromboembolism after 18. D’Angelo A, Kluft C, Verheijen J, et al. Fibrinolytic knee arthroscopy with low-molecular weight heparin shut down after surgery: impairment of the balance (reviparin): results of a randomized controlled trial. between tissue-type plasminogen activator and its Arthrosc J Arthroscopic Relat Surg. 2001;17(4): 393–9. speci fi c inhibitor. Eur J Clin Invest. 1985;15:308–12. 35. Michot M. Prevention of deep-vein thrombosis in 19. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention ambulatory arthroscopic knee surgery: a randomized of venous thromboembolism. Chest. 2008;133: trial of prophylaxis with low-molecular weight hepa- S381–453. rin. Arthrosc J Arthrosc Relat Surg. 2002;18(3): 20. Falck-Ytter Y, Francis CW, Johanson NA, et al. 257–63. Prevention of VTE in orthopedic surgery patients. 36. Ramos J. Interventions for preventing venous throm- Chest 2012;141(2) (Suppl):287S–325S. boembolism in adults undergoing knee arthroscopy 21. Caprini J. Risk assessment as a guide for the preven- (Review). Cochrane Database of Systematic Reviews tion of the many faces of venous thromboembolism. 2008; Issue 4. Am J Surg. 2010;199:S3–10. 37. Galanis T, Thomson L, Palladino M, Merli G. New 22. Bahl V, Hu HM, Henke PK, et al. A valid study of a oral anticoagulants. J Thromb Thrombolysis. 2011;31: retrospective venous thromboembolism risk scoring 310–20. method. Ann Surg. 2010;2:344–50. 38. Raghavan N, Frost CE, Yu Z, et al. Apixaban metabo- 23. Johanson N, Lachiewicz PF, Lieberman JR, et al. lism and pharmacokinetics after oral administration to Prevention of symptomatic pulmonary embolism in humans. Drug Metab Dispos. 2009;37:74–81. patients undergoing total hip or knee arthroscopy. 39. Frost C, Yu Z, Moore K, et al. Apixaban, an oral direct J Am Acad Orthop Surg. 2009;17(17):183–96. factor Xa inhibitor: multiple-dose safety, pharmacoki- 24. White RH, Romano PS, Zhou H, et al. Incidence and netics and pharmacodynamics in healthy subjects. time course of thromboembolic outcomes following J Thromb Haemost. 2007;5:P-M-664. total hip or knee arthroplasty. Arch Intern Med. 40. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, 1998;158:1525–31. Portman RJ. Apixaban or enoxaparin for thrombopro- 25. Hull RD, Pineo GF, Stein PD, et al. Extended out of phylaxis after knee replacement. N Eng J Med. hospital low molecular weight heparin prophylaxis 2009;361:594–604. against deep vein thrombosis in patients after elective 41. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, hips arthroplasty: a systemic review. Ann Intern Med. Hornick P. ADVANCE-2 Investigators. Apixaban ver- 2001;135:858–69. sus enoxaparin for thromboprophylaxis after knee 26. Eikelboom JW, Quinlan DJ, Douketis JD. Extended replacement (ADVANCE-2): a randomised double- duration prophylaxis against venous thromboembo- blind trial. Lancet. 2010;375:807–15. lism after total hip or knee replacement: a meta analy- 42. Lassen MR, Gallus A, Raskob GE, et al. Apixaban sis of the randomized trials. Lancet. 2001;358:9–15. versus Enoxaparin for thromboprophylaxis after hip 27. Prandoni P, Bruchi O, Sabbion P, et al. Prolonged replacement. N Eng J Med. 2010;363:2487–98. thromboprophylaxis with oral anticoagulations after 43. Kubitza D, Becka M, Wensing G, et al. Safety, phar- total hip arthroplasty: a prospective controlled ran- macodynamics, and pharmacokinetics of BAY domized study. Arch Intern Med. 2002;162:1966–71. 59-7939: an oral, direct Factor Xa inhibitor after mul- 28. Sansone JM, Munoz del Rio A, Anderson A. The tiple dosing in healthy male subjects. Eur J Clin prevalence of and specifi c risk factors for venous Pharmacol. 2005;61:873–80. 56 T. Galanis and G.J. Merli

44. Kubitza D, Becka M, Voith B, et al. Safety, pharmaco- dabigatran etexilate, a new oral direct thrombin dynamics, and pharmacokinetics of single doses of inhibitor, in healthy male subjects. Br J Clin BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol. 2007;64:292–303. Pharmacol Ther. 2005;78:412–21. 51. European Medicines Agency (EMEA). European 45. Kubitza D, Becka M, Zuehlsdorf M, et al. Effects of public assessment report: pradaxa. http://www/emea. food, an antacid, and the H2 antagonist ranitidine on europa.eu/humandocs/PFFs/EPAR/pradaxa/ the absorption of BAY 59-7939 (rivaroxaban), an oral H-829-PI-en.pdf . Accessed 5 Dec 2010. direct Factor Xa inhibitor, in healthy subjects. J Clin 52. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Pharmacol. 2006;46:549–58. Dijk CN, Frostick SP, Kalebo P, Christiansen AV, 46. Eriksson BI, Borris LC, Friedman RJ, Haas S, Hantel S, Hettiarachchi R, Schnee J, Buller HR. Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Oral dabigatran etexilate vs. subcutaneous enox- Muehlhofer E, Misselwitz F, Geerts W. Rivaroxaban aparin for the prevention of venous thromboembo- versus enoxaparin for thromboprophylaxis after hip lism after total knee replacement: the RE-MODEL arthroplasty. N Engl J Med. 2008;358:2765–75. randomized trial. J Thromb Haemost. 2007;5: 47. Lassen MR, Ageno W, Borris LC, Lieberman JR, 2178–85. Rosencher N, Bandel TJ, Misselwitz F, Turpie AG. 52. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Rivaroxaban versus enoxaparin for thromboprophy- Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, laxis after total knee arthroplasty. N Engl J Med. Hantel S, Schnee J, Buller HR. Dabigatran etexilate 2008;358: 2776–86. versus enoxaparin for prevention of venous throm- 48. Kakkar AK, Brenner B, Dahl OE, Eriksson BI, boembolism after total hip replacement: a randomised, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz double-blind, non-inferiority trial. Lancet. 2007;370: F, Haas S. Extended duration rivaroxaban versus 949–56. short-term enoxaparin for the prevention of venous 54. Eriksson BI, Dahl OE, Huo MH, et al. Oral dabigatran thromboembolism after total hip arthroplasty: a versus enoxaparin for thromboprophylaxis after pri- double-blind, randomised controlled trial. Lancet. mary total hip arthroplasty (RE-NOVATE II). Thromb 2008;372:31–9. Haemost. 2011;105:721–9. 49. Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent 55. Ginsberg JS, Davidson BL, Comp PC, Francis CW, M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Friedman RJ, Huo MH, Lieberman JR, Muntz JE, Bandel TJ, Benson A, Misselwitz F, Fisher WD. Raskob GE, Clements ML, Hantel S, Schnee JM, Rivaroxaban versus enoxaparin for thromboprophylaxis Caprini JA. Oral thrombin inhibitor dabigatran after total knee arthroplasty (RECORD4): a randomised etexilate vs North American enoxaparin regimen trial. Lancet. 2009;373: 1673–80. for prevention of venous thromboembolism after 50. Stangier J, Rathgen K, Stahle H, et al. The pharma- knee arthroplasty surgery. J Arthroplasty. 2009;24: cokinetics, pharmacodynamics and tolerability of 1–9. Preoperative Cardiovascular Risk Assessment 5

C. Ronald MacKenzie and Michael K. Urban

This chapter reviews the literature pertaining Introduction to the role of infl ammation in the genesis of coronary artery disease, the enhanced prevalence of The contribution of cardiac disease, especially atherosclerosis in the patient with connective tissue ischemic heart disease, to the risk of noncardiac disease, and concludes with a review of the surgery cannot be overstated. The literature per- approach to the these patients in the perioperative taining to the evaluation and treatment of patients setting. Through a juxtaposition of these consid- with cardiac conditions in the perioperative erations, the goal is to establish a view of the setting is by far the most investigated and connective tissue disease patient as a high-risk developed domain of perioperative medicine. surgical candidate, a notion underappreciated in This association has spawned consensus state- the perioperative literature. ments that guide best medical practice [ 1 ] and is a major consideration in professional societies devoted to this clinical domain. In parallel, the Coronary Artery Disease rheumatology literature is replete with observa- and Infl ammation tions concerning the implication of cardiovascu- lar disease, particularly the contribution of the Until recently, atherosclerosis was viewed pri- atherosclerotic processes to the morbidity and marily as a lipid storage disease, biochemically mortality of the infl ammatory connective tissue bland in nature though certainly not benign in its diseases [2Ð 12 ] . These observations, coupled clinical expression [14 ] . Advances in basic sci- with the growing awareness of the role played by ence have substantially altered this view, promot- in fl ammation in the genesis of coronary artery ing a central role of infl ammation in the initiation disease [13Ð 15 ] , promote the notion of the con- and development of atherogenesis. A number of nective tissue disease patient as at increased risk papers have comprehensively reviewed the puta- in the surgical setting. tive mechanisms involved in this process [ 13Ð 15 ] . Further subsequent work links the in fl ammatory response with the traditional risk factors for coro- C. R. MacKenzie , M.D. () nary artery disease, that is, hypertension, hyperc- Department of Rheumatology Ð Medicine , holesterolemia, diabetes mellitus, and obesity Hospital for Special Surgery , New York , NY , USA [ 14] . These observations, coupled with those e-mail: [email protected] concerning the role of acute plaque rupture, have M. K. Urban , M.D., Ph.D. greatly enhanced the understanding of the mech- Department of Anesthesia , Hospital for Special Surgery, Weil Medical College of Cornell University , New York , anisms underlying the development of acute NY , USA myocardial infarction.

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 57 DOI 10.1007/978-1-4614-2203-7_5, © Springer Science+Business Media, LLC 2013 58 C.R. MacKenzie and M.K. Urban

Despite the relevance of these pathophysio- logic events to the patient with systemic connec- Atherosclerosis and Rheumatic tive tissue disease, alternative mechanisms are Disease also germane to the development of ischemic car- diac complications in the perioperative setting. A considerable body of evidence supports the For instance, the role of perioperative hypoten- long established “bimodal” pattern of mortality sion in the genesis of acute myocardial ischemia in systemic lupus erythematosus (SLE) with early and infarction is well recognized and serves to death from infection and active disease followed unmask preexisting vulnerabilities arising as a years later by a peak attributable to atheroscle- result of the above atherogenic processes. rotic cardiovascular disease [21 ] . Recent studies Given these considerations, it is not surprising have not only confi rmed these observations [ 2, 8, that elevated levels of circulating markers of 10] but expanded them to other chronic rheumatic in fl ammation (CRP, amyloid, IL-6, IL-1 receptor diseases [2, 22 ] . antagonist) accompany the acute coronary syn- With respect to Rheumatoid Arthritis (RA), dromes and correlate with adverse prognosis numerous studies have shown an increase in the [14 ] . They also rise as a consequence of surgery. risk of myocardial infarction (MI) [ 23Ð 25 ] , For instance, patients undergoing complex spine which accounts for nearly 40% of all deaths in surgery may develop a SIRS-like (systemic this condition [23 ] . Compounding the problem in fl ammatory response) syndrome manifesting as are observations suggesting that patients with acute lung injury, systemic hypotension, multiple RA report less angina and are more likely to organ dysfunction, and coagulopathy. This syn- experience asymptomatic myocardial infarction drome is characterized by the release of and sudden death [26 ] . Relative incidence rates in fl ammatory cells in lung alveoli and both pul- for cardiovascular events in patients with chronic monary and systemic increases in cytokines [ 16 ] . RA are as high as 3.97 [22 ] , and despite the high Of even greater importance, however, is how such prevalence of traditional cardiovascular risk markers of infl ammation might be employed in factors (hypertension, hypercholesterolemia, the prediction of future cardiac events in the non- diabetes mellitus, cigarette smoking, etc.), the surgical setting. Recognition of the role played heightened association between RA and cardio- by in fl ammation in the initiation and progression vascular events is independent of these in fl uences of the atherosclerotic process provides an impor- [27, 28 ] . Rather, the chronic in fl ammatory milieu tant opportunity in prevention. In this regard, a (CRP, TNF, interleukins) appears to confer number of large epidemiological studies have much of the incremental risk. Further, corticos- suggested that elevated levels of various teroids, particularly in high doses, may contrib- infl ammatory mediators in seemingly healthy ute to the development of risk factors for subjects may have predictive value for future car- cardiovascular risk factors though recent evi- diovascular events [17Ð 20 ] . Among those stud- dence questions the role of steroids in the genesis ied, the CRP has attracted the most interest. of atherosclerotic disease in patients with (SLE) Numerous studies have demonstrated the capac- [9, 10 ] . ity of the CRP to predict future cardiovascular In SLE, the literature concerning this associa- events. Several studies have shown that statin tion is also extensive. For instance, recent studies therapy lowers CRP levels and may confer bene fi t estimate the prevalence of cardiovascular disease to those with elevated levels even in the absence in SLE in the 8Ð10% range [12, 29 ] . As in the of other cardiac risk factors (including hyper- case of RA, the increased risk also appears inde- lipidemia). Despite its promise, the CRP is not pendent of traditional cardiovascular risk factors yet fully integrated into cardiovascular risk [ 30 ] . In addition to this prevalence data, other assessment strategies, and its potential role in the studies serve to underscore the importance of this prediction of postoperative cardiovascular com- linkage. Data from the Framingham study [12 ] plications is uncertain. suggests a 50-fold increase in rate of myocardial 5 Preoperative Cardiovascular Risk Assessment 59 ab 100 120 3/3 Patients P < 0.001 P = 0.08 Patients Controls Controls (100%) 80 100 72.5 71.4 7/9 80 (78%) 60 P = 0.01 45.0 60 40 8/23 33.3 30.0 P = 0.009 40 (35%) 3/14

calcification (%) 3/20 20 2/30 (21%) 13.4 13.2 20 (15%) (7%) 0/28 0/7 Prevalence of plaque (%) 2.4 (0%) (0%)

0 Prevalence of coronary-artery 0 ≤ 4th 5th 6th ≥ 7th < 40 40–49 50–59 > 60 Decade of age Age (yr)

Fig. 5.1 Atherosclerosis in systemic lupus erythemato- among control subjects and patients with SLE accord- sus. ( a) Prevalence of atherosclerotic plaque among ing to age. The rate of increase in the prevalence of control subjects and patients with SLE according to calci fi cation with age was signi fi cantly higher in patients decade of life (Reprinted with permission from Roman than in controls (Reprinted with permission from et al. [ 9 ] ). ( b) Prevalence of coronary artery calcifi cation Asanuma et al. [10 ] )

infarction in woman with SLE in the 35Ð44-year screen for the presence of coronary artery age range as compared to age-matched controls. calci fi cation [10 ] found more coronary artery Similarly, the SLE-related risk for MI has been calcifi cation in patients with lupus (as compared reported at 2.67 [ 6 ] . Further, the prevalence of as controls); the mean coronary calcifi cation carotid plaque determined via B-mode carotid scores were 68.9 in those with lupus versus 8.8 in ultrasound is also high [9, 12 ] . Indeed, carotid those without. ultrasound data correlates well with those With respect to other major connective tissue obtained by electron-beam computed tomogra- disease, the association with atherosclerotic car- phy used to screen for the presence of coronary diovascular disease appears to hold. For instance, artery disease (Fig. 5.1 ) [ 10 ] . The prevalence of the spondyloarthropathies (SpAs) also appear to atherosclerotic plaque among patients was much have an increased risk of cardiovascular disease. greater in patients with SLE (37.1%) versus con- In addition to their observations in patients with trols (15.2%) [9 ] . Multivariate analysis using age, RA and psoriatic arthritis, Han et al. [ 2 ] have hypertension, diabetes, fasting cholesterol, smok- reported an increased risk of cardiovascular ing practices, and lupus status as univariate disease in patients with ankylosing spondylitis predictors, only age (odds ratio, 2.4 per 10 years), (AS). Figure 5.2 shows the prevalence ratios for the presence of lupus (odds ratio, 4.8 per coronary artery disease relative to controls 10 years), and a higher serum cholesterol level across; these conditions were 1.6, 1.3, and 1.7, (odds ratio, 1.1 per 10 mg per deciliter) were respectively (as compared to 1.5, 1.3, 1.2 in independently associated with the development of controls). atherosclerosis. When compared to patients with- In addition to these more common connective out carotid plaque, patients with plaque forma- tissue diseases, the phenomenon of accelerated tion were older, had longer duration of disease atherosclerosis is a feature of other important and more disease-related damage, and were less conditions of this class. For instance, studies have likely to have autoantibodies or to have been also demonstrated an amplifi cation of atheroma aggressively treated. Longer duration of corticos- development with antiphospholipid syndrome teroid therapy is also among the important poten- (APS), systemic sclerosis (SSc), and primary tiating infl uences in SLE [ 12, 31 ] . Similarly, a study systemic vasculitis (PVS) [ 22 ] . Indeed, only utilizing electron-beam computed tomography to Sjogren’s syndrome seems to be spared [22, 32 ] . 60 C.R. MacKenzie and M.K. Urban

Prevalence of Cardiovascular Disease and Cardiac Risk Factors in Patients with Connective Tissue Disease 40 RA Controls RA † † 31.0 30 28.3

24.0 23.4 20

Percent † † 10.4 8.8 10 7.6 † † 5.8 † 4.7 † 4.0 2.9 1.9 2.4 0.8 1.6 1.4 0 Atherosclerosis CHF PVDCVD IHD Type II Hyperlipidemia Hypertension Diabetes

40 PSA Controls PSA † † 30 27.8 28.5 23.7 22.3 20

Percent † 11.3 † 10 7.3 7.3 † † † † 1.9 1.9 2.9 2.3 3.1 5.5 0.8 1.1 1.3 0 Atherosclerosis CHF PVDCVD IHD Type II Hyperlipidemia Hypertension Diabetes

40 AS Controls AS 30 † † 27.1 25.4 22.0 21.7 20 Percent † 10 † 8.3 6.6 7.1 † † 5.3 † † 3.9 2.2 2.8 2.3 0.7 1.0 1.2 1.9 0 Atherosclerosis CHF PVDCVD IHD Type II Hyperlipidemia Hypertension Diabetes

Fig. 5.2 Prevalence of cardiovascular disease and cardiac risk factors in patients with connective tissue disease (Reprinted with permission from Han et al. [2 ] ) 5 Preoperative Cardiovascular Risk Assessment 61

ischemia in one report [ 32 ] . In another review of Cardiovascular Risk Assessment 1,636 consecutive hip and knee replacements, a in Major Orthopedic Surgery 6.4% incidence of serious postoperative compli- cations has been reported though the majority of Currently, 12.6% (36 million people) of the US which were cardiac [30 ] . Hence, given the aging population are over 65 years old, 16 million of the population, the increasing rates and feasi- of which suffer from “advanced arthritis.” By the bility of surgery in the elderly, and the current year 2030, the number of US citizens over 65 prevalence of perioperative cardiovascular is expected to almost double to 71.5 million. morbidity and mortality, it should be anticipated Older patients, with their multiple comorbidities that postoperative cardiac complications will and arthritis, will require increasingly more remain a common problem going forward. These orthopedic procedures. The mortality after hip observations, when coupled with the previously and knee arthroplasty surgery ranges from 0.4% discussed relationship between infl ammatory to 4.6%, the variation dependent on primary total arthritis and atherosclerosis, insure that the joint arthroplasty as compared to revision proce- preoperative evaluation and postoperative care dures [33Ð 36 ] ; hip fracture is even more daunt- in the connective tissue disease patient will con- ing. The in-hospital mortality after the repair of tinue to challenge those involved in perioperative hip fracture is as high as 4.8% and climbs to 30% medical care. What are the goals of such care and after the fi rst year [ 37 ] , [38 ] . In addition, the how are they achieved? prevalence of back pain in the geriatric population The goal of the preoperative evaluation of is upward to 70%. Hence, many of these patients the patient with cardiac disease for noncardiac may require spinal decompression and fusion, surgery is the identi fi cation of those patients at surgical procedures that carry complication rates increased risk for adverse cardiac events. Once between 2.5% and 80%; the mortality ranges identi fi ed, a reduction in perioperative cardiac from 0% to 22% [39 ] . Thus, based on both complications might then be achieved through increasing disease prevalence as well as postop- the modifi cation of surgical and/or anesthetic erative morbidity and mortality, the orthopedic procedures, the addition of specifi c anti-ischemic patient will continue to make up an important agents and possibly statin therapy, coronary proportion of the patients at risk for surgery- revascularization if indicated, and the institution related adverse events. of postoperative monitoring and interventions. This preoperative evaluation often will require the coordinated efforts of an internist, rheuma- Preoperative Risk Assessment tologist, surgeon, anesthesiologist, and often additional medical consultants. The major risk factor for perioperative mortality Over the last 30 years, several indices of is advanced age, while the primary perioperative cardiac risk have been developed by matching complication is cardiac. For example, in 4,315 medical history prior to surgery with periopera- patients undergoing major noncardiac surgery, a tive cardiac morbidity and mortality. The goal of 2.1% rate of major postoperative cardiac compli- these indices was to identify risk factors that could cations has been reported [40 ] . Similarly, in the be targeted for intervention. A few important con- POISE trial of prophylactic perioperative clusions were reached from the original risk index B-blocker therapy in patients undergoing non- studies of Goldman [42 ] and Detsky [43 ] . These cardiac surgery (n = 8,351), the incidence of a include that (1) patients with a low cardiac risk nonfatal MI was 4.4% and cardiovascular death can proceed to surgery safely without further 1.6% [41 ] . In orthopedic surgery, the incidence evaluation; (2) certain patient characteristics of a perioperative myocardial infarction was (recent myocardial infarction, critical aortic steno- 0.6% of all nonambulatory procedures (n ~ 8,000) sis) impose a high risk such that they require and 6.5% of those patients at risk for myocardial intervention prior to surgery; (3) surgical factors 62 C.R. MacKenzie and M.K. Urban

Table 5.1 Revised Cardiac Risk Index [ 1 ] . Although in the Lee Index surgical risk is High-risk surgery divided only into high risk (vascular, thoracic,

¥ Intraperitoneal, intrathoracic, suprainguinal, vascular etc.) versus everything else, the ACC/AHA Ischemic heart disease guidelines divide surgical interventions into three ¥ Myocardial infarction, positive stress test, angina, classes: low risk, intermediate risk, and high risk. nitrate therapy, pathological Q waves In one study, the impact on 30-day cardiac out- Heart failure come (death and MI) was <1%, 1Ð5%, and > 5% ¥ Congestive heart failure, paroxysmal nocturnal dyspnea, rales or S3 gallop, vascular redistribution for these three groups [ 40 ] . The ACC/AHA on chest X-ray classi fi es orthopedic surgery as intermediate-risk Cerebrovascular disease surgery. While many orthopedic patients would ¥ TIA or stroke be regarded as intermediate-risk patients, there is Insulin-dependent diabetes mellitus a wide disparity in the physiological response Renal insuf fi ciency [Cr > 2.0] Each risk factor contributes 1 point to the index: the elicited by different orthopedic procedures. incidence of major cardiac complication is 0.4%, Contrast the tissue injury and stress response 0.9%, 7%, and 11% with an index of 0, 1, 2, and ³ 3 incurred in a 1Ð2-h total hip arthroplasty to that From Lee et al. [40 ] of a 6-h spinal fusion. Further, many patients with arthritis (particularly those with systemic infl ammatory disease) undergoing orthopedic (urgency, type, and duration) infl uence cardiac surgery have an increased risk of perioperative risk; and (4) a signifi cant number of cardiac events cardiac morbidity and mortality. The possible occur in patients at intermediate cardiac risk. reasons for this increased risk are that many of The Lee Cardiac Risk Index is currently con- these patients are elderly with multiple medical sidered the best predictor of postoperative cardiac comorbidities; many are deconditioned and have morbidity [ 36 ] (Table 5.1). Derived from a pro- limited functional capacity due to their arthritis; spective assessment of 2,893 patients after non- some orthopedic procedures initiate a major sys- cardiac surgery (orthopedic 35%, vascular 21%, temic in fl ammatory response syndrome; orthope- thoracic 12%), the index is composed of fi ve dic procedures may be associated with signi fi cant independent clinical determinants of postopera- blood loss and fl uid shifts; and postoperative pain tive adverse cardiac events. Each of the relevant is a major management problem after orthopedic factors contributed equally to the risk of cardiac surgery [ 45, 46] . In addition, among those with a morbidity and the risk increases with an increas- chronic infl ammatory disease, there is the ing number of such risk factors. A subsequent increased prevalence of arteriosclerotic cardio- cohort study of 100,000 patients showed that the vascular disease as discussed earlier. In sum, predictive value of the Lee Index could be these factors, acting in concert, may trigger a improved by including age >70 years old and a stress response leading to tachycardia, hyperten- more detailed classi fi cation of the surgical proce- sion, increased oxygen demand, and myocardial dure [44 ] . ischemia often in a patient with occult, clinically All existing cardiac risk indices identify a silent cardiovascular disease. class of patients with an intermediate risk for Recognizing the diffi culties in assessing the major postoperative cardiac events, to whom an preoperative functional capacity of these patients, intervention or change in surgical strategy might coupled with an awareness of the signifi cant modify the outcome. The American College of incidence of postoperative cardiac complications Cardiology/American Heart Association (ACC/ after orthopedic surgery, clinicians often subject AHA) Preoperative Cardiovascular Evaluation such patients to preoperative cardiac testing. for Noncardiac Surgery provides guidelines for There is, however, limited data in the orthopedic preoperative cardiac testing in patients at setting to substantiate the view that preoperative increased cardiac risk based on clinical risk cardiac risk strati fi cation much less coronary profi le, functional capacity, and type of surgery revascularization has a positive effect on out- 5 Preoperative Cardiovascular Risk Assessment 63

Table 5.2 ACC/AHA recommendations for noninvasive postoperative occlusive coronary artery thrombosis ischemic testing prior to noncardiac surgery may occur in a minimally stenotic coronary Patients with active cardiac conditions artery. Given these ambiguities, what is known ¥ Unstable coronary syndromes about the value of such testing in the orthopedic ¥ Class IV congestive heart failure setting? ¥ Signi fi cant arrhythmias

¥ Severe valvular heart disease A recent report suggests that abnormal preop- Patients with ³ 3 clinical risk factors; poor functional erative noninvasive cardiac testing rarely changed status; vascular surgery medical management prior to orthopedic surgery Patients with 1Ð2 clinical risk factors; poor functional [ 49 ] . In addition, the DECREASE-II study ques- status; intermediate-risk noncardiac surgery tioned the value of preoperative cardiac testing in Patients with 1Ð2 clinical risk factors; good functional patients of intermediate risk before noncardiac status; major vascular surgery surgery [ 50] . In this case, the cardiac event rate Fleisher et al. [1 ] may have already been reduced by the adminis- tration of B-blockers in intermediate-risk patients. come. The ACC/AHA report presents recom- Thus, ischemia testing did not provide additional mendations for noninvasive ischemia testing information to institute a change in management. prior to noncardiac surgery (Table 5.2 ). The fi rst Also, with regard to coronary revascularization two recommendations were based on the best before orthopedic surgery, data from the CASS evidence-based data which included active car- registry suggests there is no reduction in overall diac conditions and patients with ³ 3 cardiac risk mortality from prophylactic revascularization factors. With the third group, one that includes [ 51, 52] . Similar results have been reported when many of the elderly undergoing orthopedic sur- percutaneous coronary intervention (PCI) was gery, the ACC/AHA recommends testing for employed prophylactically [53 ] . The incidence inducible myocardial ischemia only if the results of postoperative myocardial infarction and death will alter perioperative management. Examples were not reduced for noncardiac surgery in of such management changes include a change in patients at cardiac risk when preceded by PCI the surgical procedure, the initiation of pharma- [ 14, 15, 49 ] . cological treatment, the postponement of surgery Furthermore, patients with coronary artery for coronary revascularization, or cancelation stents who are undergoing noncardiac surgery of the procedure. Myocardial perfusion imaging present signi fi cant challenges to the clinician. using pharmacologically induced stress (dipyri- After PCI, most patients have a stent placed damole, adenosine, dobutamine) has become the within the revascularized vessel to prevent rest- standard for preoperative cardiac risk strati fi cation enosis and the need for repeated revasculariza- in patients with limited exercise capacity. If the tion. However, bare metal intracoronary stents patient can exercise, stress echocardiography has (BMS) are associated with a restenosis rate of the advantage of providing information with 20Ð30%. For this reason, cardiologists now insert regard to LV function and heart valve abnormali- stents impregnated with drugs (DES) which sup- ties, as well as the extent of stress-inducible press neointimal proliferation (stenosis) [ 54 ] . ischemia [ 47, 48] . Nonetheless meta-analysis Patients with DES represent unique perioperative evaluating the prognostic value of ischemic challenges since they are susceptible to thrombosis stress testing has provided mixed results. The if dual antiplatelet therapy is discontinued (such inconsistency of preoperative ischemia testing as may be required before surgery), a risk that to predict perioperative cardiac events is the persists for a full year after stent placement. result of two factors. First is the inability of the Therefore, if surgery cannot be deferred in patients exercise test to adequately mimic the physiologi- with recent DES placement, the potential conse- cal stress response associated with surgery quences of the discontinuation of these medications, (sympathetic drive, blood loss, pain, hypo- speci fi cally stent thrombosis and its attendant thermia, hypercoagulability). The second is that risk of myocardial infarction, even death, need to 64 C.R. MacKenzie and M.K. Urban

Previous PCI

Balloon Bare-metal Drug-eluting angioplasty stent stent

Time since < 14 days > 14 days > 35-45 days < 30-45 days < 365 days >365 days PCI

Delay for elective Proceed to the Delay for elective Proceed to the or nonurgent operation room or nonurgent operating room surgery with aspirin surgery with aspirin

Fig. 5.3 Approach to management of patients with previous percutaneous coronary intervention (PCI) who require noncardiac surgery

be fully appreciated by the patient and all those The target heart rate in the B-blocker group was involved in the patient’s care [53 ] . Further, com- 60Ð70 (bpm). The incidence of cardiac death or plicating decision-making, however, is an aware- nonfatal MI 30-days after surgery was 3.4% in the ness that the continuation of antiplatelet therapy in bisoprolol group versus 34% in the control. the surgical setting may increase postoperative Nonetheless, several recent reports have questioned bleeding complications [55 ] . As a compromise, if the effi cacy of B-blockers in preventing postoperative the decision is made to proceed with surgery cardiac complications, particularly in patients at (thus requiring the discontinuation of antiplatelet intermediate postoperative risk [ 60, 61 ] . In the therapy), then low-dose aspirin should be continued POISE trial, patients (8,351) at risk for cardiac through the perioperative period. The American events and scheduled for noncardiac surgery were College of Cardiology has published an approach randomized just prior to surgery to metoprolol to the management of patients with PCI who succinate or placebo [37 ] . While the B -blockade require noncardiac surgery (Fig. 5.3 ) [ 56 ] . group experienced a signi fi cant reduction in post- operative cardiac events, this advantage occurred at the cost, a 2-fold increase in stroke and an Preoperative B-blocker Therapy increase in mortality. Hypotension was more fre- quent in the B-blockade group and was probably If treatment of the magnitude of coronary revas- the cause of the adverse events. With the publica- cularization does not lower postoperative cardiac tion of these fi ndings, the ACC/AHA revised morbidity, then postoperative stress reduction their guidelines such that patients judged to be at might be a better approach. Pharmacological low risk for postoperative cardiac events should reduction in heart rate has been shown to lower not have B-blockers started preoperatively in a the incidence of myocardial ischemia, myocar- prophylactic manner (Table 5.3 ). dial infarction, and cardiac mortality in the surgi- Lastly, an epidemiological study on the use of cal setting [ 57Ð 59] . In the DECREASE-I study, perioperative B-blocker therapy showed that both 112 patients with echocardiographic stress test the addition of B-blockers at surgery and their confi rmed inducible ischemia were randomized continuation in patients on such a regimen preop- to standard perioperative care or bisoprolol initi- eratively were associated with a reduction in ated 30 days prior to major vascular surgery [ 50 ] . 30-day and 1-year mortality. While this study of 5 Preoperative Cardiovascular Risk Assessment 65

Table 5.3 ACC/AHA revised guidelines for perioperative hypertension (SBP ³ 180/DBP ³ 110 mmHg), B-blocker therapy there may be an increase risk of cardiac compli- Class I cations, and expert opinion recommends a delay ¥ B-blockers continued in patients taking B-blockers in surgery until the blood pressure is better con- ¥ Patients undergoing vascular surgery at high cardiac risk (positive stress test) should receive B-blockers trolled. Further, cardiac risk is increased due to Class IIa baseline hypertension in patients with LVH,

¥ Probably indicated for patients undergoing vascular carotid artery procedures, cardiac surgery, and in surgery with known ischemic heart disease the resection of pheochromocytoma [63 ] . ¥ Vascular surgery and multiple clinical risk factors

¥ Intermediate or high-risk surgery in patients with high CAD/cardiac risk Class IIb Preoperative Statin Therapy

¥ Intermediate-risk surgery with 1 cardiac risk factor ¥ Vascular surgery with low cardiac risk There is one further therapeutic consideration. If Class III indeed the infl ammatory process is a major con- ¥ B-blockers should not be given to patients for surgery who have absolute contraindications to tributor to perioperative myocardial ischemia in B-blockers some patients, statin therapy should be contem- From Fleischer et al. [59 ] plated. According to established guidelines, sta- tins are widely administered to patients at risk for ischemic heart disease not only for their lipid- 38,779 patients over a 12-year period supports lowering effects but also due to their properties of the importance of continuing chronic B-blocker preventing coronary plaque disruption via the therapy through the perioperative period, it does infl ammatory processes. Several clinical trials not answer the question as to the optimal timing have demonstrated a reduction in postoperative or dosing of B-blocker therapy prior to surgery. cardiac events in patients undergoing noncardiac Thus, in orthopedic surgery, the institution of surgery who received perioperative statin therapy, prophylactic B -blocker therapy is currently an effect independent of their lipid-lowering considered a debatable practice in patients with properties [ 64Ð 66 ] . In the DECREASE-III study, 1Ð2 cardiac risk factors. In addition, the optimal vascular surgical patients (497) were randomized dose, timing, and duration of such therapy cannot to receive an extended release statin ( fl uvastatin) be determined from the current literature. 37 days prior to surgery and continued for 30 days Finally, the POISE trial suggested that postoperatively. The incidence of myocardial B-blocker induced arterial hypotension is an ischemia, myocardial infarction, and cardiac important correlate of stroke and postoperative death were all signi fi cantly reduced in the statin- death, none of these studies have speci fi cally treated group [ 67 ] . In addition, the discontinua- addressed what would constitute a “safe” blood tion of statins prior to surgery has been associated pressure range. European guidelines recommend with an increase in cardiovascular events [ 68 ] . that B-blockers should be held for a systolic Furthermore, the complications associated with blood pressure of £ 100 mm HT, while others sug- statin administration, including myopathy and gest a 120-mmHg cutoff. rhabdomyolysis possibly accompanied by acute Turning now to the other side of blood pres- renal failure, have not been detected in the large sure control, there is limited evidence concerning perioperative statin trials. In fact, perioperative the perioperative risk associated with inadequate statin therapy appears associated with enhanced control of chronic hypertension. In the absence of recovery from acute renal failure after high-risk major cardiovascular disease or hypertensive vascular surgery [69 ] . The optimum choice and end-organ damage, the presence of mild hyper- dosage of statin prior to surgery remains uncer- tension does not increase perioperative risk in tain. Some investigators suggest that long-acting noncardiac surgery [ 62 ] . In the presence of severe statins should be given to patients at risk for 66 C.R. MacKenzie and M.K. Urban

myocardial ischemia prior to surgery since it con- regimen had prevented serious involvement of fers anti-in fl ammatory properties during the most other joints over the years. critical perioperative period [70 ] . Pertinent physical fi ndings on examination include severe scoliosis, an ICD palpable in the left anterior chest wall, and her cardiopulmonary Case Presentation examination is unremarkable. Blood pressure 120/70, heart rate 66 (paced), with no jugular The patient is a 67-year-old woman with rheuma- venous distension and a grade I/VI systolic mur- toid arthritis seen in preoperative consultation mur heard along the left sternal border. There is 10 days prior to a scheduled revision total hip no peripheral edema. The lung fi elds are clear. replacement. The diagnosis of RA was made Mild synovitis with modest deformities in the 20 year ago and has followed a relatively benign hands was present on examination. course except for the requirement of a total What cardiovascular evaluation would be hip replacement for progressive infl ammatory considered appropriate in this patient? A good destruction of the joint in 1997. Over the place to start would be with the application of the 18-month period prior to this preoperative eval- Revised Cardiac Risk Index which, based on the uation, she has experienced increasing groin pain clinical scenario presented, would rate this patient secondary to prosthetic loosening. The pain has at relatively low risk. Nonetheless, none of the become severely limiting, indeed is the primary CRI criteria apply directly, and clinical judgment determinant of her near nonambulatory status, would suggest her risk of postoperative cardiac hence the decision to proceed with corrective complications might indeed be signifi cant . surgery. Considerations relevant to this conclusion include Her past medical history is extensive, domi- the presence of traditional cardiac risk factors nated by cardiovascular disease. Mitral valvular (hypertension, hyperlipidemia) cerebrovascular disease with progressive insuffi ciency was diag- disease (TIA), and despite the absence of conges- nosed in the late 1990s and progressed to impend- tive heart failure, this patient has an underlying ing heart failure necessitating mitral valve repair cardiomyopathy secondary to valvular heart (2000). Accompanying the valvular problem, she disease. Indeed, the severity of this condition developed paroxysmal atrial fi brillation with sick was suffi cient to justify ICD placement. sinus syndrome, which in conjunction with a Also diffi cult to quantify is the risk imposed borderline ejection fraction, resulted in the place- by her rheumatoid arthritis. Based on the consid- ment of an intraventricular conduction device erations discussed earlier in this chapter, the (ICD). Additional comorbidities included chronic long-standing nature of her disease coupled with hypertension, hyperlipidemia, asthma, and pul- the chronic corticosteroid therapy supports a monary nodules (attributed to amiodarone), and view that the threat of coronary artery disease is she had suffered a transient ischemic attack (TIA) signifi cant, and as such, she should be considered in the past. In addition to her antirheumatic ther- at heightened risk for postoperative cardiac com- apy, she was taking 15 mainly cardiopulmonary plications. In addition, while orthopedic proce- medications, anticoagulants (Coumadin, Plavix), dures are generally regarded as of intermediate Procrit, and various supplements and vitamins. risk, the patient is to undergo a revision hip With respect to her RA, she had been treated replacement, a procedure of much longer dura- progressively over the years with numerous dis- tion and greater physiological stress. ease-modifying agents but at the time of the An alternative tactic for decision-making in preoperative evaluation had been on a stable regi- this patient is the utilization of the ACC/AHA men of methotrexate (15 mg weekly), Enbrel stepwise model to preoperative cardiac assess- (50 mg weekly), and prednisone 10 mg daily. She ment. Algorithms, premised on the presence or has received continuous steroid therapy through- absence of common cardiac predictors, guide out the duration of her disease. The medication decisions in the preoperative context. However, 5 Preoperative Cardiovascular Risk Assessment 67 these approaches also fall short in the patient of this chapter, a review focused only on cardiac presented. For instance, with patients who do not risk, it is important to recognize that the rheuma- possess major clinical predictors for cardiovas- tologist-internist may confront a panoply of organ- cular disease, the preoperative assessment relies related dysfunction that often accompanies such signi fi cantly on such characteristics as functional patients based on their underlying disease, further capacity. Based on commonly performed daily complicating perioperative decision-making. activities, patients are assigned metabolic equiv- Nonetheless, given the substantial burden of car- alent (MET) estimates of their performance diovascular disease, which is often occult in this capacity; patients unable to sustain a £ 4-MET population, patients with connective tissue disease demand are known to be at increased risk of should be considered at high risk for cardiac com- perioperative and long-term cardiac complica- plications in the context of surgery. This appraisal tions. In patients with chronic arthritis, such serves to authenticate their status as high-risk estimates are problematic as their joint pain, as surgical candidates and presents those clinical opposed to cardiopulmonary reserve or general considerations relevant to their evaluation and deconditioning confounds the functional capac- management in the perioperative setting. ity estimation. This patient had become essen- tially nonambulatory over a period of months as a consequence of pain. References Thus, by working through this example, it is becomes clear that the patients with a chronic 1. Fleisher LA, Beckman JA, Brown KA, et al. ACC/ rheumatic disease may present a considerable AHA 2007 guidelines on perioperative cardiovascular challenges in the preoperative context. Their evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart heightened prevalence of coronary artery disease, Association Task Force on practice guidelines. J Am usually occult, and their pain-related functional Coll Cardiol. 2007;50:e159Ð242. compromise limit the applicability of the recom- 2. Han C, Robinson DW, Hackett MV, et al. Cardiovascular mended clinical algorithms to risk assessment. As disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. such sound, intuitive, clinical judgment is often J Rheumatol. 2006;33(11):2167Ð72. required. This case illustrates not only the com- 3. Avina-Zubieta JA, Choi HK, Sadatsafavi M, et al. plexity of patients with chronic rheumatic disease Risk of cardiovascular mortality in patients with in the preoperative context but also the shortcom- rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59(12):1690Ð7. ings of current approaches to preoperative cardiac 4. Chung CP, Oeser A, Avalos I, et al. Utility of the risk assessment in these patients. Thus, in the Framingham risk score to predict the presence of patient presented, a noninvasive cardiovascular coronary atherosclerosis in patients with rheumatoid evaluation with nuclear stress testing and echocar- arthritis. Arthritis Res Ther. 2006;8(6):1Ð7. 5. Manzi S, Wasko MC. In fl ammation-mediated rheu- diography would appear justi fi ed based on clini- matic diseases and atherosclerosis. Ann Rheum Dis. cal intuition. Fortunately, there is suf fi cient time 2000;59:321Ð5. to complete these assessments prior to surgery 6. Fischer LM, Schlienger RG, Matter C, et al. Effect of though this clinical scenario underscores the rheumatoid arthritis or systemic lupus erythematosus on the risk of fi rst-time acute myocardial infarction. advantages of seeing such patients well in advance Am J Cardiol. 2004;93:198Ð200. of the surgical procedure. 7. Hak AE, Karlson EW, Feskanich D, et al. Systemic lupus erythematosus and the risk of cardiovascular disease: results for the Nurses’ health study. Arthritis Rheum. 2009;61(10):1396Ð402. Conclusion 8. Roman MJ, Crow MK, Lockshin MD, et al. Rate and determinants of progression of atherosclerosis in In conclusion, the patient with chronic connective systemic lupus erythematosus. Arthritis Rheum. 2007; tissue disease who is confronting surgery presents 56(10):3412Ð9. 9. Roman MJ, Shanker BA, Davis A, et al. Prevalence and substantial challenges to those charged with their correlates of accelerated atherosclerosis in systemic lupus medical management. Although beyond the bounds erythematosus. N Eng J Med. 2003;349:2399Ð406. 68 C.R. MacKenzie and M.K. Urban

10. Asanuma Y, Oeser A, Shintani AK, et al. Premature matoid arthritis clinical manifestations to atheroscle- coronary-artery atherosclerosis in systemic lupus ery- rosis. Arthritis Rheum. 2005;52:3413Ð23. thematosus. N Eng J Med. 2003;349:2407Ð15. 29. Urowitz MB, Ibanez D, Gladman DD. Athersclerotic 11. Manzi S, Selzer F, Sutton-Tyrrell K, et al. Prevalence and vascular events in a single large lupus cohort: preva- risk factors of carotid plaque in women with systemic lence and risk factors. J Rheumatol. 2007;34:70Ð5. lupus erythematosus. Arthritis Rheum. 1999;42(1):51Ð60. 30. Esdaile JM, Abrahamowicz M, Grodzicky T, et al. 12. Manzi S, Meilahn EH, Rairie JE, et al. Age-speci fi c Traditional Framingham risk factors fail to fully account incidence rates of myocardial infarction and angina in for accelerated atherosclerosis in systemic lupus erythe- woman with systemic lupus erythematosus: compari- matosus. Arthritis Rheum. 2001;44:2331Ð7. son with the Framingham study. Am J Epidemiol. 31. Petri M, Perez-Gutthann S, Spence D, et al. Risk factors 1997;145(5):408Ð15. for coronary artery disease in patients with systemic 13. Ross R. Atherosclerosis-an in fl ammatory disease. N lupus erythematosus. Am J Med. 1992;93:513Ð9. Eng J Med. 1999;340(2):115Ð26. 32. Manoussakis MN, Georgopoulou C, Zintzaras E, 14. Libby P, Ridker PM, Maseri A. In fl ammation and ath- et al. Sjogren’s syndrome associated with SLE: clini- erosclerosis. Circulation. 2002;105:1135Ð43. cal and laboratory profi les and comparison with 15. Hansson GK. In fl ammation, atherosclerosis, and coro- primary SS. Arthritis Rheum. 2004;50:882Ð91. nary artery disease. N Eng J Med. 2005;352:1685Ð95. 33. Mantilla CB, Horlocker TT, Schroeder DR. Frequency 16. Urban MK, Jules-Elysee KM, Beckman JB, et al. of myocardial infarction, pulmonary embolism, Pulmonary injury in patients undergoing complex deep venous thrombosis, and death following primary spine surgery. Spine J. 2005;5:269Ð76. hip or knee arthroplasty. Anesthesiology. 2002; 17. Maradit-Kremers H, Crowson CS, Nicola PJ, et al. 96:1140Ð6. Increased unrecognized coronary heart disease and 34. Parviz J, Keshavarzi NR, et al. Revision total hip sudden deaths in rheumatoid arthritis: a population- arthroplasty in octogenarians. A case control study. based cohort study. Arthritis Rheum. 2005;52:402Ð11. J Bone Joint Surg. 2007;89:2612Ð8. 18. Ridker PM, Cushman CH, Buring JE, et al. C-reactive 35. Zhan C, Kaczmarek R, Layo-Berrios N, et al. protein and other markers of in fl ammation in the pre- Incidence and short-term outcome of primary and diction of cardiovascular disease in woman. N Eng J revision hip replacements in the United States. J Bone Med. 2000;342:836Ð43. Joint Surg. 2007;89:526Ð33. 19. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma con- 36. Urban MK, Jules-Elysee K, Loughlin C et al. The centration of interleukin-6 and the risk of future myo- one-year incidence of postoperative myocardial cardial infarction among apparently healthy men. infarction in an orthopedic population. HSS Jour Circulation. 2000;101:1767Ð72. 2008;4(1):76Ð80. 20. Harris TB, Ferrucci L, Tracy RP, et al. Associations of 37. Pioli G, Barone A, Oliveri M, et al. Predictors of mor- elevated interleukin-6 and C-reactive protein levels with tality after hip fracture: results from 1-year follow-up. mortality in the elderly. Am J Med. 1999;106:506Ð12. Aging Clin Exp Res. 2006;5:381Ð7. 21. Ridker PM, Rifai N, Pfeffer M, et al. Elevation of 38. Lawrence VA, Hilslenbeck SG, Noveck H, et al. tumor necrosis factor-a and increased risk of recurrent Medical complications and outcomes after hip frac- coronary events after myocardial infarction. ture repair. Arch Intern Med. 2002;14(1620):2053Ð7. Circulation. 2000;101:2149Ð53. 39. Cloyd JM, Acosta FL, Ames CP. Complications and 22. Shoenfeld Y, Gerli R, Doria A, et al. Accelerated outcomes of lumbar spine surgery in elderly people: a atherosclerosis in autoimmune rheumatic diseases. review of the literature. JAGS. 2008;56:1318Ð27. Circulation. 2005;112:3337Ð47. 40. Lee TH, Marccantonio ER, Mangione CM, et al. 23. Urowitz MB, Bookman AA, Koehler BE, et al. Am J Derivation and prospective validation of a simple Med. 1976;60:221Ð5. index for prediction of cardiac risk of major noncardiac 24. del Rincon ID, Williams K, Stern MP, et al. High inci- surgery. Circulation. 1999;100:1043Ð9. dence of cardiovascular events in a rheumatoid arthri- 41. Devereaux PI, Yang H, Yusef S, et al. Effects of tis cohort not explained by traditional cardiac risk extended release metoprolol succinate in patients factors. Arthritis Rheum. 2001;44:2727Ð45. undergoing noncardiac surgery (POISE Trial): A ran- 25. Solomon DH, Karlson EW, Rimm EB, et al. domized control trial. Lancet. 2008;371:1839Ð47. Cardiovascular morbidity and mortality in women 42. Goldman L, Caldera DL, Nussbaum SR, et al. diagnosed with rheumatoid arthritis. Circulation. Multifactorial index of cardiac risk in noncardiac sur- 2003;107:1303Ð7. gical procedures. N Eng J Med. 1977;297:845Ð50. 26. Wolfe F, Michaud K. The risk of myocardial infarc- 43. Detsky AS, Abrams HB, McLaughlin JR, et al. tion and pharmacologic and nonpharmacologic myo- Predicting cardiac complications in patients undergo- cardial infarction predictors in rheumatoid arthritis. ing noncardiac surgery. J Gen Intern Med. 1986;1: Arthritis Rheum. 2008;58:2612Ð21. 211Ð9. 27. Gabriel SE, Crowson CS, O’Fallon WM. Comorbidity 44. Boersma E, Kertai MD, Schouten O, et al. Perioperative in arthritis. J Rheumatol. 1999;26:2475Ð9. cardiovascular mortality in noncardiac surgery: 28. del Rincon I, Freeman GL, Haas RW, et al. Relative validation of the Lee cardiac risk index. Am J Med. contribution of cardiovascular risk factors and rheu- 2005;118:1134Ð41. 5 Preoperative Cardiovascular Risk Assessment 69

45. Lawrence VA, Hilsenbeck SG, Noveck H, et al. 58. Urban MK, Markowitz SM, Gordon MA, et al. Medical complications and outcomes after hip frac- Postoperative prophylactic administration of beta- ture repair. Arch Intern Med. 2002;14(162):2053Ð7. adrenergic blockers in patients at risk for myocardial 46. Sinatra RS, Torres J, Bustos AM. Pain management ischemia. Anesth Analg. 2000;90:1257Ð61. after major orthopedic surgery: current strategies and 59. Fleischer LA, Beckman JA, Brown KA, et al. ACC/ new concepts. J Am Acad Orthop Surg. 2002;10:117Ð29. AHA guideline update on perioperative cardiovascu- 47. Kertai MD, Boersma E, Bax BJ, et al. A meta-analysis lar evaluation for noncardiac surgery: focused update comparing the prognostic accuracy of six diagnostic on perioperative beta-blocker therapy. Anesth Analg. tests for predicting perioperative cardiac risk in 2007;104:15Ð26. patients undergoing major vascular surgery. Heart. 60. Devereaux PJ, Beattie WS, Chou PT, et al. How strong 2003;89:1327Ð34. is the evidence for the use of perioperative beta block- 48. Etchells E, Meade M, Tomlinson G, et al. ers in noncardiac surgery? Systematic review and Semiquantitative dipyridamole myocardial stress meta-analysis of randomized controlled trials. BMJ. perfusion imaging for cardiac risk assessment before 2005;331:313Ð21. noncardiac vascular surgery: a metaanalysis. J Vasc 61. Weisbauer F, Schlager O, Domanovits H, et al. Surg. 2002;36:535Ð40. Perioperative B-blockers for preventing surgery 49. Salerno Sm, Carlson DW, Soh EK, Lettieri CJ. Impact related mortality and morbidity: a systematic review of perioperative cardiac assessment guidelines on and meta-analysis. Anesth Analg. 2007;104:27Ð41. management of orthopedic surgery patients. Am J 62. Howell SJ, Sear JS, Foex P. Hypertension, hyperten- Med. 2007;120:185e1Ð6. sive heart disease and perioperative risk. Br J Anaesth. 50. Poldermans D, Bax JJ, Schoufen O, et al. Dutch 2004;92:570Ð83. echocardiographic cardiac risk evaluation applying 63. Abou-Chebl A, Yadav JS, Reginelli JP, et al. stress echo study group. J Am Coll Cardiol. 2006;48: Intracranial hemorrhage and hyperperfusion syn- 964Ð9. drome following carotid surgery. Risk factors, pre- 51. Eagle KA, Rihai CS, Mickel MC, et al. Cardiac risk of vention and treatment. J Am Coll Cardiol. 2004;43: noncardiac surgery: in fl uence of coronary disease and 1596Ð601. type of surgery in 3368 operations. Circulation. 64. Durazzo AD, Marchado FS, Ikeoka DT, et al. 1997;96:1882Ð7. Reduction in cardiovascular events after vascular 52. McFalls EO, Ward HB, Moritz TE, et al. Coronary- surgery with atorvastatin: a randomized trial. J Vasc artery revascularization before elective major vascular Surg. 2004;39:967Ð76. surgery. N Eng J Med. 2004;351:2795Ð804. 65. Lindenauer PK, Pekow P, wang K, et al. Lipid- 53. Vicenzi MN, Meislitzer T, Heitzinger B, et al. Coronary lowering therapy and in-hospital mortality following artery stenting and noncardiac surgery Ð-a prospective major noncardiac surgery. JAMA. 2004;291: outcome study. Br J Anaesth. 2006;96:686Ð93. 2092Ð9. 54. Biondi-Zoccai GC, Agostoni P, Abbate A, et al. 66. Poldermans D, Bax JJ, Kertai MD, et al. Statins are Adjusted indirect comparison of intracoronary drug associated with a reduced incidence of perioperative eluting sten: evidence for a metaanalysis of random- mortality in patients undergoing major noncardiac ized bare metal stent controlled trials. Int J Cardiol. vascular surgery. Circulation. 2003;107:1848Ð51. 2005;100:119Ð23. 67. Schouten O, Boersma E, Hoeks SE. The Dutch 55. Spahn Dr, Howell SJ, Delabays A, et al. Coronary echocardiographic cardiac risk evaluation applying stents and perioperative anti-platelet regimen: stress echocardiography study group. Fluvastatin and dilemma of bleeding and stent thrombosis. Br J perioperative events in patients undergoing vascular Anaesth. 2006;96:675Ð7. surgery. N Engl J Med. 2009;361:980Ð9. 56. Fleisher LA, Beckman JA, Brown KA, et al. ACC/ 68. Heeschen C, Hamm CW, Laufs U, et al. Withdrawal AJA 2007 guidelines on perioperative cardiovascular of statins increases event rates in patients with evaluation and care for noncardiac surgery: a report of acute coronary syndromes. Circulation. 2002; the American College of Cardiology/American Heart 105:1446Ð52. Association Task Force on practice guidelines 69. Welten GMJM, Chonchol M, Schouten O, et al. Statin (Writing Committee to revise the 2002 guidelines on use is associated with early recovery of kidney injury perioperative cardiovascular evaluation for noncar- after vascular surgery and improved long-term out- diac surgery). Circulation 2007;116 (17):1971Ð1996. come. Nephrol Dial Transplant. 2008;23:3867Ð73. 57. Raby KE, Brull SJ, Yimimi F, et al. The effect of heart 70. Poldermans D. Statins and non-cardiac surgery: rate on myocardial ischemia among high-risk patients current evidence and practical considerations. Cleve after vascular surgery. Anesth Anal. 1999;88:477Ð82. Clin J Med. 2009;76:S79Ð83. Management of Medications in Patients with Rheumatic Diseases 6 During the Perioperative Period

Gregory C. Gardner

NSAID, has the unique property of permanently Introduction inactivating a platelet while in the circulation. Aspirin should therefore be stopped 10–14 days Patients with rheumatic illness are generally tak- before surgery to allow for unaffected platelets to ing one or more medications designed to alter replace the ASA-inactivated cells even though immune function and or suppress infl ammation. ASA itself has a very short half-life. Should Infl ammation, though, is a key element in the everybody stop ASA prior to surgery? What healing process and a functioning immune sys- about those who are using low-dose ASA for pri- tem is important in preventing postoperative mary and secondary cardiovascular prophylaxis? infections. Thus, the balancing act in managing What about using an NSAID to prevent hetero- medications in the perioperative period is to topic ossi fi cation postoperatively? These sorts of modify dosing to allow the normal process of issues illustrate the variables involved in thinking wound healing to occur and preventing wound about medications in the perioperative period. infections while minimizing the risk of a disease This chapter will discuss evidence-based fl are. A disease fl are can lead to further organ or information regarding the use of rheumatic medi- joint damage and impair rehabilitation efforts. cations in the perioperative period. When quality Factors that affect decision-making regarding data is lacking, recommendations will be pro- perioperative medication management include vided based on the available information and will drug mechanism of action, elimination half-life, be so noted in the text. intensity of the surgical procedure (Table 6.1 ), the underlying rheumatic disease, and patient characteristics. Suggestions about modifying the Nonsteroidal Anti-infl ammatory use of medications in the perioperative period in Drugs patients with rheumatologic disease are not cut and dry. For example, nonselective nonsteroidal Nonsteroidal anti-infl ammatory drugs or NSAIDs anti-infl ammatory drugs (NSAIDs) are generally have been a mainstay of therapy for pain and held fi ve half-lives prior to surgery to prevent in fl ammation for the rheumatic diseases. They bleeding complication. Aspirin (ASA), though an have become somewhat less important in recent years for diseases such as rheumatoid arthritis due the therapeutic philosophy that began in the early 1990s of early aggressive intervention  G. C. Gardner , M.D., F.A.C.P . ( ) designed to prevent joint damage [ 1 ] . With less Division of Rheumatology , University of Washington , Seattle , WA , USA joint damage accruing, and better control of e-mail: [email protected] infl ammation with newer immunomodulating

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 71 DOI 10.1007/978-1-4614-2203-7_6, © Springer Science+Business Media, LLC 2013 72 G.C. Gardner

Table 6.1 Surgical intensity based on anesthesia time and tissue injury Procedure type Procedure Minor procedure/minimal stress • Carpal tunnel release 25 mg of hydrocortisone or equivalent • Tenosynovectomy on day of procedure • Knee arthroscopy • Hammertoe correction • 1st MTP fusion Moderate procedure/moderate stress • Hip arthroplasty 50–75 mg of hydrocortisone or • Knee arthroplasty equivalent on day of the procedure • Shoulder arthroplasty • Elbow arthroplasty • MCP arthroplasties • Hand/wrist reconstruction with tendon transfers • 1st MTP fusion with forefoot reconstruction • Limited midfoot arthrodesis with local bone graft • Laparoscopic abdominal surgery • Lung biopsy Intensive procedure/signi fi cant stress • Bilateral knee arthroplasties 100–150 mg of hydrocortisone or • Ankle arthroplasty equivalent on the day of the procedure; • Revision arthroplasties rapid taper over 1–2 days back to • Ankle or hindfoot arthrodeses with iliac preoperative dose crest bone graft • Complex foot reconstructions with arthrodeses and tendon transfers • Spine surgery • Open abdominal surgery Adapted from [18 ] . © 2006 American Academy of Orthopaedic Surgeons. Reprinted from the J Am Acad Orthop Surg. 14(9): 544–551 with permission

agents, NSAIDs have taken a secondary role in as COX-1 and COX-2. COX-1 is produced con- therapy. Nonetheless, many patients continue to stitutively in the stomach, intestines, in platelets, take these agents as part of their treatment regi- and in kidneys [ 2] . The products of COX-1 are men, and modi fi cation during the perioperative important in gastrointestinal cytoprotection, vas- period is generally necessary. cular homeostasis, and maintaining renal func- The mechanism of action of the NSAIDs lies tion. COX-2, on the other hand, is produced by partly in their ability to inhibit cyclooxygenase macrophages and synoviocytes during an activity of the enzyme prostaglandin synthetase infl ammatory process and is inducible at the site that converts arachidonic acid into prostaglan- of in fl ammation [2 ] . The products of COX-2 dins, prostacyclins, and thromboxanes. Inhibiting activity promote swelling and pain. NSAIDs dif- the production of these compounds contributes to fer in their levels of effects on COX-1 and COX-2 NSAID effects on pain and infl ammation but also with only nonacetylated salicylates and celecoxib their side effects. Nonacetylated salicylates have having no effect on platelet COX-1 activity. little or no effect on cyclooxygenase activity but One of the major side effects of COX-1 inhibi- can modulate infl ammation due to their ability to tion is an increase risk of bleeding both from the intercalate into the lipid bilayers of neutrophils operative wound site during and after surgery and and macrophages. Mechanism of action is also from the GI tract. Studies that have explored the infl uenced by isoforms of cyclooxygenase known bleeding risk of NSAIDs in the perioperative 6 Management of Medications in Patients with Rheumatic Diseases During the Perioperative Period 73

Table 6.2 Nonsteroidal anti-in fl ammatory drugs and half-lives NSAID Brand names Half-life (h) Hold time before surgery Ibuprofen Motrin, Advil 1.6–1.9 10 hrs Naproxen Aleve, Naprosyn 12–15 3 days Diclofenac Voltaren, Arthrotec 2 10 hrs Indomethacin Indocin 4.5 1 day Piroxicam Feldene 30 6.25 days Etodolac Lodine 6–7 1.5 days Nabumetone Relafen 24–29 6 days Celecoxiba Celebrex 11 0 hrs Meloxicam Mobic 15–20 5 days Information obtained from MICROMEDEX a Celecoxib has little if any antiplatelet effect

period in patients undergoing orthopedic surgery prior to the procedure. Table 6.2 has the half-lives have all concluded that nonselective NSAIDs of commonly used NSAIDs. ASA should be should be stopped preoperatively [ 3– 5 ] . Robinson stopped 10–14 days before surgery due to its and colleagues evaluated a group of 128 patients effects on platelets as discussed above. who underwent 160 hip replacement surgeries The only pure COX-2 inhibitor remaining on over a 5-year period [ 3 ] . Eighty- fi ve surgeries the market is celecoxib. Others were withdrawn where the patients had continued NSAIDs up to due to an increased risk of myocardial ischemic the time of surgery were compared to a group of events. The advantage of a COX-2 inhibitor is the 75 who used analgesics prior to the procedure. lack of effect on platelet function associated with Blood loss estimates by intraoperative sponge COX-1 inhibition. This has allowed celecoxib to weights, suction volumes, as well as estimates for be used in patients taking anticoagulants such as the fi rst 24 h postoperatively and transfusion warfarin without increasing the risk of bleeding. requirements were compared. The results show a Can celecoxib be safely used in the perioperative signi fi cant increase in blood loss intraoperatively period? Celecoxib has been used for heterotopic and for the 24 h postoperatively in the NSAID ossifi cation prophylaxis (discussed below) and in group. Loss was up to twice the control group, postoperative pain therapy. A recent controlled and transfusion requirements were signifi cantly trial of celecoxib together with pregabalin and higher in the NSAID group. Connelly and Panush acetaminophen was compared to standard PCA/ found in a similar population (patients undergo- opiate postoperative pain therapy. The results ing THA) that perioperative NSAID use, espe- show that the celecoxib, pregabalin, and Tylenol cially those with long half-lives, resulted in cocktail was similar to a PCA/opiate-based pain higher rates of hypotension, postoperative GI regimen in overall patient satisfaction but supe- bleeding, and blood loss compared to those not rior in terms of better overall pain control, less on NSAIDs before surgery [4 ] . In a randomized painful rehabilitation, and fewer medication controlled trial of 2 weeks of 1,800 mg of ibupro- adverse effects [ 6 ] . A similar positive response fen daily or placebo preoperatively, Slappendel was seen when celecoxib was added to standard and colleagues reported a 45% increase in peri- opiate therapy post-total knee arthroplasty operative blood loss in the ibuprofen group so (TKA). Hunag and colleagues found that by add- that even a short half-life NSAID taken up to the ing celecoxib to a standard opiate regimen, time of surgery appears to in fl uence bleeding. It patients had signi fi cantly better pain control, is recommended that NSAIDs be stopped at least improved postoperative range of motion, and 5 half-lives before surgery to assure elimination used 40% less opiate medications. They 74 G.C. Gardner specifi cally noted that there was no increase in appears to be as effective as indomethacin but blood loss in the celecoxib group compared to with fewer side effects [11 ] . those taking placebo [7 ] . What about ASA used for prophylaxis against coronary events? In a recent randomized con- Glucocorticoids trolled trial, Oscarsson et al. evaluated the use of low-dose ASA (75 mg) or placebo in 220 high- Glucocorticoids are frequently used in patients risk cardiovascular patients in the perioperative with rheumatologic disorders as a way to control period. The ASA or placebo was started 1 week signi fi cant in fl ammation. The major glucocorti- before surgery and continued through the third coid produced in the body is cortisol which is pro- postoperative day. Postoperative myocardial duced by the adrenal cortex. Production and release injury within 30 days of surgery was the primary of cortisol is under the control of corticotropin endpoint. Secondary endpoints included docu- (ACTH) produced by the pituitary which is in turn mented myocardial infarction, arrhythmias, car- regulated by corticotropin-releasing hormone diac arrest, cardiac death, or cerebral vascular (CRH) from the hypothalamus. CRH production events. The results show that in high-risk patients, and release is in fl uenced by neural, endocrine, and continuing ASA in the perioperative period cytokine input. Cortisol has pleiotropic effects as reduced the absolute risk of a major cardiac event the glucocorticoid receptor, which is present on by 7.2 percent with a relative risk reduction of virtually every cell, has downstream infl uence on 80% and a number needed to treat of 14 [8 ] . multiple signaling pathways which selectively While the use of ASA does increase periopera- in fl uences DNA transcription [12 ] . Glucocorticoids tive blood loss and transfusion requirements, it may be the only available method for controlling does not appear to increase mortality [ 9 ] . underlying joint or visceral infl ammation in the Mollmann and colleagues recommend that ASA perioperative period. They may also be neces- be stopped in patients who are using ASA for pri- sary to prevent glucocorticoid insuf fi ciency in mary prevention but continued in patients who patients who have taken these agents long term. are on ASA for secondary prevention unless peri- On the other hand, the glucocorticoid-suppressed operative bleeding would pose a signi fi cant risk in fl ammatory response is also important for heal- (i.e., intracranial or spinal surgery) [9 ] . ing and preventing infection. There is a defi nite place for NSAIDs in the Under normal physiologic conditions, the perioperative period for the prevention of hetero- body produces 10–12 mg of cortisol/day. With topic ossifi cation postarthroplasty surgery. moderate stress, the level of cortisol production is Patients with ankylosing spondylitis (AS) and approximately 25–50 mg/day, and with major psoriatic arthritis (PsA) are considered to be at stress, up to 75–150 mg cortisol may be released increased risk for this complication [ 10 ] . into the circulation. Levels of cortisol generally Prophylactic therapy to prevent clinically return to baseline within 24–48 h following the signifi cant heterotopic bone formation should be stressful event. Exogenous glucocorticoids can considered: previous postarthroplasty heterotopic lead to adrenal insuf fi ciency (AI) due to feedback ossifi cation, simultaneous bilateral procedures, suppression of CRH from the hypothalamus lead- prior surgery, or signifi cant bone proliferation ing to a decrease in ACTH release from the pitu- around the native diseased joint [ 10 ] . Prophylaxis itary gland. Eventually, iatrogenic AI may against heterotopic ossi fi cation can include the develop as the adrenal glands atrophy. Patients following: a preoperative local radiation dose of treated with as little as 20 mg of prednisone a day 800 Gy to the operative site or a 7–10-day course for 5 days can demonstrate AI [ 13 ] . Patients on of an NSAID started 24–48 h after surgery [ 10 ] . long-term therapy may require up to a year to Indomethacin 25 mg TID has been used most fre- fully recover adrenal function after the external quently but can increase the risk of postoperative glucocorticoids are stopped and can be assessed bleeding from 1.5% to 3.2% [ 10 ] . Celecoxib by an ACTH stimulation test [13 ] . 6 Management of Medications in Patients with Rheumatic Diseases During the Perioperative Period 75

Historically, patients with suspected AI were and the authors questioned the validity of such provided at least 200–300 mg of hydrocortisone testing in the perioperative period as being too sen- perioperatively, but after an extensive review of sitive and not correlated with clinic outcomes. the literature, Salem et al. suggested a more ratio- Perioperative stress dosing of glucocorticoids nal approach to perioperative glucocorticoid dos- should mimic the required physiologic response. ing. They suggest the following parameters be The following guidelines are recommended for considered: the preoperative dose of glucocorti- patients undergoing surgical procedures who have coids taken, the preoperative duration of gluco- been on chronic corticosteroids based on intensity corticoid therapy, and the “stressfulness” of the of the surgical procedure (Table 6.1 ) [13, 14, 17 ] . surgical procedure [14 ] . All patients that have been on chronic corticoster- It is important to remember that the more oids require their regular dose of corticosteroids severe manifestations of AI occur in primary AI perioperatively. Patients who take 5 mg/day of (adrenal failure due to conditions such as tuber- prednisone or its equivalent preoperatively do not culosis or autoimmune adrenalitis) where aldos- need additional corticosteroids if the procedure is terone production is also affected. Aldosterone less than 1 h or only requires local anesthetic. The undersecretion can lead to nausea, vomiting, and data also suggests that minimally stressful proce- vascular collapse. Aldosterone production is dures, such as a routine knee arthroscopy, require under control of renin-angiotensin from the kidney 25 mg of hydrocortisone (5 mg of methylpredni- and thus is spared in corticosteroid-associated sone intravenously) on the day of the procedure adrenal suppression. Symptoms of secondary AI only. Moderately stressful procedures, i.e., ACL (i.e., corticosteroid insuf fi ciency) may include reconstruction and simple arthroplasties, require psychiatric symptoms, myalgias, fatigue, hypona- 50–75 mg of hydrocortisone (10–15 mg of meth- tremia, hypoglycemia, and hypotension. ylprednisone intravenously) on the day of the pro- Development of AI is a rare but real issue in cedure with resumption of the preoperative dose corticosteroid-treated patients undergoing surgery the following day. Severe stress from complex sur- [13, 14 ] . Two studies are reassuring with regard to geries such as challenging revisions, bilateral the rarity of AI and call into question the utility of arthroplasties, and involved spinal cases requires testing the HPA-axis preoperatively. In 1991, 100–150 mg of hydrocortisone (20–30 mg of Bromberg et al. prospectively studied 40 renal methylprednisone intravenously) on the day of the transplant patients, chronically taking prednisone, procedure with a rapid taper to the preoperative admitted to the hospital with diagnoses including dose in 1–2 days. The critically ill, i.e., severe sepsis, metabolic abnormalities, and surgery [ 15 ] . trauma, will require 50–100 mg of hydrocortisone Although baseline prednisone doses were not intravenously every 6–8 h or 0.18 mg/kg/h as a changed (5–10 mg/day), there were no instances continuous infusion plus 50 m g/day of of clinical adrenal insuf fi ciency despite subnormal fl udrocortisone until shock resolves, which may cosyntropin stimulation test results in 63% of the take days to weeks [ 17 ] . Intravascular volume and patients. Friedman et al. prospectively studied 28 a normal serum sodium level can be used to assess glucocorticoid-treated patients who underwent a the response of corticosteroid supplementation in total of 35 major orthopedic operations without patients with suspected AI on replacement therapy. traditional stress-dose steroids [ 16 ] . The patients Several papers have included tables of a variety of had been taking doses of prednisone ranging from surgical procedures divided by the level of “stress- 1 to 20 mg of prednisone daily from 6 months to fulness” and may be useful to review [13, 17, 18 ] . 32 years prior to the index surgical procedure and Howe et al. focused on orthopedic procedures and received their preoperative dose on the day of sur- assembled a list of surgeries and suggested gluco- gery. None of the patients developed evidence of corticosteroid replacement strategies [18 ] . adrenal insuf fi ciency as assessed by clinical and Corticosteroids can also be used in low dose, laboratory data including a 24-h urinary free corti- i.e., 5–10 mg of prednisone, perioperatively to sol levels. ACTH stimulation testing was not done, control infl ammatory disease in patients with 76 G.C. Gardner rheumatoid arthritis or other forms of infl ammatory action of methotrexate include inhibition of ade- arthritis in order to replace other medications such nosine which affects neutrophil migration, a as TNF inhibitors that have been discontinued. decrease in in fl ammatory cytokines such as IL-6 Certain antibiotics (antifungals and clarithromy- and IL-1, and a decrease of IgG production [22 ] . cin) may increase levels of corticosteroids when Methotrexate is cleared rapidly from the circula- used concurrently. tion but forms intracellular polyglutamates with a half-life of approximately 1 week and may be responsible for the continued control of disease Disease-Modifying Antirheumatic manifestations for up to 4 weeks after stopping Drugs the medication. Data gathered on infection rates, wound heal- Perioperative Infection and Wound ing, and disease fl are with methotrexate during Healing the perioperative period in the 1990s were mixed. Carpenter et al. reported prospective data on two The two main issues of concern in the manage- small groups of patients undergoing orthopedic ment of DMARDs in the perioperative period are procedures while continuing methotrexate or wound infections and wound healing. Rheumatoid after stopping the week before and the week after arthritis (RA) itself has a higher risk of postop- the surgery [23 ] . The 19 patients who stopped erative orthopedic infection when compared to had no postoperative infections, while the 13 who osteoarthritis by a factor of 2.6 [ 19 ] . Factors that continued had 4 signifi cant infections (p = .03). infl uence the risk of infection in RA patients The authors suggested that methotrexate should undergoing orthopedic procedures include prior be held in the perioperative period. Papers by and skin infection, prior wound infection, foot Bridges and Moreland as well as Alarcon and and ankle surgery, or surgery on the elbow [20 ] . colleagues published about the same time sup- A postoperative wound or prosthetic joint infec- ported the recommendation of a temporary dis- tion can be minor to devastating. At least one continuation of methotrexate [ 24, 25 ] . In contrast, additional hospitalization is usually required with Perhala et al. reported a 10-year retrospective 14 more days of inpatient care required to address study of RA patients undergoing surgery with or such complications [21 ] . The cost of treating the without exposure to methotrexate and did not infectious complication quadruples the overall fi nd a signifi cant difference with either infection cost of care compared to an uninfected patient. or wound healing between the groups that com- prised 92 and 110 arthroplasties, respectively [ 26 ] . Likewise, Sany et al. did not fi nd a signi fi cant Nonbiologic Disease-Modifying difference for wound infections or healing for 64 Antirheumatic Drugs patients undergoing orthopedic surgery who were randomized prospectively to continuing metho- Methotrexate trexate or halting for 1 week before surgery [27 ] . Methotrexate is a mainstay of therapy for RA In 2001, the results of a large, well-organized, either alone or in combination with other nonbio- prospective study was published that many feel logic and biologic agents. Current dosing of answered the question as to whether methotrex- methotrexate is in the 15–25 mg/week range, ate should or should not be interrupted in the while earlier studies utilized 7.5–15 mg/week. perioperative period. Grennan and colleagues Methotrexate is administered 1 day of the week prospectively randomized 388 patients with rheu- either by mouth or by subcutaneous injection. matoid arthritis into three groups. One group Methotrexate is a competitive inhibitor of continued methotrexate while undergoing elec- dihydrofolate reductase which interferes with the tive orthopedic procedures, while another group production of purines and pyrimidines and thus discontinued methotrexate 2 weeks prior to and 2 DNA synthesis. The proposed mechanisms of weeks postsurgery. A third group consisted of 6 Management of Medications in Patients with Rheumatic Diseases During the Perioperative Period 77 rheumatoid arthritis patients that had not received active metabolite is between 15 and 18 days due previous methotrexate treatment. The group that to enterohepatic circulation and biliary recycling continued methotrexate therapy had signifi cantly [ 22 ] . Its mechanism of action includes inhibition fewer infections and complications compared to of pyrimidine synthesis, activity of tyrosine the two other groups (p < .003). This group was kinase and of NFkB. also free of postoperative fl ares as opposed to The data regarding the use of lefl unomide in the increased disease activity occurring in 8% of perioperative is limited but of some concern. Fuerst those discontinuing methotrexate and 4% who et al. retrospectively reviewed wound healing in had not been treated previously with methotrex- 201 patients with infl ammatory arthritis (189 RA, ate (p = .04). A more recent report organized in a 8 PsA, 4 JRA) who had undergone orthopedic similar fashion from Japan came to a similar con- procedures [ 32] . The healing issues of concern clusion [28 ] . Finally, a systemic review of the included necrotic eschars, wound dehiscence or data from the last 20 years published in 2009 persistent drainage, and superfi cial/deep wound concluded that methotrexate is safe to continue infection. They reported that 40% of the 32 patients during the perioperative period [29 ] . on lefl unomide or lefl unomide plus corticosteroids Is there ever a reason to hold methotrexate in for at least 3 months prior to surgery developed the perioperative period? The patient with renal wound complications postoperatively. This is in dysfunction is at particular risk of toxicity, and contrast to 13% of 59 patients using methotrexate therefore the withholding of methotrexate in or methotrexate plus corticosteroids developing patients with mild renal insuf fi ciency undergoing wound healing issues (p = .001). The infection rate moderate to intensive surgery should be consid- for the lefl unomide group as a whole (monother- ered [30 ] . If renal insuf fi ciency develops postop- apy or in combination with other agents) was eratively, methotrexate should be held and 9.3%, and on logistic regression, lefl unomide was medicine or rheumatology services consulted. the only agent signifi cantly associated with wound Symptoms of methotrexate toxicity include oral healing problems. Other medications evaluated ulcers and bone marrow suppression. These can besides methotrexate included the TNF inhibitors be managed by the use of folinic acid supplemen- etanercept and infl iximab. The authors strongly tation. Folate supplementation should be consid- recommended interrupting lefl unomide therapy ered for patients on methotrexate who may be before orthopedic surgery. NPO for a prolonged period or may have a In contrast, Tanaka et al. prospectively ran- reduced PO intake as low folate levels may lead domized 161 RA patients undergoing joint to methotrexate toxicity. Methotrexate should arthroplasties to either continuous le fl unomide or also be held in patients who develop a postopera- interruption of le fl unomide for 2 weeks prior to tive infection. Other reported situations of con- surgery and restarting 2 weeks postoperatively cern include elderly patients and those with [ 33] . They did not fi nd a difference in postopera- poorly controlled diabetes, i.e., groups that may tive wound healing issues between the two groups have fragile renal function [ 31 ] . It might be in with the infection rate for both around 6%. Six these patients that methotrexate should be avoided percent versus 40% is a large discrepancy and is the day before surgery and dosed following sur- diffi cult to explain based on available data. The gery as long as renal function is unchanged. Tanaka et al. data, has a larger number of patients, is prospective, is more uniform in the types of Le fl unomide surgical procedures, and appears to be more Le fl unomide was approved for use in RA in 1998. convincing. It is used primarily for RA and occasionally for For low-intensity procedures, le fl unomide can other forms of in fl ammatory arthritis. Le fl unomide be continued. For elective procedures where large is a prodrug and is rapidly converted into its postoperative wounds are anticipated, one could active metabolite by the liver, plasma, and sub- consider holding the drug 2 half-lives, i.e., 4 weeks. mucosa of the intestine [ 22 ] . The half-life of For rapid reduction of levels of lefl unomide, 78 G.C. Gardner cholestyramine given orally at a dose of 8 g three no reason to stop hydroxychloroquine in the times a day for 24 h to three healthy volunteers perioperative period except while NPO. decreased plasma levels by approximately 40% in 24 h and by 49–65% in 48 h. Le fl unomide can be Azathioprine completely eliminated by using cholestyramine Azathioprine is an antimetabolite that inhibits using the above protocol for 11 days if needed. purine metabolism affecting nucleic acid produc- tion and protein synthesis. It is a prodrug that is Sulfasalazine converted to 6-mercaptopurine as the active form Sulfasalazine is a molecule developed in Sweden of the medication. It is metabolized by the liver in 1938 for use in rheumatoid polyarthritis by and excreted in the urine. The elimination half- combining sulfapyridine and 5-aminosalicylic life is approximately 5 h. Azathioprine is used acid (5-ASA) [22 ] . Gut bacteria cleave the azo less for RA than in previous years but is still used bond between the two moieties releasing the in SLE, myositis, and various forms of 5-ASA which stays in the gut and the sulfapyri- vasculitis. dine which is absorbed and is felt to be the active The mechanism of action of azathioprine component in in fl ammatory arthritis. Sulfapyridine seems to suggest that its use in the perioperative interferes with folate metabolism. Its principle period might be bode poorly for wound healing. clinical uses have been in RA and in infl ammatory Escalante and Beardmore reported that RA bowel disease. patients who used azathioprine preoperatively There are little data regarding its safety in the had an elevated relative risk of 2.13 (95% CI perioperative period. A report from den Broeder 1,04–4.37) for postoperative wound complica- et al. from 2007 reviewing 1,219 postoperative tions compared to other DMARDS by univariate wound infections in RA patients suggested that analysis [35 ] . The signi fi cance of this association sulfasalazine was actually protective against disappeared though when multivariate analysis infection [ 20 ] . The half-life of sulfasalazine is was performed. 6–10 h, and elimination is primarily renal. The Although there is limited data for patients with only reason to hold sulfasalazine might be for rheumatologic disease, there are more data for declining renal function or prolonged poor nutri- patients with Crohn’s disease undergoing abdom- tion where folate depletion might occur. Otherwise, inal surgery. Busti et al. reviewed these data and sulfasalazine can be continued for most surgeries concluded that there was no suggestion that aza- except when being NPO is required. thioprine or its metabolite, 6-mercapopurine, adversely affected postoperative wound infection Hydroxychloroquine or healing [37 ] . Hydroxychloroquine was developed in the There does not appear to be a reason to hold 1940s as a safer alternative to quinine for anti- azathioprine for routine surgeries except in the malarial treatment and prophylaxis. Mechanism case of postoperative liver or renal dysfunction or of action includes interference with Toll-like while NPO. receptors and antigen presenting cell handling of antigen via elevation of pH of lysosomal vac- Mycophenolate Mofetil uoles. It is used for RA, systemic lupus (SLE), Mycophenolate mofetil (MMF) is a selective, and a variety of other forms of infl ammatory noncompetitive, and reversible inhibitor of inos- diseases. Hydroxychloroquine was used at one ine monophosphate dehydrogenase via its active time as postoperative prophylaxis against throm- metabolite, mycophenolic acid, which results in bosis but has been supplanted by more effective the inhibition of the de novo synthesis pathway of therapies [34 ] . There is a paucity of data evalu- purines. T and B lymphocyte proliferation depends ating hydroxychloroquine in the perioperative on the de novo synthesis of purines, while other period, but what is available suggests that this cell types can utilize the salvage pathways. agent is safe to use [ 35, 36] . In general, there is Elimination is 93% via kidney and 6% via feces. 6 Management of Medications in Patients with Rheumatic Diseases During the Perioperative Period 79

Table 6.3 Biologic agents and half-livesa Generic name Brand names Type Half-life (days) Etanercept Enbrel TNF inhibitor 3.5–5.5 Adalimumab Humira TNF inhibitor 10–20 In fl iximab Rituximab TNF inhibitor 9.5 Certolizumab Cimzia TNF inhibitor 14 Golimumab Simponi TNF inhibitor 14 Abatacept Orencia T cell inhibitor 12.6 Rituximab b Rituxan B cell inhibitor 18–22 Effects on B cells may be 6 months or more Tocilizumab Actemra IL-6 receptor antagonist 11–13 Anakinra Kineret IL-1 receptor antagonist 4–6 h aBiologics are suggested to be not given at least 2 half-lives prior to major elective surgery; half-life data from medication prescribing information b Please see text regarding rituximab recommendations

The elimination half-life is approximately 17 h. Biologic Disease-Modifying MMF is used in SLE, vasculitis, and extensively Antirheumatic Drugs in organ transplant patients. There are no available data on MMF in the The current biologic agents are proteins with perioperative period for patients with rheumato- human or human/murine constructs that are logic disease. Humar and colleagues reviewed directed against infl ammatory cytokine activity data on wound complications in 2,013 kidney or against cells that participate in the in fl ammatory transplant recipients and found that MMF use process. They are administered either IV or SC. had a signi fi cant relationship with both super fi cial Many of the cytokines inhibited by these mole- and deep wound infections and wound herniation cules, such as IL-1 or TNF, contribute to disease or dehiscence [ 38 ] . In an experimental model of activity but are also important in the response to colon anastomoses using rats, Zeeh et al. found invading organisms and may play a role in wound that MMF impaired healing by disturbing colonic healing. There was an increased mortality from epithelium proliferation [ 39 ] . On the other hand, gram-positive sepsis in patients given anti-TNF Flechner et al. reviewed wound healing complica- therapy during the clinical trials to evaluate the tion of 513 kidney transplant patients and could fi nd role of anti-TNF therapy during sepsis [40 ] . no indication that any of the immunosuppressive Table 6.3 summarizes the current biologic agents, medications including MMF posed any increased their generic and trade names, MOA, and half- risk, although these medications were given in lives. various fi xed combinations which made teasing out individual agents dif fi cult. The most Anti-Tumor Necrosis Factor a Medications signifi cant risk factor in this and other studies for Currently, there are fi ve anti-TNF agents. The wound complications was body weight. fi rst agent to be approved was etanercept, a fusion For minor procedures, MMF can be contin- protein combining two TNF p75 receptors with ued. For surgeries where large wounds may be an IgG1 Fc region. The circulating half-life of anticipated or for GI surgeries, holding MMF for etanercept is 3.5–5.5 days, the shortest of all the two half-lives before surgery (half-life 18 h) and TNF agents. In fl iximab is a chimeric monoclonal waiting until wound healing is well established is antibody against TNF with a half-life of 9.5 days suggested but not based on specifi c data in but is generally infused every 6–8 weeks for patients with rheumatologic disease. maintenance therapy. Adalimumab is a fully 80 G.C. Gardner humanized monoclonal antibody against TNF patients undergoing foot and ankle surgery were and has the longest half-life of the TNF agents of divided into two groups based on use of anti-TNF 10–20 days and is generally dosed every 2 weeks. therapy or conventional DMARDs both of which Golimumab is a fully humanized monoclonal were continued during the perioperative period. antibody with a half-life of 14 days and is dosed There was no association between use of TNF once a month. Finally, certolizumab is a Fab’ agents and wound complications or wound infec- against TNF combined with polyethylene glycol. tions [47 ] . In fact, the TNF group had a The half-life is also 14 days with dosing every signi fi cantly lower combined healing problem/ 2 weeks. In general, the monoclonal antibodies infection rate than the group continuing on non- seem to have broader activity than etanercept and biologic DMARDs (p = 0.033). In only one study are associated with a slightly increased risk of by Giles et al. was an association between TNF certain infections including reactivation of use and postoperative wound infection noted tuberculosis. [ 48] . The odds ratio of infection for TNF users There is a paucity of data regarding the use of versus TNF naive RA patients was 5.3 (95% CI TNF agents in the perioperative period with 1.1–24.9) (multivariate analysis). The problem regard to infection and wound healing. In a report with this study, as with most of the data to date, is using the British Society for Rheumatology that it is retrospective, and the groups are often Biologics Register, the overall incidence rate unequal with regard to the types of surgical pro- ratio of serious infections for RA patients on TNF cedures being compared. Nonetheless, it is reas- agents verses those on nonbiologic DMARDs suring that no consistent negative association was not different, but the incidence rate ratio for between anti-TNF use and wound complications the subset of serious skin and soft tissue infec- has been found in spite of a legitimate concern. tions was signifi cantly increased to 4.28 (95% CI Mushtaq et al. reviewed data regarding in fl iximab 1.06–17.17) for those using anti-TNF therapy and abdominal surgery in patients with [41 ] . No difference was detected between the in fl ammatory bowel disease and found no con- three major TNF agents (etanercept, infl iximab, cerning signal regarding infection or wound heal- adalimumab) for serious skin and soft tissue ing in this group of patients either [43 ] . infection rates. Since these are major causes of In the absence of high-quality prospective data morbidity in the perioperative period, these data regarding anti-TNF use in the perioperative should raise concern. The issue of TNF agents period, we temporarily interrupt TNF therapy. and postoperative wound complications was Pappas and Giles in their 2008 review of this topic reviewed in 2008 and again in 2010 [ 42, 43 ] . recommended a 3–5 half-life interruption prior to There are 6 studies that have explored the question surgery and resumption of 10–14 days postopera- of TNF agents and postoperative complications, tively to allow for adequate wound healing [42 ] . 5 showing no increased risk and one fi nding a This translates into holding etanercept for signi fi cant relationship between anti-TNF use 2 weeks, in fl iximab for 4 weeks, and the three and deep wound infection. In one of the negative other TNF agents for 4–6 weeks. Since adopting studies, no difference in infection rates was noted these criteria, the authors state that they have not for those who continued (32/50) compared to had to their knowledge a serious postoperative those who stopped TNF agents (18/50) before infection. This same time table, holding 3–5 half- surgery. There was, though, an increase in fl are lives, has been advocated by the British Society rate for those who interrupted TNF agents for Rheumatology [49 ] . Mushtaq et al. suggest a (p = 0.02) [44 ] . In three additional studies, no somewhat different approach which is to wait one signi fi cant relationship between TNF use and dosing cycle and restarting when wound healing postoperative wound problems or infections was is suf fi ciently progressed to allow suture removal noted, although trends unfavorable for TNF use [43 ] . So for etanercept that would be 1 week, for were present in two studies [ 20, 45, 46 ] . In one of adalimumab and certoluzimab 2 weeks, goli- the only prospective studies on this topic, RA mumab 4 weeks, and in fl iximab 8 weeks. 6 Management of Medications in Patients with Rheumatic Diseases During the Perioperative Period 81

In general, anti-TNF agents can be continued demonstrating depletion up to 3 years after a sin- for minor procedures and held at least 2 half-lives gle treatment. A minority of patients develop a for moderate to intense elective surgical proce- signi fi cant reduction in immunoglobulin levels, dures and waiting until wounds have healed and less than 10% still have reductions at before restarting. In the event of a postoperative 6 months (mostly IgM). The elimination half-life infection, TNF agents should be held until infec- is 18–22 days. tion clearance and restarted with caution. Note Bacterial infections in lymphoma patients that like steroids, the TNF agents may blunt signs receiving chemotherapy and rituximab are not and symptoms of infection. increased compared to chemotherapy alone, and renal transplant patients receiving rituximab as Abatacept induction therapy or for rejection therapy did not Abatacept is a CTLA4 Ig fusion protein that develop more infections than those not receiving interferes with T cell activation by inhibiting the the drug [43, 50 ] . Certain viral infections are second signal necessary to activate T cells. It has increased during therapy with rituximab including a half-life of 12.6+/−4.6 days. There is currently reactivation of hepatitis B and progressive multi- no data regarding the use of abatacept in the peri- focal leukoencephalopathy caused by JC virus operative period. In initial clinical trials, there infection [51 ] . Neither of these are of importance were no signals for an unusual risk of infection in in the perioperative management of this agent. RA patients beyond that seen with methotrexate With regard to perioperative use, Mushtaq or the TNF inhibitors [43 ] . Abatacept can be con- et al. suggest waiting until B cell counts normal- tinued in the perioperative period for minor sur- ize before undergoing elective surgery, but there geries, but we hold this agent at least 2 half-lives does not appear to be data to support this sug- for moderate to intense procedures. An increased gestion, especially since it has been used as risk of adverse events (respiratory compromise induction therapy for renal transplantation with- and infection) occurred in RA patients with con- out apparent risk [ 43 ] . Hypogammaglobulinemia comitant COPD, and it is likely that such patients has been associated with an increased risk of will not be on abatacept, but extra caution in the bacterial, fungal, and viral infection in solid perioperative period is warranted for pulmonary organ transplant recipients, and replacement infections, and a longer period of interruption doses of IVIg have been suggested for such may be warranted if there are any respiratory patients when the total IgG level is under concerns or complications. There are no speci fi c 500 mg/dl [ 52, 53] . Rather than waiting for B data to support the above recommendations for cells to return, we suggest measuring immuno- holding abatacept. globulin levels (especially IgG) for elective sur- gery of moderate to severe intensity. If normal Rituximab and it has been approximately 100 days since Rituximab is a chimeric monoclonal antibody the last dose (5 half-lives), no further reduction directed against the CD-20 antigen on the surface in immunoglobulins would be anticipated and of B cells. CD-20 is present on B cells in the surgery could proceed. If immunoglobulin lev- post-stem cell stage and pre-plasma cell/memory els are low and surgery is required, IVIg replace- cell stage. It was developed for use in the treat- ment should be given. ment of lymphomas, and literature has been There have been reports of late-onset neutro- available for several years regarding rituximab penia (LON), in some cases severe, in patients and infection. After a dose of rituximab, B cell who have received rituximab. Most patients with depletion occurs in the fi rst 2–3 weeks, and most LON had been treated for hematologic malignan- patients show depletion for up to 6 months (pre- cies, but at least one case of LON has been scribing information). The circulating B cell reported in RA (the author has seen a case occur- counts return to normal by 9–12 months in the ring 2 months after the last dose of rituximab majority of patients with an occasional patient lasting 10 days), and it has also been reported to 82 G.C. Gardner occur in 2 patients receiving rituximab for refrac- These data are reassuring with regard to post- tory ANCA-associated vasculitis [ 54– 56 ] . LON operative complications but involve small numbers appears from 14 to 295 days posttreatment and of patients. Signs and symptoms of postoperative lasts from 1 to 349 days. Etiology is uncertain, infection may be masked, and a delay in diagnosis and it is apparently rare enough in RA patients to and treatment might occur [ 43 ] . only be aware of and not anticipate LON as an As with other agents, tocilizumab probably issue in the perioperative period. does not need to be held for minor procedures, but for moderate to intense procedures, a hold for Tocilizumab at least 2 half-lives (26 days) is reasonable in the Tocilizumab is a monoclonal antibody directed absence of defi nitive data, restarting 10–14 days against the IL-6 receptor. IL-6 is an important postoperatively. Neutropenia and thrombocy- cytokine generated during infection and is respon- topenia have been reported to occur with tocili- sible for fever and elevation of acute phase reac- zumab therapy and generally occur in the fi rst tants especially CRP. IL-6 is also produced in 3–4 days postinfusion but should not be an issue response to tissue trauma as part of the if treatment is interrupted. in fl ammation/healing process. After a single dose, the elimination half-life of tocilizumab is Anakinra 6 days, but because of concentration dependent Anakinra is an IL-1 receptor antagonist developed elimination, once steady state has been reached, to treat RA. It currently used off label to treat the elimination half-life is 11–13 days (prescrib- acute gout and other infl ammatory disorders. ing information). The usual dose is 4–8 mg/kg Anakinra has an elimination half-life of 4–6 h. administered IV once a month. There are two There are no current data regarding anakinra small studies investigating the effects of tocili- and perioperative complications, although the zumab during the perioperative period. Hirao author has seen a case of a signi fi cant postopera- et al. compared a variety of parameters for 22 tive wound infection occurring in a patient treated joint surgeries in RA patients while receiving with anakinra for postoperative gout. Holding the tocilizumab (uninterrupted) and 22 joints surger- drug 1–2 days before surgery for moderate to ies in patients who were on nonbiologic DMARDs intense surgeries will permit complete elimina- [57 ] . No superfi cial or deep wound infections tion of the drug, and it can be restarted 10–14 days were observed in either group nor were there any postoperatively. There is no need to hold for problems reported for wound healing. In addi- minor surgeries. tion, there was no reduction in neutrophils nor lymphocytes in either group in the perioperative period. There was a suppression in the expected Herbal Supplements rise in body temperature in the tocilizumab group and complete suppression in the rise of CRP Herbal supplement use is widespread, and postoperatively. In the second study, Hiroshima patients who have surgery appear to use these et al. evaluated the effects of tocilizumab in 8 supplements more frequently than the general RA-associated joint surgeries where the agent population [59 ] . Many patients do not volunteer had been held 4 weeks before and 4 weeks after to physicians that they use these supplements, surgery (skipping one dose) compared to 16 sur- and there can be adverse effects from commonly geries in RA patients on TNF agents and 16 sur- used supplements in the perioperative period. geries where the patients were using nonbiologic Ginko’s (used in dementia) antiplatelet activity DMARDs [58 ] . Again, no infection or delayed may increase bleeding risk [ 59, 60 ] . It should be wound healing was reported for the tocilizumab held 36 h before surgery. Ginseng can decrease group, but as in the Hirao et al. study, postopera- the effect of anticoagulation and can also inhibit tive temperature rise and CRP were both platelets, perhaps irreversibly. It should be suppressed. stopped 7 days before surgery [ 60 ] . Valerian is 6 Management of Medications in Patients with Rheumatic Diseases During the Perioperative Period 83 used to treat insomnia and anxiety, and it modu- 13. Axelrod L. Perioperative management of patients lates GABA receptors. It may potentiate the seda- treated with glucocorticoids. Endocrinol Metab Clin North Am. 2003;32:367–83. tive effects of benzodiazepines and anesthetic 14. Salem M, Tainsh Jr RE, Bromberg J, Loriaux DL, agents. Additionally, patients could experience a Chernow B. Perioperative glucocorticoid coverage. withdrawal syndrome after surgery similar to A reassessment 42 years after emergence of a problem. benzodiazepine withdrawal. Tapering valerian Ann Surg. 1994;219:416–25. 15. Bromberg JS, Alfrey EJ, Barker CF, et al. Adrenal sup- weeks before surgery should be considered. pression and steroid supplementation in renal trans- Physicians need to ask every patient specifi cally plant recipients. Transplantation. 1991;51:385–90. about herbal supplement use in the preoperative 16. Friedman RJ, Schiff CF, Bromberg JS. Use of supple- history to ensure safe use of these supplements in mental steroids in patients having orthopaedic opera- tions. J Bone Joint Surg Am. 1995;77:1801–6. the perioperative period. 17. Coursin DB, Wood KE. Corticosteroid supplementa- tion for adrenal insuf fi ciency. JAMA. 2002;287: 236–40. 18. Howe CR, Gardner GC, Kadel NJ. Perioperative med- References ication management for the patient with rheumatoid arthritis. J Am Acad Orthop Surg. 2006;14:544–51. 1. Healey LA, Wilske KR. Reforming the pyramid. A 19. Poss R, Thornhill TS, Ewald FC, Thomas WH, Batte plan for treating rheumatoid arthritis in the 1990s. NJ, Sledge CB. Factors in fl uencing the incidence and Rheum Dis Clin North Am. 1989;15:615–9. outcome of infection following total joint arthroplasty. 2. Needleman P, Isakson PC. The discovery and function Clin Orthop Relat Res. 1984;182:117–26. of COX-2. J Rheumatol Suppl. 1997;49:6–8. 20. den Broeder AA, Creemers MC, Fransen J, et al. Risk 3. Robinson CM, Christie J, Malcolm-Smith N. factors for surgical site infections and other complica- Nonsteroidal antiinfl ammatory drugs, perioperative tions in elective surgery in patients with rheumatoid blood loss, and transfusion requirements in elective arthritis with special attention for anti-tumor necrosis hip arthroplasty. J Arthroplasty. 1993;8:607–10. factor: a large retrospective study. J Rheumatol. 2007; 4. Connelly CS, Panush RS. Should nonsteroidal anti- 34:689–95. infl ammatory drugs be stopped before elective sur- 21. Whitehouse JD, Friedman ND, Kirkland KB, gery? Arch Intern Med. 1991;151:1963–6. Richardson WJ, Sexton DJ. The impact of surgical- 5. Slappendel R, Weber EW, Benraad B, Dirksen R, site infections following orthopedic surgery at a com- Bugter ML. Does ibuprofen increase perioperative munity hospital and a university hospital: adverse blood loss during hip arthroplasty? Eur J Anaesthesiol. quality of life, excess length of stay, and extra cost. 2002;19:829–31. Infect Control Hosp Epidemiol. 2002;23:183–9. 6. Post ZD, Restrepo C, Kahl LK, van de Leur T, Purtill 22. Ranganath VK, Furst DE. Disease-modifying anti- JJ, Hozack WJ. A prospective evaluation of 2 different rheumatic drug use in the elderly rheumatoid arthritis pain management protocols for total hip arthroplasty. patient. Rheum Dis Clin North Am. 2007;33: J Arthroplasty. 2010;25:410–5. 197–217. 7. Huang YM, Wang CM, Wang CT, Lin WP, Horng LC, 23. Carpenter MT, West SG, Vogelgesang SA, Casey Jiang CC. Perioperative celecoxib administration for Jones DE. Postoperative joint infections in rheuma- pain management after total knee arthroplasty - a ran- toid arthritis patients on methotrexate therapy. domized, controlled study. BMC Musculoskelet Orthopedics. 1996;19:207–10. Disord. 2008;9:77. 24. Bridges Jr SL, Moreland LW. Perioperative use of 8. Oscarsson A, Gupta A, Fredrikson M, et al. To con- methotrexate in patients with rheumatoid arthritis tinue or discontinue aspirin in the perioperative undergoing orthopedic surgery. Rheum Dis Clin North period: a randomized, controlled clinical trial. Br J Am. 1997;23:981–93. Anaesth. 2010;104:305–12. 25. Alarcon GS, Moreland LW, Jaffe K, Phillips RM, 9. Mollmann H, Nef HM, Hamm CW. Antiplatelet ther- Bocanegra T, Russell IJ. The use of methotrexate peri- apy during surgery. Heart. 2010;96:986–91. operatively in patients with rheumatoid arthritis 10. Iorio R, Healy WL. Heterotopic ossi fi cation after hip undergoing major joint replacement surgery: will we and knee arthroplasty: risk factors, prevention, and ever have consensus about Its use? J Clin Rheumatol. treatment. J Am Acad Orthop Surg. 2002;10:409–16. 1996;2:6–8. 11. Romano CL, Duci D, Romano D, Mazza M, Meani E. 26. Perhala RS, Wilke WS, Clough JD, Segal AM. Local Celecoxib versus indomethacin in the prevention of infectious complications following large joint replace- heterotopic ossifi cation after total hip arthroplasty. ment in rheumatoid arthritis patients treated with J Arthroplasty. 2004;19:14–8. methotrexate versus those not treated with methotrex- 12. Rhen T, Cidlowski JA. Antiinfl ammatory action of ate. Arthritis Rheum. 1991;34:146–52. glucocorticoids–new mechanisms for old drugs. N Engl 27. Sany J, Anaya JM, Canovas F, et al. In fl uence of J Med. 2005;353:1711–23. methotrexate on the frequency of postoperative 84 G.C. Gardner

infectious complications in patients with rheumatoid 41. Dixon WG, Watson K, Lunt M, Hyrich KL, Silman arthritis. J Rheumatol. 1993;20:1129–32. AJ, Symmons DP. Rates of serious infection, includ- 28. Murata K, Yasuda T, Ito H, Yoshida M, Shimizu M, ing site-speci fi c and bacterial intracellular infection, Nakamura T. Lack of increase in postoperative com- in rheumatoid arthritis patients receiving anti-tumor plications with low-dose methotrexate therapy in necrosis factor therapy: results from the British society patients with rheumatoid arthritis undergoing elective for rheumatology biologics register. Arthritis Rheum. orthopedic surgery. Mod Rheumatol. 2006;16:14–9. 2006;54:2368–76. 29. Loza E, Martinez-Lopez JA, Carmona L. A system- 42. Pappas DA, Giles JT. Do antitumor necrosis factor atic review on the optimum management of the use of agents increase the risk of postoperative orthopedic methotrexate in rheumatoid arthritis patients in the infections? Curr Opin Rheumatol. 2008;20:450–6. perioperative period to minimize perioperative mor- 43. Mushtaq S, Goodman SM, Scanzello CR. Perioperative bidity and maintain disease control. Clin Exp management of biologic agents used in treatment of Rheumatol. 2009;27:856–62. rheumatoid arthritis. Am J Ther. 2011;18:426–34. 30. Wluka A, Buchbinder R, Mylvaganam A, et al. 44. Wendling D, Balblanc JC, Brousse A, et al. Surgery in Longterm methotrexate use in rheumatoid arthritis: patients receiving anti-tumour necrosis factor alpha 12 year followup of 460 patients treated in community treatment in rheumatoid arthritis: an observational practice. J Rheumatol. 2000;27:1864–71. study on 50 surgical procedures. Ann Rheum Dis. 31. Rosandich PA, Kelley 3rd JT, Conn DL. Perioperative 2005;64:1378–9. management of patients with rheumatoid arthritis in 45. Ruyssen-Witrand A, Gossec L, Salliot C, et al. the era of biologic response modifi ers. Curr Opin Complication rates of 127 surgical procedures per- Rheumatol. 2004;16:192–8. formed in rheumatic patients receiving tumor necrosis 32. Fuerst M, Mohl H, Baumgartel K, Ruther W. factor alpha blockers. Clin Exp Rheumatol. 2007; Le fl unomide increases the risk of early healing com- 25:430–6. plications in patients with rheumatoid arthritis under- 46. Talwalkar SC, Grennan DM, Gray J, Johnson P, going elective orthopedic surgery. Rheumatol Int. Hayton MJ. Tumour necrosis factor alpha antagonists 2006;26:1138–42. and early postoperative complications in patients with 33. Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, in fl ammatory joint disease undergoing elective ortho- Ishii S. Examination of the risk of continuous paedic surgery. Ann Rheum Dis. 2005;64:650–1. lefl unomide treatment on the incidence of infectious 47. Bibbo C, Goldberg JW. Infectious and healing com- complications after joint arthroplasty in patients with plications after elective orthopaedic foot and ankle rheumatoid arthritis. J Clin Rheumatol. 2003;9: surgery during tumor necrosis factor-alpha inhibition 115–8. therapy. Foot Ankle Int. 2004;25:331–5. 34. Loudon JR. Hydroxychloroquine and postoperative 48. Giles JT, Bartlett SJ, Gelber AC, et al. Tumor necrosis thromboembolism after total hip replacement. Am J factor inhibitor therapy and risk of serious postopera- Med. 1988;85:57–61. tive orthopedic infection in rheumatoid arthritis. 35. Escalante A, Beardmore TD. Risk factors for Arthritis Rheum. 2006;55:333–7. early wound complications after orthopedic surgery 49. Ding T, Ledingham J, Luqmani R, et al. BSR and for rheumatoid arthritis. J Rheumatol. 1995;22: BHPR rheumatoid arthritis guidelines on safety of 1844–51. anti-TNF therapies. Rheumatology (Oxford). 2010;49: 36. Bibbo C, Anderson RB, Davis WH, Norton J. The 2217–9. infl uence of rheumatoid chemotherapy, age, and pres- 50. Scemla A, Loupy A, Candon S, et al. Incidence of ence of rheumatoid nodules on postoperative compli- infectious complications in highly sensitized renal trans- cations in rheumatoid foot and ankle surgery: analysis plant recipients treated by rituximab: a case-controlled of 725 procedures in 104 patients [corrected]. Foot study. Transplantation. 2010;90:1180–4. Ankle Int. 2003;24:40–4. 51. Gea-Banacloche JC. Rituximab-associated infections. 37. Busti AJ, Hooper JS, Amaya CJ, Kazi S. Effects of Semin Hematol. 2010;47:187–98. perioperative antiin fl ammatory and immunomodulating 52. Mawhorter S, Yamani MH. Hypogammaglobulinemia therapy on surgical wound healing. Pharmacotherapy. and infection risk in solid organ transplant recipients. 2005;25:1566–91. Curr Opin Organ Transplant. 2008;13:581–5. 38. Humar A, Ramcharan T, Denny R, Gillingham KJ, 53. Goldfarb NS, Avery RK, Goormastic M, et al. Payne WD, Matas AJ. Are wound complications after Hypogammaglobulinemia in lung transplant recipi- a kidney transplant more common with modern immu- ents. Transplantation. 2001;71:242–6. nosuppression? Transplantation. 2001;72:1920–3. 54. Jones RB, Ferraro AJ, Chaudhry AN, et al. A multi- 39. Zeeh J, Inglin R, Baumann G, et al. Mycophenolate center survey of rituximab therapy for refractory anti- mofetil impairs healing of left-sided colon anastomo- neutrophil cytoplasmic antibody-associated vasculitis. ses. Transplantation. 2001;71:1429–35. Arthritis Rheum. 2009;60:2156–68. 40. Fisher Jr CJ, Agosti JM, Opal SM, et al. Treatment of 55. Marotte H, Paintaud G, Watier H, Miossec P. septic shock with the tumor necrosis factor receptor:Fc Rituximab-related late-onset neutropenia in a patient fusion protein. The soluble TNF receptor sepsis study with severe rheumatoid arthritis. Ann Rheum Dis. group. N Engl J Med. 1996;34:1697–702. 2008;67:893–4. 6 Management of Medications in Patients with Rheumatic Diseases During the Perioperative Period 85

56. Wolach O, Bairey O, Lahav M. Late-onset neutrope- joint surgery in rheumatoid arthritis patients treated nia after rituximab treatment: case series and compre- with a perioperative 4-week interruption of tocili- hensive review of the literature. Medicine (Baltimore). zumab. Mod Rheumatol. 2011;21:109–11. 2010;89:308–18. 59. Ang-Lee MK, Moss J, Yuan CS. Herbal medi- 57. Hirao M, Hashimoto J, Tsuboi H, et al. Laboratory cines and perioperative care. JAMA. 2001;286: and febrile features after joint surgery in patients with 208–16. rheumatoid arthritis treated with tocilizumab. Ann 60. Ernst E. The risk-bene fi t pro fi le of commonly used Rheum Dis. 2009;68:654–7. herbal therapies: Ginkgo, St. John’s Wort, Ginseng, 58. Hiroshima R, Kawakami K, Iwamoto T, et al. Analysis Echinacea, Saw Palmetto, and Kava. Ann Intern Med. of C-reactive protein levels and febrile tendency after 2002;36:42–53. Prophylactic Antibiotic Use in Patients with Rheumatic Diseases 7

Lucileia Teixeira

prostheses, when compared with patients with Introduction metal-to-plastic knee prostheses, were 20 times more likely to develop infection [ 1 ] . Other risk Patients with RA who undergo total hip or knee factors for surgical site infection (SSI) after replacement are at increased risk for prosthetic elective orthopedic surgery of the foot and knee joint infection, which is further increased in the include previous SSI, active rheumatoid arthritis, setting of revision arthroplasty and a previous and corticosteroid use [ 8 ] . It is unclear whether prosthetic joint infection [ 1, 2 ] . Perioperative the use of disease-modifying antirheumatic drugs prophylactic measures and vigilance during the (DMARDs) constitutes an independent risk factor postoperative period are important in assuring for postoperative infection. In the only random- good outcomes in such patients. ized clinical trial addressing this issue, the The risk of prosthetic joint infection varies infection rate was lower among patients who according to the type of procedure and the joint continued methotrexate treatment periopera- replaced. Infections occur in 0.8–1.9% of tively than in patients where methotrexate was patients undergoing knee arthroplasty [ 3– 5 ] and held [9 ] . The impact of tumor necrosis factor 0.3–1.7% of patients having hip arthroplasty (TNF) inhibitors, such as infl iximab, etanercept, [5– 7] . A retrospective review of 4,240 hip, knee, and adalimumab, on surgical site infection risk and elbow arthroplasties found an overall infec- also has not been studied extensively. In a retro- tion rate of 1.3%. Certain groups were at higher spective study of 1,219 procedures in 768 risk of infection following arthroplasty. Patients patients, the greatest risk factor for surgical site with rheumatoid arthritis were at 2.6 times infections was a history of a previous surgical site greater risk for infection than patients with or skin infection. Perioperative treatment with osteoarthritis. Patients undergoing total hip TNF inhibitors did not increase the risk for surgi- arthroplasty as a revision of a previous opera- cal site infection [ 10 ] . tion were eightfold more likely to develop joint Another study [11 ] found that TNF blockers infection than those undergoing a primary oper- were associated with an increased risk of acute ation. Patients with metal-to-metal hinged knee surgical site infections after major orthopedic procedures in patients with rheumatoid arthritis. A surgeon’s volume of joint arthroplasties is associated with the rate of infection. Orthopedists that perform 10 or more arthroplasties annually  L. Teixeira , M.D., M.S. ( ) have infection and dislocation rates one-third or Department of Infectious Diseases , Cleveland Clinic , Cleveland , OH , USA less than their colleagues who perform less than e-mail: [email protected] 10 surgeries per year [12 ] .

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 87 DOI 10.1007/978-1-4614-2203-7_7, © Springer Science+Business Media, LLC 2013 88 L. Teixeira

Patients with rheumatologic diseases under- an alternative for patients who are allergic or going surgery should receive routine preopera- intolerant to vancomycin. Clindamycin is less tive antibiotic prophylaxis the same as other active against coagulase-negative Staphylococci patients to decrease their risk of surgical site and MRSA than vancomycin. infection. Patients with heart valve disease who Because vancomycin must be infused slowly, are at increased risk for developing endocardi- it should be started within 2 h prior to incision. tis should also receive antibiotic prophylaxis If a proximal tourniquet is used, administration before dental procedures that involve manipula- of prophylactic antibiotics should be completed tion of gingival tissue or the periapical region before the tourniquet is in fl ated. The dose of the teeth or perforation of oral mucosa as should be adjusted for patients weighing more recommended by the American Heart than 80 kg; the dose of cefazolin should be Association [13, 14 ] . doubled. In general, all patients should be examined and Additional intraoperative doses of antibi- treated for common infections such as furunculo- otic are advised if major blood loss occurs sis, upper respiratory infections, and urinary tract during the procedure or if the procedure infection prior to joint replacement or other major exceeds one to two times the antibiotic’s half- surgical procedures. [15 ] . Perioperative manage- life. In such settings, cefazolin administered ment of medications used for treating patients (1 g IV if less than 80 kg and 2 g IV if more with rheumatologic diseases is discussed in than 80 kg) should be administered at 2–5-h another chapter. intervals or cefuroxime (1.5 g IV) should be given at 3–4-h intervals. The general guidelines for frequency of intra- Recommendations for Intravenous operative administration are as follows: Antibiotic Prophylaxis in Primary Antibiotic Frequency of administration Total Joint Arthroplasty Cefazolin Every 2–5 h Cefuroxime Every 3–4 h Preoperative antimicrobial prophylaxis is Clindamycin Every 3–6 h recommended by the American Association of Vancomycin Every 6–12 h Orthopaedic Surgery for all patients undergoing joint replacement [15– 17 ] . The medical literature does not support the The choice of antibiotics used for prophylaxis continuation of prophylactic antibiotics until all should be consistent with current recommenda- drains or catheters are removed, and they should tions and guidelines from the literature and taken not be continued past 24 h [18 ] . into account local microbial resistance patterns and patient drug allergies. The recommended reg- imen for patients with normal renal function is Antibiotic Prophylaxis After Total cefazolin (1 g IV if less than 80 kg and 2 g IV if Joint Replacement more than 80 kg) or cefuroxime (1.5 g IV). Clindamycin or vancomycin may be used for Dental Procedures patients with allergies to penicillins or cepha- losporins. Vancomycin 1 g (10–15 mg/kg) IV and Oral infections in patients with prosthetic joints repeated once postoperatively at 12 h may be used should be promptly treated in order to decrease the in patients with known colonization with methi- likelihood of bacteremic seeding of the joint. The cillin-resistant Staphylococcus aureus (MRSA) or use of antibiotic prophylaxis prior to dental proce- in facilities where recent t MRSA outbreaks have dures does not reduce the risk of subsequent pros- occurred. Clindamycin (600–900 mg IV and thetic hip or knee infection [19, 20 ] . Fewer than 25 repeated twice postoperatively at 6 h intervals) is documented cases of late-onset prosthetic joint 7 Prophylactic Antibiotic Use in Patients with Rheumatic Diseases 89 infection after dental procedures have been No second doses are recommended for any of reported, and the association between dental treat- these regimens [21 ]. ment and prosthetic joint infection is weak. No In 2009, the American Academy of experimental observations suggesting a link Orthopaedic Surgeons (AAOS) recommended between bacteremia induced from a dental source that clinicians consider antibiotic prophylaxis and prosthetic joint infection have been reported. [ 20] for all patients with prosthetic joints prior to The 2003 guidelines from the American Dental any invasive procedure that may cause bactere- Association and American Academy of mia. This recommendation is not endorsed by the Orthopaedic Surgeons [21, 22 ] state that antibiotic ADA. No new data or meta-analyses were cited prophylaxis may be considered in selected patients in revising the earlier AAOS/ADA guideline. with prosthetic joints who are at increased risk for bacteremia in association with a dental procedure, although the evidence is limited. Patients at Urological Procedures increased risk include patients with rheumatoid arthritis or systemic lupus erythematosus; patients The American Urological Association and the receiving immunosuppressive drugs or radiation; American Academy of Orthopaedic Surgeons those with conditions such as diabetes, HIV, and issued similar recommendations for patients with malignancy; and patients within 2 years of joint prosthetic joints who underwent urologic proce- replacement. Antibiotics for these patient groups dures [23 ] . Their guidelines state that antibiotic pro- may be considered for high-risk dental procedures, phylaxis can be considered in some patients, such as dental extractions, periodontal procedures especially those with immunosuppression undergo- including surgery, subgingival placement of anti- ing a higher risk procedure for bacteremia, such as biotic fi bers/strips, scaling and root planing, prob- lithotripsy or surgery involving bowel segments. ing, and recall maintenance; dental implant placement and replantation of avulsed teeth; endo- dontic (root canal) instrumentation or surgery only References beyond the apex; initial placement of orthodontic bands but not brackets; intraligamentary and 1. Poss R, Thornhill TS, Ewald FC, Thomas WH, Batte intraosseous local anesthetic injections; and pro- NJ, Sledge CB. Factors infl uencing the incidence and outcome of infection following total joint arthroplasty. phylactic cleaning of teeth or implants where Clin Orthop. 1984;182:117–26. bleeding is anticipated. 2. Bongartz T, Halligan CS, Osmon DR, Reinalda MS, Bamlet WR, Crowson CS, Hanssen AD, Matteson EL. Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in patients with rheumatoid Suggested Antibiotic Prophylaxis arthritis. Arthritis Rheum. 2008;59(12):1713–20. Regimens 3. Jamsen E, Huhtala H, Puolakka T, Moilanen T. Risk factors for infection after knee arthroplasty: a register- • Patients not allergic to penicillin: cephalexin, based analysis of 43,149 cases. J Bone Joint Surg Am. 2009;91:38–47. cephradine, or amoxicillin 2 grams orally 1 h 4. Peersman G, Laskin R, Davis J, Peterson M. Infection prior to dental procedure in total knee replacement: a retrospective review of • Patients not allergic to penicillin and unable to 6489 total knee replacements. Clin Orthop Relat Res. take oral medications: cefazolin 1 g or ampi- 2001;392:15–23. 5. Pulido L, Ghanem E, Joshi A, Purtill JJ, Parvizi J. cillin 2 g IM/IV 1 h prior to the procedure Periprosthetic joint infection: the incidence, timing, • Patients allergic to penicillin: clindamycin and predisposing factors. Clin Orthop Relat Res. 600 mg orally 1 h prior to the dental procedure 2008;466:1710–5. • Patients allergic to penicillin and unable to 6. Choong PF, Dowsey MM, Carr D, Daffy J, Stanley P. Risk factors associated with acute hip prosthetic joint take oral medications: clindamycin 600 mg infections and outcome of treatment with a rifampin- IM/IV 1 hour prior to the procedure based regimen. Acta Orthop. 2007;78:755–65. 90 L. Teixeira

7. Phillips JE, Crane TP, Noy M, Elliott TS, Grimer RJ. 14. Wilson W, Taubert KA, Gewitz M, Lockhart PB, The incidence of deep prosthetic infections in a spe- Baddour LM, Levison M, et al. American Heart cialist orthopaedic hospital: a 15-year prospective sur- Association Prevention of infective endocarditis: guide- vey. J Bone Joint Surg Br. 2006;88:943–8. lines from the American Heart Association: a guideline 8. Gilson M, Gossec L, Mariette X, Gherissi D, Guyot from the American Heart Association Rheumatic Fever, MH, Berthelot JM, Wendling D, Michelet C, Endocarditis and Kawasaki Disease Committee, Dellamonica P, Tubach F, Dougados M, Salmon D. Council on Cardiovascular Disease in the Young, and Risk factors for total joint arthroplasty infection in the Council on Clinical Cardiology, Council on patients receiving tumor necrosis factor a -blockers: a Cardiovascular Surgery and Anesthesia, and the Quality case-control study. Arthritis Res Ther. 2010;12(4): of Care and Outcomes Research Interdisciplinary R145. Working Group. American Heart Association. J Am 9. Grennan DM, Gray J, Loudon J, et al. Methotrexate Dent Assoc. 2008;139(Suppl):3S–24. and early postoperative complications in patients with 15. Bratzler DW, Houck PM, Surgical Infection Prevention rheumatoid arthritis undergoing elective orthopedic Guidelines Writers Workgroup, et al. Antimicrobial surgery. Ann Rheum Dis. 2001;60:214. prophylaxis for surgery: an advisory statement from 10. den Broeder AA, Creemers MC, Fransen J, de Jong E, the National Surgical Infection Prevention Project. de Rooij DJ, Wymenga A, de Waal-Malefi jt M, van Clin Infect Dis. 2004;38:1706. den Hoogen FH. Risk factors for surgical site infec- 16. American Academy of Orthopaedic Surgeons tions and other complications in elective surgery in (AAOS). Advisory Statement. Recommendations for patients with rheumatoid arthritis with special atten- the use of intravenous antibiotic prophylaxis in pri- tion for anti-tumor necrosis factor: a large mary total joint arthroplasty 2004. http://www.aaos. retrospective study. J Rheumatol. 2007;34(4): org/about/papers/advistmt/1027.asp . Accessed 2 Mar, 689–95. 2011. 11. Momohara S, Kawakami K, Iwamoto T, Yano K, 17. Antimicrobial prophylaxis for surgery. Treat Guidel Sakuma Y, Hiroshima R, Imamura H, Masuda I, Med Lett 2006; 4:83. Tokita A, Ikari K. Prosthetic joint infection after total 18. Bratzler DW, Hunt DR. The surgical infection preven- hip or knee arthroplasty in rheumatoid arthritis tion and surgical care improvement projects: national patients treated with nonbiologic and biologic dis- initiatives to improve outcomes for patients having ease-modifying antirheumatic drugs. Mod Rheumatol. surgery. Clin Infect Dis. 2006;43:322. 2011;21(5):469–75. 19. Berbari EF, Hanssen AD, Duffy MC, Ilstrup DM, 12. Solomon DH, Losina E, Baron JA, Fossel AH, Harmsen WS, Osmon DR. Risk factors for prosthetic Guadagnoli E, Lingard EA, Miner A, Phillips CB, joint infection: case-control study. Clin Infect Dis. Katz JN. Contribution of hospital characteristics to 1998;27:1247–54. the volume-outcome relationship: dislocation and 20. Wahl MJ. Myths of dental-induced prosthetic joint infection following total hip replacement surgery. infections. Clin Infect Dis. 1995;20(5):1420–5. Arthritis Rheum. 2002;46(9):2436–44. 21. American Dental Association; American Academy of 13. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Orthopedic Surgeons. Antibiotic prophylaxis for den- Baddour LM, Levison M, et al. Prevention of infec- tal patients with total joint replacements. J Am Dent tive endocarditis: guidelines from the American Assoc. 2003;134:895–8. Heart Association: a guideline from the American 22. American Academy of Orthopedic Surgeons. Heart Association Rheumatic Fever, Endocarditis, Information statement: prophylaxis for bacteremia in and Kawasaki Disease Committee, Council on patients with joint replacements. http://www.aaos.org/ Cardiovascular Disease in the Young, and the about/papers/advistmt/1033.asp . Accessed 2 Mar, Council on Clinical Cardiology, Council on 2011. Cardiovascular Surgery and Anesthesia, and the 23. American Urological Association. American Academy Quality of Care and Outcomes Research of Orthopaedic Surgeons Antibiotic prophylaxis for Interdisciplinary Working Group. Circulation. 2007; urological patients with total joint replacements. 116(15):1736–54. J Urol. 2003;169(5):1796–7. Perioperative Management of Antiphospholipid Antibody 8 Positive Patients During Noncardiac Surgeries

Katherine H. Saunders and Doruk Erkan

The presence of aPL without characteristic Introduction clinical complications does not indicate APS, and asymptomatic (no history of vascular or Antiphospholipid syndrome (APS) is defi ned as pregnancy events) aPL-positive patients exist. vascular thrombosis and/or pregnancy morbidity Although the prevalence of aPL is up to 10% in in patients with persistently positive antiphos- the general healthy population, persistent LA test pholipid antibodies (aPL) (Table 8.1 ) [1 ] . positivity or moderate-to-high titer aCL/ab 2 GPI Catastrophic APS is a rare but rapidly progres- positivity is relatively uncommon. A prospective sive life-threatening form of APS that causes follow-up study of healthy blood donors who were multiple organ thromboses, generally associated tested twice for aPL demonstrated, at baseline, with small vessel involvement [ 2 ] . The most 10% and 1% positivity for the aCL and LA tests, commonly used tests to detect aPL are lupus anti- respectively. However, after 1 year, fewer than 1% coagulant (LA) test (a functional coagulation of healthy blood donors tested positive for the aCL assay), anticardiolipin antibody (aCL) enzyme- or LA tests [3 ] . The number of general population linked immunosorbent assay (ELISA), and anti- studies analyzing persistent LA test positivity and/

b2 -glycoprotein-I antibody (ab 2 GPI) ELISA. or the moderate-to-high titer aCL/ab 2 GPI positiv- Antiphospholipid syndrome can occur in other- ity in thrombosis patients is limited; the prevalence wise healthy individuals without underlying of aPL ranges between 5% and 20% and is largely autoimmune disease (primary APS) or in patients dependent upon the aPL test type and the clinical with other systemic autoimmune diseases, par- population studied [4– 6 ] . Thirty to forty percent of ticularly systemic lupus erythematosus (SLE). SLE patients [5 ] and approximately 20% of women Stroke is the most common arterial manifesta- with recurrent fetal loss possess aPL [7 ] . tion, and deep vein thrombosis (DVT) is the In humans, although cross-sectional and pro- most common venous manifestation of APS. spective cohort studies demonstrate a predictive role of aPL for future vascular events, a direct casual association between aPL and thrombosis K.H. Saunders, M.D. New York-Presbyterian Hospital, 525 East 68th St., does not exist. In the currently accepted “second New York, NY 10021, USA hit hypothesis,” a trigger event (such as a surgical e-mail: [email protected] procedure), which may not otherwise cause D. Erkan , M.D. () thrombosis, is required for an aPL-positive The Barbara Volcker Center for Women and Rheumatic patient (with a prothrombotic and proinfl am- Disease, Hospital for Special Surgery, Weill Medical matory phenotype) to develop a vascular event College of Cornell University , 535 East 70th St , New York , NY 10021 , USA [ 8, 9] . Support for this hypothesis comes from e-mail: [email protected] studies demonstrating that the risk of thrombosis

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 91 DOI 10.1007/978-1-4614-2203-7_8, © Springer Science+Business Media, LLC 2013 92 K.H. Saunders and D. Erkan

Table 8.1 Revised Sapporo classi fi cation criteria for the Thus, physicians should always keep in mind a, b antiphospholipid syndrome that thrombosis is multifactorial, and the ideal Clinical criteria thrombosis prevention strategy should be risk 1. Vascular thrombosis stratifi ed and determined based on age, traditional • One or more clinical episodes of arterial, venous, cardiovascular and venous thrombosis risk factors, or small vessel thrombosis, in any tissue or organ other comorbidities, systemic autoimmune diseases, 2. Pregnancy morbidity • One or more unexplained deaths of a morphologi- and the aPL profi le. Furthermore, identifi cation and cally normal fetus at or beyond the 10th week of ges- elimination of non-aPL reversible thromboses risk tation or factors, as well as aggressive prophylaxis during • One or more premature births of a morphologically high-risk periods (especially during surgical proce- normal neonate before the 34th week of gestation because of eclampsia, severe preeclampsia, or dures), are crucial for thrombosis prevention in recognized features of placental insuf fi ciency persistently aPL-positive individuals. • Three or more unexplained consecutive spontaneous The purpose of this chapter is to review peri- abortions before the 10th week of gestation, with operative management of aPL-positive patients maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded undergoing noncardiac surgeries and to provide Laboratory criteria the reader with information that may aid in deci- 1. Lupus anticoagulant present in plasma, on two or more sion-making. The detailed description of APS occasions at least 12 weeks apart, detected according to the and the general management of aPL-positive guidelines of the International Society on Thrombosis and patients can be found elsewhere [8, 14 ] . Haemostasis 2. Anticardiolipin antibody of IgG and/or IgM isotype in serum or plasma, present in medium or high titer (i.e. >40 GPL or MPL, or > the 99th percentile), on two or General Perioperative Considerations more occasions, at least 12 weeks apart, measured by a in aPL-Positive Patients standardized enzyme-linked immunosorbent assay (ELISA) Antiphospholipid syndrome patients are classi fi ed 3. Anti-b 2 -glycoprotein-I antibody of IgG and/or IgM isotype in serum or plasma (in titer > the 99th percen- in the very high-risk category for perioperative tile), present on two or more occasions, at least complications. Perioperative arterial and/or venous 12 weeks apart, measured by a standardized ELISA thromboses can occur due to (a) withdrawal of a Modi fi ed from Ref. [1 ] warfarin [15, 16 ] , (b) increased hypercoagulability bDe fi nite APS is present if at least one of the clinical crite- (with multiple simultaneous thrombosis risk fac- ria and one of the laboratory criteria are met. Classifi cation tors), and (c) catastrophic exacerbation of APS of APS should be avoided if less than 12 weeks or more than 5 years separate the positive aPL test and the clinical [17 ] . In addition to thromboses, perioperative life- manifestation threatening bleeding can occur due to (a) exces- sive anticoagulation, (b) thrombocytopenia (which occurs in 20% of APS and 40% of catastrophic in aPL-positive patients rises with increasing APS patients) [ 1, 13] , and (c) associated coagula- numbers of thrombosis risk factors, similar to the tion factor defi ciencies such as high-affi nity anti- risk in the general population [ 10 ] . At least half prothrombin (factor II) antibodies [18 ] . Thus, any of APS patients with vascular events possess decision about a surgical or interventional proce- another non-aPL reversible risk factor at time dure requires a multidisciplinary risk-bene fi t of thrombosis; of note, in two different cross- assessment in aPL-positive patients. When a surgi- sectional studies, we have demonstrated that cal procedure is absolutely necessary, the least 6–18% of APS patients with history of vascular invasive procedure should be performed, and peri- events had had a surgical procedure at the time of operative thrombosis prevention strategies should their thrombotic events [11, 12 ] . More than a half be clearly identi fi ed beforehand. of the catastrophic APS episodes are preceded by Perioperative thrombosis prophylaxis is cru- a precipitating event: 35% by infections and 13% cial in aPL-positive patients with or without his- by trauma and invasive procedures [13 ] . tory of thrombosis: (a) pharmacological methods 8 Perioperative Management of Antiphospholipid Antibody Positive… 93 should always be combined with physical methods; In addition to the identifi cation of comorbidities (b) periods without anticoagulation should be (e.g., cardiac, pulmonary) that can infl uence the kept to an absolute minimum in APS patients perioperative decisions, aPL-specifi c evaluation with history of vascular events; (c) postoperative should include (a) assessing the aPL profi le, (b) anticoagulation should be restarted as soon as assessing the aPL-/APS-associated thrombosis possible; (d) patients should be encouraged to risk, (c) assessing the aPL-/APS-associated ambulate as soon (and as much) as they can toler- bleeding risk, (d) planning the management of ate; and (e) physicians should always keep in anticoagulation during perioperative period, and mind that despite optimal thrombosis prophy- (e) conveying the message to the patient, the laxis, APS patients can develop recurrent throm- anesthesiologist, and the surgical team. bosis during the perioperative period [19 ] . Physical methods like intermittent pneumatic compression (IPC) and/or gradual compression Antiphospholipid Antibody Profi le stockings (GCS) prevent venous stasis, increase venous return, and increase tissue factor pathway Every positive aPL test is not clinically signi fi cant. inhibitor (TFPI) [20 ] . A recent Cochran systemic Firstly, as transient aPL positivity is common review of high-risk patients for thrombosis dem- during infections [22 ] , the documentation of the onstrated that combined prophylactic modalities persistence (at least 12 weeks apart [1 ] ) of aPL is (IPC and pharmacological) (a) signifi cantly important. Secondly, the specifi city of aCL and decrease the incidence of venous thromboembo- a b2 GPI ELISA tests for aPL-related clinical lism when compared with compression alone and events increases with higher titers, and IgG/M (b) signifi cantly decrease the incidence of DVT isotypes are more commonly associated with (but not pulmonary embolism) when compared aPL-related clinical events compared to IgA with pharmacological prophylaxis alone [21 ] . isotype. Thirdly, although a positive LA test is a Thus, physical thrombosis prevention methods better predictor of aPL-related events compared are crucial in all aPL-positive patients with or with other aPL ELISA tests [23 ] , both false-positive without history of thrombosis. They should be and false-negative LA test results can occur in initiated during the surgery when possible con- anticoagulated patients [24 ] . Lastly, documenta- tinuing until the patient is fully ambulatory. tion of a positive LA test requires a four-step Additional considerations for aPL-positive process: (a) demonstration of a prolonged phos- patients undergoing surgeries include the follow- pholipid-dependent coagulation screening test, ing: (a) intravascular manipulation for access and such as activated partial thromboplastin time monitoring should be minimized; (b) pneumatic (aPTT) or dilute Russell viper venom time blood pressure cuffs should be set to infl ate infre- (dRVVT); (b) failure to correct the prolonged quently to minimize stasis in the distal vascular screening test by mixing the patient’s plasma bed; (c) tourniquets should be avoided as much as with normal platelet-poor plasma, demonstrating possible; (d) patients should be closely observed the presence of an inhibitor; (c) shortening or for signs and symptoms of thrombosis; and (e) correction of the prolonged screening test by the high suspicion should be maintained that any addition of excess phospholipid, demonstrating deviation from a normal course may refl ect arte- phospholipid dependency; and (d) exclusion of rial or venous thrombosis [19 ] . other inhibitors [25 ] . In summary, the preoperative assessment should determine if a patient has a “clinically Preoperative Assessment signifi cant” aPL profi le. Our recommendation for of aPL-Positive Patients “clinically signi fi cant” aPL pro fi le is as follows: LA test positive based on the guidelines of International Since aPL-positive patients are at very high risk Society of Thrombosis and Haemostasis [ 25 ] , for perioperative complications, it is crucial to eval- aCL IgG/M ³ 40U, and/or a b2 GPI IgG/M ³ 40U uate them thoroughly before surgical procedures. tested twice at least 12 weeks apart. However, 94 K.H. Saunders and D. Erkan caution and clinical judgment are required to not associated with major bleeding, and rarely determine the thrombosis risk when: (a) LA test is requires treatment. When severe thrombocytope- performed in anticoagulated patients, (b) aCL or nia exists in aPL-positive patients in the setting of ab 2 GPI IgG/M titers are in the range of 20–39U, urgent or emergency surgery, the fi rst-line thera- and/or (c) aCL or ab 2 GPI IgA is the only positive peutic options include high-dose corticosteroids aPL ELISA test. and/or intravenous immunoglobulin (IVIG). Rituximab has been also used successfully to treat thrombocytopenia in aPL-positive patients [ 26, 28 ] ; Thrombosis Risk however, as the time course of effect can vary from one patient to another, rituximab may not be the Clinical manifestations of aPL represent a spec- best option in an urgent setting. trum: (a) asymptomatic aPL positivity (no history Patients with positive LA tests rarely can of vascular or pregnancy events); (b) noncriteria present with life-threatening bleeding complica- manifestations of aPL only, e.g., livedo reticu- tions due to concomitant antiprothrombin anti- laris, thrombocytopenia, cardiac valve disease; bodies, resulting in hypoprothrombinemia (c) pregnancy morbidity only (Table 8.1 ); (d) (lupus anticoagulant hypoprothrombinemia syn- arterial and/or venous thrombosis with/without drome [LA-HPS]) [ 18, 29, 30 ] . These patients pregnancy morbidity (Table 8.1 ); and (e) cata- are usually asymptomatic with normal or slightly strophic APS (multiple thromboses occurring elevated prothrombin time (PT). However, PT is over a short period). As a general rule, any patient signi fi cantly prolonged when the prothrombin with a “clinically signifi cant” aPL profi le is at (factor II) level is less than 30% of normal [ 31 ] . high risk for thrombosis during the perioperative Although the risk of bleeding in LA-HPS period; however, despite the lack of comparative patients does not correlate with the degree of the studies, patients with history of catastrophic APS prolongation of the PT as it may be artifactually are generally considered to have the highest risk prolonged in the presence of a positive LA test, of thrombosis followed by aPL-positive patients signi fi cant prolongation of PT should prompt with history of arterial and/or venous events. physicians to order prothrombin levels during Furthermore, non-aPL arterial and venous throm- the preoperative assessment. Corticosteroids are bosis risk factors should also be assessed and the fi rst-line treatment in LA-HPS if bleeding incorporated into the equation while determining occurs as they decrease the clearance of the the risk of perioperative thrombosis. prothrombin–antithrombin antibody complexes In summary, every patient with a “clinically (factor replacement is generally not effective signifi cant” aPL profi le does not have the same as the mechanism of hypoprothrombinemia thrombosis risk. In addition to the aPL pro fi le, it is destructive). Corticosteroid-resistant cases is important to factor the aPL manifestations and responsive to immunosuppression (azathioprine, other non-aPL thrombosis risk factors into the cyclophosphamide, rituximab) have been equation while assessing the perioperative throm- reported [18, 31 ] ; a recent report described the bosis risk. use of rituximab with plasma exchange in a LA-HPS patient to normalize the prothrombin level [32 ] . In summary, if an LA-positive (with Bleeding Risk signi fi cant PT prolongation) patient develops unexplained bleeding during or after the sur- About 20% of patients with APS develop throm- gery, high-dose corticosteroids should be started bocytopenia. Although the mechanism is not clear, immediately. A complete discussion of the there is some evidence that aPL bind to platelet pathogenesis, diagnosis, and treatment of this membranes and cause platelet destruction [ 26 ] . condition can be found elsewhere [ 18 ] . In most aPL-positive patients, the thrombocytopenia Physicians should also keep in mind that is mild (>70,000 platelets per microliter) [ 27 ] , is (a) thrombocytopenia does not protect against 8 Perioperative Management of Antiphospholipid Antibody Positive… 95 thrombosis; (b) platelet transfusions are usually crucial for successful outcomes as (a) the surgical not helpful in patients with APS as the mecha- team may not be familiar with the risks involved nism of thrombocytopenia is thought to be in operating on aPL-positive patients and (b) the destructive [ 33] and it may even increase the risk perioperative anticoagulation plan can be fi nalized of thrombosis; and (c) aPL interfere with phos- during this discussion based on the anesthesiolo- pholipid-dependent coagulation studies in vitro gists’ and surgeons’ comfort level with the dose and cause prolongation of aPTT or dRVVT; thus, as well as the timing of stopping and starting prolonged aPTT and/or slightly prolonged PT anticoagulation. when known to be due to APS are not contra- In summary, risks associated with the surgery indications for surgical procedures. (thrombosis, bleeding) and the perioperative In summary, preoperative assessment of plate- plan (thrombosis prophylaxis and the manage- let count and coagulation profi le is important; ment of potential postoperative complications) mild thrombocytopenia, slight PT prolongation, should be clearly discussed with the patient, the and/or slight-to-signifi cant aPTT prolongation anesthesiologist, and the surgical team before can occur in aPL-positive patients. However, the surgery. signifi cant PT prolongation should prompt further work-up. Perioperative Anticoagulation

Planning the Perioperative Summary of Recommendations for the Anticoagulation General Population

Once the patient’s aPL profi le as well as the Stasis, intimal injury, and hypercoagulability are thrombosis and bleeding risks have been deter- the three major factors that contribute to the mined, it is crucial to devise a comprehensive development of a postoperative thromboembolic perioperative thrombosis prophylaxis plan event [34 ] . In addition to hospitalization and (further discussed in section “Perioperative immobilization-related stasis, the surgical proce- Anticoagulation”). dure itself activates clotting by exposing tissue factor to the blood circulation [35 ] . Thus, as the perioperative period is a high-risk time for any Effective Communication patient to develop thromboembolism, it is neces- with the Patient and Surgical Team sary to devise perioperative anticoagulation strat- egies for all surgical patients. Antiphospholipid antibody positive patients The necessity and the regimen of the antico- should understand the potential risks associ- agulation are usually determined based on ated with any surgery. During preoperative patients’ individual predisposing risk factors for assessment, the medical necessity of the proce- thromboembolism (low-high thrombosis risk) dure should be reviewed with the patient, and and the type of the surgery (low-moderate-high elective surgeries, e.g., cosmetic, should be thrombosis risk). Table 8.2 summarizes recom- strongly discouraged in high-thrombosis-risk mended postoperative anticoagulation regimens aPL-positive patients. If the surgical procedure for high-thrombosis-risk patients during selected is absolutely necessary, the importance of com- low- to moderate- to high-thrombosis-risk pliance with the prophylaxis plan including the surgeries [ 36 ] . The details of these recommenda- medications, physical thrombosis prevention tions can be found in the recently published methods, and early ambulation should be dis- eighth edition of the American College of Chest cussed in detail with the patient. Physicians (ACCP) evidence-based guidelines Effective communication, preferably verbal, for the perioperative management of antithrom- between the medical and surgical teams is also botic therapy [36 ] . 96 K.H. Saunders and D. Erkan

Table 8.2 Thrombosis risk based on selected surgical procedures and prophylactic agent recommendations for patients at high risk for thrombosisa Recommended perioperative prophylaxis Perioperative thrombosis risk Type of surgery regimens for high-thrombosis-risk patientsb Low Dental procedures No Dermatological procedures No Transurethral urologic procedures No Laparoscopic surgery LMWH, UFH, or FPX Knee arthroscopy LMWH Moderate General/vascular surgery LMWH, UFH, or FPX Major urologic surgery LMWH or UFH Major open gynecologic surgery LMWH or UFH Neurosurgery LMWH or UFH High Orthopedic surgery – Elective THR/TKR LMWH, FPX, or adjusted-dose warfarin – Hip fracture surgery FPX, LMWH, adjusted-dose warfarin, or UFH Major trauma surgery LMWH Spinal cord injury LMWH or UFH a Modi fi ed from Ref. [36 ] b For each agent, manufacturer-suggested dosing guidelines should be followed. Mechanical thrombosis prevention methods such as gradual compression stockings or intermittent pneumatic compression devices are generally recom- mended in addition to anticoagulation. FPX fondaparinux, LMWH low-molecular-weight heparin, UFH unfractionated heparin, THR total hip replacement, TKR total knee replacement

Table 8.3 Summary of the recommendations for neuraxial anesthesia in patients receiving perioperative anticoagulationa Subcutaneous unfractionated heparin No contraindication with twice-daily dosing and total daily dose <10,000 U The safety of neuraxial blockade in patients receiving doses >10,000 U daily or more than twice-daily dosing is not established Intravenous unfractionated heparinb Needle placement and/or catheter removal 2–4 h after stopping heparin after con fi rmation of a normal aPTT test Start heparin 1 h after needle placement and/or catheter removal Low-molecular-weight heparin Needle placement and/or catheter removal 12 h after last prophylactic dose heparin and 24 h after one therapeutic dose heparin Start heparin 2–4 h after needle placement and/or catheter removal a Modi fi ed from Ref. [39 ] bOf personal note, many anesthesiologists prefer not to keep the epidural catheter when patients continuously receive intravenous heparin

Patients receiving perioperative anticoagula- Bridging Anticoagulation tion are at risk of developing epidural or spinal hematomas when they undergo regional (spinal or In the context of perioperative anticoagulation, epidural) anesthesia. Since a US Food and Drug “bridging anticoagulation” is de fi ned as the Administration Public Health Advisory called administration of a short-acting anticoagulant, attention to patients who developed epidural or such as subcutaneous (SQ) LMW heparin or spinal hematomas with concurrent low-molecu- intravenous (IV) unfractionated (UF) heparin, lar-weight (LMW) heparin prophylaxis and typically as a therapeutic-dose regimen for regional anesthesia [37 ] , there have been several approximately 8–10 days (or until the patient is guidelines by different organizations about the ambulatory) during interruption of the warfarin management of anticoagulation in patients under- therapy when the international normalized ratio going regional anesthesia (Table 8.3 ) [ 38, 39 ] . (INR) is not within a therapeutic range [ 40 ] . The 8 Perioperative Management of Antiphospholipid Antibody Positive… 97

Table 8.4 Summary of the bridging anticoagulation protocol with low-molecular-weight heparin (LMWH) in general populationa −5 days Discontinue warfarin −3 days Check INR and kidney function Start therapeutic dose LMWH (e.g., enoxaparin 1 mg/kg BID or 1.5 mg/kg QD) Adjust LMWH dose based on creatinine clearance −24 h Administer the last dose of LMWH 24 h prior to the surgery (50% of the dose for once daily regimens) Day 0 Schedule for early morning surgery Check INR if needed If INR is still elevated (INR ³ 1.5), consider low-dose (1–2 mg) oral vitamin K Employ aggressive perioperative mechanical DVT prophylaxis Start Warfarin in the evening (regular dose) +24 h Start prophylactic or therapeutic dose LMWH (can be delayed for 48–72 h for patients undergoing high bleeding risk surgeries) +4 to 5 days Discontinue LMWH when INR is therapeutic BID twice daily, DVT deep vein thrombosis, INR international normalized ratio, QD daily a Modi fi ed from Ref. [40 ]

purpose of bridging anticoagulation is to mini- erature on perioperative medical management of mize a patient’s risk of thrombosis without increas- APS is based on a limited number of case reports. ing the risk of bleeding. In the general population, Thus, critical decisions can be challenging due to “bridging anticoagulation” is generally a safe pro- lack of evidence. The practice patterns can vary cedure; McBane et al. recently demonstrated that based on physicians’ experiences; however, the the incidence of thromboembolism, bleeding, or following points should be incorporated in the death is low among moderate-to-high thrombosis perioperative anticoagulation planning of patients risk patients with history of thrombosis in whom with “clinically signi fi cant” aPL-positive pro fi les. anticoagulation is temporarily interrupted and In patients receiving epidural anesthesia, the tim- patients were “bridged” with LMW heparin for an ing of catheter placement/removal in accordance invasive procedure [ 41 ] . with stopping/starting anticoagulation should be During “bridging anticoagulation,” the most discussed with the anesthesiologist. Furthermore, recent guidelines suggest using therapeutic dose in patients requiring physical therapy, the thera- LMW heparin over IV UF heparin for high- pist should be informed about the increased risk thrombosis-risk patients because of substantial of thrombosis (and bleeding, if patients receive experience with LMW heparin and the “cost- early postoperative anticoagulation). containment” perspective [ 40 ] . However, some physicians still prefer IV UF heparin over LMW Antiphospholipid Syndrome Patients heparin due to ease of reversibility. Table 8.4 with History of Arterial and/or Venous summarizes a commonly used “bridging antico- Thrombosis agulation” schedule with LMW heparin for high- As APS patients with history of thrombosis and thrombosis-risk patients . who receive warfarin are at high risk for throm- bosis recurrence during interruption of anticoag- ulation, careful “bridging anticoagulation” Recommendations for “Clinically (Table 8.4 ) and vigorous physical antithrombosis Signifi cant” aPL-Positive Patients interventions are almost always warranted. During “bridging anticoagulation,” aPL-/APS- Patients with “clinically signifi cant” aPL profi les speci fi c considerations should include the follow- should be included in the high-thrombosis-risk ing: (a) if the target INR during chronic warfarin category during the perioperative period. The lit- treatment of an APS patient is higher than 3, a 98 K.H. Saunders and D. Erkan longer period (>5 days) of warfarin interruption that recommended prophylactic doses of anti- may be required; (b) stopping LMW heparin 12 h thrombotic regimens, e.g., enoxaparin 30 mg (rather than 24 h) before the surgery should be q12 h or 40 mg SQ q24 h, can result in “under- considered in high-thrombosis-risk APS patients , anticoagulation” in aPL-positive patients [ 45 ] but increased risk of bleeding during the surgery and a more aggressive approach with higher than is a potential risk (anti-factor Xa levels often standard recommended prophylactic doses remain high at the time of surgery if the last dose should be considered in aPL-positive patients of a twice-daily regimen of LMW heparin is with multiple other thrombosis risk factors. As given the evening before surgery [ 42, 43 ] ); and discussed above, the anticoagulation dose/timing/ (c) restarting LMW heparin (prophylactic dose) duration need be individualized depending on 12 h after the surgery should be strongly consid- the type of surgery and anesthesia as well as the ered until the surgical team is comfortable (from patient’s duration of immobility. a bleeding perspective) with advancing the LMW heparin dose to a therapeutic range. All these Monitoring Anticoagulation considerations need to be individualized based on in aPL-Positive Patients the type of surgery (thrombosis and bleeding Antiphospholipid antibodies may interfere with risks associated with surgery) and anesthesia in vitro tests of hemostasis by impeding the (epidural versus general). anchoring of coagulation proteins to phospho- lipid surfaces. For those patients with a positive Antiphospholipid Syndrome Patients LA test that elevates the baseline aPTT, monitor- with History of Pregnancy Morbidity Only ing heparin dose to ensure adequate anticoagula- or Asymptomatic aPL-Positive Patients tion can be accomplished by monitoring activated As non-aPL thrombosis risk factors signi fi cantly anti-factor Xa levels. The College of American in fl uence the risk of thrombosis by acting as a Pathologists recommends the anti-factor Xa chro- trigger in “clinically signifi cant” aPL-positive mogenic assay, which is the most widely avail- patients, the use of prophylaxis during high-risk able method [ 46] . The anti-factor Xa activity periods (surgical procedures) is crucial. Thus, peaks approximately 4 h after the heparin is APS patients diagnosed based on pregnancy mor- injected, when the monitoring assay should be bidity only as well as asymptomatic (no history performed [ 46 ] . Although the target range for of vascular or pregnancy events) aPL-positive anti-factor Xa levels depends on the dosing inter- patients with or without non-criteria features, val and the heparin preparation, the target anti- e.g., livedo reticularis, mild thrombocytopenia, factor Xa levels for therapeutic and prophylactic should also be managed very aggressively during dose LMW heparin therapy are generally 0.5–1.1 the perioperative period. In these groups of units/mL and 0.2–0.4 units/mL, respectively. patients, it is crucial to employ both pharmaco- For APS patients who are on warfarin before or logical and physical antithrombosis interventions after surgery, the effectiveness of anticoagulation vigorously and start anticoagulation as soon as has traditionally been measured by international possible postoperatively. normalized ratio (INR). Approximately 10% of Standard prophylactic dose antithrombotic LA-positive patients may have unreliable and/or regimens recommended by Geerts et al. for high- largely variable INR test results (depending on the thrombosis-risk patients undergoing general or reagent used). In this setting, chromogenic factor orthopedic surgeries can be found elsewhere X test, factor II or factor X activity assay, and [44 ] , which should be the minimum adminis- prothrombin–proconvertin time are alternative tered dose in patients with APS and should be tests in addition to the use of a PT reagent that is continued until the patient is fully ambulating. insensitive to LA. In a recent editorial, Kasthuri Extended anticoagulation should be considered and Roubey emphasized that factor II level is the depending on the type of surgery and patient’s most important indicator of warfarin effectiveness, thrombosis risk. Physicians should keep in mind as it more accurately refl ects thrombin generation; 8 Perioperative Management of Antiphospholipid Antibody Positive… 99 however, the INR level is most dependent on Dental Surgery factor VII levels and least dependent on factor II levels [47 ] . Thus, periodic monitoring of factor II Based on general population experience, low- level can be considered after warfarin is restarted bleeding-risk procedures (such as minor dental postoperatively in APS patients who are at high and outpatient procedures, cataract extractions, risk of recurrent thrombosis. or skin and laparoscopic surgeries) can be per- formed without stopping anticoagulation, and INR can be maintained around 2 on the day of Other Special Considerations these procedures. Douketis et al. recommend that in aPL-Positive Patients for patients who are on long-term warfarin treat- ment and require minor dental procedures, warfa- Emergency Surgery rin should be continued around the time of the procedure and an oral prohemostatic agent can be In the general population, low-dose (2.5–5.0 mg) coadministered [40 ] (oral prohemostatic agents intravenous or oral vitamin K is often adminis- include antifi brinolytic agents such as e -amin- tered for patients who are taking vitamin K ocaproic acid and tranexamic acid as well as antagonists and require emergency surgery. For 1-deamino-8-D-arginine vasopressin, which more immediate reversal of the anticoagulant increase the plasma levels of von Willebrand fac- effect, fresh frozen plasma (FFP), prothrombin tor and factor VIII) [40 ] . No data exist on the use complex concentrate (PCC), or activated recom- of prohemostatic agents in aPL-positive patients; binant factor VII is used. Of note, although many given the low bleeding risk of dental procedures, patients who require rapid reversal of anticoagu- most likely these agents are not required. lation are currently treated with FFP, PCC is a There have been no reports of vascular events strong alternative as it provides a quicker correc- in aPL-positive patients undergoing dental proce- tion of the INR and improved bleeding control dures; however, Bernstein et al. reported a child [48 ] . There were concerns about PCC-associated with LA-HPS who developed signi fi cant bleed- infections in the past; however, current formula- ing following tooth extraction [ 50 ] . Although tions are relatively safe. LA-HPS is rare (further discussed in section Emergency surgery in aPL-positive patients is “ Thrombosis Risk ”), caution is warranted in particularly challenging because there is limited LA-positive patients with a known signifi cantly time to devise perioperative strategies. In patients prolonged PT. receiving warfarin, the agents discussed above should be avoided when possible as, in case of overcorrection, it may be dif fi cult to obtain rapid Neurosurgery (Including Spine Surgery) therapeutic range anticoagulation after the sur- gery. Furthermore, there have been reports of In the general population of patients undergoing PCC-induced thrombosis [ 49 ] , and FFP, which neurosurgeries, although physical methods of contains all coagulation factors, may theoreti- prophylaxis have been preferred because of con- cally increase the risk of thrombosis. cerns about intracranial or spinal bleeding [ 51 ] , In summary, reversal of anticoagulation is not randomized trials have demonstrated that low- advisable in aPL-positive patients. When reversal dose unfractionated or LMW heparin is also is absolutely needed, the lowest possible dose of effective for venous thromboembolism prophy- vitamin K (1–2 mg) or FFP should be used, keeping laxis without excessive bleeding risk [ 52 ] . In in mind that in those APS patients on chronic addition, the combination of LMW heparin and anticoagulation with a target INR of 3–4, it may elastic stockings is found to be more effective in take longer than expected to correct the antico- risk reduction than elastic stockings alone [53 ] . agulant effect. In the general population undergoing spine sur- 100 K.H. Saunders and D. Erkan geries, the risk of postoperative thrombosis is from the lower extremity deep venous system to higher in trauma and deformity spine surgery the pulmonary arteries. The utility of IVC fi lters patients compared to degenerative spine surgery in APS patients is controversial as both DVT and patients [54 ] . In patients with multiple thrombo- IVC thrombosis may result from the procedure sis risk factors, postoperative prophylaxis with itself [56, 57 ] . low-dose unfractionated or LMW heparin com- Although there are APS patients who have bined with GCS and/or IPC is preferred [36 ] . been thrombosis-free following uncomplicated In aPL-positive patients undergoing neurosur- IVC fi lter insertions [ 58 ] , recurrent thromboses gery, preoperative INR should be lower than 1.5. despite IVC fi lter placement also have been The number of reported APS patients undergoing reported [ 56, 58, 59 ] . Ebato et al. demonstrated neurosurgical procedures is limited [ 55 ] . Roth the failure of an IVC fi lter in an APS patient; et al. reported a 49-year-old who had foramen a 62-year-old woman with APS and an IVC magnum meningioma removal complicated by fi lter implanted 5 years earlier presented with postoperative ischemic stroke. In this patient, tricuspid valve thrombus and pulmonary emboli therapeutic dose LMW heparin was continued [ 59] . Thus, IVC fi lters may fail in APS patients until 12 h before the surgery, and LMW heparin and may not protect them from pulmonary was resumed 12 h after the surgery. Although this emboli if collateral vessels develop around the patient did not receive minidose heparin, the fi lter or if a thrombus is present on the proxi- authors recommended that minidose heparin 2 h mal side of the fi lter. prior to surgery may have additive anticoagula- In summary, the role of IVC fi lters in APS tion effects without “increasing the bleeding patients remains controversial as they may not be risk” [ 55 ] . helpful and may actually aid in the formation of a In summary, neurosurgery and spine surgery thrombus. These fi lters should be considered only in aPL-positive patients create additional chal- in acute lower extremity DVT patients with active lenges for physicians due to potentially serious bleeding. neurologic complications even with a minor bleed. No evidence-based guidelines exist about the dose and the safest timing of antico- Renal Transplantation agulation [ 54] . Physical methods of DVT pro- phylaxis are crucial, and patients warrant very Due to the limited number of aPL-positive close monitoring of the neurologic examina- patients undergoing renal transplantation, the tion postoperatively. optimal perioperative management is unknown. Antiphospholipid syndrome patients are at high risk for renal allograft failure, and anticoagula- Inferior Vena Cava (IVC) Filters tion before or at the time of kidney transplanta- tion generally reduces posttransplant thrombosis As APS patients have an especially high risk of [ 60] . However, despite anticoagulation, graft fail- thrombosis with any procedure or instrumenta- ure may occur [61 ] . Even without history of tion, the clinical dilemma often arises when thrombosis, aPL positivity in lupus patients patients need a potentially lifesaving intervention increases graft failure, morbidity, and mortality such as an IVC fi lter, yet are at increased risk of [ 62– 64 ] . In a non-SLE population, the role of aPL forming a clot around the foreign body. Although in graft failure is controversial, with some studies anticoagulation is the fi rst-line treatment for showing a correlation between asymptomatic thromboembolic disease, it may be contraindi- aPL positivity and graft failure [ 65 ] and others cated when bleeding occurs or patients may not fi nding this relationship [66 ] . develop venous thromboses despite anticoagula- Many patients, independent of their aPL sta- tion. In these situations, IVC fi lters are often con- tus, will require immunosuppressive agents (cor- sidered to prevent the embolization of a thrombus ticosteroids, rituximab, mycophenolate mofetil, 8 Perioperative Management of Antiphospholipid Antibody Positive… 101

IVIG, and/or thymoglobulin) during the trans- purulent material was found. On POD 7, her plantation preparation period due to their high- radial and ulnar pulses were present by Doppler risk histocompatibility pro fi les, e.g., donor fl ow examination. One week later, the hand appeared crossmatch, donor-speci fi c antibodies. The effect duskier with scattered vesicles. Magnetic reso- of immunosuppression on aPL and graft preven- nance angiography of her left upper extremity tion is unknown. In those patients who develop revealed that the radial, ulnar, and interosseous allograft renal vascular thrombosis despite anti- arteries were occluded distal to the elbow and coagulation, plasmapheresis may be of some that the muscle was necrotic distal to the mid- bene fi t [67 ] . Montgomery et al. described seven forearm. On POD 21, she underwent amputation patients in whom donor-speci fi c antibodies of her hand through the middle forearm, follow- developed posttransplant humoral rejection; plas- ing which she made an uneventful recovery. mapheresis alternating with IVIG in addition to Pathology showed fi brin clots as well as diffuse FK-506, mycophenolate mofetil, and pulse corti- dilation of the vessels including the vasa vaso- costeroids reversed the rejection [68 ] . rum, which supported the concept that overall In summary, in the absence of defi nitive data, dilation was due to continued perfusion in the we recommend prophylactic dose perioperative face of restriction of out fl ow (due to thrombosis heparin for aPL-positive patients without history induced by aPL), rather than to extrinsic com- of thrombosis undergoing renal transplant, pression (compartment syndrome). although the risks and benefi ts must be weighed In summary, given that early postoperative in a given clinical situation. The aPL-/APS- vascular imaging studies were normal, micro- specifi c role of pretransplant plasmapheresis or thrombosis was thought to be the initial throm- immunosuppression requires further studies. botic event in this patient. Thus, physicians should be on high alert for microthrombotic post- operative complications in aPL-positive patients. Postoperative Microthrombosis: Biopsy confi rmation of microthrombosis may not Caution in Antiphospholipid Syndrome be possible in certain clinical situations; clinical judgment is required to start anticoagulation in a We previously reported a 49-year-old female timely manner. patient with rheumatoid arthritis and APS (on LMW heparin prior to the surgery) who was admitted for an elective hysterectomy [19 ] . Managing Simultaneous Bleeding Enoxaparin was discontinued one night prior to and Thrombosis surgery, and the procedure was performed with- out incident under general anesthesia. One dif fi cult clinical dilemma is when an APS In the recovery room, she developed edema, patient develops simultaneous thrombosis and pain, and numbness of her left hand, which bleeding. Not addressing the clot may be life- appeared dusky, and felt cool. Radial and ulnar threatening, while anticoagulation can cause a pulses were palpable, and capillary refi ll was nor- similarly threatening bleed. During acute bleed- mal. A Doppler study was negative for venous ing, physical methods like IPC and/or GCS thrombosis. The next day, she noted increasing should be used aggressively, and low-dose anti- numbness in her hand and worsening swelling. coagulation should be started as soon as bleeding Compartment pressures were elevated. Urgent is controlled, knowing that the risk of further fasciotomies were performed and enoxaparin bleeding remains high [69 ] . (60 mg SQ BID) was restarted. On postoperative In patients with simultaneous thrombosis and day (POD) 4, she developed violaceous blistering bleeding, a high index of suspicion is required and erythema at the incision site. Enoxaparin was for evolving catastrophic APS. Early diagnosis changed to intravenous heparin. Incision and and aggressive therapy are vital for the survival drainage of the fasciotomy was performed; no of catastrophic APS patients; the best treatment 102 K.H. Saunders and D. Erkan outcomes are achieved when catastrophic APS Although some surgeons still advise patients to patients are treated with the combination of discontinue aspirin at least 1 week preoperatively anticoagulation, corticosteroids, and plasma to reduce the risk of perioperative bleeding, aspi- exchange or intravenous immunoglobulin [ 70 ] . rin-associated risk of bleeding does not necessar- As discussed above, severe thrombocytopenia ily increase the morbidity or mortality [73 ] . resulting in bleeding should be managed by Increasing evidence suggests that aspirin should high-dose corticosteroids and/or IVIG during not be stopped in the perioperative period unless acute bleeding. the risk of bleeding related to a speci fi c proce- Diffuse alveolar hemorrhage due to micro- dure appears to be greater than the increased thrombosis and/or pulmonary capillaritis should thrombotic risk secondary to withholding the be strongly considered in APS patients with drug [73, 74] . The ASPIRIN trial (Antiplatelet hemoptysis and/or acute pulmonary in fi ltrates Strategies in the Perioperative Period in Patients [71 ] . Diffuse alveolar hemorrhage is relatively at Risk of Ischaemic Events), an ongoing multi- more common in catastrophic APS patients with center trial comparing low-dose aspirin therapy multiple thromboses. A lung biopsy may not with placebo during the perioperative period in always be feasible and treatment may need to be noncardiac surgery, will provide de fi nitive guide- instituted without a pathologic diagnosis. Patients lines for patients taking aspirin in the periopera- usually respond to corticosteroids; however, the tive period [75 ] . recurrence risk is higher without immunosup- In summary, aspirin-receiving aPL-positive pressive treatment [ 71 ] . Thus, intravenous pulse patients should continue aspirin, and the physi- corticosteroids with plasma exchange or intrave- cians should consider starting aspirin preopera- nous immunoglobulin alone is the most com- tively in high-risk aPL-positive patients, monly used initial approach in aPL-positive especially for those with history of arterial patients presenting with diffuse alveolar hemor- events. rhage. These patients should be started on antico- agulation as soon as bleeding is controlled as bleeding in aPL-positive patients does not protect Hydroxychloroquine against thrombosis. In summary, there are no evidence-based rec- In addition to its anti-in fl ammatory effects, ommendations for the management of bleeding hydroxychloroquine (HCQ) possesses an anti- in APS patients. When bleeding occurs, the tim- thrombotic effect by inhibiting platelet aggrega- ing of anticoagulation initiation is a dif fi cult deci- tion and arachidonic acid release from stimulated sion. In general, anticoagulation should be started platelets [76 ] . Other immunomodulatory effects as soon as bleeding is controlled, with the under- of HCQ include increasing the pH of intracellular standing that the risk of further bleeding remains vacuoles, interfering with antigen processing high. [ 77] , and inhibiting T-cell-receptor- and B-cell- antigen-receptor-induced calcium signaling [ 78 ] . In aPL-injected mice, HCQ decreases the throm- Aspirin bus size and the time of thrombus in a dose- dependent manner [79 ] . Furthermore, HCQ A group of aPL-positive patients receives aspirin, inhibits the aPL-induced platelet GPIIb/IIIa which has been the most widely prescribed anti- receptor expression (platelet activation) in a dose- platelet drug in the general population for cardio- dependent fashion [80 ] . Of interest, Rand et al. vascular disease prevention [ 72 ] . Aspirin alone recently showed that HCQ also reverses the binding has minimal protection against venous thrombosis of aPL–b 2 GPI complexes to phospholipid during the perioperative period; however, acute bilayers [81 ] . aspirin withdrawal can be associated with car- In humans, HCQ was historically used as a diovascular events in high-risk patients [73 ] . prophylactic agent against deep venous thrombosis 8 Perioperative Management of Antiphospholipid Antibody Positive… 103 and pulmonary embolism after hip surgeries [82 ] . compared with placebo [ 91 ] . In healthy persons In lupus patients, based on observational studies, with normal low-density-lipoprotein (LDL) lev- HCQ decreases the thrombosis risk [83– 85 ] , els of less than 130 mg/dL and elevated C-reactive although not all studies agree [ 86 ] . In a cross- protein (CRP) levels greater than 2.0 mg/dL, sectional study in which we compared 77 APS rosuvastatin 20 mg daily signifi cantly reduced patients with vascular events (65% had no other the occurrence of the fi rst major cardiovascular systemic autoimmune diseases) to 56 asymptom- event and symptomatic venous thromboembo- atic (no history of thrombosis or fetal loss) aPL- lism [92, 93 ] . positive patients (18% had no other systemic Recent studies also suggest that perioperative autoimmune diseases), we demonstrated in a statin use provides a cardioprotective effect. In a logistic regression analysis that HCQ may be meta-analysis, Hindler et al. reported a 44% protective against thrombosis in asymptomatic reduction in mortality associated with preopera- aPL-positive individuals [87 ] . tive statin therapy [ 94 ] . In addition, Le Manach In summary, although there is experimental et al. found that postoperative statin withdrawal and clinical evidence in lupus patients that HCQ for longer than 4 days was an independent may decrease the incidence of thrombosis, con- predictor of postoperative myonecrosis [95 ] . trolled studies are needed to determine the effec- Although most of the current data is observa- tiveness of HCQ for thrombosis prevention in tional, the American College of Cardiology and APS. Even though there are not enough data to American Heart Association recommend that recommend HCQ during the perioperative period patients currently taking statins should continue for thrombosis prevention, it may be considered the drug for noncardiac surgery; it is reasonable to add HCQ to the pharmacological and physical for patients undergoing vascular surgery with or anticoagulation regimen in high-risk APS patients without clinical risk factors to initiate statin ther- undergoing surgery. apy, and statins should be considered for patients with at least one clinical risk factor who are undergoing intermediate-risk procedures [96 ] . Statins In summary, although statins have been used in primary, secondary, and perioperative cardio- Statins are cholesterol-lowering agents, which vascular event prevention in the general popula- also have modest anti-infl ammatory effects tion, no data exist for thrombosis prevention in including decreasing the expression of adhesion aPL-positive patients. Given that there are experi- molecules in monocytes, interfering with leuko- ments demonstrating that statins can interfere cyte–endothelial interaction, inhibiting platelet with aPL-mediated thrombosis and statins are function, and downregulating in fl ammatory recommended for high-thrombosis-risk patients cytokines in endothelial cells [ 79 ] . In aPL-treated undergoing surgeries in the general population, mice, fl uvastatin diminishes thrombus size, an they should also be considered for high-thrombo- effect independent of the cholesterol-lowering sis-risk APS patients undergoing surgeries. effects of statins [88 ] . Statins also interfere with aPL-induced endothelial cell activation [89 ] and reverse tissue factor (TF) upregulation in a dose- Other Antithrombotic Medications dependent manner [90 ] . In the general population, double-blind, pla- Physicians should follow the general population cebo-controlled ATROCAP—Atorvastatin and perioperative guidelines for nonaspirin anti- Thrombogenicity of the Carotid Atherosclerotic platelet agents (i.e., clopidogrel, abciximab, or Plaque—randomized controlled trial, 4–6 months dipyridamole) and new anticoagulant agents of treatment with atorvastatin (20 mg/d) was (i.e., oral thrombin inhibitors). No data exist on associated with 29% lower TF antigen levels and using these medications in aPL-positive patients 56% lower TF activity in atherosclerotic plaques undergoing surgeries. 104 K.H. Saunders and D. Erkan

8. Erkan D, Lockshin M. New approaches for managing Conclusion antiphospholipid syndrome. Nat Clin Pract Rheumatol. 2009;5:160–70. 9. Fischetti F, Durigutto P, Pellis V, et al. Thrombus for- This chapter provides clinicians with a frame- mation induced by antibodies to beta2-glycoprotein I work to evaluate and manage aPL-positive is complement dependent and requires a priming fac- patients who require surgery. As patients with tor. Blood. 2005;106:2340–6. 10. Rosendaal FR. Thrombosis in the young: epidemiol- “clinically signi fi cant” aPL pro fi les (with or ogy and risk factors: a focus on venous thrombosis. without history of thrombosis) are at high risk for Thromb Haemost. 1997;78:1–6. thrombosis, it is crucial that the patient’s medical 11. Kaul M, Erkan D, Sammaritano L, Lockshin MD. and surgical teams work together to minimize the Assessment of the 2006 revised antiphospholipid syn- drome classi fi cation criteria. Ann Rheum Dis. patient’s risk of thrombosis without increasing 2007;66:927–30. the bleeding risk. 12. Erkan D, Yazici Y, Peterson MG, Sammaritano L, During the perioperative period, the most effec- Lockshin MD. A cross-sectional study of clinical tive pharmacological methods should be combined thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford). with physical methods like intermittent venous 2002;41:924–9. compression, patients should be closely observed 13. Asherson RA, Cervera R, Piette JC, et al. Catastrophic for the signs and symptoms of thrombosis, any antiphospholipid syndrome: clues to the pathogenesis deviation from the normal course should be con- from a series of 80 patients. Medicine (Baltimore). 2001;80:355–76. sidered a potential aPL-related event, and physi- 14. Erkan D, Lockshin MD. What is antiphospholipid cians should keep in mind that thrombosis can syndrome? Curr Rheumatol Rep. 2004;6:451–7. occur despite optimal thrombosis prophylaxis. 15. Asherson RA, Chan JK, Harris EN, Gharavi AE, Hughes GR. Anticardiolipin antibody, recurrent thrombosis, and warfarin withdrawal. Ann Rheum Dis. 1985;44:823–5. References 16. Palareti G, Legnani C, Guazzaloca G, et al. Activation of blood coagulation after abrupt or stepwise with- 1. Miyakis S, Lockshin MD, Atsumi T, et al. International drawal of oral anticoagulants – a prospective study. consensus statement on an update of the classifi cation Thromb Haemost. 1994;72:222–6. criteria for de fi nite antiphospholipid syndrome (APS). 17. Yamamoto T, Ito M, Nagata S, et al. Catastrophic exac- J Thromb Haemost. 2006;4:295–306. erbation of antiphospholipid syndrome after lung ade- 2. Asherson RA, Cervera R, de Groot PG, et al; for the nocarcinoma biopsy. J Rheumatol. 2000; 27:2035–7. Catastrophic Antiphospholipid Syndrome Registry 18. Erkan D, Bateman H, Lockshin MD. Lupus anticoag- Project Group. Catastrophic antiphospholipid syn- ulant-hypoprothrombinemia syndrome associated drome: international consensus statement on with systemic lupus erythematosus: report of 2 cases classifi cation criteria and treatment guidelines. Lupus. and review of literature. Lupus. 1999;8:560–4. 2003;12:530–4. 19. Erkan D, Leibowitz E, Berman J, Lockshin MD. 3. Vila P, Hernández MC, López-Fernández MF, Batlle Perioperative medical management of antiphospho- J. Prevalence, follow-up and clinical signi fi cance of lipid syndrome: hospital for special surgery experi- the anticardiolipin antibodies in normal subjects. ence, review of literature, and recommendations. Thromb Haemost. 1994;72:209–13. J Rheumatol. 2002;29:843–9. 4. Mateo J, Oliver A, Borrell M, Sala N, Fontcuberta J. 20. Chouhan VD, Comerota AJ, Sun L, Harada R, Laboratory evaluation and clinical characteristics of Gaughan JP, Rao AK. Inhibition of tissue factor path- 2,132 consecutive unselected patients with venous way during intermittent pneumatic compression: a thromboembolism – results of the Spanish Multicentric possible mechanism for antithrombotic effect. Study on Thrombophilia (EMET-study). Thromb Arterioscler Thromb Vasc Biol. 1999;19:2812–7. Haemost. 1997;77:444–51. 21. Kakkos SK, Caprini JA, Geroulakos G, Nicolaides 5. Petri M. Epidemiology of the antiphospholipid anti- AN, Stansby GP, Reddy DJ. Combined intermittent body syndrome. J Autoimmun. 2000;15:145–51. pneumatic leg compression and pharmacological pro- 6. Lim W, Crowther MA, Eikelboom JW. Management phylaxis for prevention of venous thromboembolism of antiphospholipid antibody syndrome: a systematic in high-risk patients. Cochrane Database Syst Rev. review. JAMA. 2006;295:1050–7. 2008;4:CD005258. 7. Stephenson MD. Frequency of factors associated with 22. Avcin T, Toplak N. Antiphospholipid antibodies in habitual abortion in 197 couples. Fertil Steril. 1996; response to infection. Curr Rheumatol Rep. 2007;9: 66:24–9. 212–8. 8 Perioperative Management of Antiphospholipid Antibody Positive… 105

23. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anti- 37. Lumpkin MM. FDA public health advisory. coagulants are stronger risk factors for thrombosis Anesthesiology. 1998;88:27A–8. than anticardiolipin antibodies in the antiphospholipid 38. Horlocker TT, Heit JA. Low molecular weight heparin: syndrome: a systematic review of the literature. Blood. biochemistry, pharmacology, perioperative prophylaxis 2003;101:1827–32. regimens, and guidelines for regional anesthetic man- 24. Pengo V, Biasiolo A, Gresele P, et al; for the agement. Anesth Analg. 1997;85:874–5. Participating Centres of Italian Federation of 39. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Thrombosis Centres (FCSA). Survey of lupus antico- Regional anesthesia in the patient receiving anti- agulant diagnosis by central evaluation of positive thrombotic or thrombolytic therapy: American Society plasma samples. J Thromb Haemost. 2007;5:925–30. of Regional Anesthesia and Pain Medicine evidence- 25. Pengo V, Tripodi A, Reber G, et al; for the based guidelines (3rd ed). Reg Anesth Pain Med. Subcommittee on Lupus Anticoagulant/ 2010;35:64–101. Antiphospholipid Antibody of the Scienti fi c and 40. Douketis JD, Berger PB, Dunn AS, et al; for the Standardisation Committee of the International American College of Chest Physicians. The perioper- Society on Thrombosis and Haemostasis. Update of ative management of antithrombotic therapy: the guidelines for lupus anticoagulant detection. American College of Chest Physicians evidence- J Thromb Haemost. 2009;7:1737–40. based clinical practice guidelines (8th ed). Chest. 26. Trappe R, Loew A, Thuss-Patience P, Dörken B, Riess 2008;133:299S–339S. H. Successful treatment of thrombocytopenia in pri- 41. McBane RD, Wysokinski WE, Daniels PR, et al. mary antiphospholipid antibody syndrome with the Periprocedural anticoagulation management of anti-CD20 antibody rituximab—monitoring of patients with venous thromboembolism. Arterioscler antiphospholipid and anti-GP antibodies: a case Thromb Vasc Biol. 2010;30:442–8. report. Ann Hematol. 2006;85:134–5. 42. O’Donnell MJ, Kearon C, Johnson J, et al. Brief com- 27. Cuadrado MJ, Mujic F, Muñoz E, Khamashta MA, munication: preoperative anticoagulant activity after Hughes GR. Thrombocytopenia in the antiphospho- bridging low-molecular-weight heparin for temporary lipid syndrome. Ann Rheum Dis. 1997;56:194–6. interruption of warfarin. Ann Intern Med. 28. Tenidios F, Erkan D, Lockhsin MD. Rituximab in pri- 2007;146:184–7. mary antiphospholipid syndrome (abstract). Arthritis 43. Douketis JD, Woods K, Foster GA, Crowther MA. Rheum. 2005;52:4078. Bridging anticoagulation with low-molecular-weight 29. Shaulian E, Shoenfeld Y, Berliner S, Shaklai M, heparin after interruption of warfarin therapy is Pinkhas J. Surgery in patients with circulating lupus associated with a residual anticoagulant effect prior anticoagulant. Int Surg. 1981;66:157–9. to surgery. Thromb Haemost. 2005; 94:528–31. 30. Vinet E, Rich E, Senécal JL. Thromboembolism com- 44. Geerts WH, Heit JA, Clagett GP, et al. Prevention of plicating the treatment of lupus anticoagulant hypo- venous thromboembolism. Chest. 2001;119:132S–75. prothrombinemia syndrome. J Rheumatol. 2006;33: 45. Madan R, Khoursheed M, Kukla R, al-Mazidi M, 2088–90. Behbehani A. The anaesthetist and the antiphospho- 31. Simel D, St. Claire EW, Adams J, Greenberg C. lipid syndrome. Anaesthesia. 1997;52:72–6. Correction of hypothrombinemia by immunosuppres- 46. Faltas B, Kouides PA. Update on perioperative bridg- sive treatment of lupus anticoagulant-hypoprothrom- ing in patients on chronic oral anticoagulation. Expert binemia syndrome. Am J Med. 1987;83:563–6. Rev Cardiovasc Ther. 2009;7:1533–9. 32. Ra fl ores MB, Kaplan RB, Spero JA. Pre-operative 47. Kasthuri RS, Roubey RA. Warfarin and the antiphos- management of a patient with hypoprothrombinemia- pholipid syndrome. Does one size fi t all? Arthritis lupus anticoagulant syndrome. Thromb Haemost. Rheum. 2007;57:1346–7. 2007;98:248–50. 48. Levy JH, Tanaka KA, Dietrich W. Perioperative hemo- 33. Galli M, Finazzi G, Barbui T. Thrombocytopenia in static management of patients treated with vitamin K the antiphospholipid syndrome. Br J Haematol. antagonists. Anesthesiology. 2008;109:918–26. 1996;93:1–5. 49. Vigué B. Bench-to-bedside review: optimising 34. Sevitt S. Pathology and pathogenesis of deep vein emergency reversal of vitamin K antagonists in severe thrombosis. In: Bergan J, Yao J, editors. Venous prob- haemorrhage – from theory to practice. Crit Care. lems. Chicago: Year Book; 1976. p. 257–69. 2009;13:209. 35. Kraai EP, Lopes RD, Alexander JH, Garcia D. 50. Bernstein ML, Salusinsky-Sternbach M, Belle fl eur Perioperative management of anticoagulation: guide- M, Esseltine DW. Thrombotic and hemorrhagic com- lines translated for the clinician. J Thromb plications in children with the lupus anticoagulant. Thrombolysis. 2009;28:16–22. Am J Dis Child. 1984;138:1132–5. 36. Geerts WH, Bergqvist D, Pineo GF, et al; for the 51. Cerrato D, Ariano C, Fiacchino F. Deep vein throm- American College of Chest Physicians. Prevention of bosis and low-dose heparin prophylaxis in neurosur- venous thromboembolism: American College of gical patients. J Neurosurg. 1978;49:378–81. Chest Physicians evidence-based clinical practice 52. Iorio A, Agnelli G. Low-molecular-weight and guidelines (8th ed). Chest. 2008;133:381S–453S. unfractionated heparin for prevention of venous 106 K.H. Saunders and D. Erkan

thromboembolism in neurosurgery: a meta-analysis. 66. Forman JP, Lin J, Pascual M, Denton MD, Tolkoff- Arch Intern Med. 2000;160:2327–32. Rubin N. Signifi cance of anticardiolipin antibodies on 53. Agnelli G, Piovella F, Buoncristiani P, et al. Enoxaparin short and long term allograft survival and function plus compression stockings compared with compres- following kidney transplantation. Am J Transplant. sion stockings alone in the prevention of venous 2004;4:1786–91. thromboembolism after elective neurosurgery. N Engl 67. Ruffatti A, Marson P, Valente M, et al. Plasma J Med. 1998;339:80–5. exchange in a patient with primary antiphospholipid 54. Cheng JS, Arnold PM, Anderson PA, Fischer D, syndrome undergoing kidney transplantation. Transpl Dettori JR. Anticoagulation risk in spine surgery. Int. 2007;20:475–7. Spine (Phila Pa 1976). 2010;35:S117–24. 68. Montgomery RA, Zachary AA, Racusen LC, et al. 55. Roth J, Margalit NS, Kesler A, Korn A, Ram Z. Peri- Plasmapheresis and intravenous immune globulin operative brainstem infarct in a patient with antiphos- provides effective rescue therapy for refractory pholipid antibody (APLA) syndrome. Acta Neurochir humoral rejection and allows kidneys to be success- (Wien). 2006;148:1111–5. fully transplanted into cross-match-positive recipi- 56. Cherian J, Gertner E. Recurrent pulmonary embolism ents. Transplantation. 2000;70:887–95. despite inferior vena cava fi lter placement in patients 69. Silverberg M, Erkan D, Lockshin MD. Hemorrhage in with the antiphospholipid syndrome. J Clin Rheumatol. the antiphospholipid syndrome: the challenge of anti- 2005;11:56–8. coagulation. Arthritis Rheum. 2002;46:S52. 57. Decousus H, Leizorovicz A, Parent F, et al. A clinical 70. Erkan D. Therapeutic and prognostic considerations trial of vena caval fi lters in the prevention of pulmo- in catastrophic antiphospholipid syndrome. nary embolism in patients with proximal deep-vein Autoimmun Rev. 2006;6:98–103. thrombosis. Prévention du Risque d’Embolie 71. Deane KD, West SG. Antiphospholipid antibodies as Pulmonaire par Interruption Cave Study Group. N a cause of pulmonary capillaritis and diffuse alveolar Engl J Med. 1998;338:409–15. hemorrhage: a case series and literature review. Semin 58. Zifman E, Rotman-Pikielny P, Berlin T, Levy Y. Arthritis Rheum. 2005;35:154–65. Insertion of inferior vena cava fi lters in patients with 72. Elwood PC, Cochrane AL, Burr ML, et al. A random- the antiphospholipid syndrome. Semin Arthritis ized controlled trial of acetyl salicylic acid in the sec- Rheum. 2009;38:472–7. ondary prevention of mortality from myocardial 59. Ebato M, Kitai H, Kumakura H, Nakamura Y, Shimizu infarction. Br Med J. 1974;1:436–40. N, Takeyama Y. Thrombus on the tricuspid valve in a 73. Llau JV, Lopez-Forte C, Sapena L, Ferrandis R. patient with primary antiphospholipid syndrome after Perioperative management of antiplatelet agents in non- implantation of an inferior vena cava fi lter. Circ J. cardiac surgery. Eur J Anaesthesiol. 2009;26:181–7. 2002;66:425–7. 74. Samama CM, Bastien O, Forestier F, et al; for the 60. Vaidya S, Sellers R, Kimball P, et al. Frequency, French Society of Anesthesiology and Intensive Care. potential risk and therapeutic intervention in end- Antiplatelet agents in the perioperative period: expert stage renal disease patients with antiphospholipid recommendations of the French Society of antibody syndrome: a multicenter study. Anesthesiology and Intensive Care (SFAR) 2001-sum- Transplantation. 2000;69:1348–52. mary statement. Can J Anaesth. 2002;49:S26–35. 61. Vaidya S, Gugliuzza K, Daller JA. Effi cacy of anticoagu- 75. O’Riordan JM, Margey RJ, Blake G, O’Connell PR. lation therapy in end-stage renal disease patients with Antiplatelet agents in the perioperative period. Arch antiphospholipid antibody syndrome. Transplantation. Surg. 2009;144:69–76. 2004;77:1046–9. 76. Jancinová V, Nosál R, Petríková M. On the inhibitory 62. Stone JH, Amend WJ, Criswell LA. Antiphospholipid effect of chloroquine on blood platelet aggregation. antibody syndrome in renal transplantation: occur- Thromb Res. 1994;74:495–504. rence of clinical events in 96 consecutive patients with 77. Lombard-Platlet S, Bertolino P, Deng H, Gerlier D, systemic lupus erythematosus. Am J Kidney Dis. Rabourdin-Combe C. Inhibition by chloroquine of the 1999;34:1040–7. class II major histocompatibility complex-restricted 63. McIntyre JA, Wagenknecht DR. Antiphospholipid presentation of endogenous antigens varies according antibodies. Risk assessments for solid organ, bone to the cellular origin of the antigen-presenting cells, marrow, and tissue transplantation. Rheum Dis Clin the nature of the T-cell epitope, and the responding T North Am. 2001;27:611–31. cell. Immunology. 1993;80:566–73. 64. Raklyar I, DeMarco J, Wu J, Light J, Timbil S, 78. Goldman FD, Gilman AL, Hollenback C, Kato RM, Weinstein A. Anticardiolipin antibody positivity cor- Premack BA, Rawlings DJ. Hydroxychloroquine relates with poor graft survival in renal transplantation inhibits calcium signals in T cells: a new mechanism for systemic lupus erythematosus (abstract). Arthritis to explain its immunomodulatory properties. Blood. Rheum. 2005;52:S384–5. 2000;95:3460–6. 65. Wagenknecht DR, Becker DG, LeFor WM, McIntyre 79. Pierangeli SS, Vega-Ostertag M, Harris EN. JA. Antiphospholipid antibodies are a risk factor for Intracellular signaling triggered by antiphospholipid early renal allograft failure. Transplantation. 1999;68: antibodies in platelets and endothelial cells: a pathway 241–6. to targeted therapies. Thromb Res. 2004;114:467–76. 8 Perioperative Management of Antiphospholipid Antibody Positive… 107

80. Pierangeli SS, Vega-Ostertag ME, González EB. New lipid (anti-beta2- glycoprotein I) antibodies: effect on targeted therapies for treatment of thrombosis in the proadhesive and proin fl ammatory phenotype. antiphospholipid syndrome. Expert Rev Mol Med. Arthritis Rheum. 2001;44:2870–8. 2007;9:1–15. 90. Ferrara DE, Swerlick R, Casper K, et al. Fluvastatin 81. Rand JH, Wu XX, Quinn AS, Chen PP, Hathcock JJ, inhibits up-regulation of tissue factor expression by Taatjes DJ. Hydroxychloroquine directly reduces the antiphospholipid antibodies on endothelial cells binding of antiphospholipid antibody-beta2-glyco- (abstract). J Thromb Haemost. 2004;2:1558–63. protein I complexes to phospholipid bilayers. Blood. 91. Cortellaro M, Cofrancesco E, Arbustini E, et al. 2008;112:1687–95. Atorvastatin and thrombogenicity of the carotid ath- 82. Johnson R, Charnley J. Hydroxychloroquine in pro- erosclerotic plaque: the ATROCAP study. Thromb phylaxis of pulmonary embolism following hip Haemost. 2002;88:41–7. arthroplasty. Clin Orthop Relat Res. 1979;144: 92. Ridker PM, Danielson E, Fonseca FA, et al; for the 174–7. JUPITER Trial Study Group. Reduction in C-reactive 83. Wallace DJ. Does hydroxychloroquine sulfate prevent protein and LDL cholesterol and cardiovascular event clot formation in systemic lupus erythematosus? rates after initiation of rosuvastatin: a prospective Arthritis Rheum. 1987;30:1435–6. study of the JUPITER trial. Lancet. 2009;373: 84. Petri M. Hydroxychloroquine use in the Baltimore 1175–82. Lupus Cohort: effects on lipids, glucose and thrombo- 93. Glynn RJ, Danielson E, Fonseca FA, et al. A random- sis. Lupus. 1996;5:S16–22. ized trial of rosuvastatin in the prevention of venous 85. Kaiser R, Cleveland CM, Criswell LA. Risk and pro- thromboembolism. N Engl J Med. 2009;360:1851–61. tective factors for thrombosis in systemic lupus ery- 94. Hindler K, Shaw AD, Samuels J, Fulton S, Collard thematosus: results from a large, multi-ethnic cohort. CD, Riedel B. Improved postoperative outcomes Ann Rheum Dis. 2009;68:238–41. associated with preoperative statin therapy. 86. Ho KT, Ahn CW, Alarcón GS, et al. Systemic lupus Anesthesiology. 2006;105:1260–72. erythematosus in a multiethnic cohort (LUMINA): 95. Le Manach Y, Godet G, Coriat P, et al. The impact of XXVIII. Factors predictive of thrombotic events. postoperative discontinuation or continuation of Rheumatology (Oxford). 2005;44:1303–7. chronic statin therapy on cardiac outcome after major 87. Ruiz-Irastorza G, Hunt BJ, Khamashta MA. A sys- vascular surgery. Anesth Analg. 2007;104:1326–33. tematic review of secondary thromboprophylaxis in 96. Fleisher LA, Beckman JA, Brown KA, et al. ACC/ patients with antiphospholipid antibodies. Arthritis AHA 2007 guidelines on perioperative cardiovascular Rheum. 2007;57:1487–95. evaluation and care for noncardiac surgery: executive 88. Ferrara DE, Liu X, Espinola RG, et al. Inhibition of the summary: a report of the American College of thrombogenic and in fl ammatory properties of antiphos- Cardiology/American Heart Association Task Force pholipid antibodies by fl uvastatin in an in vivo animal on practice guidelines (writing committee to revise model. Arthritis Rheum. 2003;48:3272–9. the 2002 guidelines on perioperative cardiovascular 89. Meroni PL, Raschi E, Testoni C, et al. Statins prevent evaluation for noncardiac surgery). Anesth Analg. endothelial cell activation induced by antiphospho- 2008;106:685–712. Perioperative Management of Anticoagulation in the Patient 9 with the Antiphospholipid Syndrome in Cardiac Surgery and Cardiac Interventions

John R. Bartholomew

Introduction international consensus statement guidelines for the diagnosis of APS, laboratory testing must be The antiphospholipid syndrome (APS) is consid- confi rmed on two separate occasions at least 12 ered the most common acquired hypercoagulable weeks apart [3 ] . disorder associated with thrombosis. It is an anti- Patients with the APS requiring cardiac surgery or body-mediated prothrombotic state characterized a cardiac interventional procedure such as percutane- by venous and/or arterial thrombosis or obstet- ous coronary intervention (PCI), percutaneous trans- rical morbidity in conjunction with laboratory luminal coronary angioplasty (PTCA), or mitral or identi fi cation of antiphospholipid antibodies (aPL). aortic valvuloplasty present unique problems to the These antibodies, recently referred to as the physician before, during, and after their procedure. “antiphospholipid triangle,” include anticardio- They not only have a higher rate of thrombosis lipin antibodies (aCL), anti-b 2-glycoprotein I leading to both increased early and late morbidity antibodies (ab 2GPI), and the lupus anticoagulant but may also pose additional problems if they have an (LA) [ 1 ] . Antiphospholipid antibodies identi fi ed LA. The presence of an LA can affect interpretation in otherwise healthy individuals after a venous or of coagulation tests commonly used for monitoring arterial thrombotic or obstetrical event is referred cardiac procedures and the amount of anticoagulant to as primary APS. Secondary APS is the term used [4Ð 6 ] . Additionally, patients with APS may be used when APS coexists with an underlying prone to bleeding complications if they have throm- systemic autoimmune disease such as systemic bocytopenia or, less commonly, hypoprothrombine- lupus erythematosus (SLE). Antibodies also occur mia due to decreased prothrombin levels. in asymptomatic individuals with no history of It is crucial that cardiologists and cardiothoracic thrombosis. They can also be detected in persons surgeons recognize the APS syndrome prior to any on medications particularly important to the surgical or invasive procedure (or consider the cardiac patient including procainamide, hydrala- diagnosis if unexplained thrombotic or bleeding zine, quinidine, and the angiotensin-converting complications develop during or after) and plan enzyme (ACE) inhibitors [2 ] . and/or treat accordingly using the expertise of the Individuals may have one antibody or any anesthesiologist, internist, hematologist, rheuma- combination of the three. To meet the revised tologist, vascular specialist, and laboratory to mini- mize the potential for catastrophic complications. Although the majority of persons (29Ð55%) J. R. Bartholomew , M.D., FACC () with APS will have deep vein thrombosis (DVT) Department of Cardiovascular Medicine , Cleveland or pulmonary embolism (PE), the most common Clinic , 9500 Euclid Avenue , Cleveland , OH 44195 , USA arterial thrombosis is a cerebrovascular event e-mail: [email protected] (TIA or stroke), accounting for almost 50% of

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 109 DOI 10.1007/978-1-4614-2203-7_9, © Springer Science+Business Media, LLC 2013 110 J.R. Bartholomew arterial complications [ 7, 8 ] . Patients with APS There is growing evidence that aPL is linked to are at increased risk for coronary and valvular an increased risk of MI [14, 31 ] . Myocardial infarc- heart disease leading to angina, myocardial tion was the presenting manifestation in 2.8% of infarction (MI), coronary artery bypass rethrom- 1,000 patients in a multicenter prospective cohort bosis, recurrent coronary stent thrombosis, heart study of patients with APS [14, 31 ] . Colli et al. failure, valvular vegetations, intracardiac thrombi, reported the prevalence of aPL in young survivors nonbacterial thrombotic endocarditis, Libman- of MI under the age of 45 years at 21%, while Sacks endocarditis, pulmonary hypertension, or Zuckerman and colleagues found aCL in 17% of peripheral embolization [6, 9Ð 13 ] . relatively young survivors (aged 65 or younger) of Valvular involvement, which may be asymp- acute MI [ 8, 16, 32] . Zuckerman et al. also reported tomatic, is the most common cardiac manifesta- a higher rate of thromboembolic events and myocar- tion and includes lea fl et thickening, nodules, dial reinfarction in aCL-positive patients [32 ] . In a vegetations, and dysfunction, having a preference prospective cohort of 4,081 dyslipidemic middle- for the mitral valve but also affects the aortic and aged men participating in the Helsinki Heart Study, tricuspid valves. Regurgitation is much more the presence of high aCL titers was an indepen- common than stenosis, which is rare [14Ð 19 ] . dent risk factor for MI or cardiac death [33 ] . Farsi Myocardial microthrombosis is another mani- et al. noted that there was a higher prevalence festation of coronary APS. It is more commonly of anti-§2GPI antibodies (30%) in patients with found in patients with catastrophic APS. These ischemic heart disease compared to controls, while patients can present with an acute MI but generally Brey et al. in a case control study of 2,000 patients have a normal coronary angiogram, making the found an increased risk for MI in patients with diagnosis dif fi cult without a cardiac biopsy [14 ] . IgG aCL directed against §2GPI [ 34, 35 ] . Bick et al. indicated that up to 18% of premature coro- nary artery thrombosis may be due to APS, while Incidence of APS in the Cardiac Grzybczak and colleagues felt that APS should be Patient considered as a cause for ACS in younger patients because of the high prevalence of aCL in the gen- Cross-sectional studies have found IgM aCL in eral population [11, 36 ] . 9.4%, IgG aCL in 6.5%, and LA in 8% of healthy Intracardiac thrombi were reported in 5 of 31 blood donors [ 20Ð 22 ] . Jervis et al. and Cartwright patients evaluated by Erdogan et al. who observed et al. report that aCL antibodies are found in thrombus formation in all chambers of the heart 4Ð14% of otherwise healthy individuals, with [ 37] . Turiel et al. reported a signifi cant correla- levels as high as 50% in select patient popula- tion among aCL titer, mitral leafl et thickening, tions [4, 23, 24 ] . Levine et al. reported that and embolic sources in 33 of 40 (82%) consecu- approximately one-third of patients with SLE tive APS patients undergoing transesophageal have aPL, while Long and Bruce states this num- echocardiography [38 ] . They also described ber may be as high as 50% [7, 25, 26 ] . spontaneous echo contrast in the left atrium of The prevalence of valvular lesions in patients 16% of patients with APS and reported that as a with APS is reported to be as high as 40% in pri- risk factor for left atrial thrombus formation and mary APS and 60% of patients with SLE and a potential for embolization [6 ] . APS [27Ð 29 ] . Patients with valvular abnormali- Less is known about the incidence of APS in ties have a higher incidence of arterial throm- patients requiring cardiac surgery. Most case boembolism compared to APS patients without studies include few patients [ 4, 8, 23, 24, 39Ð 42 ] . valvular involvement [ 14, 30 ] . However, accord- Hedge et al. report that in their surgical popula- ing to Colli, only rarely do patients with APS tion of 4,000 reviewed charts, only 9 (0.002%) develop severe valvular disease (4Ð6%) requiring were affected with the APS [24 ] . surgery and most patients remain asymptomatic Coronary artery bypass rethrombosis due to for years [8, 29 ] . premature restenosis of vein grafts has been 9 Perioperative Management of Anticoagulation in the Patient… 111 reported in patients with APS. Morton et al. found too soon before adequate hemostasis is attained. a direct correlation between the incidence of late The risk of bleeding also increases in patients graft occlusion and the presence of preoperative with thrombocytopenia and/or hypoprothrom- aPL, noting that 8 of 15 patients (53%) had at binemia [ 42 ] . Therefore, perioperative strate- least one graft occlusion [43 ] . gies should be clearly de fi ned and planned In 60 consecutive ischemic heart disease before any type of interventional or surgical patients, Ludia et al. investigated the role of aPL in procedure is performed in the APS patient. restenosis after PTCA [44 ] . Anticardiolipin antibodies (aCL and LA) were drawn before the procedure. Fifteen of sixty patients were aPL Preoperative Approach positive and restenosis was observed in 40%. Not only did restenosis occur more often but earlier following The history and physical examination are espe- PTCA compared to non-aPL patients [44 ] . cially important for the patient preparing for Stent thrombosis is unusual and only a few cardiac surgery or intervention with suspected case reports linking aPL with this complication or confi rmed APS as well as the individual with have been published [45Ð 47 ] . known aPL antibodies but no previous history of thrombosis or obstetrical complications. Pertinent information should include questions Perioperative Management of the APS regarding a previous history of/or active venous Patient Requiring Cardiac Surgery or arterial thrombosis, obstetrical complica- or Intervention tions, and whether thrombosis or bleeding occurred with previous procedures. Other The perioperative management of patients with symptoms or fi ndings including livedo reticu- APS undergoing cardiac surgery or intervention laris; unexplained renal failure; neurological can be challenging due to the potential for com- complications including a previous TIA, stroke, plications of thrombosis and/or bleeding. or cognitive defects; or known SLE should alert Thrombosis is a particular concern during with- the physician to a search for aPL preoperatively drawal and/or reversal of warfarin or the new if the diagnosis has not been previously made direct thrombin inhibitor (DTI) dabigatran (or in [ 27] . Additionally, APS should be considered in some cases a parenteral anticoagulant). It is also individuals with abnormal base line coagula- problematic during surgery or intervention due to tion tests including a prolonged prothrombin the potential to under- or overestimate the amount time (PT), international normalized ratio (INR), of anticoagulation required in patients with an activated partial thromboplastin time (APTT), LA, and postoperatively during periods of or thrombocytopenia. hypercoagulability before resuming full-dose anticoagulation [42 ] . Perioperative thrombosis may also result from development of the cata- Bridging the Patient with APS strophic APS syndrome which may be triggered by the surgical or interventional procedure. Most cardiovascular patients meeting the criteria Catastrophic APS is diagnosed based on involve- for diagnosis of APS will be on vitamin K antag- ment of three or more organ systems developing onist (VKA) warfarin or the newly approved DTI, in less than 1 week’s time in a patient with labora- dabigatran, and will require bridging therapy tory con fi rmation and histopathology (small vessel preoperatively. A VKA should be discontinued occlusion) fi ndings [8 ] . approximately 4Ð5 days before cardiac surgery Paradoxically, bleeding can also result either or any interventional procedure, allowing time from anticoagulation during or following sur- for the INR to return to normal [48 ] (see Table 9.1 ). gery or intervention as well as during the post- According to van Ryn et al., dabigatran , procedural period if anticoagulation is resumed approved for patients with nonvalvular atrial 112 J.R. Bartholomew

Table 9.1 Preoperative anticoagulant bridging recommendations for patients with APS requiring CABG or interventional procedure Anticoagulation agent used Time to discontinue parenteral anticoagulant prior Agent to be discontinued to bridge to surgery or procedure VKA 5 days before surgery Therapeutic subcutaneous LMWH 24 h prior to the procedure for LMWH assuming normal renal function VKA 5 days before surgery Therapeutic intravenous UFH 4Ð6 h prior to the procedure for UFH VKA 5 days before surgery Fondaparinux 2.5 mg dose 36 h prior to the procedure assuming normal renal function and 2.5 mg dose Fondaparinux 5, 7.5, or 10 mg 48 h or more with doses of 5Ð10 mg assuming normal renal function Modi fi ed from Refs. [58, 59 ]

Table 9.2 Periprocedural antiplatelet recommendations for patients with APS requiring surgery or intervention Anticoagulation agent used Time to discontinue antiplatelet agent prior to surgery Agent to be discontinued to bridge or procedure Aspirin None No need to discontinue before surgery or PCI The EACTS recommends stopping 2Ð10 days before surgery Clopidogrel None Discontinue 5 but preferably 10 days before surgery No need to discontinue before PCI Modi fi ed from Ref. [ 58 ]

fi brillation, should be discontinued at least 24 h transfusion requirements [54Ð 56 ] . If the APS before any procedure in the patient with normal patient is undergoing PCI, neither aspirin nor renal function (de fi ned as a creatinine clearance clopidogrel need be interrupted prior to their ³ 50 mL/min) with minimal bleeding risks, intervention [57, 58 ] (see Table 9.2 ). whereas in the cardiac surgical patient with a higher risk of bleeding or the person with impaired renal function, it should be withheld 4 days or Parenteral Anticoagulants Used longer [49 ] . The manufacturer, however, recom- for Bridging mends stopping dabigatran 1 to 2 days before invasive or surgical procedure if the creatinine There are currently three parenteral anticoagu- clearance is ³ 50 mL/min and longer in patients lants that can be administered subcutaneously undergoing major surgery or a spinal puncture or (SC) either as an outpatient or inpatient including placement of a spinal or epidural catheter or port the low molecular weight heparin (LMWH) in which complete hemostasis is required [50 ] . preparations enoxaparin (Lovenox¨), dalteparin According to Bypee et al., Mangano, and (Fragmin¨), unfractionated heparin (UFH), or Topol, patients undergoing coronary artery the anti-Xa inhibitor, fondaparinux (Arixtra¨). bypass grafting (CABG) should not discontinue The LMWH preparations should be dose-adjusted their aspirin prior to surgery, although this if the patient’s creatinine clearance is less than recommendation is not universal [ 51Ð 53 ] . The 30 mL/min, while fondaparinux is contraindicated European Association for Cardio-Thoracic if the creatinine clearance is less than 30 mL/min, Surgery (EACTS) advises stopping aspirin 2Ð10 and neither is advised in patients on dialysis. days before elective cardiac surgery to reduce Unfractionated heparin can be given either full perioperative blood loss [48 ] . Clopidogrel should dose subcutaneously or intravenously. be discontinued 5 and preferably 10 days prior to If full-dose SC LMWH is used for bridging CABG due to a higher risk for bleeding and purposes, it should be discontinued 24 h before 9 Perioperative Management of Anticoagulation in the Patient… 113 either surgery or an interventional procedure, ponents of the native valve and promotes better whereas intravenous UFH should be discontin- postoperative ventricular function [68 ] . The ued approximately 4Ð6 h before. According to choice between a mechanical or bioprosthetic Landenhed et al., if fondaparinux is used, it valve is dependent in part on a patient’s willing- should be discontinued a minimum of 36 h prior ness to take a long-term VKA for their mechanical to surgery if the patient is receiving the prophy- valve, or if they have a contraindication to antico- laxis dose of 2.5 mg/day [ 59] . It is advisable it be agulation. The newer DTI, dabigatran is not yet held 48 h or longer if higher doses of 5Ð10 mg are FDA approved for mechanical heart valves but used (see Table 9.1 ). may be available in the future pending additional testing. The American College of Cardiology (ACC) and the American Heart Association Surgical Options: Conventional (AHA) guidelines recommend mechanical valves On-Pump Versus Off-Pump CABG for patients under 65 years of age with chronic atrial fi brillation and a bioprosthetic valve in per- The choice of CABG (on-pump or off-pump) sons greater than 65 years of age, or under 65 remains controversial. Several randomized trials years of age in normal sinus rhythm who choose have suggested that off-pump coronary artery this valve over mechanical after the risks of each bypass grafting (OPCAB) is superior in lowering valve type are explained (i.e., need for long-term mortality and morbidity due to less blood loss, anticoagulation and potential need for repeat less myocardial enzyme release, less early neu- valve surgery for bioprosthetic valves) [69 ] . rocognitive dysfunction, and less renal Gorki et al. prefer the mechanical valve for the insuffi ciency [ 60 ] . More recent studies, however, APS patient requiring surgery but point out that there have not confi rmed these fi ndings, and many sur- are no long-term results for this population [ 27 ] . geons now advise that only patients at the greatest Colli and colleagues initially recommended risk of CABG (the elderly or those with ascending mechanical valve replacement for their APS aortic and arch atherosclerosis) benefi t from patients due to a continued and independent need OPCAB [ 61Ð 63 ] . for long-term anticoagulation because of their There are only a few case reports of APS hypercoagulable state. However, after reviewing patients undergoing OPCAB [ 23, 64, 65 ] . their operative and postoperative data from nine Horimoto and colleagues felt that OPCAB was patients, including two perioperative deaths, they useful for patients with thromboembolic diseases recommended that a bioprosthetic valve be con- in general, citing data from Casati et al. of sidered. They cited easier management of routine increased levels of plasminogen and D-dimer for- oral anticoagulation therapy and safer manage- mation in patients who undergo on-pump CABG ment of thromboembolic and bleeding complica- [64, 66] . They suggested that OPCAB might tions in patients with bioprosthetic valves [8 ] . reduce the possibility of increased coagulation Bouma et al. reported four patients, two with and fi brinolytic complications in the APS patient mitral valve repair and two with replacement, in [ 64, 66, 67 ] . patients with Libman-Sacks endocarditis due to SLE and/or APS [ 70 ] . They emphasized the advantages of valve repair over replacement Heart Valve Surgery Options: including lower operative mortality rates, higher Valvuloplasty (Repair) or Mechanical survival, better maintenance of left ventricular or Bioprosthetic Valve Replacement function, lower risk of endocarditis, lower risk of thromboembolic complications, less use of The type of heart valve surgery (repair, mechani- lifelong anticoagulation, and lower costs [68, cal, or bioprosthetic) is dependent on a number of 70, 71 ] . Although their two patients with APS factors. Valve repair (valvuloplasty) is generally had mitral valve replacement, Bouma et al. sug- preferred because it preserves the functional com- gested that mitral valve repair could be justifi ed 114 J.R. Bartholomew if they are relatively stable, younger, if intraop- Additionally, heparin, LMWH, the anti-Xa inhib- erative macroscopic examination reveals rela- itor fondaparinux, and the DTIs including bivali- tively normal leafl ets with only localized rudin, lepirudin (Refl udan ¨), and argatroban abnormalities, and if repair seems feasible [ 70 ] . (Argatroban¨) and the glycoprotein IIb/IIIa However, Bouma et al. also noted that antico- inhibitors tirofi ban (Aggrastat¨), abciximab agulation is necessary to prevent future throm- (ReoPro¨), or eptifi batide (Integrilin¨) have all been boembolic events. used for cardiac interventional procedures. There are several case reports citing the use of Lepirudin and argatroban are more frequently bioprosthetic valves in patients with APS [4, 27, used for patients with HIT not requiring interven- 39, 72, 73 ] . Myers and Hirsch used a Baxter peri- tion or surgery, while bivalirudin and the GP IIb/ cardial aortic valve and a Medtronic Intact mitral IIIa inhibitors are used more frequently in cardiac prosthesis, while Kato et al. used a Carpentier- interventional procedures (PCI and PTCA). Edwards pericardial bioprosthesis for mitral The major disadvantage of the DTIs and fonda- valve replacement in patients with LA and APS parinux is the lack of an antidote as well as their [ 73, 74] . Both authors felt that the bioprosthesis increased expense compared to heparin. offered less risk of thromboembolism compared to a mechanical valve [ 73, 74 ] . Hogan et al. favored a bioprosthetic valve in their patient Intraoperative Management: because of the presence of hypoprothrombinemia Standard Dosing for On- and Off- and thrombocytopenia fearing an increased Pump CABG for the Non-APS Patient potential for bleeding and because postoperative monitoring of a VKA would be more complex Heparin remains the standard of care for cardiac [72 ] . In the series by Berkun et al., two patients surgery and many interventional procedures. were given bioprosthetic valves because of their Conventional on-pump coronary artery bypass own preference [39 ] . surgery (CABG) requires high doses (³ 300 U/kg or more), although doses ranging from 200 to 500 U/kg targeting an ACT of between 300 and Anticoagulation Management During 480 s or more are reported [75Ð 78 ] . An empirical Cardiac Surgery or Intervention dose of 300Ð400 U/kg of heparin is accepted by most surgeons targeting an ACT of greater than There is no consensus for the intraoperative man- 480 s [ 76] . The heparin concentration corre- agement of anticoagulation in APS patients under- sponding to an ACT of >480 ranges from 4 to going cardiac surgery or interventional procedures 5 U/mL, approximately ten times the amount of if they have an LA [4, 42] . These individuals pres- heparin used to treat venous thromboembolism ent special problems with dosing and monitoring (VTE) [79 ] . An additional dose of 10,000 U of anticoagulation because of the effect their LA has heparin is applied to the circuit to most patients, on coagulation testing. Antiphospholipid syn- depending on the equipment used [ 79 ] . Off-pump drome patients with aCL and/or ab 2GPI (who do coronary bypass (OPCAB) dosing also varies, not have prolongation of their coagulation tests) ranging from 80 to 350 U/kg, targeting ACT are still at increased risk for thrombosis and/or values between 250 s to greater than 400 s [77 ] . bleeding but do not pose the same challenges in dosing and/or monitoring anticoagulation. Heparin is the agent of choice for surgical pro- Dosing Heparin for On- and Off-Pump cedures although the LMWH preparations and CABG for the APS Patient DTIs have been used. Bivalirudin (Angiomax¨) is generally preferred for the patient requiring Dosing heparin in patients with APS who have an open heart surgery who has active or a recent his- LA remains controversial and is often empirical. tory of heparin-induced thrombocytopenia (HIT). Gorki et al. recommended giving as much hepa- 9 Perioperative Management of Anticoagulation in the Patient… 115 rin as usual for CABG but adding “extra doses” For the non-ST-segment ACS patient, the dose to double the ACT [ 27 ] . Cartwright et al. advised recommended is an initial bolus of 60Ð70 U/kg consultation with a hematologist and felt that a (maximum of 5,000 U) followed by an infusion greater amount of heparin may be required for of 12Ð15 U/kg (maximum dose of 1,000 U/h), these prothrombotic patients [4 ] . Weiss et al. titrating an aPTT of 50Ð75 s [85 ] . stressed that intraoperative management strate- Additional anticoagulants commonly used for gies vary considerably for the APS patient and patients with ACS include LMWH (enoxaparin), felt that the optimal approach remains elusive the DTI (bivalirudin), the anti-Xa inhibitor after reviewing six previously published cases (fondaparinux), and the GP IIb/IIIa inhibitors and their own [ 42 ] . Initial dosages reported have (abciximab epti fi batide, or tiro fi ban). However, ranged from 260 U/kg reported by Weiss et al. to there is little experience with these anticoagulants 600 U/kg for aortic valve replacement and coro- in the patient with APS. nary revascularization performed by Cartwright For PCI patients on chronic aspirin therapy, et al. to as high as 775 U/kg as reported by Sheikh it is advised that they receive an additional [4, 15, 24, 27, 42, 70, 72, 74, 80Ð 84 ] . 75Ð325 mg of aspirin given prior to their pro- There are only a few case reports that mention cedure. If not on aspirin therapy, 300Ð325 mg the dose of heparin in APS patients undergoing of aspirin should be given at least 2 h and OPCAB [23, 64, 65 ] . Maddali and Albahrani used preferably 24 h before the PCI [ 86 ] . A loading 100 U/kg of heparin for their OPCAB patient with dose of 300Ð600 mg of clopidogrel should be an LA, while no dosage is mentioned by Horimoto given before the PCI, depending on whether et al. in their case [64, 65 ] . Jervis et al. did not or not it is a non-ST-segment elevation ACS mention their patient’s weight but administered a or acute ST-segment elevation myocardial bolus of 18,000 U of heparin followed by an addi- infarction [ 85 ] . tional dose of 4,000 units 1 h later [23 ] .

Anticoagulation Dosing for ACS and PCI Standard Anticoagulation Dosing for in the APS Patient ACS and PCI in the Non-APS Patient There are only a few case reports that mention The standard dosing of heparin recommended by dosing regimens for patients with ACS who the American College of Chest Physicians undergo PCI [ 11, 45Ð 47, 87Ð 92] . Su et al. per- (ACCP) guidelines for patients with acute coro- formed elective coronary angiography on a nary syndrome (ACS) depends on whether the patient with APS using 5,000 U of heparin. patient has an acute ST-segment MI or non-ST- Intracoronary stenting was performed because of segment ACS [85 ] . a 75% stenosis found in the LAD, and an addi- For the acute ST-segment MI, heparin dosing tional heparin bolus of 4,000 U was given is also dependent on whether the patient receives because of a subtherapeutic ACT [46 ] . Following thrombolytic therapy or undergoes PCI. The PCI, the patient had chest pain and underwent an dose for patients receiving thrombolytic ther- emergency PTCA for a totally occluded LAD apy varies between a 4,000 and 5,000 U bolus stent, requiring additional heparin with the addi- followed by 1,000 U/h or 12 U/kg/h, depend- tion of a GP IIb/IIIa antagonist. Timurkaynak ing on which thrombolytic agent (streptokinase et al. used 5,000 U of heparin for a coronary [Streptase¨], tenecteplase [TNKase¨P], or reteplase angiogram in a patient with APS. A proximal [Retavase¨]) is used. For the patient receiving a total occlusion of the right coronary artery was GP IIb/IIIa inhibitor, a dose of 50Ð70 U/kg of noted and PTCA was performed after an addi- heparin is advised, whereas in patients not tional bolus of 5,000 U of heparin and 500 mg of receiving a GPIIb/IIIa inhibitor, a 60Ð100 U/kg ticlopidine were administered [ 91 ] . There are is recommended [ 85 ] . additional case reports of patient with the APS 116 J.R. Bartholomew who required either PCI or PTCA; however, no dosage is mentioned [ 47, 87 ] . Monitoring Anticoagulation for Cardiopulmonary Bypass in the APS Patient Monitoring Anticoagulation During Surgery or Interventional Procedures Because the ACT may be affected by factors other than heparin during cardiopulmonary There are a number of coagulation tests, devices, bypass (CPB) including hemodilution, hypo- and strategies that have been developed for thermia, and extreme thrombocytopenia, monitoring anticoagulation during cardiac sur- monitoring heparin concentrations directly has gery and interventional procedures. These tests been recommended as an alternative approach must be performed in a timely and accurate [ 72, 93, 94] . Point-of-care testing is also avail- manner as rapid turnaround time is essential. able for monitoring heparin concentrations This has led to the development of “point-of- including the heparin neutralization assays using care testing” that in most cases utilizes whole either protamine or polybrene. Other methods blood and can be performed rapidly at bedside that determine the functional capacity of hepa- or in the operating room or interventional suite rin based on the ability of heparin to accelerate rather than sending a blood sample to the labo- the inhibition of a standard concentration of fac- ratory. There are several point-of-care tests tor Xa or thrombin include the chromogenic and available for heparin monitoring including the fl uorogenic assays. However, these are per- ACT and calculation of the heparin concentra- formed in the central laboratory and not gener- tion. The ACT is most commonly used for both ally available as point-of-care testing. They are interventional and surgical procedures. It also more time-consuming and thus not used requires an activator (generally celite or kaolin) often in cardiac surgery [ 79 ] . The most com- to initiate clotting via the intrinsic pathway of monly used is protamine titration targeting coagulation similar to the way an aPTT is per- heparin concentrations of 3Ð4 U/mL [ 72, 79 ] . formed [93 ] . Unlike the aPTT, however, the There are several commercial tests available ACT can measure the effect of higher concen- including the Hepcon¨ HMS Plus (Medtronic, trations of heparin required for coronary artery Parker, CO) (which also measures the ACT), the surgical procedures. The ACT is performed Hemochron¨RxDX (International Technidyne every 30Ð60 min throughout surgery, with addi- Corp., Edison, NJ), and the HEPTEST-HI tional heparin administered as needed to main- (Haemachem, Inc., St. Louis, MO). The Hepcon¨ tain an ACT >480 s [ 79 ] . HMS Plus and Hemochron¨RxDX measure There are several commercially available ACT heparin concentrations by protamine titration test systems including the Hemochron¨ ACT using whole blood [93 ] . The HEPTEST¨ (International Technidyne Corp., Edison NJ), uti- requires citrated whole blood or plasma to lizing a celite activator, while the Hemochron measure anti-Xa activity and thus requires more Jr¨ (International Technidyne Crop., Edison NJ), time to complete [ 72, 93 ] . It also requires prepa- the HemoTec¨ (Medtronic, Englewood, CO), ration of a standard curve with known amounts the ACT Plus¨ (Medtronic, Englewood, CO), of heparin in order to calculate heparin concen- and the Automated Coagulation Timer (ACT) II tration in the patient’s sample [ 93 ] . (Medtronic, Englewood, CO) all use kaolin. The The thromboelastogram (TEG) is another Actalyke MAX-ACT, (Helena Laboratories Corp, point-of-care testing used in the perioperative Beaumont, TX) utilizes celite and kaolin. The period [72 ] . It calculates the speed and strength devices are manufactured by different companies of clot formation measuring the coagulation sys- that use different activators and are therefore not tem, platelet function, and fi brinolysis. The pat- interchangeable. terns of changes in strength and elasticity in the 9 Perioperative Management of Anticoagulation in the Patient… 117 clot provide information about clot formation. prolonged in the presence of aPL while celite The EACTS advises that it may be useful as a is less affected [ 42, 95] . They targeted an ACT guide to transfusion in the postoperative period, ³500 s, reaching an ACT of 601 s after several and studies have demonstrated a reduction in boluses of heparin [ 42 ] . blood product usage if used in conjunction with a Cartwright et al. used three different coagu- treatment algorithm [48 ] . lation monitors: two point-of-care analyzers Patients with APS who have anticardiolipin along with laboratory confi rmation using the antibodies (aCL) or anti-b 2-glycoprotein I antibod- heparin assay in a patient requiring aortic valve ies (ab 2GPI) do not require special monitoring of replacement [ 4 ] . Their point-of-care devices their anticoagulation during surgical or interven- included both celite and kaolin ACTs. Cartwright tional procedures. However, patients with the LA et al. felt that the gold standard was to measure may have prolongation of their baseline coagula- anti-factor Xa activity; however, they noted that tion assays because the LA interferes with in vitro its availability makes it dif fi cult to use during tests of coagulation relying on phospholipid sur- the operative period [4 ] Others have used factor faces to promote coagulation. These include the Xa levels to check the heparin effect but this activated clotting time (ACT), activated partial test is more time-consuming and less suitable thromboplastin time (aPTT), prothrombin time for a quick turnaround time required in surgical (PT), and international normalized ratio (INR). procedures [ 15, 27 ] . This presents unique challenges for the surgical or East et al. used a patient-specifi c in vitro hep- interventional team because their baseline studies arin-celite ACT titration curve [ 15 ] Heparin was may no longer be reliable. There have been a num- diluted with normal saline and added to whole ber of approaches suggested to help monitor the blood to obtain heparin concentrations of 1, 2.5, LA patient requiring surgery or intervention. These and 5.0 U/mL. Therapeutic anticoagulation include no change to the standard ACT accepted (based on their patient-speci fi c titration curve) time (usually 400Ð480 s for cardiac surgery and was considered at a whole blood heparin concen- 250Ð350 s for PCI), setting an ACT goal that is tration (WBHC) of >3.0 U/mL for cardiopulmo- twice the normal goal or creating a patient-specifi c nary bypass [ 15 ] . This level had been determined ACT titration curve [15, 23, 27, 41 ] . by Despotis who reported heparin concentrations Unfortunately, according to Weiss et al., of 2Ð3 U/mL minimize activation of coagulation there is no consensus about which tests to rely during cardiopulmonary bypass [ 94] . As a sec- on for intraoperative monitoring under these ondary confi rmation, East et al. performed an conditions [ 42] . They reviewed monitoring anti-Xa level concurrently during the CABG and strategies for seven APS patients undergoing considered it the “gold standard.” CABG patients (including their own), noting Sheikh et al. empirically targeted an ACT to each was monitored differently [ 15, 42, 72, 80, more than 999 s, while others including Erkan 83] . All adopted a target ACT that was greater et al. and Gorki et al. have advised targeting an than normal, apparently believing that more ACT twice the normal value [27, 80, 96 ] . anticoagulation was better than inadequate Other strategies reported have included the anticoagulation [ 15, 42, 72, 80, 83] . Two cases use of a high-dose thrombin time (HiTT, arbitrarily targeted an ACT of 600Ð999 s, one Hemochron, International Technidyne Corp., monitored heparin concentrations and another Edison, NJ), a modifi cation of the thrombin time performed a protamine titration assay, and two assay [23 ] . This test is more speci fi c to heparin’s used anti-Xa concentrations in conjunction effects than the ACT and is not in fl uenced by with a patient-specifi c ACT titration curve [ 15, hemodilution or hypothermia. Larger amounts 42, 72, 80, 83 ] . Weiss et al. used a celite-activated of thrombin are added to counteract the higher ACT instead of a kaolin ACT because of reports concentrations of heparin required for cardiac by Gall and others that the kaolin ACT is surgery [ 23, 97 ] . 118 J.R. Bartholomew

dosage is 2 million kallikrein inactivator units Monitoring Anticoagulation for ACS (KIU) given intravenously to both the patient and or PCI in the APS Patient the bypass pump prime followed by 500,000 KIU/h during the surgery [98, 101, 102 ] . There are no reported guidelines for monitoring the ACT in the patient with an LA requiring PCI. For non-LA patients, an ACT of 250Ð350 s is rec- Anti fi brinolytic Agents ommended [85, 86] . Case reports by Su et al. and for the APS Patient Timurkaynak et al. have mentioned attaining “adequate ACT levels” which were reported to be There are questions about the use anti fi brinolytic 292 and 332 s, respectively, in their patients agents in the APS patient for concerns there could [46, 91] . However, Timurkaynak’s patient had be an increase in thrombosis in this highly pro- aCL (and the ACT should not have been affected), thrombotic population. East et al. published the while Su et al. had an LA and speculated that fi rst account for perioperative use of an underdosing could occur because of the LA. Most antifi brinolytic agent in two patients with APS. other cases reported describing PCI in APS do They administered EACA as a 10-g bolus follow- not refer to ACT times [11, 44Ð 47, 87Ð 92 ] . ing heparin administration but before CABG fol- lowed by an infusion of 1 g per hour until arrival in the intensive care unit [15 ] . They could not Anti fi brinolytic Agents for fi nd any data to suggest an increased risk for Cardiopulmonary Surgery thrombosis, nor did they have complications. Others including Rand et al. have used EACA in Bleeding leading to transfusion is among the patients undergoing cardiac surgery without com- most common complication of cardiac surgery, plications [102 ] . resulting in an increased risk for infectious dis- In an effort to minimize complement activa- ease transmission, transfusion reactions, graft- tion and reduce trauma to the platelet, Brownstein versus-host disease, transfusion-induced lung et al. performed mitral valve replacement in a injury, and decreased resistance to postoperative patient with an LA using aprotinin prior to CABG infection [98 ] . Prophylactic administration of [ 81 ] . They had no thrombotic complications. anti fi brinolytic agents including the synthetic However, Massoudy et al., observing that aproti- lysine analogues (epsilon-aminocaproic acid nin had been suspected as a causative agent for [EACA]) (Amicar; Amgen, Inc., Thousand Oaks, sudden thrombotic events in other case series, CA) and tranexamic acid [TXA] (Cyklokaprin; reported serious problems. In their series of 5 Pharmacia Corporation, Peapack, New Jersey) patients, four died within 1 year of surgery from and the nonspeci fi c serine protease inhibitor thromboembolic complications, including three aprotinin (Trasylol¨, Bayer, Leverkusen, perioperative deaths [ 41 ] . All had received apro- Germany) has helped reduce bleeding complica- tinin, leading the authors to conclude that because tions and prevent blood loss through the preven- experience with inhibitors of fi brinolysis is sparse tion of primary fi brinolysis while preserving in APS, any potentially procoagulant activity platelet function by preventing platelet activation (such as the use of anti fi brinolytic agents) should [98, 99 ] . A loading dose of 100Ð150 mg/kg of be avoided [41 ] . EACA or 1.5Ð10 mg/kg of TXA is usually given Cartwright et al. also preferred TXA over followed by a constant infusion at one-tenth of aprotinin because of the report by Massoudy the loading dose per hour, although the optimal et al. They also expressed a concern whether dose is not universally agreed upon [98, 100 ] . anti fi brinolytic agents should be used in patients Aprotinin is the most potent antifi brinolytic agent with a tendency to thrombosis [4 ] . known. It is a protein serine protease inhibitor According to Henry et al., the risk of death is derived from bovine lung. The recommended higher with aprotinin compared to the lysine 9 Perioperative Management of Anticoagulation in the Patient… 119 analogues (TXA or EACA) and recommend using the amount used varies from half or less to none of TXA or EACA rather than aprotinin to prevent the normal calculated dose [4, 27, 41, 80, 83, 108 ] . bleeding after cardiac surgery [ 103 ] . Aprotinin is Cartwright et al.’s approach was to give half the no longer available in the United States except calculated dose and administer further doses titrated under an investigational new drug (IND) process to the combination of surgical impression, ACT, for patients who are at increased risk of bleeding and thromboelastogram readings [4 ] . and transfusion during CABG surgery with no Gorki and others advocated less protamine, acceptable therapeutic alternative [103 ] . by giving half of the calculated dose or no Weiss et al. felt that the potential risk of post- protamine at all [ 27, 41, 80, 81, 83, 108] . Sheikh operative thrombosis needs to be balanced against et al. suggested that protamine given to antagonize the benefi t of decreased bleeding and transfusion heparin should be administered in a stepwise requirements and their use should be limited until manner in a low dose by continuous infusion more data is available [42 ] . (e.g., 50 mg/h) until the bleeding tendency slows down to an acceptable amount [ 80] . Weiss et al. reversed heparin using a protamine dose calcu- Reversal with Protamine lated by the protamine response time using the Hemochron system, while Massoudy et al. Protamine is a positively charged polypeptide advised a modi fi ed protamine strategy using half prepared from salmon milt that is administered the calculated dose or no protamine at all after after CABG to neutralize the anticoagulant affect observing three perioperative deaths in their fi ve of heparin and establish normal hemostasis patient series [ 41, 42 ] . [104, 105] . The recommended dose of protamine The optimal dose of protamine for OPCAB is required to neutralize heparin in CABG is contro- also not well known, according to Mariani et al. versial. A recent European survey among 750 and Jervis et al. [23, 109 ] . They recommend not European cardiothoracic surgeons reported 91% reversing the heparin effect in patients undergoing used protamine at the end of surgery but the proto- OPCAB unless there is uncontrollable bleeding col for reversal varied between institutions. Full because of the increased procoagulation activity in reversal, considered at 1 mg of protamine to 1 mg the APS patient. [ 23, 109] Jervis et al. also reported of heparin, was performed by 52% of respondents, that a number of different reversal strategies have while 30% advocated a half dose and the others been used but felt that maintaining some level of suggested using two-thirds of the calculated dose anticoagulation seemed sensible [ 23 ] . They also [ 106] . According to Arens and Andersen, a pointed out that there is no data to support any par- protamine dose that is too low increases the risk of ticular protocol and that full reversal must always bleeding, while in excess may increase side effects be placed in balance with bleeding and its related including postoperative bleeding due to the antico- complications. Of note, however, Jervis et al. used agulant effect of protamine at higher concentra- a protamine reversal dose based on Hepcon testing tions [ 104, 107 ] . Many physicians, however, use in their patient, while Maddali MA et al. used a 1:1 protocols that give amounts in slight excess of the ratio after completion of the coronary anastomosis standard dose cited above using 1.3 mg of in their OPCAB patient [23, 65 ] . protamine sulfate to 1 mg of heparin [79 ] . This dose can be calculated using protamine titration. The ideal dose of protamine used to reverse Recommendations for Postoperative heparin in patients with the LA following on-pump Anticoagulation and Antiplatelet cardiac surgery is not well known, and doses ranging Agents from 160 to 750 mg of protamine have been reported in the literature [ 23, 84 ] . According to For the non-APS patient, resuming therapeutic Cartwright et al., most reports suggest that less than doses of UFH or LMWH approximately 24 h after the normal calculated dose should be given but that invasive procedures such as cardiac catheterization 120 J.R. Bartholomew is advised by Douketis et al., assuming there is adequate hemostasis [ 58 ] . Delaying resumption Recommendations for Postprocedural of therapeutic doses of LMWH or UFH for up to Antiplatelet Agents 48Ð72 h after CABG or other high-bleeding-risk cardiac surgical procedures is advised by Dunn In general, aspirin should be continued for at least and Turpie, assuming adequate hemostasis is 1 month following PCI after bare-metal stent place- obtained [ 110, 111] . Administering lower doses ment, 3 months after a sirolimus-eluting stent, and of LMWH or UFH after surgery or completely longer (6 months) for paclitaxel-eluting stents [ 86 ] . avoiding these anticoagulants altogether may be Similarly, clopidogrel 75 mg daily should be given necessary if the bleeding risk and postoperative for at least 1 month after bare-metal stent implan- hemostasis remains a concern and must be deter- tation, 3 months for sirolimus-eluting stent, and mined on a case-by-case basis dependent on the 6 months after paclitaxel stent implantation [ 86 ] . risk of thrombosis versus bleeding. For the According to Grzybczak et al., the management patient receiving a VKA, resuming therapy the of patients with APS and ACS should include pro- evening of surgery is reasonable because full longed high-dose antiplatelet therapy (aspirin anticoagulation will take several days [ 58] . In 150 mg or higher) and possibly clopidogrel two different studies totaling almost 900 patients, (150 mg) as well [ 11 ] . Others have recommended the mean duration to achieve a therapeutic INR ticlopidine 500 mg daily plus aspirin 325 mg/day was 4.6Ð5.1 days after surgery [ 57, 112 ] . or combinations of aspirin and clopidogrel plus or For the postoperative APS individual, resump- minus the addition of a VKA [46, 47, 88, 89, 91 ] . tion of anticoagulation as soon as feasible (whether prophylactic or full dose) is imperative once adequate hemostasis is attained. This can be Complications and Outcomes complicated because this group of patients are of Surgical APS Patients also are at risk for bleeding if they have thrombo- cytopenia and/or hypoprothrombinemia. There are a number of cases series and reports Cartwright et al. recommended postoperative that have demonstrated the increased morbidity anticoagulation should be implemented as soon as and mortality in the APS patient population. possible to prevent thrombosis [ 4 ] . Massoudy Hedge et al. retrospectively reviewed their et al. resumed anticoagulation with low-dose hep- 20-year experience involving nine APS patients arin 2 h after their patients arrived in the ICU, undergoing cardiothoracic surgery (six of the nine while Weiss et al. and Berkun and colleagues had CABG), and although they had no mortali- resumed full-dose anticoagulation with heparin ties, 89% developed major complications [24 ] . In and warfarin on postoperative day 1 following spite of aggressive anticoagulation, 37.5% devel- mitral valve repair and discontinued heparin on oped thromboembolic events between days 7 and postoperative day 3 after the INR reached their 60 following surgery including ischemic stroke in targets of between 2.5 and 3.5 or 4.0 [39, 41, 42 ] . multiple vascular territories, MI from complete If aspirin was stopped prior to surgery, it occlusion, and thrombosis of the SVG graft to should be given in doses between 150 and 325 mg the left anterior descending artery and vena within 24 h after CABG and optimally within 6 h cava thrombosis [ 24 ] . Additional complications once hemostasis is adequate, although Massoudy included sepsis, a redo CABG at day 19 postop- et al. gave two of their four patients intravenous eratively with stenosis of three of four vascular acetylsalicylic acid within 4 h after admission grafts, and the development of HIT in two patients. to the ICU in an effort to prevent thrombosis The authors concluded that APS patients undergo- [ 41, 48, 58 ] . Similarly, in patients who have had ing cardiothoracic surgery are high-risk surgical temporary interruption of clopidogrel, it is candidates owing to their hypercoagulable state advised to resume approximately 24 h later (or and have high rates of postoperative clinical the next morning) after surgery. events. Hegde et al. recommend aggressive 9 Perioperative Management of Anticoagulation in the Patient… 121 anticoagulation and close monitoring to help with APS [ 8 ] . In nine cases spanning the years reduce the high risk of thromboembolism and the 1998Ð2007, there were no intraoperative deaths; major cause of perioperative morbidity and mor- however, two died in the early postoperative period, tality in this population [24 ] . one due to a massive ischemic stroke and the other Berkun et al. reported their experience involv- due to a subdural hematoma while on VKA treat- ing 10 patients with APS who underwent mitral, ment. Another patient had recurrent episodes of aortic, or combined aortic and mitral valve replace- peripheral thromboembolism and the other had ment [39 ] . Two of the 10 (20%) patients died recurrent episodes of metrorrhagia requiring gyne- within 2 weeks of surgery including one intraop- cological surgery. The authors felt that the high erative death due to intractable right heart failure mortality was a result of several factors including and one a result of staphylococcal sepsis, dissemi- comorbidities due to poor NYHA class, renal nated intravascular coagulation (DIC), and cardiac insuf fi ciency, anemia, history of thromboembo- tamponade. Two others developed major compli- lism, steroid treatment, and advanced nature of cations including acute respiratory distress syn- their heart valve disease at the time of surgery [8 ] . drome (ARDS), splenic infarction, and stroke. Gorki et al. carried out a meta-analysis of They concluded that valve replacement in patients valve operation on 57 APS patients, noting high with APS carries signi fi cant early and late mortal- morbidity and mortality rates [ 27 ] . The mortality ity and morbidity. Berkun et al. also suggested that rates were 7% for early deaths and 12% for late early institution of antiplatelet and anticoagulation deaths after a mean follow-up period of less than therapy should be strongly considered [39 ] . 3 years. Only 43% of the completely reported A 1-year mortality rate of 80% (four of fi ve patients (9 out of 21) had an uneventful short- APS patients) was reported by Massoudy et al. [ 41 ] . and long-term recovery. Three patients died due Three of their deaths occurred perioperatively to valve thromboses, one aortic valve homograft including one 10 h after surgery due to myocardial required reoperation after 15 months, and another failure likely related to clotting of the extracorpo- had recurrent thromboses treated with thrombol- real circuit during surgery. A second patient died ysis while two bioprosthetic valves had to be of refractory myocardial failure 15 h after surgery replaced less than 10 years after surgery. Other despite placement of an intra-aortic balloon pump complications included myocardial (MI, CHF), (IABP). Emergency coronary angiography docu- cerebral (TIA/stroke and seizures), and periph- mented occlusion of 3 of the 4 anastomoses. The eral thromboembolism [27 ] . third death occurred 6 days after surgery due to recurrent arterial thromboembolic events to the upper and lower extremities while the fourth Complications and Outcomes death occurred 8 months following surgery due of Interventional Procedures to intestinal thromboembolism [41 ] . in APS Patients Ciocca et al. did a retrospective analysis of 71 aPL-positive cardiovascular patients identi fi ed There are few case reports describing the morbidity between the years 1989 and 1994 [40 ] . Nineteen and mortality of APS patient undergoing coronary had cardiovascular surgery including lower angiography, PCI, and stenting [ 45, 46, 78 ] . Su extremity revascularizations, eight cardiac valve et al. described one patient with APS who devel- replacements, and fi ve CABG. Sixteen of the oped acute in-stent thrombosis within 30 min after nineteen (84%) had major postoperative compli- deployment, requiring repeat PTCA and the addi- cations including coronary graft thrombosis, MI, tion of a GPIIb/IIIa inhibitor [46 ] . They also stroke, PE, and major bleeding events, and 12 of reviewed six other cases of APS patients treated the 19 eventually died of complications related to with PTCA: three PTCA alone and three with stent- their surgical intervention [40 ] . ing. Two of six PTCA patients had complications Colli et al. observed high morbidity (50%) and including one death and one with recurrent early mortality (22%) in their valve replacement patients PTCA failures leading to CABG. One of the three 122 J.R. Bartholomew patients who underwent PTCA with stenting had restenosis and required CABG [46 ] . Conclusion Weissman and Coplan described a woman with recurrent coronary stent thrombosis who was The APS patient undergoing cardiac surgery or found to have aPL [78 ] . She initially received four intervention is at high risk for thrombosis and paclitaxel drug-eluting stents to her right coronary bleeding complications. These events can develop artery and discharged home but returned within 2 during the surgical or interventional procedure but months for restenoses leading to more stent place- also preoperatively when weaning off anticoagula- ment. Despite placement of additional drug-elut- tion and/or antiplatelet agents and postoperatively ing stents, she once again presented with stenosis until full-dose anticoagulation and/or antiplatelet and subsequently underwent CABG [78 ] . agents are resumed. Thrombosis leading to Chambers et al. reported failure of PTCA on signifi cant morbidity and mortality may result three attempts in a case report involving a from the manipulation that occurs during venous 56-year-old woman with inferior wall MI [ 45 ] . or arterial line placement, balloon expansion, and/ Their patient’s LA was not recognized during or stenting during PCI and the surgical procedure two previous admissions, and the authors felt itself. In addition, a surgical or interventional pro- that her PTCA failure was likely due to her APS, cedure can trigger the catastrophic APS leading to balloon catheter infl ations, and manipulation of potentially devastating complications as well. guide wires [ 45] . Their patient underwent Further complicating these procedures is the APS successful CABG. individual with an LA who has prolongation of Despite the failures reported above, Takeuchi their clotting studies, making dosing and monitor- et al. and Badak et al. report that they were the fi rst ing of their anticoagulation challenging. There are to perform successful PTCA for APS patients with currently no guidelines for monitoring or dosing acute MI [87, 90 ] . Takeuchi et al. were the fi rst to anticoagulation in this group of patients who succeed in using PTCA for a patient with acute require surgery or intervention, and most articles MI, while Badak et al. performed primary stenting in the literature are small series or case reports. of the right coronary artery during reinfarction in Heparin dosing varies in these reports as do rec- an individual initially treated with streptokinase ommendations for monitoring which include dou- [45, 78, 90] . Jankowski et al. also reported suc- bling the ACT time, using a factor Xa inhibition cessful PTCA and coronary stenting in a young assay, obtaining heparin concentrations by patient with acute MI, commenting that APS protamine titration, and using a patient-speci fi c appears to be a risk factor for abrupt closure and target ACT levels or a high-dose thrombin time. early restenosis after balloon angioplasty [88 ] . In addition, this group is at risk for bleeding, There are additional case reports describing especially if they have hypoprothrombinemia, successful coronary stent implantation in patients thrombocytopenia, and during surgery or intervention with APS. [87, 88, 92] Umesan et al. described an if overdosing of anticoagulation is used. unusual case of recurrent ischemic events in two It is advised that each institution establish different coronary territories managed success- their own protocol using a multidisciplinary fully with intracoronary stenting while Musuraca approach including the expertise of the internist, and colleagues reported successful treatment of a rheumatologist, hematologist, anesthesiologist, patient with an acute MI by primary angioplasty cardiac surgeon, and cardiologist and vascular and stenting [89, 92 ] . specialist to manage these individuals to prevent Timurkaynak et al. reported successful pri- catastrophic complications. mary angioplasty and stenting in an APS patient Several general rules (Table 9.3 ) to follow with severe thrombocytopenia (platelet count of include the following: Avoid surgery or interven- 14,000 mm3) and cardiogenic shock. The authors tion if at all possible, but if necessary, keep noted that platelet counts of >50,000 are gener- periods without anticoagulation to a minimum ally considered safe for PCI [91 ] . with the use of preoperative bridging and early 9 Perioperative Management of Anticoagulation in the Patient… 123

Table 9.3 Perioperative management of anticoagulation in the patient with the antiphospholipid syndrome in cardiac surgery and cardiac interventions History and physical examination If there is a previous history of venous or arterial thrombosis or miscarriages or a previous history of thrombosis or bleeding with prior surgical or interventional procedures (delay surgery or intervention if not emergent pending further investigations) Laboratory testing If there is a prolonged PT/INR or aPTT or unexplained thrombocytopenia (delay surgery or intervention and investigate further to determine if the patient has a LA) Preoperative bridging therapy for patients with a history of thrombosis and APS Minimize time off of anticoagulation (or antiplatelet agent if applicable) prior to surgery or intervention using the LMWH or anti-Xa preparations, or if hospitalized bridge with heparin Surgery or intervention Minimize (additional) invasive procedures when possible Develop a plan for dosing and monitoring heparin (or if using an alternative agent) if the patient has an LA (be aware that under- or overanticoagulation can easily result if an LA is not recognized or appropriately monitored) Postoperative anticoagulation/antiplatelet therapy Resume anticoagulation and antiplatelet agents as soon as hemostasis is adequate Use intermittent pneumatic compression devices and/or graduated compression stockings as additional prophylaxis agents If multiorgan system complications develop, consider catastrophic APS and treat aggressively Modi fi ed from Ref. [18 ] resumption of anticoagulation following their 8. Colli A, Mestres CA, Espinosa G, et al. Heart valve procedure while minimizing invasive procedures surgery in patients with the antiphospholipid syn- drome; analysis of a series of nine cases. Eur J such as intravascular manipulation for access and Cardiothorac Surg. 2010;37:154Ð8. monitoring. Lastly, be vigilant for any unexpected 9. Cervera R, Khamsata MA, Font J, et al. High preva- complications during or after surgery or interven- lence of signifi cant heart valve lesions in patients with the primary antiphospholipid syndrome. Lupus. tion which may suggest the catastrophic APS. 1991;1:43Ð7. 10. Christodoulou C, Sangle S, D’Cruz DP. Vasculopathy and arterial stenotic lesions in the antiphospholipid syndrome. Rheumatology. 2007;46:907Ð10. References 11. Grzybczak R, Undas A, Rostoff P, et al. Life-threatening cardiac manifestations of primary antiphospholipid 1. Galli M. The antiphospholipid triangle. J Thromb syndrome. Heart Vessels. 2010;25:267Ð9. Haemost. 2009;8:234Ð6. 12. Roldan C. A valvular and coronary heart disease in sys- 2. Park KW. The antiphospholipid syndrome. Int temic in fl ammatory diseases. Heart. 2008;94:1089Ð101. Anesthesiol Clin. 2004;42:45Ð57. 13. Silbiger JJ. The cardiac manifestations of antiphos- 3. Miyakis S, Lockshin MD, Atsumi T, et al. International pholipid syndrome and their echocardiographic consensus statement on an update of the classi fi cation recognition. J Am Soc Echocardiogr. 2009;22:1100Ð8. criteria for de fi nite antiphospholipid syndrome. 14. George D, Erkan D. Antiphospholipid syndrome. J Thromb Haemost. 2006;4:295Ð306. Prog Cardiovasc Dis. 2009;52:115Ð25. 4. Cartwright BL, Bean M, Cooper JO. Lupus anticoag- 15. East CJ, Clements F, Matthew J, Slaughter T. ulant, antiphospholipid syndrome and cardiac surgery. Antiphospholipid syndrome and cardiac surgery: Anaesth Intensive Care. 2010;38:364Ð9. management of anticoagulation in two patients. 5. Gurlek A, Pamir G, Ozdol C, et al. Association Anesth Analg. 2000;90:1098Ð101. between anticardiolipin antibodies and recurrent car- 16. Hamsten A, Norberg R, Bjorkholm M, et al. Antibodies diac events in patients with acute coronary syndrome. to cardiolipin in young survivors of myocardial infarc- Int Heart J. 2005;46:631Ð8. tion: an association with recurrent cardiovascular 6. Turiel M, Sarzi-Puttini P, Peretti R, et al. Five-year events. Lancet. 1986;1(8473):113Ð5. follow up by transesophageal echocardiographic stud- 17. Cervera R, Piette JC, Font J, et al. Antiphospholipid ies in primary antiphospholipid syndrome. Am J syndrome. Arthritis Rheum. 2002;46:1019Ð27. Cardiol. 2005;96:574Ð9. 18. Tenedios F, Erkan D, Lockshin MD. Cardiac manifes- 7. Levine JS, Branch DW, Rauch J. The antiphospho- tations in the antiphospholipid syndrome. Rheum Dis lipid syndrome. N Engl J Med. 2002;346:752Ð63. Clin North Am. 2006;32:491Ð507. 124 J.R. Bartholomew

19. Long BR, Leya F. The role of antiphospholipid syn- 34. Farsi A, Domeneghetti MP, Fedi S, et al. High prevalence drome in cardiovascular disease. Hematol Oncol Clin of anti-§2 glycoprotein I antibodies in patients with North Am. 2008;22:79Ð94. ischemic heart disease. Autoimmunity. 1999;30:93Ð8. 20. Shi W, Krillis SA, Chong BH, et al. Prevalence of 35. Brey RL, Abbott RD, Curb JD, et al. Beta-2-glycoprotein lupus anticoagulant and anticardiolipin antibodies in a 1-dependent anticardiolipin antibodies and risk of healthy population. Aust N Z J Med. 1990;20:231Ð6. ischemic stroke and myocardial infarction: the Honolulu 21. Vila P, Hernandez MC, Lopez-Fernandez MF. heart program. Stroke. 2001;32:1701Ð6. Prevalence, follow up and clinical signi fi cance of the 36. Bick RL, Arun B, Frenkel EP. Antiphospholipid anticardiolipin antibodies in normal subjects. Thromb thrombosis syndromes. Haemostasis. 1999;29:100Ð10. Haemost. 1994;72:209Ð13. 37. Erdogan D, Goren MT, Diz-Kuckkaya R, et al. Assessment 22. Lim W, Crowther MA, Eikelboom JW. Management of cardiac structure and left atrial appendage functions in of antiphospholipid antibody syndrome. JAMA. primary antiphospholipid syndrome: a transesophageal 2006;295:1050Ð7. echocardiographic study. Stroke. 2005;36:592Ð6. 23. Jervis K, Senthilnathan V, Lerner AB. Management of 38. Turiel M, Muzzupappa S, Gottardi B. Evaluation of a patient with lupus anticoagulant and antiphospho- cardiac abnormalities and embolic sources in primary lipid syndrome for off-pump coronary artery bypass antiphospholipid syndrome by transesophageal grafting using the Hepcon¨ system. Anesth Analg. echocardiography. Lupus. 2000;9:406Ð12. 2009;108:1116Ð9. 39. Berkun Y, Elami A, Meir K, et al. Increased morbidity 24. Hegde VAP, Vivas Y, Shah H, Haybron D, Srinivasan and mortality in patients with antiphospholipid V, Dua A, Gradman A. Cardiovascular surgical out- syndrome undergoing valve replacement surgery. comes in patients with the antiphospholipid syndrome J Thorac Cardiovasc Surg. 2004;127:414Ð20. Ð a case series. Heart Lung Circ. 2007;16:423Ð7. 40. Ciocca RG, Choi J, Graham AM. Antiphospholipid 25. Long AA, Ginsberg JS, Brill-Edwards P, et al. The antibodies lead to increased risk in cardiovascular sur- relationship of antiphospholipid antibodies to gery. Am J Surg. 1995;170:198Ð200. thromboembolic disease in systemic lupus erythema- 41. Massoudy P, Cetin SM, Thielmann M, et al. tosus: a cross-sectional study. Thromb Haemost. Antiphospholipid syndrome in cardiac surgery Ð an under- 1991;66:520Ð4. estimated coagulation disorder. Eur J Cardiothorac 26. Bruce IN, Clark-Soloninka CA, Spitzer KA, et al. Surg. 2005;28:133Ð7. Prevalence of antibodies in beta2-glycoprotein I in 42. Weiss S, Nyzio JB, Cines D, Detre J, Milas BL, Narula systemic lupus erythematosus and their association N, Floyd TF. Antiphospholipid syndrome: intraopera- with antiphospholipid antibody syndrome criteria: a tive and postoperative anticoagulation in cardiac single center study and literature review. J Rheumatol. surgery. J Cardiothorac Vasc Anesth. 2008;22:735Ð9. 2000;27:2833Ð7. 43. Morton KE, Gavaghan TP, Krilis SA, et al. Coronary 27. Gorki H, Malinovski V, Stanbridge RDL. The artery bypass graft failure Ð an autoimmune phenom- antiphospholipid syndrome and heart valve surgery. enon? Lancet. 1986;2:1353Ð7. Eur J Cardiothorac Surg. 2008;33:168Ð81. 44. Ludia C, Domenico P, Monia C, et al. Antiphospholipid 28. Hojnik M, George J, Ziporen L, et al. Heart valve antibodies: a new risk factor for restenosis after involvement (Libman-Sacks endocarditis in the percutaneous transluminal coronary angioplasty. antiphospholipid syndrome). Circulation. 1996;93: Autoimmunity. 1998;27:141Ð8. 1579Ð87. 45. Chambers JD, Haire WD, Deligonul U. Multiple early 29. Nesher G, Ilany J, Rosenmann D, et al. Valvular dys- percutaneous transluminal coronary angioplasty fail- function in antiphospholipid syndrome: prevalence, ures related to lupus anticoagulant. Am Heart J. clinical features and treatment. Semin Arthritis 1996;132:189Ð90. Rheum. 1997;27:27Ð35. 46. Su HM, Lee KT, Chu CH, et al. Acute thrombosis 30. Galve E, Ordi J, Barquinero J, et al. Valvular heart after elective direct intracoronary stenting in primary disease in primary antiphospholipid syndrome. Ann antiphospholipid syndrome: a case report. Kaohsiung Intern Med. 1992;16:293Ð8. J Med Sci. 2003;19:177Ð82. 31. Roman MJ, Salmon JE, Sobel R, et al. Prevalence and 47. Weissman A, Coplan NL. Antiphospholipid antibody relation to risk factors of carotid atherosclerosis and syndrome and acute stent thrombosis. Rev Cardiovasc left ventricular hypertrophy in systemic lupus erythe- Med. 2006;7:244Ð6. matosus and antiphospholipid syndrome. Am J 48. Dunning J, Versteegh M, Fabbri A, et al. Guideline on Cardiol. 2001;87:663Ð6. antiplatelet and anticoagulation management in cardiac 32. Zuckerman E, Toubi E, Shiran A, et al. Anticardiolipin surgery. Eur J Cardiothorac Surg. 2008;34:73Ð92. antibodies and acute myocardial infarction in non- 49. van Ryn J, Stangier J, Haertter S, et al. Dabigatran systemic lupus erythematosus patients: a controlled etexilate- a novel, reversible, oral direct thrombin prospective study. Am J Med. 1996;101:381Ð6. inhibitor: interpretation of coagulation assays and 33. Vaarala O, Manttari M, Manninen V, et al. reversal of anticoagulant activity. Thromb Haemost. Anticardiolipin antibodies and risk of myocardial 2010;103:1116Ð27. infarction in a prospective cohort of middle-aged 50. Boehringer Ingelheim. Pradaxa (dabigatran etexilate men. Circulation. 1995;91:23Ð7. package insert). Ridge fi eld. 2010. 9 Perioperative Management of Anticoagulation in the Patient… 125

51. Bybee KA, Powell BD, Valeti U, et al. Preoperative 66. Casati V, Gerli C, Franco A, et al. Activation of coag- aspirin therapy is associated with improved postoper- ulation and fi brinolysis during coronary surgery: on ative outcomes in patients undergoing coronary artery pump versus off-pump techniques. Anesthesiology. bypass grafting. Circulation. 2005;112:1286Ð92. 2001;95:1103Ð9. 52. Mangano DT. Multicenter study of perioperative isch- 67. Tanaka KA, Thourani VH, Williams WH, et al. emia research: aspirin and mortality from coronary Heparin anticoagulation in patients undergoing off- bypass surgery. N Engl J Med. 2002;347:1309Ð17. pump and on-pump coronary bypass surgery. J Anesth. 53. Topol E. Aspirin with bypass surgery: from taboo to new 2007;21:297Ð303. standard of care. N Engl J Med. 2002;347:1359Ð60. 68. Gillinov AM, Cosgrove DM. Current status of mitral 54. Alexander JH, Berger PB, Ha fl ey G et al. Impact of valve repair. Am Heart Hosp J. 2003;1:47Ð54. early clopidogrel use on angiographic and clinical 69. Bonow RO, Carabello BA, Chatterjee K, et al. Focused outcomes following coronary artery bypass surgery; update incorporated into the ACC/AHA 2006 guide- fi ndings from PREVENT IV. J Am Coll Cardiol. lines for the management of patients with valvular 2006;47(suppl A) (4):178A. heart disease. A report of the American College 55. Mehta RH, Roe MT, Mulgund J, et al. Acute clopi- of Cardiology/American Heart Association Task Force dogrel use and outcomes in patients with non-ST-seg- on practice guidelines (writing committee to revise ment elevation acute coronary syndromes undergoing the 1998 guidelines for the management of patients coronary artery bypass surgery. J Am Coll Cardiol. with valvular heart disease). Circulation. 2008;118: 2006;48:281Ð6. e523Ð660. 56. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopi- 70. Bouma W, Klinkenberg TJ, van der Horst ICC, et al. dogrel in addition to aspirin in patients with acute Mitral valve surgery for mitral regurgitation caused coronary syndromes without ST-segment elevation. N by Libman-Sacks endocarditis: a report of four cases Engl J Med. 2001;345:494Ð502. and a systematic review of the literature. J Cardiothorac 57. Douketis JD, Johnson JA, Turpie AG. Low-molecular- Surg. 2010;5:1Ð13. weight-heparin as bridging anticoagulation during 71. Yun KI, Miller DC. Mitral valve repair versus replace- interruption of warfarin; assessment of a standardized ment. Cardiol Clin. 1991;9:315Ð27. periprocedural anticoagulation regimen. Arch Intern 72. Horrow JC, Mueksch JN. Coagulation testing. In: Med. 2004;164:1319Ð26. Gravlee G, Davis RF, Stammers AH, et al., editors. 58. Douketis JD, Berger PB, Dunn AS, et al. The peri- Cardiopulmonary bypass: principles and practice. operative management of antithrombotic therapy. The Philadelphia: Lippincott; 471. p. 459Ð71. eighth ACCP conference on antithrombotic and throm- 73. Myers GJ, Hirsch GM. Double valve replacement in a bolytic therapy. Chest. 2008;133(suppl):299SÐ339. patient with anticardiolipin syndrome. Perfusion. 59. Landenhed M, Johansson M, Eringe D, et al. 1999;14:397Ð401. Fondaparinux or enoxaparin: a comparative study of 74. Kato Y, Isobe F, Sasaki Y, et al. Secondary mitral postoperative bleeding in coronary artery bypass graft- valve replacement in antiphospholipid syndrome and ing surgery. Scand Cardiovasc J. 2010;44(2):100Ð6. chronic renal failure. Jpn J Thorac Cardiovasc Surg. 60. Selke FW, DiMaio JM, Caplan LR, et al. Comparing 2001;49:728Ð31. on-pump and off-pump coronary artery bypass graft- 75. Fitzgerald DJ, Patel A, Body SC, et al. The relationship ing: numerous studies but few conclusions: a scientifi c between heparin level and activated clotting time in the statement from the American Heart Association adult cardiac surgery. Perfusion. 2009;24:93Ð6. Council on cardiovascular surgery and anesthesia in 76. Shuhaibar MN, Hargrove M, Millat MH, et al. How collaboration with the interdisciplinary working group much heparin do we really need to go on pump? A on quality of care and outcomes research. Circulation. rethink of current practices. Eur J Cardiothorac Surg. 2005;111:2858Ð64. 2004;26:947Ð50. 61. Hirose H, Amano A, Takahashi A. Off-pump coro- 77. Tanaka K, Takao M, Yada I, et al. Alteration in coagu- nary artery bypass grafting for elderly patients. Ann lation and fi brinolysis associated with cardiopulmo- Thorac Surg. 2001;72:2013Ð9. nary bypass during open heart surgery. J Cardiothorac 62. Hoff SJ, Ball SK, Coltharp WH, et al. Coronary artery Anesth. 1989;3:181Ð8. bypass in patients 80 years and over; is off-pump the 78. Weisinger AS, Levy JH. Current hematologic issues operation of choice? Ann Thorac Surg. 2002; in cardiac surgery and cardiopulmonary bypass. Sem 74:S1340Ð3. Cardiothorac Vasc Anesth. 1998;2:259Ð71. 63. Sabik JF, Blackstone EH, Lytle BW, et al. Equivalent 79. Olson Jd, Arkin CF, Brandt JT, et al. College of midterm outcomes after off-pump and on-pump coronary American Pathologists conference XXXI on labora- surgery. J Thorac Cardiovasc Surg. 2004;127:142Ð8. tory monitoring of anticoagulant therapy. Arch Pathol 64. Horimoto S, Horimoto H, Sawada Y, et al. Off-pump Lab Med. 1998;122:782Ð98. coronary artery bypass in a patient with the antiphoso- 80. Sheikh F, Lechiowicz A, Setlur R, Rauch A, Dunn pholipid syndrome. J Cardiovasc Surg. 2005;46:81Ð3. H. Recognition and management of patients with 65. Maddali MM, Albahrani MJ. Lupus anticoagulant and antiphospholipid antibody syndrome undergoing off-pump coronary bypass; dilemma of anticoagulation. cardiac surgery. J Cardiothorac Vasc Anesth. Asian Cardiovasc Thorac Ann. 2007;15:246Ð8. 1997;11:764Ð6. 126 J.R. Bartholomew

81. Brownstein L, Bartholomew TP, Silver DG, Berry monitoring on blood conservation. A prospective, CM. A case report of mitral valve replacement in a randomized evaluation in patients undergoing patient with lupus antibody syndrome. Perfusion. cardiac operation. J Thorac Cardiovasc Surg. 1995; 2003;18:373Ð6. 110:46Ð54. 82. Lango R, Pawlaczyk R, Raszeja-Specht A, Smolenski 95. Galli M, Ruggeri L, Barbui T. Differential effects of RT, Rogowski J, Rutkowski B, Szutowicz A. Aortic anti-beta2-glycoprotein I and antiprothrombin anti- valve replacement and perioperative management bodies on the anticoagulant activity of activated pro- in hemodialyzed patient with antiphospholipid tein C. Blood. 1998;91:1999Ð2004. syndrome. Int J Artif Organs. 2004;27:69Ð73. 96. Erkan D, Leibowitz E, Berman J, et al. Perioperative 83. Ducart AR, Collard EL, Osselaer JC, et al. Management medical management of antiphospholipid syndrome; of anticoagulation during cardiopulmonary bypass hospital for special surgery experience, review of lit- in a patient with a circulating lupus anticoagulant. erature, and recommendations. J Rheumatol. J Cardiothorac Vasc Anesth. 1997;11:878Ð9. 2002;29: 843Ð9. 84. Lennon MJ, Thackray NM, Gibbs NM. Anti-factor 97. Perry DJ, Fitzmaurice DA, Kitchen S, et al. Point of Xa monitoring of anticoagulation during cardiopul- care testing in haemostasis. Br J Haematol. monary bypass in a patient with antiphospholipid 2010;150:501Ð14. syndrome. Anaesth Intensive Care. 2003;31:95Ð8. 98. Green JA, Spiess BD. Current status of 85. Goodman SG, Menon V, Cannon CP, et al. Acute anti fi brinolytics in cardiopulmonary bypass and ST-segment elevation myocardial infarction. elective deep hypothermic circulatory arrest. American College of Chest Physicians evidence- Anesthesiol Clin North Am. 2003;21:527Ð51. based clinical practice guidelines (8th ed). Chest. 99. Munoz JJ, Birkmeyer NJO, Birkmeyer JD, et al. Is 2008;133: 708SÐ75S (epsilon)-aminocaproic acid as effective as aprotinin 86. Smith SC, Feldman TE, Hirshfeld JW, et al. ACC/ in reducing bleeding with cardiac surgery? A meta- AHA/SCAI 2005 guideline update for percutaneous analysis. Circulation. 1999;99:81Ð9. coronary intervention. A report of the American 100. Verstraete M. Clinical application of inhibitors of College of Cardiology/American Heart Association fi brinolysis. Drugs. 1985;29:236Ð61. Task Force on practice guidelines (ACC/AHA/SCAI 101. Royston D. The serine antiprotease aprotinin writing committee to update the 2001 guidelines for (Trasylol): a novel approach to reducing post-opera- percutaneous coronary intervention). Circulation. tive bleeding. Blood Coagul Fibrin. 1990;1:55Ð69. 2006;113:e166Ð286. 102. Rand JH, Wu XX, Andree HA, et al. Antiphospholipid 87. Badak O, Guneri S, Kirimli O, et al. Primary stent- antibodies accelerate plasma coagulation by inhibit- ing in a patient with acute myocardial infarction and ing annexin-V binding to phospholipids: a “lupus pro- primary antiphospholipid syndrome. J Invasive coagulant” phenomenon. Blood. 1998;92:1652–60. Cardiol. 2002;14:194Ð7. 103. Henry D, Carless P, Fergusson D, et al. The safety of 88. Jankowski M, Dudek D, Dubiel JS, et al. Successful aprotinin and lysine-derive antifi brinolytic drugs in coronary stent implantation in a patient with primary cardiac surgery: a meta analysis. CMAJ. antiphospholipid syndrome. Blood Coagul 2009;180:183Ð93. Fibrinolysis. 1998;9:753Ð6. 104. Aren C. Heparin and protamine during cardiac sur- 89. Musuraca G, Imperadore F, Terraneo C, et al. gery. Perfusion. 1989;4:171Ð81. Successful treatment of post-exertion acute myocardial 105. Teoh KKT, Young E, Blackall ME, et al. Can extra infarction by primary angioplasty and stenting in a protamine eliminate heparin rebound following car- patient with antiphospholipid antibody syndrome. diopulmonary bypass surgery? J Thorac Cardiovasc Blood Coagul Fibrinolysis. 2004;15:95Ð8. Surg. 2004;12:211Ð9. 90. Takeuchi S, Obayashi T, Toyama J. Primary antiphos- 106. Englberger L, Streich M, Tevaeari H, et al. Different pholipid syndrome with acute myocardial infarction anticoagulation strategies in off-pump coronary recanalised by PTCA. Heart. 1998;79:96Ð8. artery bypass operations: a European survey. Interact 91. Timurkaynak T, Cemri M, Ozdemir M, et al. Primary Cardiovasc Thorac Surg. 2008;7:378Ð82. angioplasty and stenting in a patient with primary 107. Andersen MN, Mendelow M, Alfano CA. antiphospholipid syndrome and thrombocytopenia. Experimental studies of heparin-protamine activity J Invasive Cardiol. 2001;13:395Ð400. with special reference to protamine inhibition of 92. Umesan CV, Kapoor A, Nityanand S, et al. Recurrent clotting. Surgery. 1959;46:1060Ð8. acute coronary events in a patient with primary 108. Dornan RIP. Acute postoperative biventricular fail- antiphospholipid syndrome; successful manage- ure associated with antiphospholipid antibody syn- ment with intracoronary stenting. Int J Cardiol. drome. Br J Anaesth. 2004;5:748Ð54. 1999;71:99Ð102. 109. Mariani MA, Gu YJ, Boonstra PW, et al. Procoagulant 93. Santrach PJ. Devices for monitoring heparin and activity after off-pump coronary operation: is the protamine in the operating room. Sem Cardiothorac current anticoagulation adequate? Ann Thorac Surg. Vasc Anesth. 2003;7:379Ð85. 1999;67:1370Ð5. 94. Despotis GJ, Joist JH, Hogue Jr CW, et al. The impact 110. Dunn AS, Spyropoulous A, Turpie AG. Bridging of heparin concentration and activated clotting time therapy in patients on long term oral anticoagulation 9 Perioperative Management of Anticoagulation in the Patient… 127

who require surgery: the Prospective Peri-operative of surgery or an invasive procedure. Blood. Enoxaparin Cohort Trial (PROSPECT). J Thromb 2004;104:202A. Haemost. 2007;5:2211Ð8. 112. Kovacs MJ, Kearon C, Rodger M, et al. Single-arm 111. Turpie AG, Douketis JD. Enoxaparin is effective study of bridging therapy with low-molecular-weight and safe in bridging anticoagulation in patients heparin for patients at risk of arterial embolism with a mechanical prosthetic heart valve who who require temporary interruption of warfarin. require temporary interruption of warfarin because Circulation. 2004;110:1658Ð63. Perioperative Management of the Patient with Immune 1 0 Thrombocytopenic Purpura De Novo and the Thrombocytopenia of Antiphospholipid Antibody Syndrome

Raja S. Bobba and Mark A. Crowther

Introduction Classi fi cation of ITP

Immune thrombocytopenic purpura (ITP) was Primary immune thrombocytopenia purpura came fi rst recognized in the fi fteenth century by the to be de fi ned as a platelet count less than 100 × 109 /L physician Avicenna [ 1 ] . Thrombocytopenia was and the absence of an initiating or underlying further elaborated on in the 1600s, and the asso- cause other than a presumed immune mechanism ciation between thrombocytopenia and purpura [8 ] . ITP usually presents as chronic thrombocy- was drawn by Krauss [ 1 ] . Harrington proved that topenia detected on a routine complete blood ITP was due to an element in the plasma (likely examination; occasionally, it presents acutely with an antibody) by transfusing plasma from patients petechiae, mucosal bleeding, or more serious with ITP into healthy individuals; the result was bleeding complications. Acute ITP may occur in thrombocytopenia in the recipient group [2 ] . the setting of a precipitant such as a recent viral ITP is a relatively common disease occurring infection. Patients with acute ITP usually require with a frequency of 5.8 cases/100,000 in children some form of treatment; those with chronic ITP and 4.6/100,000 in adults [ 3– 5] . The disease is more only require treatment if they have ongoing severe frequent in women (4.4 affected per 100,000 patient thrombocytopenia (with a platelet count of less years, 95% CI 4.1–4.7) than in men (3.4 affected per than 30 × 109 /L), ongoing bleeding complications, 100,000 patient years, 95% CI 3.1–3.7) [ 6 ] . ITP is or in the setting of an interventional procedure much more common in patient with rheumatologi- associated with a risk of bleeding. Proposals for cal diseases; for example, up to 25% of patients with standardization of terminology, as well as recom- systemic lupus erythematosus will develop throm- mendations around the diagnosis and treatment of bocytopenia during the course of their illness [ 7 ] . ITP, have been recently reviewed [8– 10 ] .

R. S. Bobba , M.D., B.Sc., M.Sc. Pathophysiology of ITP Department of Internal Medicine , McMaster University , Ste. 610, 25 Charlton Ave East , Hamilton , ON L8N 1Y2 , Canada The inciting events which trigger ITP are M. A. Crowther , M.D., M.Sc., FRCPC () unknown. In theory, ITP is due to autoantibodies Department of Medicine, Hematology and that bind specifi c platelet surface glycoproteins. Thromboembolism and Pathology and Molecular Targets may include GP Ia/IIa, GPIIb/IIIA, and Medicine , McMaster University, St Joseph’s Healthcare GP 1b-alpha – however, the search for a common and Hamilton Health Sciences , L-301-2, 50 Charlton Ave East , Hamilton , ON L8N 1Y2, Canada target epitope has proved fruitless, and as a result, e-mail: [email protected] there is no reliable serological test for ITP [ 3 ] .

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 129 DOI 10.1007/978-1-4614-2203-7_10, © Springer Science+Business Media, LLC 2013 130 R.S. Bobba and M.A. Crowther

It is now apparent that platelet destruction is not and the patient’s response to immunosuppressive the sole cause of ITP; many patients with this treatment [3 ] . disorder have inappropriately low platelet pro- duction, despite thrombocytopenia [ 2 ] . Whether this reduced synthetic capacity is due to failure of General Management of ITP thrombopoietin-mediated feedback or to a direct in the Perioperative Period marrow effect is unknown. Viral infections can precipitate ITP. Both Perioperative management of ITP should be indi- varicella and HIV infection are associated vidualized and based on a careful assessment of with the development of ITP – effective treat- the patient’s history, the degree of thrombocy- ment of HIV infection can normalize the plate- topenia, and the type of surgery. let count [9, 11 ] . In children, ITP can follow Agents that might be considered in the man- both infections with measles, mumps, or agement of patients with ITP include primarily rubella or (potentially) vaccinations designed corticosteroids and IVIg. Other agents used in the to prevent these illnesses [9, 12] . Helicobacter management of recalcitrant ITP might include pylori infection is associated with ITP in azathioprine, cyclosporin A, cyclophosphamide, selected ethnic groups, and effective treatment danazol, dapsone, mycophenolate mofetil, and of H. pylori infection may normalize the plate- rituximab [ 9 ] . Romiplostim and eltrombopag are let count [9, 13 ] . recently introduced drugs that are indicated for the treatment of chronic ITP – although their use in the perioperative setting is attractive, their cost, Diagnosis of ITP slow onset of action, potential for toxicity, and lack of evidence of effi cacy suggest their use ITP should be suspected in all patients with should be con fi ned to research protocols. otherwise unexplained thrombocytopenia and a There are no agents that acutely increase the normal complete blood cell count with or with- platelet count in patients with ITP: thus, for truly out clinical fi ndings of mild bruising, mucosal emergent surgery, platelet transfusion during the bleeding, and/or hemorrhage [ 10, 14, 15 ] . operation might be considered for patients with Primary ITP occurs in the absence of any severe thrombocytopenia or for those with milder identifi able underlying cause. Secondary causes thrombocytopenia who develop bleeding. Pre- include autoimmune disorders such as lupus, operative transfusion is generally not performed antiphospholipid antibody syndrome, infections due to the very short half-life of transfused plate- such as human immunode fi ciency virus and hep- lets. Truly emergent surgery can often times be car- atitis, and certain medications [ 7, 16 ] . Congenital ried out even despite severe thrombocytopenia. For causes of thrombocytopenia are rare, but may example, laparoscopic splenectomy in some cen- mimic ITP. The “diagnostic threshold” for ITP is ters is routinely performed in patients with chronic controversial; although the “lower limit of ITP and severe thrombocytopenia with little or no normal” in most laboratories is 150 × 109 /L, increase in the risk of major bleeding [18 ] . recent recommendations have suggested that a If emergent surgery is required in patients with threshold of less than 100 × 109 /L is more appro- severe thrombocytopenia and bleeding, platelets priate since patients presenting with a platelet should be administered with the start of surgery. count between 100 and 150 × 10 9/L have only a Platelets can be provided as a continuous infusion 6.9% chance of developing a persistent platelet through surgery. Intravenous immunoglobulin and count of less than 100 × 10 9/L over 10 years of corticosteroids in high doses should be adminis- follow-up [17 ] . tered concomitantly. Splenectomy has been per- As there are no validated laboratory tests for formed as a heroic, lifesaving measure in isolated ITP, diagnosis rests on a typical presentation, the patients with ITP (e.g., in the case of life-threaten- exclusion of other causes of thrombocytopenia, ing gastrointestinal or intracerebral bleeding). 10 Perioperative Management of the Patient with Immune Thrombocytopenic Purpura De Novo... 131

Urgent surgery should be delayed for 24–48 h the platelet count is usually sustained beyond the to allow the administration of IVIg and corticos- discontinuation of steroids. Patients with ITP who teroids which will start to increase the platelet are chronically treated with steroids may require count within 24 h in many patients. Elective sur- increased doses around the time of surgery if there gery should only be planned after a careful hema- is evidence of adrenal suppression [19 ] . tological assessment allowing planning for a In patients presenting with newly diagnosed “safe” platelet count at the time of surgery. ITP, pulsed high-dose oral dexamethasone at a Clinicians frequently demand a “safe” level of dose of 40 mg/day for 4 days is an alternative to platelets for surgery or other procedures. standard IV or oral methylprednisolone. Initial Unfortunately no “evidence-based” thresholds response rates of 85% have been reported [9 ] . describing a “safe” platelet count exist. Thus, a There is no evidence that high-dose dexametha- recent consensus guideline was unable to make sone produces a more rapid rise in the platelet speci fi c threshold recommendations for patients count than other forms of corticosteroids. How- with ITP [ 9] . In general, the platelet count should ever, it would be an appropriate intervention for be more than 50 × 109 for “lower-risk” surgery. responding patients undergoing elective or urgent For surgery with a higher risk of bleeding (or surgery. After discontinuation (or reductions in where the consequences of bleeding would be dose to the patient’s baseline) of steroids, the plate- more severe), a threshold of 80 or 100 × 109 might let count should be checked regularly to insure be chosen. Although there is no evidence, a patients do not develop severe thrombocytopenia threshold platelet count of more than 80 × 109 is while they are at risk of surgical bleeding. frequently used for neuroaxial anesthesia. Side effects of corticosteroids are widely known Bleeding will be increased if agents that inhibit and act as a strong disincentive to chronic therapy. either coagulation or platelet function are used. In patients with ITP, very low platelet counts may Thus, heparins, warfarin, novel antithrombotics be tolerated without bleeding – thus, chronic ther- (such as dabigatran), direct antiplatelet agents apy should only be used with caution and in (such as aspirin, clopidogrel, prasugrel), and patients with signi fi cant bleeding complications or indirect antiplatelets (such as NSAIDs) should those perceived to be at high risk of bleeding. only be used with caution in patients with ITP and with additional caution in the perioperative period. Use of nonselective NSAIDs as a compo- IVIG nent of routine perioperative pain management should probably be discouraged for patients with Intravenous immunoglobulin (IVIg) increases clinically important thrombocytopenia. the platelet count in 75% of patients and may increase the platelet count to normal levels in as many as 50% of ITP patients. The duration of Steroids response is only 3–4 weeks after which recurrent thrombocytopenia is expected. Sustained eleva- Corticosteroids are the primary agents used to tion of the platelet count is rare [9 ] . For urgent or acutely increase the platelet count in patients with emergent surgery, a dose of 1 g/kg should be ITP. In patients requiring urgent or emergent sur- administered. This dose can be repeated if gery, intravenous corticosteroids in high dose (e.g., there is no evidence of an increase in the platelet methylprednisolone 100 mg once daily) may be count within 24–48 h. Complications of intrave- initiated with the anticipation that the platelet nous immunoglobulin therapy are rare but count will begin to rise by 24–48 h. For elective include allergy (usually due to concomitant IgA surgical procedures, corticosteroids are usually de fi ciency) and volume overload (due to the large initiated at high dose 7–10 days before the surgery; volume of colloid being administered). Serum the dose can be tapered rapidly if a signi fi cant sickness-like reactions, hemolysis, acute renal platelet response is observed as the increment in injury, and aseptic meningitis all can occur. 132 R.S. Bobba and M.A. Crowther

once a week for 4 weeks. Platelet recovery may Other Options for the Treatment of ITP take months to fully manifest precluding the use of rituximab for urgent or emergent surgery. Several other fi rst-, second-, and third-line treat- However, rituximab may be useful in patients ments are available for the management of ITP. undergoing elective surgery who have chronic As described by Arnold and Kelton, the approach clinically signi fi cant ITP and who require elec- to the treatment of ITP requires a stepwise tive surgery. Predictors of poor response to approach from the least toxic therapy to more rituximab include prior splenectomy, chronic ITP toxic treatments if bleeding persists [ 9 ] . Many of for 10 years or greater, and prior use of multiple these agents, which act slowly, cannot be used in treatment regimens. Rituximab is well tolerated. the setting of urgent surgery since their onset of Side effects generally occur at the fi rst infusion action is greatly delayed. However, they might be and include fever, chills, and rash. considered in the setting of elective surgery.

Splenectomy Anti-D Antibodies Splenectomy is the only treatment for ITP proven Anti-D antibodies are effective when adminis- to induce long-term remission in a high proportion tered to patients who are Rh+ and who have not of patients [ 9] . Splenectomy is usually carried out had splenectomy [9, 14 ] . Advantages over IVIg prior to other required surgical procedures. Platelet include more rapid administration, reduced transfusion immediately after cross clamping of expense, and a lower risk of adverse reactions. the splenic hilum may result in substantial of incre- However, recent cases of severe hemolytic anemia ments in the platelet count; this increment may be and other complications temper enthusiasm for further enhanced through concomitant administra- the use of anti-D; they should not be used in tion of IVIg and/or high-dose corticosteroids. patients with severe anemia or those with evi- However, emergency splenectomy should be dence of hemolysis [9 ] . The onset of action will regarded as a heroic surgery used only in the set- be delayed with a rise in the platelet count noted ting of a life-threatening hemorrhage. Preoperative at 24–48 h – thus, they are of limited utility in the vaccination against encapsulated bacteria, nor- setting of emergent surgery. Anti-D antibodies at mally required in patients undergoing splenectomy, a dose of 50–75 m g/kg produce important incre- is not possible in those patients undergoing emergent ments in the platelet count in 80–90% in splenectomy – the ef fi cacy of intra- or postoperative Rh-positive patients [ 20 ] . Rh(D)-positive cells vaccination is unknown, but it is thought to be less (coated with anti-D) are preferentially removed effective than when administered preoperatively. In by the reticuloendothelial system, sparing autoan- experienced surgical centers, splenectomy can be tibody-coated platelets. Side effects include mild carried out using open or laparoscopic techniques. hemolytic anemia, fevers, and chills The risk of overwhelming infections after splenec- tomy is estimated to be an excess of mortality of 0.73 per 1,000 patient years [23 ] . Rituximab

Rituximab is a chimeric mouse/human antiCD20 Thrombopoietic Agents monoclonal antibody that works, at least in part, through complement-dependent cell lysis of Thrombopoietic agents stimulate platelet produc- CD20-positive B cells [ 21, 22 ] . Rituximab tion. Romiplostim (AMG351) and eltrombopag depletes B cell clones which are responsible for are examples, both approved for the second-line producing autoreactive platelet antibodies. Usual treatment of ITP [ 9 ] . Both agents initiate doses for the treatment of ITP are 375 mg/m2 megakaryocytic differentiation, proliferation, and 10 Perioperative Management of the Patient with Immune Thrombocytopenic Purpura De Novo... 133 platelet production. Their biology has been recently the equivalent of one to 2 usual adult platelet reviewed [ 24 ] . These agents are slower acting doses. A larger dose of intravenous corticoster- (taking months in some cases to fully manifest) and oids should be considered (e.g., the equivalent of would not be indicated in the context of emergent 100 mg of intravenous methylprednisolone). bleed secondary to thrombocytopenia. However, for Although the platelet count can be checked after elective surgery, use of these agents might be con- this therapy, an increment may not be observed. sidered in patients with platelet counts suffi ciently Generally, surgery should not be delayed pend- low to cause concern about perioperative bleeding ing a platelet count. If bleeding is encountered but whose platelet count is not suffi ciently low to intraoperatively, then additional platelets may be justify chronic treatments. A formal evaluation of transfused. There is no rationale for immediate their utility in this setting is required. Caution administration of additional doses of IVIg or ste- should be employed when using these agents roids. Additional doses might be considered on because of the potential for a rebound drop in plate- the day following surgery. For patients present- let count after the agonist is withdrawn. Autoantibody ing with exsanguination, immediate surgical formation, stem cell depletion, increased bone mar- intervention will be required. Platelet transfu- row reticulin, and thrombosis have been reported as sion, IVIg, and corticosteroids can be adminis- complications of these agents [25 ] . tered intraoperatively. Acute splenectomy could be considered as a truly heroic measure in a patient who is exsanguinating and who requires Other Agents abdominal surgery; platelet transfusion, IVIg, and corticosteroids could be considered after the A variety of other agents have been used in the splenic hilum is clamped. In all cases, the post- treatment of ITP. These agents are either used operative platelet count will need to be moni- infrequently (e.g., cyclosporine), are relatively tored closely and intervened upon as indicated. ineffective (e.g., danazol), or have signi fi cant toxicities (e.g., cyclophosphamide). Although they might be used in the perioperative setting to Urgent Surgery in the Setting increase the platelet count, their use is suf fi ciently of Clinically Important Reductions esoteric to exclude a discussion of them in this in the Platelet Count text. Interested readers are referred to recent consensus documents discussing their use [ 8 ] . If surgery is required in 24–48 h, IVIg and higher doses of steroids should be administered as quickly as possible and the platelet count moni- Recommendations for Management tored. An increment in the platelet count should of ITP in the Perioperative Setting be expected at 24–48 h. If the platelet increment is insuffi cient, platelet transfusion could be con- Emergent Surgery in the Setting sidered and a more sustained than usual response of Clinically Important Reductions anticipated given the recent administration of in the Platelet Count IVIg and steroids. Steroids should be continued on a daily basis, as discussed previously. Patients with clinically important reductions in the platelet count (a threshold defi ned by physi- cian familiarity, the type of surgery and its bleed- Elective Surgery in the Setting ing risk, and the patient’s bleeding history) of Clinically Important Reductions require acute increments in their platelet count to in the Platelet Count undergo surgery safely. If time permits, IVIg (at a dose of 1 g/kg) should be administered, fol- In this setting, the approach to treatment of lowed immediately by platelet transfusion with clinically important thrombocytopenia can be 134 R.S. Bobba and M.A. Crowther more measured. Assuming the diagnosis of ITP 5. Zeller B, Helgestad J, Hellebostad M, et al. Immune is reliable, agent such as rituximab or a throm- thrombocytopenic purpura in childhood in Norway: a prospective, population-based registration. Pediatr bopoietic drug might be considered; however, the Hematol Oncol. 2000;17(7):551–8. platelet count increment may be delayed for 6. Schoonen WM, Kucera G, Coalson J, et al. weeks or months. Further, neither of these inter- Epidemiology of immune thrombocytopenic pur- ventions is supported by good-quality evidence, pura in the general practice research database. Br J Haematol. 2009;145(2):235–44. and both are “off-label” uses. The introduction of 7. Cines DB, Liebman H, Stasi R. Pathobiology of sec- IVIg and/or steroids 1–2 weeks before surgery ondary immune thrombocytopenia. Semin Hematol. allowing maximal platelet count increments and 2009;46(1 Suppl 2):S2–14. careful monitoring will be possible. However, the 8. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and manage- response to IVIg will taper after 2–3 weeks, and ment of primary immune thrombocytopenia. Blood. the effect of corticosteroids will wane within 2010;115(2):168–86. 1–2 weeks in many patients after corticosteroids 9. Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr. are stopped or are reduced to their baseline doses. L, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune If splenectomy has been considered, it may be thrombocytopenia. Blood. 2011;117:4190–207. useful to perform this procedure at the same time 10. Rodeghiero F, Stasi R, Gernsheimer T, et al. as the planned procedure with appropriate preop- Standardization of terminology, defi nitions and out- erative IVIg and/or steroids administered to come criteria in immune thrombocytopenic purpura of adults and children: report from an international produce a “safe” platelet count. Vaccination as per working group. Blood. 2009;113(11):2386–93. guideline recommendations should be provided. 11. Chia WK, Blanchette V, Mody M, Wright JF, Freedman J. Characterization of HIV-1-speci fi c anti- bodies and HIV-1-crossreactive antibodies to plate- lets in HIV-1-infected haemophiliac patients. Br Conclusion J Haematol. 1998;103(4):1014–22. 12. Mantadakis E, Farmaki E, Buchanan GR. Advances in the treatment of ITP have occurred Thrombocytopenic purpura after measles-mumps- quite rapidly over the past few years. The initiat- rubella vaccination: a systematic review of the literature and guidance for management. J Pediatr. ing event however remains elusive. Operative 2010;156(4):623–8. management will require some comfort on the 13. Arnold DM, Bernotas A, Nazi I, et al. Platelet count part of the surgeons or interventionalists in dealing response to H. pylori treatment in patients with with patients at risk of bleeding; if time allows, immune thrombocytopenic purpura with and without H. pylori infection: a systematic review. Haemato- elective surgery can be approached with a more logica. 2009;94(6):850–6. measured series of interventions designed to pro- 14. British Society of Haematology. Guidelines for the duce a safe platelet count at the time of surgery. investigation and management of idiopathic thrombo- cytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120(4):574–96. 15. Kuwana M, Okazaki Y, Satoh T, Asahi A, Kajihara M, References Ikeda Y. Initial laboratory fi ndings useful for predict- ing the diagnosis of idiopathic thrombocytopenic 1. Blanchette V, Freedman J, Garvey B. Management of purpura. Am J Med. 2005;118(9):1026–33. chronic immune thrombocytopenic purpura in children 16. Arkfeld DG, Weitz IC. Immune thrombocytopenia in and adults. Semin Hematol. 1998;35(1 Suppl 1):36–51. patients with connective tissue disorders and the 2. Bromberg ME. Immune thrombocytopenic purpura– antiphospholipid antibody syndrome. Hematol Oncol the changing therapeutic landscape. N Engl J Med. Clin North Am. 2009;23(6):1239–49. 2006;355(16):1643–5. 17. Stasi R, Amadori S, Osborn J, Newland AC, Provan 3. Psaila B, Bussel JB. Immune thrombocytopenic pur- D. Long-term outcome of otherwise healthy individ- pura. Hematol Oncol Clin North Am. 2007;21(4): uals with incidentally discovered borderline thrombo- 743–59. vii. cytopenia. PLoS Med. 2006;3(3):e24. 4. Segal JB, Powe NR. Prevalence of immune thrombo- 18. Delaitre B, Blezel E, Samama G, et al. Laparoscopic cytopenia: analyses of administrative data. J Thromb splenectomy for idiopathic thrombocytopenic purpura. Haemost. 2006;4(11):2377–83. Surg Laparosc Endosc. 2002;12(6):412–9. 10 Perioperative Management of the Patient with Immune Thrombocytopenic Purpura De Novo... 135

19. Shaw M, Mandell BF. Perioperative management of 22. Andemariam B, Bussel J. New therapies for immune selected problems in patients with rheumatic thrombocytopenic purpura. Curr Opin Hematol. diseases. Rheum Dis Clin North Am. 1999;25(3): 2007;14(5):427–31. 623–38, ix. 23. Schilling RF. Estimating the risk for sepsis after sple- 20. Arnold DM, Kelton JG. Current options for the nectomy in hereditary spherocytosis. Ann Intern Med. treatment of idiopathic thrombocytopenic purpura. 1995;122(3):187–8. Semin Hematol. 2007;44(4 Suppl 5):S12–23. 24. Kuter DJ. Biology and chemistry of thrombopoietic 21. Reff ME, Carner K, Chambers KS, et al. Depletion agents. Semin Hematol. 2010;47(3):243–8. of B cells in vivo by a chimeric mouse human 25. Newland A. Thrombopoietin mimetic agents in the monoclonal antibody to CD20. Blood. 1994;83(2): management of immune thrombocytopenic purpura. 435–45. Semin Hematol. 2007;44(4 Suppl 5):S35–45. Perioperative Management of the Patient with Pulmonary 1 1 Hypertension

Adriano R. Tonelli , Omar A. Minai, and Raed A. Dweik

Introduction De fi nition and Classifi cation

The number of patients with pulmonary hyper- Pulmonary hypertension is characterized by an tension (PH) has increased because of increased increase in pulmonary pressures caused by dif- awareness, better diagnostic techniques, and lon- ferent etiologies that can lead to heart failure and ger survival with the development of more effec- death [ 6 ] . The fourth World Symposium on tive treatment options [ 1– 4] . In view of this, more Pulmonary Hypertension proposed using a mean patients with PH are likely to require elective or pulmonary artery pressure (mPAP) ³ 25 mmHg emergency surgery. The management of PH or above as a single criterion for its diagnosis patients in the perioperative period is challenging [ 7, 8] . A large number of diseases are known to as this condition is associated with an increased cause PH. These conditions have been grouped morbidity and mortality. Little information is into different categories depending on histopa- available regarding the risk and management of thology, clinical presentation, diagnostic fi ndings, PH in the perioperative period and even less is and response to treatment. The most updated known about the role of several recently approved revision of this classifi cation (Dana Point, 2008) PH speci fi c therapies. Controlled trials are lacking [ 6] divides PH into fi ve major categories: (1) and most recommendations are based on uncon- PAH, (2) PH due to left heart disease, (3) PH due trolled or anecdotal evidence [ 5 ] . In this chapter, to lung disease and/or hypoxia, (4) chronic we will discuss the epidemiology, management, thromboembolic PH, and (5) PH with unclear and outcomes of patients with PH that undergo multifactorial mechanisms. Some of these forms cardiac and noncardiac surgeries. of PH require further discussion.

A. R. Tonelli , M.D. • O. A. Minai , M.D., F.C.C.P., Pulmonary Hypertension in CTD D.A.B.S.M. Department of Pulmonary, Allergy, Critical Care Medicine , Cleveland Clinic Foundation , 9500 Euclid Pulmonary arterial hypertension is characterized Avenue , Cleveland , OH 44195 , USA by a progressive vascular cell proliferation, in R. A. Dweik , M.D. () situ thrombosis, and remodeling of the pulmo- Pulmonary Vascular Program, Department of Pulmonary, nary vasculature. This group encompasses several Allergy, Critical Care Medicine , Cleveland Clinic diseases including PH associated with connective Foundation , 9500 Euclid Avenue, Desk A90, Cleveland , OH 44195 , USA tissue diseases (PH-CTD) [6 ] . Data from the e-mail: [email protected] French National Registry on 674 patients with

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 137 DOI 10.1007/978-1-4614-2203-7_11, © Springer Science+Business Media, LLC 2013 138 A.R. Tonelli et al.

PAH revealed that 15% of them had PH-CTD and systemic sclerosis (SSc) comprised 76% Prognostic Factors for PH-CTD these patients [9 ] . Although the prevalence of PH is higher in patients with SSc than in other CTD Pulmonary hypertension is a major cause of death (7.9–13%) [9– 14] , PH has been observed in in patients with SSc [29– 31 ] with a worse prog- systemic lupus erythematosus (SLE) (4.2%) nosis than patients with idiopathic PAH [30, 32, 33 ] [ 15– 18 ] , mixed connective tissue disease [ 19 ] , or other PH-CTD [ 4, 32] . Risk factors for the Sjögren’s syndrome [ 20 ] , dermatomyositis/poly- development of PH in SSc are older age, limited myositis [21 ] , and rheumatoid arthritis (RA) [ 22, systemic sclerosis, Raynaud phenomenon, many 23 ] . A UK National registry pooled data on 429 telangiectasias, presence of anticentromere or incident cases of PH-CTD diagnosed between U3-RNP antibodies, rapid or isolated decrease in 2001 and 2006 and found that SSc, mixed tissue lung diffusion capacity for carbon monoxide connective disease and SLE encompassed 74%, (DLCO), forced vital capacity over DLCO <1.6, 8%, and 8% of the cases, respectively. The rest of and elevated or rising serum BNP [34 ] . Risk the subjects had dermatomyositis/polymyositis, factors for PH in SLE include lupus anticoagu- RA, undifferentiated CTD and Sjögren’s syn- lant and antiphospholipid syndrome [18 ] . Risk drome [4 ] . It is important to remember that factors for PH are not identi fi ed for other CTD. studies reviewed in this chapter pertain to the In general, hemodynamic indices of right heart broad category of PAH that includes patients with failure (raised mean right atrial pressure and mPAP, PH-CTD. decreased cardiac index) predict an adverse out- come in patients with CTD [12, 13] . Pulmonary artery pressures alone may not accurately re fl ect Etiology and Pathology of PH-CTD prognosis in PH since they decrease when the RV starts to fail [ 5 ] . Independent predictors of worse Histopathological fi ndings observed in PH-CTD survival are presence of CTD, older age, male are similar to those present in idiopathic PAH gender, and lower mixed venous oxygen saturation with some signi fi cant differences. Patients with [ 4 ] . Although the survival of patients with PH-CTD, PH-CTD have more pulmonary artery and pul- after the introduction of advanced PH therapies, monary venule fi brosis with fewer plexiform seems to be better than historical controls, the over- lesions [ 24 ] . all prognosis is worse than other etiologies of PH Patients with CTD may have PH due to other [ 4 ] . This may be due to the fact that PH-CTD etiologies besides PAH [ 11, 17 ] . Not uncom- patients are older and have associated interstitial monly, this group of patients have PH due to left lung disease, diastolic or systolic left ventricular heart disease (diastolic or systolic dysfunction) dysfunction, and more severe vasculopathy. Delays caused by primary myocardial involvement [ 25 ] in diagnosis are due to a lack of good screening or PH due to lung disease and/or hypoxia as a tests and the fact that poor exercise tolerance may result of pleuropulmonary disease (e.g., pulmo- be attributed to the underlying CTD without con- nary fi brosis) [26 ] . Other less common etiologies sidering PH. These factors result in late initiation include chronic thromboembolic PH (including of appropriate therapy for PH. antiphospholipid syndrome), PH due to associ- ated comorbidities, or pulmonary venoocclusive disease [27, 28 ] . Hachulla et al. studied 18 newly Need for Surgeries in PH Patients diagnosed SSc with PH. The PH was due to PAH, left heart disease, and pulmonary fi brosis Pulmonary hypertension represents one of most in 44%, 44%, and 11% of the cases, respectively important risk factors for perioperative morbidity [ 11 ] . Similarly, Pan et al. described the presence and mortality during the perioperative or peri- of PH other than PAH in 52% of SLE patients partum period [ 35– 40 ] . Patients have tradition- with PH [ 17 ] . ally been counseled against having elective 11 Perioperative Management of the Patient with Pulmonary Hypertension 139

RV contractility RV preload RV afterload RV wall stress RV O2 demand

RV dilation and dysfunction

Right-to-left shunt Acute TR RV CO Septal shift RV ischemia

Ventricular RV O2 Arrhythmia LV preload interdependence demand

LV CO

coronary Hypoxemia Hypotension perfusion

Fig. 11.1 Pathophysiology of RV failure in patients with PH [Adapted from Refs. [ 41, 44 ] ] surgeries or becoming pregnant, but recent Right ventricular dilation can lead to a paradoxical signi fi cant advances in the management of PH shift of the interventricular septum towards the may challenge these recommendations. left ventricle, compromising LV fi lling reducing systemic cardiac output and coronary perfusion pressure (ventricular interdependence) leading to Pathophysiological Considerations RV myocardial ischemia and worsening right heart failure [ 41, 44] . The development of acute In order to understand why PH adversely affects tricuspid regurgitation may lead to further reduc- patients during the perioperative and peripartum tions in RV output and LV preload [ 41 ] . The high period and to help devise appropriate interven- end-diastolic pressure associated with right heart tion strategies, it is critical to understand several failure may allow the emergence of right-to-left key pathophysiological concepts. shunt through a patent foramen ovale, with wors- The normal pulmonary vascular resistance ening hypoxemia. (PVR) is 80–90% lower than the resistance in the During the perioperative or peripartum period, systemic circulation. Chronic elevation of the right-sided circulatory failure can be precipi- pulmonary pressures in patients with PH leads to tated by a combination of different factors that progressive dilation and hypertrophy of the right impair RV contractility, RV preload, or RV after- ventricle (RV). These factors generate higher load (Fig. 11.1). Reductions in RV contractility ventricular wall stress that limits RV myocardial can be due to ischemia or medications used perfusion predominantly in diastole, increasing during surgery. RV preload can be affected by the risk of ischemia and failure in the presence of arrhythmias, positive intrathoracic pressure, systemic hypotension (which may occur acutely excessive use of diuretics and physiologically in the preoperative period) [41 ] . inappropriate fl uid restriction. Perioperative Acute increases in RV afterload are poorly increases in PVR may be precipitated by several tolerated, the RV dilates and the stroke volume factors such as sympathetic stimulation (e.g., decreases because of a limited ability to appro- pain and endotracheal intubation), hypoxemia, priately increase preload or contractility [ 42, 43 ] . hypercarbia, hypothermia, acidemia, or high 140 A.R. Tonelli et al.

Table 11.1 Mechanisms involved in PVR increase during most experts agree that PH poses an increased surgery risk for noncardiac surgery; however, no major Increased sympathetic tone during airway instrumentations study has been performed to prove this concept or with pain [ 55] . The few studies on this topic [ 37– 39, 56 ] Anesthetic agents that can affect RV afterload have been summarized in Table 11.2 . Positive pressure mechanical ventilation Kaw et al. showed that PH was an indepen- Hypoxemia dent predictor of postoperative complications Hypercapnia in patients undergoing noncardiac surgery [57 ] . Acidemia The same group described that left ventricular ejection fraction, right atrium size, RV systolic airway pressures in mechanically ventilated pressure, PAOP, and PVR were associated patients (Table 11.1 ) [45– 49] . PH can also be with these postoperative complications [58 ] . aggravated by occurrence of thromboembolism, A summary of factors known to increase the

CO 2 or fat embolism, use of protamine, or extra- operative risk in PH patients is presented in corporeal circulation [ 50 ] . Table 11.3 . None of these studies was able to Signi fi cant cardiopulmonary changes occur determine whether the anesthetic approach during pregnancy and puerperium. During preg- (regional versus general), type of anesthetic nancy, the intravascular volume and cardiac out- used, or use of advanced PH therapies was put increase by approximately 50% when compared associated with any difference in outcome. with the nonpregnant state. Cardiac output may These studies have indicated that the perioper- increase even further during labor and the immedi- ative risk correlates with the type of procedure ate postpartum period [51, 52 ] . The return to base- performed (e.g., hip replacement can be com- line hemodynamic values may take up to 6 months plicated by embolization of air, bone marrow, postdelivery [52 ] . As PH patients have a limited and cement that may trigger RV failure). It is ability to compensate due to fi xed resistance of the important to keep in mind that the results pre- pulmonary vasculature, increases in heart rate and sented predominantly applied to PH patients circulatory volume can lead to increases in PVR that underwent surgeries in referral centers. It and RV failure, especially under the presence of is unclear if similar outcomes will be observed hypoxemia, hypercarbia, and acidemia [ 40, 52 ] . in centers with less experience in the manage- Other reasons for worsening PH in pregnancy are ment of this disease. vasoconstriction and increased venous return fol- lowing delivery (uterine contraction and relieve of inferior vena cava compression) as well as pulmo- Pulmonary Hypertension in Cardiac nary embolism. Surgery

Patients with CTD such as RA and SLE have Pulmonary Hypertension premature or accelerated coronary atherosclerosis in Noncardiac Surgery [ 59] . Coronary artery bypass grafting in these patients has acceptable early but less favorable Pulmonary hypertension is an identi fi ed indepen- midterm results in regard to survival and need dent risk factor for worse outcomes in noncardiac for reintervention [60 ] . Patients with SLE can surgery predominantly in the early postoperative develop Libman-Sacks endocarditis that can be period [53, 54 ] . The most updated guidelines on associated with mitral valve regurgitation and perioperative cardiovascular evaluation for non- may require surgery [61 ] . cardiac surgery from the American College of Pulmonary hypertension is a recognized risk Cardiology and American Heart Association do factor for increased morbidity and mortality not include PH as part of the risk stratifi cation related to cardiac surgery. Among 2,149 patients of these patients. These guidelines recognize that that underwent coronary artery bypass grafting, Table 11.2 Studies assessing the perioperative risk of pulmonary hypertension in noncardiac surgery Predominant PH NYHA Author, year Type of study type of PH diagnosed functional Advanced Type Perioperative (Ref) and timeframe n n° proc. disease by: class PH therapies of surgery Anesthesia morbiditya Mortality Comments Ramakrishna, Retrospective 145 145 PAH Echo I/II: 73% 14% Noncardiothoracic 100% general 42% 7% Predictors 2005 [37 ] 1991–2003 III/IV: 27% Nonobstetric of mortality Major: 79% include: Hx of PE Evidence of RV dysfunction or hypertrophy Use of vasopressors Ratio RVSP/ Systemic BP Minai, 2006 Retrospective 21 28 PAH RHC I/II:38% 76% Noncardiothoracic 79% general 19% 18% Of patients [ 39 ] 1996–2002 III/IV:62% Non-obstetric that underwent Major 86% general anesthesia, 55% were extubated in the OR Lai, 2007 [38 ] Retrospective, 62 62 PVH Echo N/A 0% Noncardiothoracic 58% general 24.2% 9.7% Only in the case–control Nonobstetric postoperative 1999–2004 Major: 65% period PH patients had more complica- tions than controls Predictors of mortality were Emergency surgery CAD Systolic PAP (continued) Table 11.2 (continued) Predominant PH NYHA Author, year Type of study type of PH diagnosed functional Advanced Type Perioperative (Ref) and timeframe n n° proc. disease by: class PH therapies of surgery Anesthesia morbiditya Mortality Comments Price, 2010 Retrospective 28 28 PAH RHC I/II: III/IV: Noncardiothoracic 50% general 29% (most 7% Higher [ 56 ] 2000–2007 Nonobstetric occurred in the complication Major: 75% fi rst 48 hs after rates were the procedure) associate with Emergency surgeries Major surgeries Longer operative time BP blood pressure, CAD coronary artery disease, Echo echocardiography, N/A not available, NYHA New York Heart Association, OR operating room, PAP pulmonary artery pressure, PAH pulmonary arterial hypertension, PE pulmonary embolism, PH pulmonary hypertension, proc procedure, PVH pulmonary venous hypertension, RHC right heart catheterization, RV right ventricle, RVSP right ventricular systolic pressure a Perioperative morbidity was de fi ned differently depending on the study (see text) 11 Perioperative Management of the Patient with Pulmonary Hypertension 143

Table 11.3 Risk factors for perioperative morbidity and surgery [ 68] . A ratio of pulmonary over systemic mortality in PH [37, 38, 56 ] vascular resistance (on ~100% oxygen and Related to the surgical procedure inhaled NO) <0.33, or a decrease of 20% when Emergency surgery compared to baseline, reliably identi fi ed patients Major surgery at low risk for perioperative complications [69 ] . High-risk surgery Long operative time (> 3 h) Intraoperative use of vasopressors Pulmonary Hypertension Comorbidities in Pregnancy History of pulmonary embolism Obstructive sleep apnea Connective tissue diseases commonly affect women Underlying coronary artery disease during the childbearing years. Some of these PH severity and hemodynamics: NYHA class ³ II patients with known or unknown PH may become Right ventricular hypertrophy pregnant. This leads to concerns about the optimal Right ventricular systolic pressure/systolic blood management of this hemodynamic condition in the pressure ³ 0.66 context of the signi fi cant physiological changes Right ventricular myocardial performance index ³ 0.75a that occur during pregnancy and peripartum. Right axis deviation The estimated overall maternal mortality for Dilated right atrium individuals with PH ( ³25 mmHg) has tradition- Higher systolic PAP or PVR ally been between 30% and 56%. Most of the Lower left ventricular ejection fraction maternal fatalities occurred in the early postpar- a Right ventricular performance index = RV isovolumic tum period (fi rst month) and were due to either relaxation and contraction times divided by the ejection sudden or progressive heart failure [40, 70 ] . time interval Mortality depends on the etiology of PH, time of recognition, and medical treatment received PH was an independent predictor of mortality during pregnancy, delivery, and postpartum [35 ] . Similarly, PH was an independent risk period [ 54, 70, 71 ] . Patients with Eisenmenger’s factor for mortality in patients that underwent syndrome have higher maternal mortality (40–52%) heart surgery in the EuroSCORE study [ 62 ] . than other groups, although most of the data come Other studies have also shown that a mPAP ³ 25 from studies performed before the introduction or >30 mmHg is a useful preoperative predictor of PH specifi c therapies [ 72, 73 ] . Late diagnosis of perioperative morbidity, mortality, and ICU and late hospital admission are strong predictors length of stay in patients undergoing cardiac of maternal mortality [ 70 ] . Recent studies using surgery [63, 64 ] . Mitral valve replacement in PH advanced PH therapies and a multidisciplinary patients carries an increased risk, especially approach showed a lower maternal mortality when the pulmonary pressures are above sys- (11–33%) than historical controls [40, 74 ] . temic levels [65, 66 ] . Even though the early mor- Maternal mortality, however, remains prohibi- tality is high, the long-term results are comparable tively high and few women stay clinically stable to patients without PH [66 ] . Similarly, aortic during the peripartum period [ 40, 54 ] . Thus, valve replacement in PH patients is associated pregnancy must be discouraged and early contra- with higher mortality; nevertheless, the conserva- ception advice should be provided to these tive management of aortic stenosis and PH has an patients [ 54 ] . In individuals already pregnant, the even more dismal prognosis [67 ] . risks should be carefully discussed with the Few factors that predict outcomes in PH patient including considerations for early termi- patients that undergo cardiac surgery have been nation of pregnancy, especially in the event of PH identi fi ed. A mean systemic-to-pulmonary artery deterioration [ 54, 75 ] . If the pregnancy is to be pressure ratio less than 4, after anesthesia induc- continued, early hospital admission with careful tion, predicts hemodynamic complications after multidisciplinary management is the standard of 144 A.R. Tonelli et al. practice. In patients who desire to become Table 11.4 Preoperative management in patients with PH pregnant after understanding the risks involved, a Perform a thorough history and physical examination year of successful PH therapy with the goal of Recognize PH and diagnose the cause improving the RV function to near-normal is Assess the severity of the disease usually suggested [ 76 ] . Multidisciplinary team evaluation The main objectives before or during pregnancy Assess risks and bene fi ts of the intervention are to recognize and manage PH, prevent its Plan the anesthetic and surgical approach progression, and minimize side effects of various Continue oxygen (keep SO2 ³ 90%) therapies [ 77 ] . The optimal mode of delivery Administer diuretics for RV overload (vaginal versus caesarean section) and best anes- Bridge with heparin in patients that require oral anticoagulation thetic approach (epidural versus general) remain Continue calcium channel blockers in vasoreactive PH controversial [ 40, 45, 54, 71, 74– 76] . Although Maintain or initiate (if indicated) PH advanced therapies promising, the effects of advanced PH therapies on pregnancy outcomes remain largely unknown [40 ] . Worth mentioning is that endothelin receptor antagonists (including bosentan and ambrisentan) studies may show signs of RV hypertrophy on inhibited fetal growth in animal studies; therefore, electrocardiogram or dilated pulmonary arteries these medications are contraindicated during or right-sided cavities on imaging studies. The pregnancy due to potential teratogenic effects [ 78 ] . best initial screening modality when PH is clinically Although the data are insuffi cient, epoprostenol suspected is echocardiography. The defi nitive and sildena fi l appear to be well tolerated during diagnosis of this hemodynamic condition, how- pregnancy without any reported adverse conse- ever, requires right heart catheterization [14 ] quence for the baby [ 52, 76, 79, 80] . Nitric oxide which con fi rms the diagnosis, narrows potential has also been used effectively in the peripartum etiologies, provides prognostic information, and management of patients with PH [ 81 ] . guides the therapeutic approach [7, 8 ] . Limited data exist on the management and The presence of PH (mean pulmonary artery outcomes of pregnancies in patients with pressure ³ 25 mmHg) should prompt a reevalua- PH-CTD. A patient with PH and SLE success- tion of the need for surgery. The risk assessment fully underwent pregnancy and delivery under should take into account the comorbidities, prog- treatment with sildenafi l and inhaled iloprost nostic factors, and type of surgery [ 2, 85 ] . In [82 ] . Another pregnant woman with SLE, PH, patients with unacceptably high risk, the treating and pneumonitis was managed without compli- team should consider other less invasive treat- cations during the peripartum period [83 ] . ment modalities or the preprocedure administra- tion of advanced PH therapies. Evidence of worsening PH or RV failure should delay elective Preoperative Evaluation surgical procedures, until these conditions can be properly evaluated and treated [86 ] . Before proceeding with surgery it is critical that PH If the decision is to proceed with surgery, is diagnosed and its cause and severity are identi- after understanding the risks and bene fi ts of the fi ed. A summary of the suggested preoperative procedure, a multidisciplinary approach is rec- management is presented in Table 11.4 . Preoperative ommended. The preoperative management encom- evaluation starts by obtaining a thorough history passes general measurements and consideration of and physical examination with special attention advanced PH therapies. Oxygen is indicated when to symptoms of PH, such as dyspnea, fatigue, the oxygen saturation is below 90% [87 ] . Diuretics angina, dizziness, and syncope, or physical are considered in the presence of RV volume over- fi ndings such as loud pulmonary component of load, but they should be used judiciously, as exces- the second heart sound, murmurs of tricuspid sive diuresis can dangerously reduced RV preload and/or pulmonic insuffi ciency, parasternal heave, [ 45] . Digoxin may modestly improve cardiac and signs of RV failure [ 84 ] . Complementary output in patients with PH and RV failure [ 88 ] . 11 Perioperative Management of the Patient with Pulmonary Hypertension 145

Bridging with heparin is recommended in patients Table 11.5 Intraoperative management in patients with PH with indications for oral anticoagulation beyond Use opiods to block cardiorespiratory response PH alone [89 ] . Calcium channel blockers (dilti- to intubation and pain azem, nifedipine, and amlodipine) need to be con- Propofol, thiopental or etomidate can be used tinued in vasoreactive patients with PAH and in as induction agents those individuals in whom the calcium channel Volatile anesthetic agents can be utilized during maintenance blockers benefi t their Raynaud’s phenomenon In mechanically ventilated patients use high FiO2 , low [ 90] . Calcium channel blockers are contraindicated tidal volumes, and PEEP with relatively high respiratory in subjects with hemodynamic instability, heart Optimize metabolic state (prevent or correct acidemia, failure (cardiac index below 2 l/min/m2 and RA hypoxemia, and hypercarbia) pressure above 20 mmHg), or previous adverse Maintain sinus rhythm reactions to the medication [ 90 ] . Optimize RV preload (usually guided by central venous Currently, eight FDA-approved advanced PH pressure or RA pressure) Attempt to reduce RV afterload therapies are commercially available (sildenafi l Maintain systemic perfusion pressure [PO], tadala fi l [PO], bosentan [PO], ambrisentan Avoid and treat RV ischemia and failure [PO], epoprostenol [IV], teprostinil [SQ, IV and inhaled] and iloprost [inhaled]). These therapies should be continued in the perioperative period. for potential complications) [91 ] , it is commonly Patients treated with subcutaneous treprostinil utilized. Transesophageal echocardiography is a may continue the infusion for short procedures; promising tool to evaluate preload and ventric- however, for prolonged interventions, this medi- ular function in this group of patients. There are cation should be converted to intravenous trepro- no validated data to help de fi ne the best monitor- stinil or epoprostenol [86 ] . Similarly, in patients ing approach for PH patients undergoing surgery; that cannot continue inhaled iloprost, inhaled thus, the extent of monitoring required should be nitric oxide (iNO), IV, or nebulized epoprostenol determined on a case-by-case basis. should be considered [2 ] . Various anesthetic techniques have been used in patients with PH, including regional (limited or neuraxial) or general anesthesia. Regional Intraoperative Management anesthesia using a low epidural dose and slow titration is well tolerated in PH patients since it The main goals for the intraoperative period of minimizes the hemodynamic compromise asso- PH patients are presented in Table 11.5 . They are ciated with sympathetic blockade and systemic based on (1) maintenance of adequate systemic afterload reduction. This technique may not be perfusion, RV preload, and optimal contractility appropriate for many procedures or when cessa- and (2) aggressive control of PH triggers and pre- tion of anticoagulation is not possible [ 56 ] . It is vention of the PH crisis and RV failure [89 ] . uncertain if neuroaxial anesthesia is safe in Careful monitoring of arterial oxygen saturation, patients treated with prostacyclin analogues since cardiac rhythm, and blood pressure are critical to these medications have antiplatelet effects. To avoid and correct PH triggers such as hypoxia, date, there are no data suggesting increased risk hypercarbia, acidosis, hypothermia, sympathetic of epidural bleeding in association with these activation, and hyperin fl ation. medications [ 45] . Spinal anesthesia should be Most patients with PH bene fi t from arterial avoided as it may cause sudden and poorly toler- and central venous catheters in order to allow ated hemodynamic changes at induction and during continuous blood pressure monitoring, frequent recovery from the block [45 ] . Limited regional analysis of arterial blood gases, and help assess anesthesia using nerve blocks should be consid- fl uid volume status. While the need for intraop- ered when appropriate. erative insertion of a pulmonary arterial catheter General anesthesia can increase PVR by is somewhat controversial (based on lack of several mechanisms as described in Table 11.1 . evidence on improving outcomes and the concern During intubation, opioids and lidocaine can be 146 A.R. Tonelli et al. used to block the cardiorespiratory response. Table 11.6 Management of acute decompensated PH Propofol, pentothal, and etomidate are appropri- Treat known PH triggers (hypoxia, hypercarbia, acidosis, ate induction medications [2, 45, 92 ] . Although and hypothermia) concerns exist regarding the use of ketamine in Keep central venous pressure above 12–15 mmHg PH patients as it may increase PAP [ 93 ] , a recent Consider initiating inotropic therapy (dobutamine or milrinone) retrospective study looking at perioperative Maintain systemic blood pressure (norepinephrine or complications, in children with PH undergoing vasopressin) general anesthesia with ketamine, found compa- Initiate PH speci fi c therapies (inhaled nitric oxide, rable rates of complications than other medica- epoprostenol [IV or inhaled]) tions, when used alone or combined with other Consider mechanical support (ECMO or intraaortic agents [ 94 ] . Dexmedetomidine, an alpha2-agoinst balloon pump) that reduces central sympathetic out fl ow and induces sedation, may reduce the need for supplemental cations are available for the management of anesthetic medications and be benefi cial in PH decompensated PH and RV failure. The appro- patients [95, 96 ] . Volatile anesthetic agents, priated medications need to be individualized for which are regularly used for maintenance, may each patient based on effects on blood pressure, adversely affect RV preload, contractility, and preload, PVR, and cardiac output. Dobutamine afterload, leading to RV dysfunction [ 97, 98 ] . and milrinone are inotropic agents with vasodila- These agents can also decrease systemic arterial tor properties (inodilators), thereby increasing pressure, resulting in RV ischemia. The effect of RV function and reducing PVR [106– 108 ] . If volatile anesthetic agents on the pulmonary vas- systemic hypotension develops despite optimiza- culature has been contradictory, and no speci fi c tion of the fl uid volume, ventilator settings, and agent has been proven superior in its effects [ 92, medications, vasopressors may need to be added 98– 101 ] . Nitrous oxide should generally be in order to prevent or treat RV ischemia [ 109, 110 ] . avoided as it may increase PVR and postopera- Hypotension during the perioperative period tive myocardial ischemia [ 102– 104 ] . High-dose should not be managed by downward titration opioids can blunt the cardiovascular response to of PH speci fi c therapies [2 ] . Vasopressors used in surgical stimulation and reduce the dose of volatile PH include norepinephrine and vasopressin anesthetics, limiting their adverse effects [ 89 ] . [ 111– 113] . Norepinephrine decreases the ratio of In patients requiring mechanical ventilation, PAP/systemic blood pressure without a change in hyperin fl ation and the use of high levels of posi- CI [ 111 ] , and vasopressin has been used success- tive end-expiratory pressure (PEEP) should be fully in PH patients, although limited information avoided as they may reduce RV preload and is available [112, 114 ] . Dopamine and epineph- increase PVR [105 ] . It is reasonable to use high rine are not recommended as they tend to increase

FIO2 , moderate tidal volumes with low levels of heart rate and myocardial oxygen consumption PEEP and relatively high respiratory rates to more than norepinephrine [5, 115 ] . It is unknown prevent hypoxemia, hypercarbia and pulmonary if these differences in the pro fi le of vasopressors capillary vessel compression by lung overin fl ation could have a clinically signi fi cant impact in the [ 86] . However, further studies are needed to perioperative management of patients with PH. support this ventilatory approach. In patients with CTD, before the initiation of a particular vasopressor, risk and benefi ts should be considered since these agents can have serious Management of PH Crisis and RV adverse effects (e.g., digital necrosis, renal failure). Failure Pulmonary vasodilators included iNO and other PH speci fi c therapies. Inhaled nitric A summary of the recommendations regarding oxide reduces pulmonary artery pressures and management of acutely decompensated patient with PVR, and it does not produce systemic vasodi- PH during the intraoperative or postoperative lation as it is rapidly inactivated in the circula- period is presented in Table 11.6 . Several medi- tion by hemoglobin binding [90, 116– 120 ] . 11 Perioperative Management of the Patient with Pulmonary Hypertension 147

Pulmonary hypertension-speci fi c therapies, used in the perioperative period, include oral or Postoperative Care IV sildena fi l [5, 121, 122] , IV or inhaled epopros- tenol [123– 128 ] , inhaled iloprost [ 59, 129– 131 ] , Most PH patients that die in the perioperative and IV treprostinil [132 ] . Endothelin receptor period do so in the fi rst few days after the surgery. antagonists have a limited role in the acute set- Therefore, patients should be closely followed ting as they are considered long-term therapies for sudden worsening of PH and development of for PH [133, 134 ] . There is lack of data to recom- RV failure as anesthetics wear off (Table 11.7 ). mend any specifi c therapeutic strategy. Inhaled Extubation should be performed in the intensive agents are especially attractive since they pro- care unit when there is adequate oxygenation duce short-acting and preferential pulmonary (fraction of inspiratory oxygen requirements of vasodilation without other hemodynamic effects. £40%) and ventilation. The patient should have Intravenous vasodilators may decrease sys- appropriate analgesia and be hemodynamically temic blood pressure (posing a risk for RV isch- stable; in order to avoid PH triggers (e.g., pain, emia), and lead to worsening V/Q mismatch by hypoxia and hypercarbia). For less invasive reversal of hypoxia-induced vasoconstriction. In surgeries without complications, the patient can addition, IV vasodilators can increase the fl ow of be extubated in the operating room [39 ] . We do right-to-left shunts (e.g., through a patent fora- not routinely recommend pulmonary artery cath- men ovale), worsening oxygenation [5 ] . It is eter monitoring. In the patients that require this relevant to mention that IV prostacyclins should invasive monitoring in the postoperative period, not be used in patients with severe left ventricular we tend to remove it as soon as the patient dysfunction as they may worsen survival [135 ] . becomes hemodynamically stable. Frequent arte- Data are promising for the use of other thera- rial blood gases may be needed in the periopera- pies such as inhaled milrinone (less systemic tive period as pulse oximetry monitoring in the effects) [136– 139 ] , inhaled nitrogylcerin (selec- setting of severe Raynaud’s phenomenon may tive pulmonary vasodilatory effects) [140, 141 ] , not be reliable. IV iloprost [ 142 ] , IV and inhaled sildena fi l [143 ] , The management of PH crises and RV failure and IV levosimendan (acts as a myocardial cal- is analogous to the intraoperative approach cium sensitizer and vasodilator) [ 97, 144, 145 ] . described above. If started intraoperatively, ino- Further studies are needed before recommenda- tropics, vasopressors, and pulmonary vasodila- tions regarding these therapies can be provided. tors should be weaned off gradually. Sildena fi l In rare circumstances, patients may bene fi t has been used successfully in the postoperative from mechanical support such as venoarterial management of PH after heart transplantation extracorporeal membrane oxygenation (ECMO) and congenital heart surgery [151, 152 ] . As serum or intra-aortic balloon pump as a bridge to levels of brain natriuretic peptide (BNP) and tro- recovery or transplantation [ 146– 148 ] . A right ponin T are associated with outcomes in PH, it is ventricular assist device in the presence of PH is possible that these biomarkers may play a role in likely ineffective as the increased fl ow may predicting complications in the postoperative result in an increased pulmonary artery pressure period, although studies are needed to prove and lung injury [149 ] . Atrial septostomy allows the utility of these blood tests in this setting decompression of the right heart chambers, [ 153– 155 ] . decreasing wall tension and improving contrac- tility. Due to the high associated risk, this proce- Table 11.7 Postoperative care of PH patients dure should only be used in very highly selected Close monitoring cases, by experienced personnel, and only when Avoid PH triggers other interventions have failed [ 41, 150 ] . Lung Provide adequate analgesia transplantation is usually not an option as Extubate when goals are met patients are often unsuitable candidates due to Gently wean off inotropes, vasopressors, and pulmo- comorbidities. nary vasodilators (started during surgery) 148 A.R. Tonelli et al.

of pulmonary hypertension. J Am Coll Cardiol. Conclusion 2009;54(1 Suppl):S43–54. 7. Badesch DB, Champion HC, Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Patients with PH are being encountered more fre- Olschewski H, Oudiz RJ, Torbicki A. Diagnosis and quently in the perioperative period, and this trend assessment of pulmonary arterial hypertension. J Am is likely to continue. The management of these Coll Cardiol. 2009;54(1 Suppl):S55–66. 8. McGoon M, Gutterman D, Steen V, Barst R, patients is challenging due to their tenuous hemo- McCrory DC, Fortin TA, Loyd JE, American College dynamic and respiratory status. Recent advances of Chest Physicians. Screening, early detection, and in the understanding of the pathophysiology, risk diagnosis of pulmonary arterial hypertension: ACCP factors, monitoring, and treatment of the disease evidence-based clinical practice guidelines. Chest. 2004;126(1 Suppl):14S–34S. provides an opportunity to improve their out- 9. Humbert M, Sitbon O, Chaouat A, Bertocchi M, comes, during and after surgical interventions, Habib G, Gressin V, Yaici A, Weitzenblum E, with the proper care. Due to increased mortality Cordier JF, Chabot F, Dromer C, Pison C, Reynaud- and morbidity, the perioperative management of Gaubert M, Haloun A, Laurent M, Hachulla E, Simonneau G. Pulmonary arterial hypertension in these patients requires a thorough multidisci- France: results from a national registry. Am J Respir plinary approach and meticulous care that is best Crit Care Med. 2006;173(9):1023–30. provided in large centers that specialize in PH 10. Hachulla E, Gressin V, Guillevin L, Carpentier P, management. Therapy is aimed at minimizing risk Diot E, Sibilia J, Kahan A, Cabane J, Francès C, Launay D, Mouthon L, Allanore Y, Tiev KP, Clerson factors, optimizing hemodynamics (RV preload, P, de Groote P, Humbert M. Early detection of afterload, and contractility), careful monitoring, pulmonary arterial hypertension in systemic sclero- and aggressive treatment of complications. sis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005;52(12):3792–800. 11. Hachulla E, de Groote P, Gressin V, Sibilia J, Diot E, Carpentier P, Mouthon L, Hatron PY, Jego P, Allanore Y, Tiev KP, Agard C, Cosnes A, Cirstea D, Constans References J, Farge D, Viallard JF, Harle JR, Patat F, Imbert B, Kahan A, Cabane J, Clerson P, Guillevin L, Humbert 1. Macchia A, Marchioli R, Tognoni G, Scarano M, M, Itinér AIR-Sclérodermie Study Group. The three- Marfi si R, Tavazzi L, Rich S. Systematic review of year incidence of pulmonary arterial hypertension trials using vasodilators in pulmonary arterial hyper- associated with systemic sclerosis in a multicenter tension: why a new approach is needed. Am Heart nationwide longitudinal study in France. Arthritis J. 2010;159(2):245–57. Rheum. 2009;60(6):1831–9. 2. Pritts CD, Pearl RG. Anesthesia for patients with 12. Mukerjee D, St. George D, Coleiro B, Knight C, pulmonary hypertension. Curr Opin Anaesthesiol. Denton CP, Davar J, Black CM, Coghlan JG. 2010;23(3):411–6. Prevalence and outcome in systemic sclerosis asso- 3. Galiè N, Manes A, Negro L, Palazzini M, Bacchi- ciated pulmonary arterial hypertension: application Reggiani ML, Branzi A. A meta-analysis of randomized of a registry approach. Ann Rheum Dis. 2003; controlled trials in pulmonary arterial hypertension. 62(11):1088–93. Eur Heart J. 2009;30(4):394–403. 13. MacGregor AJ, Canavan R, Knight C, Denton CP, 4. Condliffe R, Kiely DG, Peacock AJ, Corris PA, Davar J, Coghlan J, Black CM. Pulmonary hyperten- Gibbs JS, Vrapi F, Das C, Elliot CA, Johnson M, sion in systemic sclerosis: risk factors for progres- DeSoyza J, Torpy C, Goldsmith K, Hodgkins D, sion and consequences for survival. Rheumatology Hughes RJ, Pepke-Zaba J, Coghlan JG. Connective (Oxford). 2001;40(4):453–9. tissue disease-associated pulmonary arterial hyper- 14. Galiè N, Manes A, Farahani KV, Pelino F, Palazzini tension in the modern treatment era. Am J Respir M, Negro L, Romanazzi S, Branzi A. Pulmonary Crit Care Med. 2009;179(2):151–7. arterial hypertension associated to connective tissue 5. Hill NS, Roberts KR, Preston IR. Postoperative diseases. Lupus. 2005;14(9):713–7. pulmonary hypertension: etiology and treatment of 15. Tanaka E, Harigai M, Tanaka M, Kawaguchi Y, Hara a dangerous complication. Respir Care. 2009;54(7): M, Kamatani N. Pulmonary hypertension in sys- 958–68. temic lupus erythematosus: evaluation of clinical 6. Simonneau G, Robbins IM, Beghetti M, Channick characteristics and response to immunosuppressive RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, treatment. J Rheumatol. 2002;29(2):282–7. Gladwin MT, Jing ZC, Krowka MJ, Langleben D, 16. Asherson RA, Higenbottam TW, Dinh Xuan AT, Nakanishi N, Souza R. Updated clinical classi fi cation Khamashta MA, Hughes GR. Pulmonary hyperten- 11 Perioperative Management of the Patient with Pulmonary Hypertension 149

sion in a lupus clinic: experience with twenty-four 29. Steen VD, Medsger TA. Changes in causes of death patients. J Rheumatol. 1990;17(10):1292–8. in systemic sclerosis, 1972–2002. Ann Rheum Dis. 17. Pan TL, Thumboo J, Boey ML. Primary and second- 2007;66(7):940–4. ary pulmonary hypertension in systemic lupus 30. Kawut SM, Taichman DB, Archer-Chicko CL, erythematosus. Lupus. 2000;9(5):338–42. Palevsky HI, Kimmel SE. Hemodynamics and sur- 18. Prabu A, Patel K, Yee CS, Nightingale P, Situnayake vival in patients with pulmonary arterial hyperten- RD, Thickett DR, Townend JN, Gordon C. Prevalence sion related to systemic sclerosis. Chest. 2003; and risk factors for pulmonary arterial hypertension 123(2):344–50. in patients with lupus. Rheumatology (Oxford). 31. Tyndall AJ, Bannert B, Vonk M, Airò P, Cozzi F, 2009;48(12):1506–11. Carreira PE, Bancel DF, Allanore Y, Müller-Ladner 19. Burdt MA, Hoffman RW, Deutscher SL, Wang GS, U, Distler O, Iannone F, Pellerito R, Pileckyte M, Johnson JC, Sharp GC. Long-term outcome in mixed Miniati I, Ananieva L, Gurman AB, Damjanov N, connective tissue disease: longitudinal clinical and Mueller A, Valentini G, Riemekasten G, Tikly M, serologic fi ndings. Arthritis Rheum. 1999;42(5): Hummers L, Henriques MJ, Caramaschi P, Scheja 899–909. A, Rozman B, Ton E, Kumánovics G, Coleiro B, 20. Launay D, Hachulla E, Hatron PY, Jais X, Simonneau Feierl E, Szucs G, Von Mühlen CA, Riccieri V, G, Humbert M. Pulmonary arterial hypertension: a Novak S, Chizzolini C, Kotulska A, Denton C, rare complication of primary Sjögren syndrome: Coelho PC, Kötter I, Simsek I, de la Pena Lefebvre report of 9 new cases and review of the literature. PG, Hachulla E, Seibold JR, Rednic S, Stork J, Medicine (Baltimore). 2007;86(5):299–315. Morovic-Vergles J, Walker UA. Causes and risk 21. Minai OA. Pulmonary hypertension in polymyositis- factors for death in systemic sclerosis: a study from dermatomyositis: clinical and hemodynamic charac- the EULAR Scleroderma Trials and Research teristics and response to vasoactive therapy. Lupus. (EUSTAR) database. Ann Rheum Dis. 2010;69: 2009;18(11):1006–10. 1809–15. 22. Gonzalez-Juanatey C, Testa A, Garcia-Castelo A, 32. Chung L, Liu J, Parsons L, Hassoun PM, McGoon Garcia-Porrua C, Llorca J, Ollier WE, Gonzalez- M, Badesch D, Miller DP, Nicolls MR, Zamanian Gay MA. Echocardiographic and Doppler fi ndings RT. Characterization of connective tissue disease in long-term treated rheumatoid arthritis patients associated pulmonary arterial hypertension from the without clinically evident cardiovascular disease. REVEAL registry: identifying systemic sclerosis as Semin Arthritis Rheum. 2004;33(4):231–8. a unique phenotype. Chest. 2010;138:1383–94. 23. Dawson JK, Goodson NG, Graham DR, Lynch MP. 33. Fisher MR, Mathai SC, Champion HC, Girgis RE, Raised pulmonary artery pressures measured with Housten-Harris T, Hummers L, Krishnan JA, Doppler echocardiography in rheumatoid arthritis Wigley F, Hassoun PM. Clinical differences patients. Rheumatology (Oxford). 2000;39(12): between idiopathic and scleroderma-related pulmo- 1320–5. nary hypertension. Arthritis Rheum. 2006;54(9): 24. Overbeek MJ, Vonk MC, Boonstra A, Voskuyl AE, 3043–50. Vonk-Noordegraaf A, Smit EF, Dijkmans BA, 34. Hassoun PM. Pulmonary arterial hypertension com- Postmus PE, Mooi WJ, Heijdra Y, Grünberg K. plicating connective tissue diseases. Semin Respir Pulmonary arterial hypertension in limited cutane- Crit Care Med. 2009;30(4):429–39. ous systemic sclerosis: a distinctive vasculopathy. 35. Reich DL, Bodian CA, Krol M, Kuroda M, Osinski Eur Respir J. 2009;34(2):371–9. T, Thys DM. Intraoperative hemodynamic predictors 25. Meune C, Avouac J, Wahbi K, Cabanes L, Wipff J, of mortality, stroke, and myocardial infarction after Mouthon L, Guillevin L, Kahan A, Allanore Y. coronary artery bypass surgery. Anesth Analg. 1999; Cardiac involvement in systemic sclerosis assessed 89(4):814–22. by tissue-doppler echocardiography during routine 36. Reich DL, Wood Jr RK, Emre S, Bodian CA, Hossain care: a controlled study of 100 consecutive patients. S, Krol M, Feierman D. Association of intraopera- Arthritis Rheum. 2008;58(6):1803–9. tive hypotension and pulmonary hypertension with 26. Leslie KO, Trahan S, Gruden J. Pulmonary pathol- adverse outcomes after orthotopic liver transplanta- ogy of the rheumatic diseases. Semin Respir Crit tion. J Cardiothorac Vasc Anesth. 2003;17(6): Care Med. 2007;28(4):369–78. 699–702. 27. Farber HW, Graven KK, Kokolski G, Korn JH. 37. Ramakrishna G, Sprung J, Ravi BS, Chandrasekaran Pulmonary edema during acute infusion of epopros- K, McGoon MD. Impact of pulmonary hypertension tenol in a patient with pulmonary hypertension and on the outcomes of noncardiac surgery: predictors of limited scleroderma. J Rheumatol. 1999;26(5): perioperative morbidity and mortality. J Am Coll 1195–6. Cardiol. 2005;45(10):1691–9. 28. Saito A, Takizawa H, Ito K, Yamamoto K, Oka T. A 38. Lai HC, Lai HC, Wang KY, Lee WL, Ting CT, Liu case of pulmonary veno-occlusive disease associated TJ. Severe pulmonary hypertension complicates with systemic sclerosis. Respirology. 2003;8(3): postoperative outcome of non-cardiac surgery. Br 383–5. J Anaesth. 2007;99(2):184–90. 150 A.R. Tonelli et al.

39. Minai OA, Venkateshiah SB, Arroliga AC. Surgical hypertension during pregnancy: mode of delivery intervention in patients with moderate to severe and anesthetic management of 15 consecutive cases. pulmonary arterial hypertension. Conn Med. 2006; Anesthesiology. 2005;102(6):1133–7. 70(4):239–43. 55. Fleisher LA, Beckman JA, Brown KA, Calkins H, 40. Bédard E, Dimopoulos K, Gatzoulis MA. Has there Chaikof EL, Fleischmann KE, Freeman WK, been any progress made on pregnancy outcomes Froehlich JB, Kasper EK, Kersten JR, Riegel B, among women with pulmonary arterial hyperten- Robb JF. 2009 ACCF/AHA focused update on peri- sion? Eur Heart J. 2009;30(3):256–65. operative beta blockade incorporated into the ACC/ 41. Piazza G, Goldhaber SZ. The acutely decompen- AHA 2007 guidelines on perioperative cardiovascu- sated right ventricle: pathways for diagnosis and lar evaluation and care for noncardiac surgery: a management. Chest. 2005;128(3):1836–52. report of the American college of cardiology founda- 42. Szabó G, Soós P, Bährle S, Radovits T, Weigang E, tion/American heart association task force on Kékesi V, Merkely B, Hagl S. Adaptation of the right practice guidelines. Circulation. 2009;120(21): ventricle to an increased afterload in the chronically e169–276. Nov 24. volume overloaded heart. Ann Thorac Surg. 2006; 56. Price LC, Montani D, Jaïs X, Dick JR, Simonneau 82(3):989–95. G, Sitbon O, Mercier FJ, Humbert M. Noncardio- 43. McIntyre KM, Sasahara AA. Determinants of right thoracic nonobstetric surgery in mild-to-moderate ventricular function and hemodynamics after pulmo- pulmonary hypertension. Eur Respir J. 2010; nary embolism. Chest. 1974;65(5):534–43. 35(6):1294–302. 44. Zamanian RT, Haddad F, Doyle RL, Weinacker AB. 57. Kaw R, Pasupuleti V, Deshpande A, et al. Pulmonary Management strategies for patients with pulmonary hypertension: an important predictor of outcomes in hypertension in the intensive care unit. Crit Care patients undergoing non-cardiac surgery. Respir Med. 2007;35(9):2037–50. Med. 2010;105:619–24. 45. Blaise G, Langleben D, Hubert B. Pulmonary arte- 58. Kaw R, Pasupuleti V, Deshpande A, et al. Noncardiac rial hypertension: pathophysiology and anesthetic surgical outcomes in patients with angiographically approach. Anesthesiology. 2003;99(6):1415–32. proven pulmonary hypertension. Chest. 46. Bristow MR, Zisman LS, Lowes BD, Abraham 2008;134:s63002. WT, Badesch DB, Groves BM, Voelkel NF, Lynch 59. Ghaffari S. Detection and management of coronary DM, Quaife RA. The pressure-overloaded right artery disease in patients with rheumatologic disor- ventricle in pulmonary hypertension. Chest. ders. Rheum Dis Clin North Am. 1999;25(3): 1998;114(1 Suppl):101S–6. 657–68. 47. Moudgil R, Michelakis ED, Archer SL. Hypoxic 60. Birdas TJ, Landis JT, Haybron D, Evers D, Papasavas pulmonary vasoconstriction. J Appl Physiol. PK, Caushaj PF. Outcomes of coronary artery bypass 2005;98(1):390–403. grafting in patients with connective tissue diseases. 48. Balanos GM, Talbot NP, Dorrington KL, Robbins Ann Thorac Surg. 2005;79(5):1610–4. PA. Human pulmonary vascular response to 4 h of 61. Bouma W, Klinkenberg TJ, van der Horst IC, Wijdh- hypercapnia and hypocapnia measured using den Hamer IJ, Erasmus ME, Bijl M, Suurmeijer AJ, Doppler echocardiography. J Appl Physiol. Zijlstra F, Mariani MA. Mitral valve surgery for 2003;94(4):1543–51. mitral regurgitation caused by Libman-Sacks endo- 49. Jardin F, Brun-Ney D, Cazaux P, Dubourg O, Hardy carditis: a report of four cases and a systematic A, Bourdarias JP. Relation between transpulmonary review of the literature. J Cardiothorac Surg. pressure and right ventricular isovolumetric pressure 2010;5:13. change during respiratory support. Cathet Cardiovasc 62. Roques F, Nashef SA, Michel P, Gauducheau E, de Diagn. 1989;16(4):215–20. Vincentiis C, Baudet E, Cortina J, David M, Faichney 50. Winterhalter M, Antoniou T, Loukanov T. A, Gabrielle F, Gams E, Harjula A, Jones MT, Pintor Management of adult patients with perioperative PP, Salamon R, Thulin L. Risk factors and outcome pulmonary hypertension: technical aspects and ther- in European cardiac surgery: analysis of the apeutic options. Cardiology. 2010;116(1):3–9. EuroSCORE multinational database of 19030 51. van Oppen AC, Stigter RH, Bruinse HW. Cardiac patients. Eur J Cardiothorac Surg. 1999;15(6): output in normal pregnancy: a critical review. Obstet 816–22. Gynecol. 1996;87(2):310–8. 63. Bernstein AD, Parsonnet V. Bedside estimation of 52. Madden BP. Pulmonary hypertension and pregnancy. risk as an aid for decision-making in cardiac surgery. Int J Obstet Anesth. 2009;18(2):156–64. Ann Thorac Surg. 2000;69(3):823–8. 53. Rodriguez RM, Pearl RG. Pulmonary hypertension 64. Tuman KJ, McCarthy RJ, March RJ, Naja fi H, and major surgery. Anesth Analg. 1998;87(4): Ivankovich AD. Morbidity and duration of ICU stay 812–5. after cardiac surgery. A model for preoperative risk 54. Bonnin M, Mercier FJ, Sitbon O, Roger-Christoph assessment. Chest. 1992;102(1):36–44. S, Jaïs X, Humbert M, Audibert F, Frydman R, 65. Mubeen M, Singh AK, Agarwal SK, Pillai J, Kapoor Simonneau G, Benhamou D. Severe pulmonary S, Srivastava AK. Mitral valve replacement in severe 11 Perioperative Management of the Patient with Pulmonary Hypertension 151

pulmonary arterial hypertension. Asian Cardiovasc 79. Stewart R, Tuazon D, Olson G, Duarte AG. Thorac Ann. 2008;16(1):37–42. Pregnancy and primary pulmonary hypertension: 66. Cesnjevar RA, Feyrer R, Walther F, Mahmoud FO, successful outcome with epoprostenol therapy. Lindemann Y, von der Emde J. High-risk mitral Chest. 2001;119(3):973–5. valve replacement in severe pulmonary hyperten- 80. Goland S, Tsai F, Habib M, Janmohamed M, sion–30 years experience. Eur J Cardiothorac Surg. Goodwin TM, Elkayam U. Favorable outcome of 1998;13(4):344–51. pregnancy with an elective use of epoprostenol and 67. Malouf JF, Enriquez-Sarano M, Pellikka PA, Oh JK, sildena fi l in women with severe pulmonary hyper- Bailey KR, Chandrasekaran K, Mullany CJ, Tajik tension. Cardiology. 2010;115(3):205–8. AJ. Severe pulmonary hypertension in patients with 81. Robinson JN, Banerjee R, Landzberg MJ, Thiet MP. severe aortic valve stenosis: clinical profi le and Inhaled nitric oxide therapy in pregnancy compli- prognostic implications. J Am Coll Cardiol. cated by pulmonary hypertension. Am J Obstet 2002;40(4):789–95. Gynecol. 1999;180(4):1045–6. 68. Robitaille A, Denault AY, Couture P, Bélisle S, 82. Streit M, Speich R, Fischler M, Ulrich S. Successful Fortier A, Guertin MC, Carrier M, Martineau R. pregnancy in pulmonary arterial hypertension asso- Importance of relative pulmonary hypertension in ciated with systemic lupus erythematosus: a case cardiac surgery: the mean systemic-to-pulmonary report. J Med Case Reports. 2009;3:7255. artery pressure ratio. J Cardiothorac Vasc Anesth. 83. Cuenco J, Tzeng G, Wittels B. Anesthetic manage- 2006;20(3):331–9. ment of the parturient with systemic lupus erythema- 69. Balzer DT, Kort HW, Day RW, Corneli HM, tosus, pulmonary hypertension, and pulmonary Kovalchin JP, Cannon BC, Kaine SF, Ivy DD, edema. Anesthesiology. 1999;91(2):568–70. Webber SA, Rothman A, Ross RD, Aggarwal S, 84. Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Takahashi M, Waldman JD. Inhaled Nitric Oxide as Brundage BH, Detre KM, Fishman AP, Goldring a Preoperative Test (INOP Test I): the INOP test RM, Groves BM, Koerner SK, et al. Primary pulmo- study group. Circulation. 2002;106(12 Suppl 1): nary hypertension. A national prospective study. I76–81. Ann Intern Med. 1987;107(2):216–23. 70. Weiss BM, Zemp L, Seifert B, Hess OM. Outcome 85. Ross AF, Ueda K. Pulmonary hypertension in tho- of pulmonary vascular disease in pregnancy: a sys- racic surgical patients. Curr Opin Anaesthesiol. tematic overview from 1978 through 1996. J Am 2010;23(1):25–33. Coll Cardiol. 1998;31(7):1650–7. 86. MacKnight B, Martinez EA, Simon BA. Anesthetic 71. Zwicke DL, Buggy BP. Pregnancy and pulmonary management of patients with pulmonary hyperten- arterial hypertension: successful management of 37 sion. Semin Cardiothorac Vasc Anesth. 2008;12(2): consecutive patients. Chest. 2008;124:AS2331. 91–6. 72. Yentis SM, Steer PJ, Plaat F. Eisenmenger’s syn- 87. Roberts DH, Lepore JJ, Maroo A, Semigran MJ, Ginns drome in pregnancy: maternal and fetal mortality LC. Oxygen therapy improves cardiac index and pul- in the 1990s. Br J Obstet Gynaecol. 1998;105(8): monary vascular resistance in patients with pulmonary 921–2. hypertension. Chest. 2001;120(5):1547–55. 73. Gleicher N, Midwall J, Hochberger D, Jaf fi n H. 88. Rich S, Seidlitz M, Dodin E, Osimani D, Judd D, Eisenmenger’s syndrome and pregnancy. Obstet Genthner D, McLaughlin V, Francis G. The short- Gynecol Surv. 1979;34(10):721–41. term effects of digoxin in patients with right ven- 74. Kiely DG, Condliffe R, Webster V, Mills GH, tricular dysfunction from pulmonary hypertension. Wrench I, Gandhi SV, Selby K, Armstrong IJ, Martin Chest. 1998;114(3):787–92. L, Howarth ES, Bu’lock FA, Stewart P, Elliot CA. 89. Teo YW, Greenhalgh DL. Update on anaesthetic Improved survival in pregnancy and pulmonary approach to pulmonary hypertension. Eur J hypertension using a multiprofessional approach. Anaesthesiol. 2010;27(4):317–23. BJOG. 2010;117(5):565–74. 90. Tonelli AR, Alnuaimat H, Mubarak K. Pulmonary 75. Smedstad KG, Cramb R, Morison DH. Pulmonary vasodilator testing and use of calcium channel hypertension and pregnancy: a series of eight cases. blockers in pulmonary arterial hypertension. Respir Can J Anaesth. 1994;41(6):502–12. Med. 2010;104(4):481–96. 76. Easterling TR, Ralph DD, Schmucker BC. Pulmonary 91. Hoeper MM, Lee SH, Voswinckel R, Palazzini M, hypertension in pregnancy: treatment with pulmo- Jais X, Marinelli A, Barst RJ, Ghofrani HA, Jing ZC, nary vasodilators. Obstet Gynecol. 1999;93(4): Opitz C, Seyfarth HJ, Halank M, McLaughlin V, 494–8. Oudiz RJ, Ewert R, Wilkens H, Kluge S, Bremer 77. Budev MM, Arroliga AC, Emery S. Exacerbation of HC, Baroke E, Rubin LJ. Complications of right underlying pulmonary disease in pregnancy. Crit heart catheterization procedures in patients with Care Med. 2005;33(10 Suppl):S313–8. pulmonary hypertension in experienced centers. 78. Madsen KM, Neerhof MG, Wessale JL, Thaete LG. J Am Coll Cardiol. 2006;48(12):2546–52. Infl uence of ET(B) receptor antagonism on preg- 92. Kaddoum RN, Mubarak K, Chidiac EJ. Pulmonary nancy outcome in rats. J Soc Gynecol Investig. hypertension and anesthesia. Middle East J Anes- 2001;8(4):239–44. thesiol. 2006;18(6):1095–111. 152 A.R. Tonelli et al.

93. Spotoft H, Korshin JD, Sørensen MB, Skovsted P. 106. Vizza CD, Rocca GD, Roma AD, Iacoboni C, The cardiovascular effects of ketamine used for Pierconti F, Venuta F, Rendina E, Schmid G, induction of anaesthesia in patients with valvular Pietropaoli P, Fedele F. Acute hemodynamic effects heart disease. Can Anaesth Soc J. 1979;26(6): of inhaled nitric oxide, dobutamine and a combina- 463–7. tion of the two in patients with mild to moderate 94. Williams GD, Maan H, Ramamoorthy C, Kamra K, secondary pulmonary hypertension. Crit Care. Bratton SL, Bair E, Kuan CC, Hammer GB, Feinstein 2001;5(6):355–61. JA. Perioperative complications in children with pul- 107. Chen EP, Bittner HB, Davis RD Jr, Van Trigt P 3rd. monary hypertension undergoing general anesthesia Milrinone improves pulmonary hemodynamics and with ketamine. Paediatr Anaesth. 2010;20(1): right ventricular function in chronic pulmonary 28–37. hypertension. Ann Thorac Surg. 1997;63(3): 95. Shinohara H, Hirota K, Sato M, Kakuyama M, 814–21. Fukuda K. Monitored anesthesia care with dexme- 108. Jenkins IR, Dolman J, O’Connor JP, Ansley DM. detomidine of a patient with severe pulmonary arte- Amrinone versus dobutamine in cardiac surgical rial hypertension for inguinal hernioplasty. J Anesth. patients with severe pulmonary hypertension after 2010;24:611–3. cardiopulmonary bypass: a prospective, randomized 96. But AK, Ozgul U, Erdil F, Gulhas N, Toprak HI, double-blinded trial. Anaesth Intensive Care. Durmus M, Ersoy MO. The effects of pre-operative 1997;25(3):245–9. dexmedetomidine infusion on hemodynamics in 109. Vlahakes GJ. Management of pulmonary hyperten- patients with pulmonary hypertension undergoing sion and right ventricular failure: another step for- mitral valve replacement surgery. Acta Anaesthesiol ward. Ann Thorac Surg. 1996;61(4):1051–2. Scand. 2006;50(10):1207–12. 110. Vlahakes GJ, Turley K, Hoffman JI. The pathophysi- 97. Forrest P. Anaesthesia and right ventricular failure. ology of failure in acute right ventricular hyperten- Anaesth Intensive Care. 2009;37(3):370–85. sion: hemodynamic and biochemical correlations. 98. Kerbaul F, Rondelet B, Motte S, Fesler P, Hubloue I, Circulation. 1981;63(1):87–95. Ewalenko P, Naeije R, Brimioulle S. Iso fl urane and 111. Kwak YL, Lee CS, Park YH, Hong YW. The effect des fl urane impair right ventricular-pulmonary arte- of phenylephrine and norepinephrine in patients with rial coupling in dogs. Anesthesiology. 2004;101(6): chronic pulmonary hypertension. Anaesthesia. 1357–62. 2002;57(1):9–14. 99. Cheng DC, Edelist G. Iso fl urane and primary pul- 112. Smith AM, Elliot CM, Kiely DG, Channer KS. The monary hypertension. Anaesthesia. 1988;43(1): role of vasopressin in cardiorespiratory arrest and 22–4. pulmonary hypertension. QJM. 2006;99(3):127–33. 100. Ciofolo MJ, Reiz S. Circulatory effects of volatile 113. Gold J, Cullinane S, Chen J, Seo S, Oz MC, Oliver anesthetic agents. Minerva Anestesiol. 1999;65(5): JA, Landry DW. Vasopressin in the treatment of 232–8. milrinone-induced hypotension in severe heart 101. Pagel PS, Fu JL, Damask MC, Davis RF, Samuelson failure. 122- Am J Cardiol. 2000 Feb 15;85(4): PN, Howie MB, Warltier DC. Desfl urane and 506–8, A11. isofl urane produce similar alterations in systemic 114. Price LC, Forrest P, Sodhi V, Adamson DL, Nelson- and pulmonary hemodynamics and arterial oxygen- Piercy C, Lucey M, Howard LS. Use of vasopressin ation in patients undergoing one-lung ventilation after caesarean section in idiopathic pulmonary arte- during thoracotomy. Anesth Analg. 1998;87(4): rial hypertension. Br J Anaesth. 2007;99(4):552–5. 800–7. 115. Lobato EB, Gravenstein N, Martin TD. Milrinone, 102. Schulte-Sasse U, Hess W, Tarnow J. Pulmonary vas- not epinephrine, improves left ventricular compli- cular responses to nitrous oxide in patients with ance after cardiopulmonary bypass. J Cardiothorac normal and high pulmonary vascular resistance. Vasc Anesth. 2000;14(4):374–7. Anesthesiology. 1982;57(1):9–13. 116. Solina A, Papp D, Ginsberg S, Krause T, Grubb W, 103. Myles PS, Chan MT, Kaye DM, McIlroy DR, Lau Scholz P, Pena LL, Cody R. A comparison of inhaled CW, Symons JA, Chen S. Effect of nitrous oxide nitric oxide and milrinone for the treatment of pulmo- anesthesia on plasma homocysteine and endothelial nary hypertension in adult cardiac surgery patients. J function. Anesthesiology. 2008;109(4):657–63. Cardiothorac Vasc Anesth. 2000;14(1):12–7. 104. Badner NH, Beattie WS, Freeman D, Spence JD. 117. Schmid ER, Bürki C, Engel MH, Schmidlin D, Nitrous oxide-induced increased homocysteine con- Tornic M, Seifert B. Inhaled nitric oxide versus centrations are associated with increased postopera- intravenous vasodilators in severe pulmonary hyper- tive myocardial ischemia in patients undergoing tension after cardiac surgery. Anesth Analg. carotid endarterectomy. Anesth Analg. 2000;91(5): 1999;89(5):1108–15. 1073–9. 118. Rajek A, Pernerstorfer T, Kastner J, Mares P, 105. Jardin F, Vieillard-Baron A. Right ventricular func- Grabenwöger M, Sessler DI, Grubhofer G, Hiesmayr tion and positive pressure ventilation in clinical M. Inhaled nitric oxide reduces pulmonary vascular practice: from hemodynamic subsets to respirator resistance more than prostaglandin E(1) during heart settings. Intensive Care Med. 2003;29(9):1426–34. transplantation. Anesth Analg. 2000;90(3):523–30. 11 Perioperative Management of the Patient with Pulmonary Hypertension 153

119. Fattouch K, Sbraga F, Bianco G, Speziale G, cardiac surgery: a prospective randomized trial. Gucciardo M, Sampognaro R, Ruvolo G. Inhaled J Cardiothorac Vasc Anesth. 2008;22(3):406–13. prostacyclin, nitric oxide, and nitroprusside in pul- 130. Rex S, Schaelte G, Metzelder S, Flier S, de Waal EE, monary hypertension after mitral valve replacement. Autschbach R, Rossaint R, Buhre W. Inhaled ilo- J Card Surg. 2005 Mar–Apr;20(2):171–6. prost to control pulmonary artery hypertension in 120. Bhorade S, Christenson J, O’connor M, Lavoie A, patients undergoing mitral valve surgery: a prospec- Pohlman A, Hall JB. Response to inhaled nitric tive, randomized-controlled trial. Acta Anaesthesiol oxide in patients with acute right heart syndrome. Scand. 2008;52(1):65–72. Am J Respir Crit Care Med. 1999;159(2):571–9. 131. Theodoraki K, Rellia P, Thanopoulos A, Tsourelis L, 121. De Santo LS, Mastroianni C, Romano G, Amarelli Zarkalis D, Sfyrakis P, Antoniou T. Inhaled iloprost C, Marra C, Maiello C, Galdieri N, Della Corte A, controls pulmonary hypertension after cardiopulmo- Cotrufo M, Caianiello G. Role of sildenafi l in acute nary bypass. Can J Anaesth. 2002;49(9):963–7. posttransplant right ventricular dysfunction: suc- 132. Fontana M, Olschewski H, Olschewski A, Schlüter cessful experience in 13 consecutive patients. KD. Treprostinil potentiates the positive inotropic Transplant Proc. 2008;40(6):2015–8. effect of catecholamines in adult rat ventricular car- 122. Lee JE, Hillier SC, Knoderer CA. Use of sildena fi l to diomyocytes. Br J Pharmacol. 2007;151(6):779–86. facilitate weaning from inhaled nitric oxide in chil- 133. Sitbon O, Badesch DB, Channick RN, Frost A, dren with pulmonary hypertension following surgery Robbins IM, Simonneau G, Tapson VF, Rubin LJ. for congenital heart disease. J Intensive Care Med. Effects of the dual endothelin receptor antagonist 2008;23(5):329–34. bosentan in patients with pulmonary arterial hyper- 123. Schroeder RA, Wood GL, Plotkin JS, Kuo PC. tension: a 1-year follow-up study. Chest. Intraoperative use of inhaled PGI(2) for acute pul- 2003;124(1):247–54. monary hypertension and right ventricular failure. 134. Williamson DJ, Wallman LL, Jones R, Keogh AM, Anesth Analg. 2000;91(2):291–5. Scroope F, Penny R, Weber C, Macdonald PS. 124. Haché M, Denault AY, Bélisle S, Couture P, Babin Hemodynamic effects of Bosentan, an endothelin D, Tétrault F, Guimond JG. Inhaled prostacyclin receptor antagonist, in patients with pulmonary (PGI2) is an effective addition to the treatment of hypertension. Circulation. 2000;102(4):411–8. pulmonary hypertension and hypoxia in the operat- 135. Califf RM, Adams KF, McKenna WJ, Gheorghiade ing room and intensive care unit. Can J Anaesth. M, Uretsky BF, McNulty SE, Darius H, Schulman 2001;48(9):924–9. K, Zannad F, Handberg-Thurmond E, Harrell Jr FE, 125. De Wet CJ, Af fl eck DG, Jacobsohn E, Avidan MS, Wheeler W, Soler-Soler J, Swedberg K. A random- Tymkew H, Hill LL, Zanaboni PB, Moazami N, ized controlled trial of epoprostenol therapy for Smith JR. Inhaled prostacyclin is safe, effective, and severe congestive heart failure: The Flolan affordable in patients with pulmonary hypertension, International Randomized Survival Trial (FIRST). right heart dysfunction, and refractory hypoxemia Am Heart J. 1997;134(1):44–54. after cardiothoracic surgery. J Thorac Cardiovasc 136. Wang H, Gong M, Zhou B, Dai A. Comparison of Surg. 2004;127(4):1058–67. inhaled and intravenous milrinone in patients with 126. Haraldsson A, Kieler-Jensen N, Nathorst-Westfelt pulmonary hypertension undergoing mitral valve U, Bergh CH, Ricksten SE. Comparison of inhaled surgery. Adv Ther. 2009;26(4):462–8. nitric oxide and inhaled aerosolized prostacyclin in 137. Buckley MS, Feldman JP. Nebulized milrinone use the evaluation of heart transplant candidates with in a pulmonary hypertensive crisis. Pharmacotherapy. elevated pulmonary vascular resistance. Chest. 2007;27(12):1763–6. 1998;114(3):780–6. 138. Lamarche Y, Perrault LP, Maltais S, Tétreault K, 127. Mikhail G, Gibbs J, Richardson M, Wright G, Lambert J, Denault AY. Preliminary experience with Khaghani A, Banner N, Yacoub M. An evaluation of inhaled milrinone in cardiac surgery. Eur J nebulized prostacyclin in patients with primary Cardiothorac Surg. 2007;31(6):1081–7. and secondary pulmonary hypertension. Eur Heart 139. Sablotzki A, Starzmann W, Scheubel R, Grond S, J. 1997;18(9):1499–504. Czeslick EG. Selective pulmonary vasodilation with 128. Rocca GD, Coccia C, Pompei L, Ruberto F, Venuta inhaled aerosolized milrinone in heart transplant F, De Giacomo T, Pietropaoli P. Hemodynamic and candidates. Can J Anaesth. 2005;52(10):1076–82. oxygenation changes of combined therapy with 140. Mandal B, Kapoor PM, Chowdhury U, Kiran U, inhaled nitric oxide and inhaled aerosolized prosta- Choudhury M. Acute hemodynamic effects of cyclin. J Cardiothorac Vasc Anesth. 2001;15(2): inhaled nitroglycerine, intravenous nitroglycerine, 224–7. and their combination with intravenous dobutamine 129. Winterhalter M, Simon A, Fischer S, Rahe-Meyer N, in patients with secondary pulmonary hypertension. Chamtzidou N, Hecker H, Zuk J, Piepenbrock S, Ann Card Anaesth. 2010 May–Aug;13(2):138–44. Strüber M. Comparison of inhaled iloprost and nitric 141. Goyal P, Kiran U, Chauhan S, Juneja R, Choudhary oxide in patients with pulmonary hypertension M. Ef fi cacy of nitroglycerin inhalation in reducing during weaning from cardiopulmonary bypass in pulmonary arterial hypertension in children with 154 A.R. Tonelli et al.

congenital heart disease. Br J Anaesth. 2006;97(2): acute ischemic right ventricular failure. Ann Thorac 208–14. Surg. 2004;78(4):1426–32. 142. Ewert R, Opitz CF, Wensel R, Winkler J, Halank M, 149. Berman M, Tsui S, Vuylsteke A, Klein A, Jenkins Felix SB. Continuous intravenous iloprost to revert DP. Life-threatening right ventricular failure in pul- treatment failure of fi rst-line inhaled iloprost therapy monary hypertension: RVAD or ECMO? J Heart in patients with idiopathic pulmonary arterial hyper- Lung Transplant. 2008;27(10):1188–9. tension. Clin Res Cardiol. 2007;96(4):211–7. 150. Reichenberger F, Pepke-Zaba J, McNeil K, 143. Ichinose F, Erana-Garcia J, Hromi J, Raveh Y, Jones Parameshwar J, Shapiro LM. Atrial septostomy in R, Krim L, Clark MW, Winkler JD, Bloch KD, Zapol the treatment of severe pulmonary arterial WM. Nebulized sildena fi l is a selective pulmonary hypertension. Thorax. 2003;58(9):797–800. vasodilator in lambs with acute pulmonary hyperten- 151. Kulkarni A, Singh TP, Sarnaik A, Walters HL, Delius sion. Crit Care Med. 2001;29(5):1000–5. R. Sildenafi l for pulmonary hypertension after heart 144. Kleber FX, Bollmann T, Borst MM, Costard-Jäckle transplantation. J Heart Lung Transplant. 2004; A, Ewert R, Kivikko M, Petterson T, Pohjanjousi P, 23(12):1441–4. Sonntag S, Wikström G. Repetitive dosing of intra- 152. Peiravian F, Amirghofran AA, Borzouee M, Ajami venous levosimendan improves pulmonary hemody- GH, Sabri MR, Kolaee S. Oral sildena fi l to control namics in patients with pulmonary hypertension: pulmonary hypertension after congenital heart sur- results of a pilot study. J Clin Pharmacol. 2009;49(1): gery. Asian Cardiovasc Thorac Ann. 2007;15(2): 109–15. 113–7. 145. Kerbaul F, Rondelet B, Demester JP, Fesler P, Huez 153. Nagaya N, Nishikimi T, Okano Y, Uematsu M, Satoh S, Naeije R, Brimioulle S. Effects of levosimendan T, Kyotani S, Kuribayashi S, Hamada S, Kakishita versus dobutamine on pressure load-induced right M, Nakanishi N, Takamiya M, Kunieda T, Matsuo ventricular failure. Crit Care Med. 2006;34(11): H, Kangawa K. Plasma brain natriuretic peptide 2814–9. levels increase in proportion to the extent of right 146. Keogh AM, Mayer E, Benza RL, Corris P, Dartevelle ventricular dysfunction in pulmonary hypertension. PG, Frost AE, Kim NH, Lang IM, Pepke-Zaba J, J Am Coll Cardiol. 1998;31(1):202–8. Sandoval J. Interventional and surgical modalities of 154. Nagaya N, Nishikimi T, Uematsu M, Satoh T, treatment in pulmonary hypertension. J Am Coll Kyotani S, Sakamaki F, Kakishita M, Fukushima Cardiol. 2009;54(1 Suppl):S67–77. K, Okano Y, Nakanishi N, Miyatake K, Kangawa 147. Boeken U, Feindt P, Litmathe J, Kurt M, Gams E. K. Plasma brain natriuretic peptide as a prognostic Intraaortic balloon pumping in patients with right indicator in patients with primary pulmonary hyper- ventricular insuf fi ciency after cardiac surgery: tension. Circulation. 2000;102(8):865–70. parameters to predict failure of IABP support. 155. Filusch A, Giannitsis E, Katus HA, Meyer FJ. High- Thorac Cardiovasc Surg. 2009;57(6):324–8. sensitive troponin T: a novel biomarker for prognosis 148. Nordhaug D, Steensrud T, Muller S, Husnes KV, and disease severity in patients with pulmonary arte- Myrmel T. Intraaortic balloon pumping improves rial hypertension. Clin Sci (Lond). 2010;119(5): hemodynamics and right ventricular effi ciency in 207–13. Perioperative Management of the Neutropenic Rheumatologic Patient 1 2

Leonard J. Horwitz

associated with ulcers which heal poorly and Introduction which could require procedures. Each of these involves surgery with a potential for serious Rheumatologic diseases often are complicated infection in a patient who is neutropenic. by cytopenias. Severe neutropenia may predis- When discussing neutropenia, a defi nition is pose a patient to infections and delayed wound in order. Automated tests will indicate any value healing. This becomes a special challenge in the two standard deviations below the mean – the perioperative setting. Although neutropenia in lowest 2.5% of the population – as abnormally the setting of rheumatologic illnesses has many low. Many people with neutrophil counts at this features that are different than those encountered level – usually about 1,800–2,000 depending on after cytotoxic chemotherapy or in primary bone the laboratory – are perfectly normal. Clinically marrow disorders, the general precautions uti- signifi cant neutropenia has been defi ned as neu- lized in patients with primary hematologic disor- trophil counts below 1,000 and severe neutrope- ders still apply. nia below 500, at which point more infectious When a patient with a rheumatologic problem problems begin to appear. and neutropenia must be taken to surgery, certain concerns arise, depending on the speci fi c proce- dure. Prosthetic devices are particularly prone to Occurrence postoperative infections, and a large proportion of procedures in such patients involve joint Leukopenia may be present in over half the replacements. In fl ammatory bowel disease may patients with active disease [1, 2 ] . Most of these coexist with other autoimmune diseases, and sur- are due to lymphopenia. Neutropenia can occur gery for this incurs a risk of perforation and/or in a proportion of several rheumatologic condi- abscess formation with a higher risk of postop- tions. The neutropenia seen in systemic lupus erative infection. Splenectomy sometimes is erythematosus (SLE) usually is of a mild degree, required for a patient with rheumatologic prob- with one series reporting 20% of those affl icted lems, such as for some with Felty’s syndrome. to have neutrophil counts below 1,800 [3, 4 ] . Immune disease of skin or blood vessels may be Moderate leukopenia, and, in particular, throm- bocytopenia, may be present in as many as 30% L. J. Horwitz , M.D. () of patients with primary Sjogren’s syndrome. Department of Hematology and Blood Disorders , However, severe neutropenia can be seen [5 ] . Taussig Cancer Institute of the Cleveland Clinic In one series, those patients with Sjogren’s syn- Foundation , 9500 Euclid Avenue , Cleveland , OH 44195 , USA drome who had either recurrent infections or e-mail: [email protected] serious systemic infections all had neutrophil

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 155 DOI 10.1007/978-1-4614-2203-7_12, © Springer Science+Business Media, LLC 2013 156 L.J. Horwitz counts ranging no higher than 210 [6 ] . Though The risk in certain rheumatologic situations must neutropenia is not a regular feature of scleroderma, not be underestimated, however. Neutropenia one rapidly progressing case of scleroderma was associated with Evans’ syndrome, which can include reported with ANC 500; she died of renal failure simultaneous or metachronous hemolytic anemia rather than infection [ 7] . Two cases of neutrope- and thrombocytopenia, poses a risk approaching that nia with primary biliary cirrhosis have been of leukemic patients. Despite treatment attempts, reported [8, 9 ] . 24% died of their disease in one series of 68, seven Although neutropenia is unusual (about 3%) in of these from infections [ 15 ] . uncomplicated rheumatoid arthritis, about 1% of Concerns about increased mortality and mor- these patients may develop Felty’s syndrome, bidity associated with lymphocyte depletion were which is associated with splenomegaly and leuko- allayed in a 12-year follow-up of persons with penia, particularly neutropenia. Neutropenia may rheumatoid arthritis treated with alemtuzumab. also occur as a complication of medical therapy When compared to case-control studies, no for severe systemic autoimmune disease [10 ] . excess of mortality or morbidity, particularly from opportunistic infections, was found, despite prolonged severe lymphopenia [16 ] . Infectious Risks

The earliest and largest number of studies of neu- Mechanisms tropenic patients were done with leukemic and bone marrow transplant patients. Subsequently, There are several mechanisms causing neutrope- patients temporarily neutropenic following che- nia which may affect the patient’s perioperative motherapy have also been studied extensively. risks and response to treatment. These are listed in What has been demonstrated is that it is not only Table 12.1 , along with the most commonly asso- the depth of the neutropenia but its duration ciated illnesses and response to possible treat- which increases the risk of infections [ 11– 14 ] . ments. Being aware of these mechanisms will Most such patients develop severe neutropenia, help keep the distinction between rheumatologic defi ned as granulocyte counts under 500/dL; their patients and leukemic patients in mind. Several risk of infection is 5.2 times that of the general mechanisms may coexist in the same patient, population if they are neutropenic for one to fi ve making estimation of risk less clear and response straight days. The risk ratio reaches 7.35 for to any particular treatment less predictable. infection when patients have been neutropenic The mechanisms of neutropenia in Felty’s 6–15 days, and virtually all bone marrow trans- syndrome require special mention [17– 19 ] . plant patients experience infection at some time Neutropenia here is particularly ominous. About during the long engraftment or recovery phase. 50% are associated with increased or recurrent It is important not to simply extrapolate data infections, particularly oropharyngeal, nasopha- concerning effects and treatments of neutrope- ryngeal, and anorectal infections, and mortality is nia developed from studies on these cohorts. 25% in 5 years, some of it from sepsis. The neu- Rheumatologic patients may exhibit neutropenia, trophils may be coated with antineutrophil anti- often profound (absolute neutrophil count under bodies, but it is the circulating immune complexes 1,000), for months or years without an infection. which are believed to coat circulating neutro- In a series of 13 patients with severe neutropenia phils, causing adhesion, margination, clearance and Sjogren’s syndrome [5 ] , infectious complica- from circulation, and eventual apoptosis. Though tions only were reported in fi ve who had absolute there are many reports of an increase of T-cell granulocyte counts of 100 or less. Furthermore, large granular lymphocytes (LGLs) and an in patients with primary bone marrow problems, increased incidence of large granular T-cell leu- neutrophil dysfunction may be present and mono- kemia (T-LGL), it is controversial whether there cyte numbers are reduced; each of these renders is an etiologic connection or just an association, infections more likely. particularly since response to treatment of 12 Perioperative Management of the Neutropenic Rheumatologic Patient 157

Table 12.1 Mechanisms behind neutropenia Risk Associated conditions Best treatment Cell-mediated T lymphocytes Inf FS Immunosuppression +/− (but not GCSF alone) GCSF NK cells Autoantibodies SLE, FS Immunosuppression Neutrophils Cytokines Growth factors CD34 Cytokines FS Methotrexate Immune complexes Healing SLE Cytotoxicity Inf Drugs Withhold; GCSF Idiosyncratic Drugs Withhold FS Felty’s syndrome, SLE systemic lupus erythematosus, Inf infections, NK natural killer

neutropenia or arthritis does not correlate with that can lead to neutropenia and which are used the LGL count [ 20 ] . The presence of immune by patients with rheumatologic conditions [ 26, complexes on the neutrophils, which also results 27] . Many of the disease-modifying drugs are in their removal, can interfere with determina- used to treat the cause of the neutropenia as well tions of etiology [21 ] . as other manifestations of the rheumatologic dis- The splenomegaly associated with Felty’s ease; these are marked with an asterisk. Classes syndrome is also enigmatic, and in fact it is no of drugs include direct cytotoxins, analgesics, longer a requirement to make the diagnosis [ 17, and antibiotics sometimes used empirically when 22 ] . Removal of the spleen helps temporarily, patients are considered more susceptible to and it even may correct the left-shifted granu- opportunistic infections due to immunosuppres- lopoiesis often observed in the bone marrow, but sion. Strict guidelines as to perioperative use of the LGLs persist and often increase. Also, unlike these drugs have not been established [28 ] . thrombocytopenia or anemia related to splenic sequestration, there is little pathologic correla- tion in spleen size and level of neutropenia. Goals for Surgical Patients Neither are LGLs apparent in the spleen. Antibodies against neutrophils occur in auto- Patients with rheumatologic diagnoses face the immune disease. These include antibodies to FC same range of possible surgical interventions as gamma RIIIb (CD16b), leukocyte adhesion mol- the general population. More frequently, they ecule (CD11b/CD18), and C3b complement may be involved in orthopedic procedures. receptor (CD35) [8, 21, 23 ] . These also are seen Splenectomy sometimes is attempted to control in autoimmune disease affecting other organ sys- symptoms. Other patients – for instance, those tems, such as multiple sclerosis [24 ] . Spontaneous with SLE who have more protean disease mani- autoantibodies to granulocyte colony-stimulating festations – may see more neurological surgery factor (GCSF) were found in 11 of 15 patients or cardiac surgery, such as pericardiectomy. Lung with Felty’s syndrome and in 12 of 32 patients, biopsies need to be performed at times for patients half of whom were neutropenic, with SLE [25 ] . with RA or scleroderma; biopsies of liver or kid- Medication-induced neutropenia is common, ney often need to be undertaken. and it may be more severe than with other etiolo- There are three primary goals in managing the gies of neutropenia seen with rheumatologic con- neutropenic patient with rheumatologic illnesses ditions. Table 12.2 lists the more common drugs prior to, during, and after surgery. For the person 158 L.J. Horwitz

Table 12.2 Medications potentially causing neutropenia Since all surgical patients are at risk for the Disease-modifying drugs problems listed in the foregoing paragraphs, stan- Azathioprinea dard treatment protocols to address many precau- Cyclophosphamidea tions already are in use. In particular, this includes Cyclosporinea perioperative antibiotics for potentially septic Hydroxychloroquine (rarely) procedures like emergency bowel resections and Gold salts (rarely used) for implantation of prosthetic devices. There is Methotrexate no lower limit of circulating granulocytes that Mycophenolate mofetila ever has been set for rheumatologic patients Penicillamine below which additional precautions need to be Sulfasalazine taken. However, patients with comorbidities, Analgesics patients with persistent granulocyte counts below Acetaminophen 500/dL, and patients who, regardless of white Phenacetin count, have had recurrent infections, particularly Acetylsalicylic acid febrile infections, generally receive prophylactic Indomethacin Sulindac treatments empirically. Antibiotics Acyclovir Ganciclovir Interventions: Growth Factors Rifampin Trimethoprim/sulfamethoxazole Many randomized studies have explored manage- Penicillins ment of patients who are neutropenic due to chemo- Cephalosporins therapy or primary bone marrow illnesses. Prophylactic Vancomycin antibiotics and growth factors such as granulocyte Perioperative medications colony-stimulating factor (GCSF) or granulocyte- Cimetidine macrophage colony-stimulating factor (GM-CSF) Ranitidine have been studied. Recommendations based on results Allopurinol of these studies have been applied to rheumatologic a Drugs also used to treat cause of neutropenia diseases with neutropenia, and GCSF has been used successfully to treat neutropenia induced by metho- facing surgery, the goals are to prevent organisms trexate [ 10 ] . However, potential differences in risks from settling on an implanted device, to mini- for infections exist between patients with leukemic mize risk of infection by native fl ora, and to versus rheumatologic conditions. These would include contain active infections which may be present dysfunction of leukemic granulocytes and a differ- already. During surgery, in addition, there are ence in the types and duration of other immunosup- concerns about infections which may be intro- pressive problems in both groups. duced through intubation, intravenous access, Use of growth factors to promote wound healing, and through the procedure itself. When recover- which requires properly functioning granulocytes ing, the goals are to maximize wound healing, as well as monocytes, seems intuitive [29 ] . limit local postoperative infections and catheter- Pediatric surgeons have tried using perioperative associated infections, and to prevent septicemia. GM-CSF with a measure of success when operat- Preventing fevers has received less attention ing on patients with hereditary storage diseases than it has for patients with neutropenia related to which impede neutrophil function [30 ] . This other conditions, particularly malignancies. One observed success is supported by reports such as reason is that with hematologic diseases, fever is one concerning patients who underwent radical often used as a proxy for existence of infection, vulvectomies. The propensity of this particular while with rheumatologic patients, fevers may be site to become infected and the tightness of the manifestations of the disease itself. skin around the suture closures render these 12 Perioperative Management of the Neutropenic Rheumatologic Patient 159 patients at high risk regardless of their normal uninfected neutropenic patient who is having a blood counts. When GCSF was used for nine con- mechanical device installed. secutive days from the day of surgery, periopera- tive wound complications such as dehiscence and infection fell from the historic 40–60% to under Interventions: Prophylactic 30%. However, overall wound healing was not Antibiotics improved [ 31 ] . Attempts to repeat these fi ndings in a randomized trial were unsuccessful [32 ] . Systematic studies of prophylactic antibiotics for There are several reported cases of rheumato- neutropenic rheumatologic patients have not been logic patients who have had sores or surgical sites undertaken. Nevertheless, extensive data support that were slow to heal with standard local mea- the bene fi ts of prophylactic antibiotics in patients sures. Even though their patients were not neutro- who have leukemia, who are post-bone marrow penic, these authors believed that addition of GCSF transplants, or who are taking chemotherapy; these sped healing, even when they were not frankly neu- patients have not necessarily had surgical proce- tropenic [3, 33 ] . In another report, a person believed dures. Their use for these patients is universally to be at high risk for developing an infection on a accepted [ 43– 45 ] . However, there are controver- prosthetic knee was treated prophylactically with sies as to their actual benefi t. One analysis showed antibiotics and GCSF, with ultimate success. that 55 leukemic or post-bone marrow patients had Physicians elsewhere used GM-CSF instead, with to be treated to prevent one death; this number was similar results [34– 37 ] . However, particularly with 82 for chemotherapy patients [46 ] . Again, there Felty’s syndrome, prolonged treatment with GCSF, are no data to apply this observation to rheumato- though feasible [38 ] and capable of improving the logic patients undergoing surgery. granulocyte counts and avoiding surgical compli- Because of the relative rarity of profound neu- cations [ 39 ] , may require doses up to four tropenia among rheumatologic patients, data of this times higher than those usually recommended in extent are not available for the use of prophylactic order to bring granulocyte counts to desired levels. antibiotics. However, short series and individual Controlled studies are not available comparing anecdotal cases have been reported wherein growth healing with and without growth factors. factors and/or immunosuppressive agents were Use of growth factors has been associated with used in attempts to prevent sepsis or promote heal- exacerbation of rheumatologic symptoms in ing of chronic infections. In addition, searching for some patients and with development of leukocy- preexisting subclinical infections, particularly in toclastic vasculitis. This may be due to nonspeci fi c the teeth and elsewhere in the upper respiratory activation of the neutrophils and monocytes [ 40 ] . tract, is advisable [47 ] . This caution extends to any Since not all patients may experience this, clini- surgery requiring placement of a foreign material cal monitoring is necessary [41 ] . in the body or vascular manipulation. One must remember that the mechanism of neu- In short, the same discretion in antibiotic pro- tropenia in patients with rheumatologic conditions phylaxis should be taken when devices are placed also may be autoimmune. A case of sepsis in a as with a patient who is not neutropenic undergo- patient with severe neutropenia (ANC 87) associ- ing the same procedure. Long-term antibiotic ated with Sjogren’s syndrome did not respond to prophylaxis should be reserved for patients with GCSF but resolved with prednisone [42 ] . frequent infections. Prudent use of growth factors, particularly GCSF, would include administering it to neutro- penic perioperative patients who have had fre- Interventions: Medications quent infections and using it for operations where infected matter may be encountered, such as large There are a wide range of medications available bowel surgery or drainage of abscesses. It is not with which to mitigate activity of the rheumato- clear if GCSF would provide an advantage to an logic illness in question. Whether these should be 160 L.J. Horwitz

Table 12.3 Medical treatments for neutropenic rheumatologic patients Medical treatments Time to effect Duration of effect References Lithium Days Short Steroids Days Short Intravenous immunoglobulin Days Short [23, 58, 59 ] GCSF Hours Short [40 ] Azathioprine Weeks Short [ 60 ] Cyclophosphamide Weeks Short [ 61 ] Cyclosporine Weeks Long [ 52, 62– 64 ] Hydroxychloroquine Weeks Short [ 51 ] Methotrexate Weeks Short [ 65 ] Alemtuzumab Months Long [ 66 ] Rituximab Months Long [ 54, 67 ] Mycophenolate mofetil [ 68 ] continued in the perioperative period continues to encing none thereafter. Regardless of response, be a source of debate [ 28, 48 ] . In particular, the 12% had fatal infections [57 ] . incidence and control of neutropenia prior to sur- Splenectomy has been performed in patients gery and the attendant risk of infections and other with Felty’s syndrome in an attempt to make an complications has not emerged as a consistent improvement in granulocyte count. There was a concern [49, 50 ] . The information is anecdotal and short-lived salutary effect observed, though not generally speci fi c for the perioperative setting many so treated have been observed to retain [40, 51, 52 ] . The time to achieve a clinical bene fi t baseline granulocyte levels higher than their may be too long to allow for timely surgery, and original levels. It was not determined whether many patients do not respond satisfactorily. these higher levels reduced surgical risks related Conversely, preoperative treatment with certain to neutropenia. Spleen size correlated with level immunosuppressive agents, particularly steroids, of anemia and thrombocytopenia but not with has been avoided due to theoretical concerns about granulocytopenia. It is not apparent that splenec- healing independent of WBC count. A partial list tomy reduced infection rates or surgical of salutary medications is in Table 12.3 . complications. In particular, there has been recent attention to rituximab [53, 54 ] . Because its mechanism is suppressing B cells, it might correct autoimmune Conclusion neutropenia but not necessarily cytopenias not due directly to autoantibodies or other disease Scarcity of controlled studies forces us to use manifestations [55 ] . empiric, often anecdotal, data and common sense when approaching a neutropenic rheumatologic patient about to undergo surgery. Fevers and sep- Interventions: Splenectomy sis can occur with any granulocyte count and without evidence of infections in this population An early presentation of ten case histories of due to their often debilitated state and other splenectomy for Felty’s syndrome showed a nor- immunologic problems. Surgical teams already malization of the absolute neutrophil count and utilize precautionary measures for the general prolonged survival in all but one, who remained healthy population when doing abdominal proce- neutropenic and died of infection within the year dures or implanting prosthetic devices, such as [56 ] . A subsequent review showed an 80% hema- artifi cial joints, in order to minimize infections tologic response after splenectomy, with 55% of and other morbidities. These include antibiotics those with infections prior to the surgery experi- and meticulous wound care. 12 Perioperative Management of the Neutropenic Rheumatologic Patient 161

Anecdotal reports have stated that adding and KARNOFSKY scoring systems as predictors of growth factors has been associated with favorable bloodstream infection onset in hematology-oncology patients. BMC Infect Dis. 2010;10:135. outcomes in high-risk situations for those who 12. Wintrobe MM, Lee GR. Wintrobe’s clinical hematol- respond appropriately. Observations supporting ogy. 10th ed. Baltimore: Williams and Wilkins; 1999. use of prophylactic antibiotics are even less clear. 13. Watts RG. Neutropenia. In: Lee GR, editor. Wintrobe’s Indiscriminate use is discouraged. Nevertheless, clinical hematology. 10th ed. Baltimore: Williams and Wilkins; 1999. p. 1777–800. those patients who have demonstrated persistent 14. Bodey GP, Buckley M, Sathe YS, Freireich EJ. granulocyte counts under 500/dL despite other Quantitative relationships between circulating leuko- treatments and who have frequent serious infec- cytes and infection in patients with acute leukemia. tions could enjoy a net benefi t from either Ann Intern Med. 1966;64(2):328–40. 15. Michel M, Chanet V, Dechartres A, et al. The spec- precaution. trum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood. 2009;114(15):3167–72. Oct 8. 16. Lorenzi AR, Clarke AM, Wooldridge T, et al. Morbidity and mortality in rheumatoid arthritis References patients with prolonged therapy-induced lymphope- nia: twelve-year outcomes. Arthritis Rheum. 1. Berliner N, Horwitz M, Loughran TP Jr. Congenital 2008;58(2):370–5. and acquired neutropenia. Hematol Am Soc Hematol 17. Starkebaum G. Chronic neutropenia associated with Educ Program. 2004: 63–79. autoimmune disease. Semin Hematol. 2002; 2. Keeling DM, Isenberg DA. Haematological manifes- 39(2):121–7. tations of systemic lupus erythematosus. Blood Rev. 18. Balint GP, Balint PV. Felty’s syndrome. Best Pract 1993;7(4):199–207. Res Clin Rheumatol. 2004;18(5):631–45. 3. Euler HH, Harten P, Zeuner RA, Schwab UM. 19. Stanworth SJ, Green L, Pumphrey RS, Swinson DR, Recombinant human granulocyte colony stimulating Bhavnani M. An unusual association of Felty syn- factor in patients with systemic lupus erythematosus drome and TCR gamma delta lymphocytosis. J Clin associated neutropenia and refractory infections. J Pathol. 1996;49(4):351–3. Rheumatol. 1997;24(11):2153–7. 20. Burks EJ, Loughran Jr TP. Pathogenesis of neutrope- 4. Courtney PA, Crockard AD, Williamson K, Irvine nia in large granular lymphocyte leukemia and Felty AE, Kennedy RJ, Bell AL. Increased apoptotic periph- syndrome. Blood Rev. 2006;20(5):245–66. eral blood neutrophils in systemic lupus erythematosus: 21. Palmblad J, Papadaki HA, Eliopoulos G. Acute and relations with disease activity, antibodies to double chronic neutropenias. What is new? J Intern Med. stranded DNA, and neutropenia. Ann Rheum Dis. 2001;250(6):476–91. Dec. 1999;58(5):309–14. 22. Campion G, Maddison PJ, Goulding N, et al. The 5. Friedman J, Klep fi sh A, Miller EB, Ognenovski V, Ike Felty syndrome: a case-matched study of clinical RW, Schattner A. Agranulocytosis in Sjogren’s syndrome: manifestations and outcome, serologic features, and two case reports and analysis of 11 additional reported immunogenetic associations. Medicine (Baltimore). cases. Semin Arthritis Rheum. 2002;31(5):338–45. 1990;69(2):69–80. 6. Yamato E, Fujioka Y, Masugi F, et al. Autoimmune neu- 23. Capsoni F, Sarzi-Puttini P, Zanella A. Primary and tropenia with anti-neutrophil autoantibody associated with secondary autoimmune neutropenia. Arthritis Res Sjogren’s syndrome. Am J Med Sci. 1990;300(2):102–3. Ther. 2005;7(5):208–14. 7. Waugh D, Ibels L. Malignant scleroderma associated 24. Kumakura S, Kobayashi S. Autoimmune neutropenia. with autoimmune neutropenia. Br Med J. 1980; Intern Med. 2003;42(2):133–4. 280(6231):1577–8. 25. Hellmich B, Csernok E, Schatz H, Gross WL, Schnabel 8. Bux J, Robertz-Vaupel GM, Glasmacher A, Dengler A. Autoantibodies against granulocyte colony-stimulating HJ, Mueller-Eckhardt C. Autoimmune neutropenia factor in Felty’s syndrome and neutropenic sys- due to NA1 specifi c antibodies in primary biliary cir- temic lupus erythematosus. Arthritis Rheum. 2002; rhosis. Br J Haematol. 1991;77(1):121–2. 46(9):2384–91. 9. Tamura H, Okamoto M, Yamashita T, et al. Pure white 26. Rajakulendran S, Gadsby K, Allen D, O’Reilly S, cell aplasia: report of the fi rst case associated with pri- Deighton C. Neutropenia while receiving anti-tumour mary biliary cirrhosis. Int J Hematol. 2007;85(2) necrosis factor treatment for rheumatoid arthritis. Ann :97–100. Rheum Dis. 2006;65(12):1678–9. 10. Ellman MH, Telfer MC, Turner AF. Bene fi t of G-CSF 27. Vidal F, Fontova R, Richart C. Severe neutropenia and for methotrexate-induced neutropenia in rheumatoid thrombocytopenia associated with infl iximab. Ann arthritis. Am J Med. 1992;92(3):337–8. Intern Med. 2003;139(3):W-W63. Aug 5. 11. Apostolopoulou E, Raftopoulos V, Terzis K, 28. Rosandich PA, Kelley 3rd JT, Conn DL. Perioperative Elefsiniotis I. Infection probability score, APACHE II management of patients with rheumatoid arthritis in 162 L.J. Horwitz

the era of biologic response modifi ers. Curr Opin 42. Vivancos J, Vila M, Serra A, Loscos J, Anguita A. Rheumatol. 2004;16(3):192–8. Failure of G-CSF therapy in neutropenia associated 29. Welte K, Dale D. Pathophysiology and treatment of with Sjogren’s syndrome. Rheumatology (Oxford). severe chronic neutropenia. Ann Hematol. 1996; 2002;41(4):471–3. 72(4):158–65. 43. Pizzo PA. Fever in immunocompromised patients. N 30. De Ugarte DA, Roberts RL, Lerdluedeeporn P, Stiehm Engl J Med. 1999;341(12):893–900. Sep 16. ER, Atkinson JB. Treatment of chronic wounds by 44. Gafter-Gvili A, Paul M, Fraser A, Leibovici L. local delivery of granulocyte-macrophage colony- Antibiotic prophylaxis in neutropenic patients. Isr stimulating factor in patients with neutrophil dysfunc- Med Assoc J. 2007;9(6):460–2. tion. Pediatr Surg Int. 2002;18(5–6):517–20. 45. Segal BH, Freifeld AG. Antibacterial prophylaxis in 31. van Lindert AC, Symons EA, Damen BF, Heintz AP. patients with neutropenia. J Natl Compr Canc Netw. Wound healing after radical vulvectomy and inguino- 2007;5(2):235–42. femoral lymphadenectomy: experience with granulo- 46. Leibovici L, Paul M, Cullen M, et al. Antibiotic pro- cyte colony stimulating factor (fi lgrastim, phylaxis in neutropenic patients: new evidence, practi- r-metHuG-CSF). Eur J Obstet Gynecol Reprod Biol. cal decisions. Cancer. 2006;107(8):1743–51. Oct 15. 1995;62(2):217–9. 47. Axford JS. Preoperative evaluation and perioperative 32. Uyl-De Groot CA, Hartog JG, Derksen JG, et al. Cost- management of patients with rheumatic diseases. effectiveness and quality of life of granulocyte-colony UpToDate. 2010 ed2010. stimulating factor ( fi lgrastim) after radical vulvectomy 48. Jain A, Maini R, Nanchahal J. Disease modifying and bilateral inguino-femoral lymphadenectomy: treatment and elective surgery in rheumatoid arthritis: results of a randomized clinical trial. Eur J Obstet the need for more data. Ann Rheum Dis. 2004;63(5): Gynecol Reprod Biol. 2004;114(1):77–82. May 10. 602–3. 33. Fohlman J, Hoglund M, Bergmann S. Successful 49. Bongartz T. Elective orthopedic surgery and periop- treatment of chronic wound infection in neutropenia erative DMARD management: many questions, fewer and rheumatoid arthritis with fi lgrastim (rhG-GSF). answers, and some opinions. J Rheumatol. 2007;34(4): Ann Hematol. 1994;69(3):153–6. Sep. 653–5. 34. Spiekermann K, Roesler J, Emmendoerffer A, Elsner J, 50. Bongartz T, Halligan CS, Osmon DR, et al. Incidence Welte K. Functional features of neutrophils induced by and risk factors of prosthetic joint infection after total hip G-CSF and GM-CSF treatment: differential effects and or knee replacement in patients with rheumatoid arthri- clinical implications. Leukemia. 1997;11(4):466–78. tis. Arthritis Rheum. 2008;59(12):1713–20. Dec 15. 35. Yong KL, Linch DC. Differential effects of granulocyte- 51. Mahevas M, Audia S, De Lastours V, Michel M, and granulocyte-macrophage colony-stimulating factors Bonotte B, Godeau B. Neutropenia in Felty’s syn- (G- and GM-CSF) on neutrophil adhesion in vitro and drome successfully treated with hydroxychloroquine. in vivo. Eur J Haematol. 1992;49(5):251–9. Haematologica. 2007;92(7):e78–9. 36. Kaiser U, Klausmann M, Richter G, P fl uger KH. 52. Sood R, Stewart CC, Aplan PD, et al. Neutropenia GM-CSF versus G-CSF in the treatment of infectious associated with T-cell large granular lymphocyte leu- complication in Felty’s syndrome–a case report. Ann kemia: long-term response to cyclosporine therapy Hematol. 1992;64(4):205–6. despite persistence of abnormal cells. Blood. 37. Lubbe AS, Schwella N, Riess H, Huhn D. 1998;91(9):3372–8. May 1. Improvement of pneumonia and arthritis in Felty’s 53. Lekharaju V, Chattopadhyay C. Ef fi cacy of rituximab in syndrome by treatment with granulocyte-mac- Felty’s syndrome. Ann Rheum Dis. 2008;67(9):1352. rophage colony-stimulating factor (GM-CSF). 54. Salama A, Schneider U, Dorner T. Bene fi cial response Blut. 1990;61(6):379–80. to rituximab in a patient with haemolysis and refrac- 38. Wandt H, Seifert M, Falge C, Gallmeier WM. Long- tory Felty syndrome. Ann Rheum Dis. 2008;67(6): term correction of neutropenia in Felty’s syndrome 894–5. with granulocyte colony-stimulating factor. Ann 55. Shipley E, Heraud A, Hennette A, Vernhes JP. Ef fi cacy Hematol. 1993;66(5):265–6. of rituximab in Felty’s syndrome. Joint Bone Spine. 39. Hailwood SJ, Harley LJ, Merry P. The use of granulo- 2008;75(5):621–2. cyte colony-stimulating factor in joint replacement 56. Sandusky WR, Rudolf LE, Leavell BS. Splenectomy surgery in a patient with Felty’s syndrome. Br J for control of neutropenia in Felty’s syndrome. Ann Rheumatol. 1997;36(11):1232–3. Surg. 1968;167(5):744–51. 40. Hellmich B, Schnabel A, Gross WL. Treatment of 57. Rashba EJ, Rowe JM, Packman CH. Treatment of the severe neutropenia due to Felty’s syndrome or systemic neutropenia of Felty syndrome. Blood Rev. lupus erythematosus with granulocyte colony-stimulat- 1996;10(3):177–84. ing factor. Semin Arthritis Rheum. 1999;29(2):82–99. 58. Mann K, Fateh-Moghadam A, Pfeiffer A, et al. Long- 41. Vreugdenhil G, Schattenberg A, Dompeling EC, term remission of immune neutropenia after treatment Swaak AJ, De Witte T. Hematopoietic growth factors with high-dose intravenous 7 S-immunoglobulin. Klin in rheumatoid arthritis: a critical approach to their use Wochenschr. 1987;65(20):985–8. Oct 15. in view of possible adverse effects. Am J Med. 59. Sorensen RU, Kallick MD. Clinical uses of intrave- 1993;94(2):229–31. nous immune globulin: immunoglobulin replacement 12 Perioperative Management of the Neutropenic Rheumatologic Patient 163

therapy and treatment of autoimmune cytopenias. large granular lymphocytosis with cyclosporine A and J Clin Apher. 1988;4(2–3):97–103. fi lgrastim. Am J Hematol. 1995;50(4):288–91. 60. Ishikawa K, Tsukada Y, Tamura S, et al. 65. Fiechtner JJ, Miller DR, Starkebaum G. Reversal of Salazosulfapyridine-induced remission of Felty’s syn- neutropenia with methotrexate treatment in patients drome along with signifi cant reduction in neutrophil- with Felty’s syndrome. Correlation of response with bound immunoglobulin G. J Rheumatol. 2003;30(2): neutrophil-reactive IgG. Arthritis Rheum. 1989;32(2): 404–6. 194–201. 61. Pixley JS, Yoneda KY, Manalo PB. Sequential adminis- 66. Willis F, Marsh JC, Bevan DH, et al. The effect of tration of cyclophosphamide and granulocyte-colony treatment with Campath-1 H in patients with auto- stimulating factor relieves impaired myeloid maturation immune cytopenias. Br J Haematol. 2001;114(4): in Felty’s syndrome. Am J Hematol. 1993;43(4):304–6. 891–8. 62. Martino R, Sureda A, Ayats R, Muniz-Diaz E, Altes 67. Chakupurakal G, Murrin RJ, Neilson JR. Prolonged A, Brunet S. Successful treatment of chronic autoim- remission of pure white cell aplasia (PWCA), in a mune neutropenia with cyclosporin A. Haematologica. patient with CLL, induced by rituximab and main- 1994;79(1):66–9. Jan–Feb. tained by continuous oral cyclosporin. Eur J Haematol. 63. Schiphorst PP, de Pauw BE. Autoimmune neutropenia 2007;79(3):271–3. successfully treated with cyclosporine. Ann Hematol. 68. Kotb R, Pinganaud C, Trichet C, et al. Ef fi cacy of 1995;70(4):223–5. mycophenolate mofetil in adult refractory auto- 64. Jakubowski A, Winton EF, Gencarelli A, Gabrilove J. immune cytopenias: a single center preliminary study. Treatment of chronic neutropenia associated with Eur J Haematol. 2005;75(1):60–4. Perioperative Management of the Patient with Chronic Kidney 1 3 Disease, Hypertension, or End-Stage Renal Disease

James F. Simon and Joseph V. Nally

Introduction Perioperative Management of the Patient with Chronic Kidney Disease Perioperative management of patients with chronic kidney disease (CKD) and end-stage De fi nition of Chronic Kidney Disease renal disease (ESRD) may be complicated by alterations in fl uid and electrolyte balance, The current defi nitions for the diagnosis and stag- acid–base homeostasis, volume status, and drug ing of CKD [ 1] require that patients show evi- metabolism, often occurring in the setting of dence of either (a) kidney damage (anatomic, coexisting comorbidities such as hypertension, pathologic, or urinary abnormalities) or (b) GFR cardiovascular disease, and diabetes mellitus. of less than 60 ml/min/1.73 m 2 for more than 3 CKD may exist in over 20 million Americans months. As seen in Table 13.1, CKD is staged and acts as a “risk multiplier” for morbidity, based upon estimations of glomerular fi ltration mortality, and cost in the perioperative period rate (GFR). Serum creatinine is an insensitive – including orthopedic surgery. This chapter marker of kidney function because of its depen- will focus on the perioperative medical and dence on both creatinine generation (muscle mass anesthesia management of patients with CKD and protein intake) and excretion and should not and ESRD as we highlight the impact of kidney be used to estimate kidney function. Because disease patient management. Selected issues GFR is not easily measured in clinical practice, related to management of dialysis patients as estimating equations such as the Modi fi cation of well as the kidney transplant recipient will be Diet in Renal Disease (MDRD) or the CKD-EPI discussed. equation are used which incorporate serum crea- tinine, age, race, and gender [2, 3 ] .

Prevalence

It is estimated that 8.3 million individuals have CKD stages 3–5 (eGFR of <60 ml/min) [ 4 ] , J. F. Simon , M.D. • J. V. Nally , M.D. () 400,000 of whom are on dialysis [ 5] . While Department of Nephrology and Hypertension , diabetes mellitus and hypertension remain the Cleveland Clinic Foundation , 9500 Euclid Avenue , Cleveland , OH 44195 , USA most common etiologies of ESRD, over a third e-mail: [email protected] of CKD stage 4/5 patients have fi led claims for

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 165 DOI 10.1007/978-1-4614-2203-7_13, © Springer Science+Business Media, LLC 2013 166 J.F. Simon and J.V. Nally

“connective tissue diseases” [5 ] . Hence, it may Preservation of Renal Function not be uncommon to see patients requiring perioperative management with rheumatologic The development of acute kidney injury (AKI) is disorders and CKD. associated with increased risk of death (both short- and long-term), length of hospital stay, cost of care, and risk of developing CKD [ 11 ] . Morbidity and Mortality Therefore, addressing modi fi able AKI risk fac- tors may have a benefi cial impact on both periop- More advanced CKD is associated with increased erative and long-term outcomes. rates of hospitalization, morbidity, and mortality AKI is defi ned as a 50% rise in serum creati- (Table 13.2 ) [ 6 ] . CKD is an independent risk fac- nine or oliguria (<0.5 mL/kg per hour urine out- tor for coronary artery disease (CAD) [ 7 ] . put for 6 h). Staging criteria are available to grade Preoperative CKD increased the risk of morbid- the severity of AKI [ 12, 13 ] . Estimation of base- ity, mortality, and cost in patients undergoing sur- line kidney function (eGFR) before the AKI epi- gery [8 ] . Ackland et al. [ 9 ] reported increased sode is important in understanding the severity of risk for morbidity, postoperative complications, the insult. During an AKI episode, estimations of and prolonged hospital stay in CKD patients GFR are of little utility, and creatinine clearance (eGFR <50 ml/min/1.73 m 2) undergoing elective for drug-dosing purposes must be assumed to be orthopedic joint replacement (Fig. 13.1 ). They <10 cc/min. suggested that a preoperative eGFR may enhance perioperative risk stratifi cation beyond traditional risk factors. Lavery et al. [ 10 ] reported decreased Etiology of AKI in the Perioperative survival after amputation in diabetic patients with Setting ESRD and high level amputations. The majority of AKI episodes in the postopera- tive setting are due to prerenal azotemia and isch- Perioperative Management emic acute tubular necrosis (ATN). Both are caused by decreased perfusion of the kidneys The following sections will review selected during the surgery with the former being readily issues in CKD patients which are critical to suc- reversible and the latter being more a severe and cessful perioperative management of the patient prolonged insult. While hypotension, excessive with coexisting rheumatologic disorders. Where blood loss, diuretics, or vasopressor medications appropriate, issues that relate both to CKD and may increase the risk of perioperative AKI, an ESRD are discussed together. Other issues more obvious insult is often missing. Treatment speci fi c to ESRD are discussed in subsequent involves removing the original insult (e.g., stabi- sections. lizing blood pressure) and providing adequate intravascular volume to restore renal perfusion (IV fl uids). Recovery from ATN may take days to Table 13.1 Staging of chronic kidney disease weeks and may require transient hemodialysis if AKI is severe. Stage Criteria Acute interstitial nephritis (AIN) should be Stage 1 GFR ³ 90 cc/min/1.73 m 2 with evidence of kidney damage considered if AKI develops within 14 days of Stage 2 GFR 60–89 cc/min/1.73 m2 with evidence of exposure to a new medication, especially proton kidney damage pump inhibitors and antibiotics. Recognition of Stage 3 GFR 30–59 cc/min/1.73 m2 AIN is important as failure to withdraw the offending Stage 4 GFR 15–29 cc/min/1.73 m2 medication will result in prolonged AKI, longer Stage 5 GFR <15 cc/min/1.73 m2 or dialysis dependent hospital stays, and increased expense. 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension… 167 (continued) 2.5 (1.9, 3.2) 4.1 (1.2, 13.5) 12.9 (0.8, 208) 30.2 (1.7, 549.4) 9.9 (2.4, 40.8) 1.6 (0.1, 39.8) 16.8 (3.1, 91.4) 5.6 (2.5, 12.4) 2.6 (1.7, 4.2) 2.8 (1.9, 4.1) 11.9 (0.7, 217.1) 5.6 (0.3, 90.2) 4.1 (0.8, 21.7) 14.6 (1.6, 134.3) 1.4 (0.4, 4.9) 2.8 (2.1, 3.7) 2.2 (1.9, 2.7) 1.9 (1.7, 2.2) 1.6 (1.3, 2.1) 2.6 (0.1, 54.2) 0.8 (0, 15.2) 1.9 (1.7, 2.2)

2.4 (1.5, 3.3) 2.9 (−0.9, 6.8) 1.3 (−1.4, 3.9) 3 (0.3, 5.7) 7.3 (−0.45, 14.9) −0.3 (−2.4, 1.8) 17.4 (−1.8, 36.6) 2.1 (0.6, 3.6) 3.5 (1.7, 5.3) 13 (8.1, 17.9) 27 (0.02, 5.3) 1.6 (−2.3, 5.6) 4.5 (−1.1, 10) 7.7 (−0.01, 15.6) 1.9 (−4.5, 8.3) 4.7 (1.7, 7.6) Absolute risk % (95% CI) difference Odds ratio (95% CI) 2.6 (1.9, 3.3) 4.7 (3.7, 5.7) 2.1 (1.1, 3.1) −0.4 (−4.1, 3.3) −4.1 (−14.2, 6.1) 2.6 (1, 4.1) (%) n/N 199/11 679 (1.7) 9/909 (1.0) 1/928 (0.1) 0/443 (0.0) 4/448 (0.9) 1/330 (0.3) 3/221 (1.4) 217/14 958 (1.5) 33/1467 (2.2) 50/529 (9.5) 0/194 (0.0) 1/273 (0.4) 2/130 (1.5) 1/162 (0.6) 5/108 (4.6) 92/2863 (3.2) 290/13 292 (2.2) 637/11 .051 (5.8) 179/5225 (3.4) 2/481 (0.4) 7/173 (4.0) 1115/30 222 (3.7) Normal kidney function (%) n/N 80/1943 (4.1) 4/102 (3.9) 1/73 (1.4) 5/166 (3.0) 4/49 (8.2) 0/68 (0.0) 3/16 (18.8) 97/2417 (4.0) 45/788 (5.7) 82/365 (22.5) 5/184 (2.7) 1/50 (2.0) 5/83 (6.0) 4/48 (8.3) 6/92 (6.5) 148/1610 (9.2) Chronic kidney disease 217/4542 (4.8) 506/4833 (10.5) 141/2571 (5.5) 0/37 (0.0) 0/13 (0.0) 864/11 996 (7.2)

† ‡ ‡ ‡ † ‡ …, …, 0 …, 0 4.1 9.6 0 10.3 …, 3 …, 0 0 0 0 0 0 …,

2 2 mol/l mol/l mol/l mol/l mol/l mol/l mol/l mol/l mol/l mol/l mol/l mol/l mol/l mol/l m m m m m m m m m m m m m m GFR < 60ml/min per 1.73m GFR < GFR <60 ml/min per 1.73m Cr >177 Cr >133 Cr >133 Cr >133 Cr >160 Cr >177 Cr >177 disease Dialysis (%) Dialysis De fi nition of chronic kidney disease Cr> 106 Cr >106 Cr >159 Cr >106 GFR <60 ml/min GFR <60 ml/min Cr >177 Cr >130 GFR <45 ml/min Cr >133 Risk of death based on preoperative kidney function in various studies studies function in various kidney of death based on preoperative Risk Lower extremity revascularization/amputation revascularization/amputation extremity Lower O’Hare (2003) O’Hare (2004) Collins (2001) Lantis (2001) Harpavat (1998) Subtotal Carotid endarterectomy Stoner (2006) Debing (2006) Hamdan (1999) Ascher (2005) Ayendi (2001) Reil (2002) Rigdon (1997) Subtotal Table 13.2 Source Thoracoabdominal/abdominal aortic aneurysm Collins (2001) Huynh (2005) Azizzadeh (2006) Komori (1997) Vasquez (2004) Powell (1997) Mehta (2004) Subtotal 168 J.F. Simon and J.V. Nally systemiatic 4.7 (4.3, 5.2) 2.4 (1.3, 4.5) 8.5 (5, 14.5) 5.3 (2.4, 11.5) 3.7 (2.1, 6.8) 7.5 (3.8, 14.9) 7.7 (3.2, 18.8) 5.1 (3.8, 6.8) mortality: a

Risk of death higher in patients diseases with chronic kidney

0.1 1 10 50 isease and postoperative Risk of death higher in patients with normal function kidney 10.1 (9.2, 10.9) 1.3 (0.4, 2.1) 27.1 (16.6, 37.7) 13.8 (3.2, 24.3) 7.8 (3.9, 11.7) 22.9 (10.9, 34.9) 12.4 (5.4, 19.4) 12.3 (5.9, 18.7) Absolute risk % (95% CI) difference Odds ratio (95% CI) (%) n/N 1327/42 822 (3.1) 15/1649 (0.9) 78/1460 (5.3) 43/1103 (3.9) 18/561 (3.2) 35.719 (4.9) 8/371 (2.2) 1524/48 685 (3.1) Normal kidney function (%) n/N 825/6259 (13.2) 36/1649 (2.2) 25/77 (32.5) 9/51 (17.6) 32/291 (11.0) 15/54 (27.8) 15/103 (14.6) 957/8484 (11.3) Chronic kidney disease

‡ ‡ ‡ † ‡ ‡ …, …, …, 0 …, …, …, mol/l mol/l mol/l mol/l mol/l m m m m m disease Dialysis (%) Dialysis De fi nition of chronic kidney disease Cr >133 Cr >115 Cr >177 Cr >400 Crcl <64 ml/min Cr >177 CrCl <50 ml/min (continued)

Table 13.2 Source Reprinted with permission from Macmillan Publishers Ltd: Mathew A, Devereaux PJ, O’Hare A, Tonelli M, et al. Chronic kidney d M, et al. Chronic kidney PJ, O’Hare A, Tonelli A, Devereaux Reprinted with permission from Macmillan Publishers Ltd: Mathew International. 2008;73:1069–1081 and meta-analysis. Kidney review Other: all types, general surgery Other: all types, general surgery O’Brien (2002) Dehne (2005) Kertai (2005) Gerrard (2002) Kertai (2003) Kertai (2005) Browner (1992) Subtotal 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension… 169

ab 100 100 Normal * Normal CKD CKD 80 * * 75 * 60 50 40 morbidity (%) 25 20 Patients remaining in hospital with POMS-defined morbidity (%) 370 140 276 119 111 64 32 27 Proportion of patients without 0 0 POD 3 POD 5 POD 8 POD 15 0358 15 Time until free of morbidity (postoperative days)

Fig. 13.1 Relationship between preoperative kidney preoperative levels of renal function. POMS postoperative function and postoperative mortality. (a ) Total number of morbidity survey, POD postoperative day (Reprinted postoperative complications according to preoperative with permission from Ackland GL, Moran N, Cone S, eGFR. *P <0.01 compared with eGFR > 60 ml/ Grocott MP, Mythen MG. Chronic kidney disease and min/1.73 m2 group. ( b) Kaplan–Meier plot depicting postoperative morbidity after elective orthopedic sur- time to become free of morbidity postoperatively, gery. Anesth Analg. 2011 Jun;112(6):1375–81. Epub according to normal or chronic kidney disease (CKD) 2010 Aug 31

Predictors of Postoperative AKI Table 13.3 Predictors of AKI Age Risk factors for perioperative AKI include epidemi- Male sex ologic factors (e.g., age, gender, diabetes mellitus, Emergent surgery hypertension, and CKD; see Table 13.3 ) and surgical Liver disease (ascites) Body mass index issues (high-risk surgery, intraperitoneal surgery, High-risk surgery (intrathoracic, major vascular, or and vasopressor or diuretic use) [ 14 ] . Patients with intra-abdominal) six or more risk factors had a 10% incidence of AKI Peripheral artery disease and a hazard ratio of 46.2 compared with patients Chronic obstructive pulmonary disease with fewer than three risk factors [ 15 ] . While many Congestive cardiac failure of these risk factors are nonmodifi able, others can be Hypertension addressed to help improve patient outcomes. Preoperative chronic kidney disease Certain medications may increase the risk of Diabetes mellitus AKI, either because they alter renal perfusion Intraoperative vasopressor or diuretic use (NSAIDs, diuretics, ACEi or ARBs, and contrast) or because they are directly nephrotoxic (amino- glycosides and contrast). Avoidance of NSAIDs Impact of AKI on Perioperative is critical in patients with preexisting CKD Outcomes because of their renal vasoconstrictive properties. Alternative analgesic agents and appropriate dose AKI is known to have negative short- and long- reductions are reviewed elsewhere. term consequences on patient outcomes, includ- Patients with CKD more frequently develop ing recovery of renal function, length of hospital AKI (30–35% of AKI) [ 16, 17] , require dialysis, stay, and survival. Ninety-day mortality rises and develop end-stage renal disease after an AKI from 13% to 35% if AKI develops [20 ] . AKI due episode (50% vs. 11%) [ 18 ] . The risk of ESRD after to hemodynamic changes is often short-lived, an AKI episode rises with lower preoperative GFR especially with preserved baseline renal function. levels. CKD is a risk factor for AKI following IV GFR will drop in the fi rst few hours after surgery contrast exposure [19 ] in rheumatologic patients. but should improve signi fi cantly at 24 h [21 ] . 170 J.F. Simon and J.V. Nally

Failure of GFR to rise promptly indicates a more drome [ 27 ] . If gadolinium is required in a dialy- prolonged course. sis patient, it is recommended that hemodialysis The literature on postoperative survival after be performed immediately following the study AKI is most complete in the cardiac surgery lit- and again the following day to clear the erature. AKI is associated with much higher mor- gadolinium. tality rates (60–70 vs. 1–4%) than patients without Unfortunately, there are no medicines known AKI [22, 23] . If AKI requires dialysis, the in- to decrease the risk of AKI perioperatively or to house mortality is 66.7% versus 1.6% for con- treat AKI once it occurs. This fact amplifi es the trols. An additional 12% of patients die within importance of identifying modifi able risk factors the next 3–4 years [ 24 ] . In noncardiac surgery, in- and minimizing potential insults to the kidney hospital mortality rate is 26.4% if dialysis is before AKI develops. These include avoiding required [25 ] . prolonged hypotension, excessive blood loss, and overly aggressive diuresis. Diuretics and NSAIDs should be stopped the day before surgery in AKI in Orthopedic Surgeries patients at risk for AKI. Other high-risk medica- tions that may be stopped under the guidance of a There are few studies concerning the risk of AKI medical consultant include ACE inhibitors or after orthopedics surgeries. Bennett performed a angiotensin receptor blockers (ARBs). If a con- single center retrospective review of 170 hip frac- trasted imaging study is required preoperatively, ture repairs. AKI occurred in 16% of patients. we recommend monitoring high-risk patients Mortality after AKI was higher before discharge (those with CKD or diabetes mellitus) for con- (5% vs. 0%), at 30 days (22% vs. 4%), and at trast nephropathy for 24–48 h before any addi- 120 days (41% vs. 13%). AKI patients were older tional procedures. In most cases, AKI is reversible and more likely to have comorbidities such as with conservative management. However, diabetes and CKD. Length of stay was on aver- repeated insult to the kidneys can lead to more age 7 days longer. Permanent kidney dysfunction severe and even permanent renal failure. A typi- was prevalent among survivors [ 26 ] . cal example is a patient who develops AKI from a contrast study and proceeds to surgery before the AKI has had a chance to recover, leading to Efforts to Avoid AKI in the Perioperative more severe perioperative AKI. Period

In the short-term perioperative period, attention Potassium Homeostasis must be focused on avoidance of both hemody- namic insults leading to renal hypoperfusion and CKD nephrotoxic insults (especially from NSAIDs, Hyperkalemia is relatively common in patients antibiotics, and IV contrast). The use of other with CKD and can lead to cardiac arrhythmias or potential nephrotoxins such as aminoglycoside, arrest if severe. Maintenance of normal serum antibiotics, or amphotericin B must be utilized potassium levels is dependent upon the balance with extreme caution in CKD patients. To pre- between intake and excretion, total body potas- vent contrast nephropathy, IV hydration with sium stores, and the distribution between extra- normal saline or sodium bicarbonate and limit- cellular and intracellular compartments. Renal ing the volume of nonionic contrast used are potassium excretion, the major route by which recommended [ 19] . The use of gadolinium for it is cleared from the body, is dependent upon magnetic resonance imaging is not recom- both adequate glomerular fi ltration (eGFR mended for patients with GFR <30 cc/min, dial- >20 ml/min) and aldosterone-dependent tubular ysis patients, or those with AKI due to the risk of secretion, both of which may be altered in the disabling nephrogenic systemic fi brosis syn- CKD patients. 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension… 171

Hyperkalemia may occur spontaneously if the gery, consultation with a nephrologist is needed. GFR is less than 20 cc/min. It can occur at higher The urgency of dialysis depends on the sever- GFR ranges in diabetics who develop a hyporenin/ ity of the hyperkalemia and the availability of hypoaldosterone state often accompanied by the urgent dialysis services. Sodium polystyrene classic type 4 renal tubular acidosis (RTA). Type (Kayexalate), given 15–30 g by mouth, may be 4 RTA can also occur in chronic interstitial used to control moderate hyperkalemia if neces- nephritis seen with autoimmune diseases. sary. If given rectally, it should not be mixed with Medications that block the renin–angiotensin– sorbitol due to the risk of colonic necrosis. aldosterone system (RAAS) and can cause hyperkalemia include aldosterone inhibitors (e.g., spironolactone), ACE inhibitors, ARBs, Volume and Sodium Homeostasis potassium-sparing diuretics (amiloride and tri- amterene), renin inhibitors, or drugs that inhibit CKD renin production (NSAIDs including COX-2 Patients with CKD can usually maintain their inhibitors, beta blockers, and heparin). ability to excrete sodium and water normally Management of CKD patients in the perioperative until a GFR <15–20 cc/min. However, the period requires vigilance when administering perioperative period can pose challenges to salt potassium-containing products and judicious use and water homeostasis that the diseased kidney of medications known to affect potassium homeo- may not be able to handle, increasing the risk for stasis. If potassium levels are elevated (>5.0) sodium and volume perturbations. Infusions of before surgery, medications that raise potassium saline may rapidly produce volume overload in levels should be stopped, and potassium intake advanced CKD, in which case IV fl uids should be (both in diet and IV fl uids) should be restricted. If held and diuresis with a loop diuretic with or hyperkalemia is severe enough to delay surgery, without a thiazide should be initiated. sodium polystyrene may be used (see below). Conversely, because CKD patients cannot fully concentrate their urine and are often on ESRD diuretics, they are also at risk for volume deple- In the ESRD patient, because kidney failure pre- tion due to inadequate intake, extrarenal losses vents any signi fi cant renal clearance of potas- (e.g., nasal gastric suction, diarrhea), or contin- sium, any exogenous potassium can lead to ued diuretic use. Volume status must be moni- hyperkalemia. Common causes of hyperkalemia tored closely in the perioperative period and that should be avoided in the perioperative setting isotonic IV fl uids be administered judiciously. include IVF fl uids containing potassium includ- Impairments in free water handling in ing lactated Ringer’s solution (4 mEq/L potas- advanced CKD predispose to disorders of sodium sium), succinylcholine, and high-potassium balance. Hyponatremia in the perioperative nutritional supplements or diet. Surgery that period is usually related to one of two potential requires extensive debridement of necrotic tissue scenarios: (1) excessive administration of hypo- may lead to an impressive hyperkalemia requir- tonic fl uids and (2) inappropriate antidiuretic ing hemodialysis postoperatively. In ESRD, hormone (AVP) secretion due to pain or medications discussed above that block renal anesthesia. potassium excretion should have no effect on potassium levels. ESRD We recommend that potassium levels be Disorders of sodium balance are not common in checked in ESRD patients the morning before ESRD. Hyponatremia that may develop due to surgery and in the immediate postoperative hypoosmotic fl uid intake between dialysis ses- period. Hyperkalemia (>5.0 mEq/L) before sur- sions is usually corrected with a single hemodial- gery warrants a delay in surgery until dialysis can ysis treatment since the standard dialysate sodium be performed. If hyperkalemia is found after sur- concentration is 140 mEq/L. Hypernatremia may 172 J.F. Simon and J.V. Nally be seen in patients receiving tube feeds and can be infl ammation. Management of the anemia corrected with small amounts of free water given includes recombinant human EPO to maintain through the feeding tube. hemoglobin >10. Nephrology consultation should be sought perioperative anemia management.

Acid–Base Homeostasis Cardiovascular Risk Metabolic acidosis may be more common and more severe in the CKD patient, but treatment of As mentioned earlier, CKD is an independent the acidosis is identical to the nonrenal patient. risk factor for the development of CAD [7 ] . CKD Early CKD is not usually associated with meta- also confers an adverse effect upon long-term bolic acidosis, but patients are more susceptible morbidity and mortality from cardiovascular dis- to developing metabolic acidosis from another ease. In fact, the chance of death from cardiovas- insult because of the kidney’s impaired ability to cular disease greatly exceeds (by eight- to tenfold) clear an acid load. A modest metabolic acidosis the risk of developing ESRD [ 31 ] . These patients may develop when GFR falls below 30 ml/min, should be considered high risk for cardiovascular usually with a normal anion gap and hyperchlor- events and require careful cardiovascular screen- emia. As the GFR falls below 20 cc/min, clear- ing prior to surgery (see Chap. 5 ). ance of organic anions such as phosphates and sulfates decreases, resulting in an elevation of the anion gap. ESRD patients are usually slightly Perioperative Management of the alkalotic due to the high bicarbonate concentra- Hypertension Patient: With or tion in the dialysate, so any signifi cant acidosis Without CKD should be a source of concern. The diagnosis of hypertension is associated with an increased risk of adverse outcomes and mor- Bone-Mineral Disorders tality after surgery. In normal subjects, systolic blood pressure may rise 20–30 mmHg during Patients with CKD and ESRD commonly have induction of anesthesia. Shortly afterward, blood secondary hyperparathyroidism and hyperphos- pressure drops, often resulting in mild hypoten- phatemia. These chronic complications can pre- sion. Hypertensive patients are characterized by dispose to pathologic bone fractures and worse more exaggerated hypertensive and hypotensive orthopedic surgical outcomes. Some case series responses. Systolic blood pressure may rise as suggest the joint failure and complications are much as 90 mmHg in untreated subjects during more common after arthroplasty in ESRD patients induction of anesthesia [32 ] . [28– 30] . Sodium phosphosoda cathartics (Fleets® Hypertension found preoperatively is cited as enema) should be avoided due to the risk of life- the most common medical reason to delay surgery threatening hyperphosphatemia. Likewise the use [ 33 ] . However, data on the impact of hypertension of magnesium- or aluminum-containing antacids on surgical outcomes does not necessarily support should be avoided to prevent intoxication. this. While severely uncontrolled hypertension (BP >180/110) has been associated with an increased risk of cardiac, neurologic, and renal Anemia complications during and after surgery, more moderate degrees of hypertension have not been Anemia is a common problem in patients with associated with such adverse outcomes. Indeed, advanced CKD and ESRD due to erythropoietin aggressive control of hypertension immediately (EPO) defi ciency. In autoimmune disease, ane- before surgery can be more hazardous than leav- mia may be more severe than expected based ing moderate hypertension untreated due to altera- upon the level of GFR due to systemic tions in autoregulation responses in the cerebral 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension… 173

Table 13.4 Medications in the management of the perioperative hypertension patient Beta blockers Continue through surgery Cannot recommend starting preoperatively Clonidine Use with caution Continue patch use if prolonged NPO status is expected, but avoid if hypotension is a concern ACE inhibitors and ARBs Controversial effects on perioperative outcomes Consider discontinuing the day before surgery if hypotension, acute renal failure, CKD, or contrast loads are expected Discuss their use with cardiology in known cardiac disease such as CHF Diuretics Hold the day before surgery unless CHF is present IV medication use The use of short-acting intermittent medications such as metoprolol or hydralazine is often ineffective. Consider drips if blood pressure is dif fi cult to control until the patient is taking po

and renal vasculature. Autoregulation allows these makes effective blood pressure control diffi cult vascular beds to maintain suf fi cient organ perfu- when either is used alone. Sodium nitroprusside, sion at a wide range of blood pressures. In chroni- while indicated for hypertensive emergencies, is cally uncontrolled hypertension, there is a shift not commonly used to control moderate degrees upward in the range of blood pressures tolerated of hypertension. It should be used with caution in for tissue perfusion. Suddenly normalizing the CKD and avoided in ESRD due to the accumula- blood pressure in a chronically hypertensive tion of cyanide metabolites. patient may drop the perfusion pressure below this Medication withdrawal is a signi fi cant prob- higher range, resulting in organ hypoperfusion. lem with beta blockers and clonidine. These This increases the risk for neurologic events, acute medications should be continued perioperatively. kidney injury at myocardial ischemia at pressures If the patient is unable to take oral medications, that would otherwise be considered normal. clonidine can be switched to a patch form during Blood pressure should be controlled to the preoperative period. However, using a cloni- <140/90 for several weeks before surgery. dine patch may be hazardous if there is a However, surgery may proceed if the blood pres- signifi cant risk of hypotension during surgery sure is <180/110 unless evidence of end organ since the antihypertensive effect will persist for damage is present [34 ] , in which case elective up to 36 h after the patch is removed. surgery should be delayed until a more accept- Since beta blockers also have cardioprotective able BP is achieved. If the surgery is emergent, properties during surgery, they should be contin- IV antihypertensive medications should be care- ued. Labetalol is the beta blocker of choice to be fully given to achieve a BP <180/110 without used IV since it can be given IV as a constant infu- inducing hypotension. Table 13.4 reviews the use sion. However, data about starting beta blockers of specifi c antihypertensive medications in the de novo before surgery for cardioprotection remains perioperative period. controversial. While this practice was previously A common problem in managing periopera- recommended in preoperative guidelines, random- tive hypertension is the effective use of intrave- ized controlled trials suggest that it may increase nous antihypertensive medications. Labetalol, the risk of mortality and other adverse events [ 35 ] . diltiazem, and nicardipine can be given as drips. Loop diuretics are not effective antihyper- Enalapril, propranolol, esmolol, hydralazine, and tensive medications. Their main purpose is for metoprolol can be given as intermittent boluses. volume management. If the patient is at While hydralazine and metoprolol may be effec- increased risk for acute kidney injury, diuretics tive when given intravenously to acutely lower should be held the morning of surgery. However, blood pressure, their brief duration of action if patients have congestive heart failure or other 174 J.F. Simon and J.V. Nally illnesses that increase the risk of peripheral or Pharmacokinetic Changes in Renal pulmonary edema, these medications should be Disease continued. ACE inhibitors and ARBs decrease fi ltration Bioavailability of medications from the GI tract pressure across the glomerular basement mem- can be impaired by factors such as diabetic gas- brane. Their use can predispose to acute renal tropathy, gut edema in nephrotic syndrome, and failure and hyperkalemia in the perioperative the use of phosphate binders that can bind medi- period when combined with other insults, such cations in the gut. The quinolone class of antibi- as hypotension or volume depletion. The use of otics is an important example, where the ACE inhibitors [ 36] and ARBs [ 37, 38] the day concomitant use of phosphate binders, calcium or before surgery in randomized controlled trials magnesium supplements, or dairy products can has been associated with more severe hypoten- render these antibiotics ineffective by inhibiting sion during induction of anesthesia, although a their absorption from their gut. retrospective study did not support these fi ndings Dialysis patients are often volume overloaded [ 39 ] . If there is an increased risk of AKI, these and therefore have increased third-spaced fl uids. medications should be held the day before sur- Water-soluble medications will have a larger vol- gery and not restarted until renal function is ume of distribution leading to lower blood levels. documented to be stable postoperatively. Alterations in protein binding affect volume Alternative medications should be considered to of distribution as well. Uremic solutes and organic control blood pressure. If the cardiac ejection acids retained in renal failure can displace drugs fraction is severely depressed, these medicines that are highly protein bound from their protein play an important role in afterload reduction to carriers or tissue binding sites. As a result, these maintain organ perfusion and consultation with medications will have a larger volume of distri- a cardiologist before surgery should be sought. bution and lower blood levels.

Medication Dosing in CKD and ESRD Hepatic Clearance via Cytochrome P450 Pathway Perhaps one of the most important reasons to rec- ognize renal dysfunction is how it impacts all The clearance of medications via the cytochrome aspects of medication prescribing in the periop- P450 (CYP450) pathway, classically attributed erative period, including choice of medication, solely to the liver, is affected by renal failure as dose, interval, and expected side effects. Renal well. The kidneys can contribute up to 18% of dysfunction can lead to changes in medication CYP450 activity [ 40 ] . Hepatic clearance of drugs bioavailability, metabolism, clearance, protein can also be affected by factors such as decreased binding, and volume of distribution. All of these hepatic blood fl ow, altered protein binding, and changes increase the risk of drug accumulation alterations in liver enzyme activity in the uremic and toxicity. In addition, patients with renal dis- milieu [ 40, 41 ] . ease tend to take multiple medications for comor- bid conditions, increasing the risk of drug interactions and dosing errors. Renal Excretion of Medications Hemodialysis therapy poses the additional and Their Metabolites problem that drug levels may drop abruptly dur- ing dialysis then remain relatively stable between Mechanisms for renal clearance of drugs include sessions. This can make dosing medicines chal- glomerular fi ltration, tubular secretion, and metab- lenging. Many medications need to be dosed after olism by proximal tubular epithelial cells. Only the dialysis treatment without redosing between medications not bound to plasma proteins will be sessions. fi ltered, unless there is signifi cant proteinuria. 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension… 175

Proper renal dosing in CKD and renal failure is in the ICU requiring continuous renal replace- most important when using antimicrobial agents. ment therapy require special attention because of Vancomycin and the aminoglycosides are discussed alterations in the volume of distribution and individually below. In general, published guidelines increased clearance by the dialysis circuit. Little should be followed when ordering antimicrobials is known about the clearance of many antibiotics in a CKD patient. Medications that are metabolized using modern continuous renal replacement ther- to active compounds such as antiseizure medicines apy techniques. should be checked as well. As stated previously, creatinine clearance should be assumed to be less than 10 cc/min if AKI is present. Rheumatology-Speci fi c Medications Vancomycin accumulates with renal dysfunc- in Renal Failure tion. The nephrotoxicity of vancomycin remains a controversial topic, but ATN has been reported at Medications used by rheumatologists for sys- very high levels. Vancomycin should be dosed to temic autoimmune diseases require special dos- achieve a trough level of 15-20 mcg/mL. This can ing considerations. Many are renally cleared and often be achieved in CKD by extending the dosing have side effect profi les that increase the risk of interval to every 18–48 h. We recommend giving signi fi cant toxicity if dosing adjustments are not a single dose and using trough levels to determine made. when it should be redosed. In ESRD, the excre- Cyclophosphamide requires dose reduction in tion rate is dramatically slowed. Levels often will the setting of any degree of renal failure. Failure not drop into acceptable ranges until after the next to reduce the dose of cyclophosphamide is a hemodialysis session, which clears about 30% of major reason for adverse reactions and toxicity in the drug. Therefore, vancomycin can often be patients with renal disease. The dose should be given at a dose of 1–1.5 g after each dialysis ses- reduced by 25–50% depending on the degree of sion without any interval dose. In general, predi- renal dysfunction. alysis levels should be checked when fi rst starting Methotrexate in general is contraindicated vancomycin to ensure a correct dosing interval. in patients with decreased renal function due Aminoglycoside dosing is quite controversial to the accumulation of active metabolites. because of the concern for toxicity but the rela- Mycophenolate mofetil does not require renal tive paucity of data regarding safe dosing in renal dosing. It can be given IV at the same dose if failure. Aminoglycoside ef fi cacy is peak-dependent needed. Azathioprine requires dose reduction in and its toxicity trough-dependent. However, in chronic kidney disease. In ESRD, it should be the setting of minimal urinary clearance in ESRD, given after dialysis due to effective clearance alterations in the area under the curve effect tox- by the dialyzer. Case reports suggest hydroxy- icity. Gentamicin use should be avoided in dialy- chloroquine should be used with caution in sis patients unless absolutely necessary. Even severe renal failure, but dosing guidelines do when very low doses (1–1.5 mg/kg) of gentami- not exist. There are no recommendations to cin are given after dialysis, ototoxicity can be reduce the dose of rituximab in renal disease. seen and is related to age and cumulative dose Colchicine should be used with extreme cau- [42 ] . When it must be used, a lower dose of tion with a GFR <30 cc/min because of the risk 1.5–2 mg/kg should be given and not redosed of leucopenia, permanent peripheral neuropathy, until the level is below 3 mcg/mL, usually after and myopathy. the next dialysis session. Administering higher While calcineurin inhibitors (cyclosporine doses runs the risk of permanent ototoxicity even and tacrolimus) are not as commonly used in after a single dose. Prolonged therapy should be rheumatologic conditions, they may be found in avoided. regimens for rheumatoid arthritis, organ trans- Many other antibiotics require dose and inter- plantation, and certain glomerulonephritides. val adjustments without checking levels. Patients Both medications are metabolized via CYP3A4. 176 J.F. Simon and J.V. Nally

Dosing is not typically adjusted for worsening safe to use in one-time doses, it should not be renal function, but effectiveness and toxicity are used for ongoing pain control in ESRD. determined by trough levels drawn 0–30 min Hydromorphone is metabolized by the liver to before a scheduled dose. Trough levels drawn metabolites that are renally excreted. Publications while admitted are often inaccurate due to altered show con fl icting risks of neuronal excitation in timing of doses and phlebotomy. Checking trough renal failure [45, 46 ] . No dose adjustment is rec- levels is not recommended while admitted unless ommended in published guidelines. Oxycodone’s explicitly recommended by the clinician manag- active metabolite, oxymorphone, exists in negli- ing that medication. gible concentrations after hepatic metabolism. Cyclosporine and tacrolimus can be given IV, Oxycodone itself has a prolonged half-life in but the dose given is 1/3 the oral dose. renal failure, and increased CNS toxicity has Cyclosporine can be divided into 2–3 doses daily been described in renal failure [47, 48 ] . Caution or given as a continuous infusion. Tacrolimus is should be taken when used for repeated dosing in given as a continuous infusion. Patients should be renal failure even though published guidelines do transitioned back to the oral form as soon as not recommend dose adjustment. One of codeine’s possible. metabolites is M6G, which was suspected to be responsible for adverse effects seen in renal Nonsteroidal Anti-infl ammatory Drugs patients in published case reports [ 49 ] . Dose (NSAIDs) reduction is recommended to 75% in moderate Most caregivers recognize the need to restrict the renal impairment (10–50 cc/min) and to 50% for use of nonsteroidal anti-infl ammatory drugs GFR <10 cc/min and ESRD. Methadone is (NSAIDs), both nonspecifi c and COX-2-specifi c metabolized to pyrrolidine , which is renally inhibitors, in any patient with chronic kidney dis- excreted. Fecal excretion of methadone is upreg- ease due to the risk of worsening renal function. ulated in renal failure [ 50 ] . Published guidelines This can become problematic in the rheumatol- suggest a dose reduction by 25–50% in ESRD. ogy patient with chronic pain issues. The use of Fentanyl’s metabolites are inactive. Its safe use these drugs in the perioperative setting can without dose adjustment has been described in increase the risk of acute renal failure. renal failure. Of the narcotic analgesics reviewed, fentanyl Narcotic Analgesics and hydromorphone are likely the safest for Narcotic analgesic medications are often thought short-term pain control. Methadone also appears to be safe to use in renal disease; in reality, many to be safe to use in renal failure. Hydromorphone of them have to be used with great caution or can most likely be used without dose adjustment avoided in renal disease. Recommendations in with regular monitoring for side effects. this section are synthesized from published Oxycodone should be used with great caution. reviews and dosing guidelines provided in the The dose of codeine should be reduced and lim- medication inserts. ited to short-term use. Meperidine should be Meperidine should be avoided due to the avoided. Morphine should not be used for ongo- increased risk of seizures. Its active metabolite, ing pain management. normeperidine, accumulates and lowers the sei- zure threshold. Although morphine is metabo- lized by the liver, morphine-6-glucuronide (M6G) Hemodialysis Removal of Narcotics is cleared by the kidney and accumulates in renal failure [43 ] . M6G is not particularly active as an Several narcotics are cleared by hemodialysis opioid, but its retention can lead to exaggerated [ 51 ] . The modality and intensity of dialysis will CNS effects which can persist after the drug is determine the rate of removal in many cases. stopped due to slow clearance across the blood– Morphine is known to be dialyzed effectively, but brain barrier [ 44 ] . Thus, while morphine may be M6G clearance from the central nervous system 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension… 177

Table 13.5 Narcotics dosing in renal disease Medication Dosing Dialyzable Fentanyl Safe without dose adjustment No Hydromorphone Safe without dose adjustment Yes Oxycodone Use with great caution Yes Codeine Consider avoiding in CKD No data Reduce dose by 25% in CKD Reduce dose by 50% in ESRD Morphine Do not use Yes Meperidine Do not use Not likely, no data Methadone Reduce dose by 25–50% No

may be delayed. Hydromorphone is readily Anticoagulation cleared (60%) by hemodialysis. Oxycodone is water-soluble and should be readily dialyzed, but Low-molecular-weight heparin (LMWH) is often no studies have established this. Methadone is used in the perioperative period, especially in highly protein bound and was shown to be poorly orthopedic procedures, for deep vein thrombosis dialyzed in one case report. No data is available prophylaxis. LMWHs are renally cleared and for codeine. Fentanyl is highly protein bound. No accumulate in renal dysfunction. Toxicity, mani- data exists to suggest it is removed by dialysis. fest as bruising or bleeding, cannot be reversed Table 13.5 summarizes the use of narcotic anal- with protamine. The use of LMWH is contraindi- gesics in renal patients. cated in patients with ESRD. Dose reduction guidelines are available for eGFRs of 15–30 cc/ min, but many recommend avoiding its use in this Anesthetics population as well. Unfractionated heparin should be used for DVT prophylaxis and systemic Epidural anesthesia is associated with spontane- anticoagulation. ous epidural hematoma formation in hemodialy- Unfractionated heparin is used during hemo- sis patients. This may be the result of increased dialysis to prevent clotting of the dialysis circuit. bleeding tendency and intracranial hypertension Systemic anticoagulation does occur. Protocols that develops at the end of dialysis due to fl uid using no anticoagulation or alternative agents and solute shifts. Heparin used with dialysis can such as citrate exist if heparin cannot be used. exacerbate bleeding risk. The use of epidural anesthesia in hemodialysis patients should be approached with caution. Heparin anticoagula- Speci fi c Perioperative Issues Related tion with dialysis may need to be held if epidural to the Hemodialysis Patient anesthesia is employed. Inhaled anesthetics that should be avoided in The patient with ESRD presents particular chal- CKD include methoxy fl urane, sevo fl urane, and lenges that must be taken into consideration when en fl urane due to fl uoride-induced polyuria and determining the timing of surgery, medications to risk of acute renal failure. Des fl urane and be used, and postoperative care. See also iso fl urane are safe to use. Neuromuscular block- Perioperative Care of the CKD Patient. Involvement ers that can accumulate in renal failure include of the patient’s nephrologist in the planning stages mivacurium, vecuronium, and rocuronium, and of surgery will facilitate a smoother process and doses should be adjusted appropriately. should reduce unforeseen complications. 178 J.F. Simon and J.V. Nally

Timing of Surgery and Hemodialysis Tunneled dialysis catheters are used if a surgical The optimal time for surgery is either immedi- access cannot be placed. The most common site ately after dialysis or the following day to mini- for a tunneled catheter is the internal jugular vein. mize the risk of volume overload and These catheters are packed with high-concentration hyperkalemia. Some surgeons avoid operating heparin or citrate, often mixed with antibiotics. after dialysis because of concerns that the dialy- Heparin toxicity has occurred after nondialysis sis procedure itself can cause transient platelet medical personnel attempted to access a dialysis dysfunction. Coordination with the nephrology catheter to obtain blood or run fl uids. The dialysis consultant should occur in advance so that dialy- catheter should not be manipulated or accessed sis can be scheduled appropriately. If surgery is for any reason other than dialysis. emergent, the nephrologist should be informed as Intravenous access is often a diffi cult issue in soon as possible. dialysis patients. Peripheral IVs should not be placed in the arm with a surgical access. Dialysis Volume Management catheters often occupy a jugular vein. Subclavian Since most patients with ESRD are anuric, any dialysis catheters lead to subclavian stenosis. volume given to the patient must be removed by Central veins are often occluded in long-term hemodialysis. The aggressive use of crystalloid dialysis patients. Peripherally inserted central or blood products to treat hemodynamic instabil- catheters (PICC) should also be avoided due to ity or bleeding perioperatively can lead to volume trauma to the arm veins (potential fi stula sites). overload, manifesting as diffi culty weaning from For central access, internal jugular and femoral mechanical ventilation or impaired wound heal- veins are preferred. If long-term IV access is ing due to edema. Hemodialysis is the only way needed, a short-tunneled central catheter (e.g., a to treat volume overload in an anuric patient. Hohn catheter) is preferred to a PICC.

Access Management Uremic Platelet Dysfunction It is critical that nonnephrologists understand the Uremia is a known cause of impaired platelet importance of protecting and properly caring for function, which can increase the risk for bleeding the means used to gain access to the patient’s complications perioperatively. In a well-dialyzed blood for hemodialysis, also known as the vascu- hemodialysis patient, uremic bleeding is not a lar access. This is the patient’s lifeline to their signifi cant issue. This may be encountered in dialysis treatments. Loss of the vascular access fl oridly uremic patients whose GFR is <15 cc/ can be a life-threatening situation. There are three min but who are not yet on dialysis or who are on types of dialysis access: arteriovenous fi stula, dialysis but are underdialyzed . The most common arteriovenous graft, and the hemodialysis cathe- reasons for chronic underdialysis include dialysis ter. Fistulae and grafts are surgical “shunts” access dysfunction and patient noncompliance placed under the skin, usually in the arms. These with their dialysis treatments. In theory, uremic accesses should not be compressed in any way, platelet dysfunction should be corrected by a such as with blood pressure cuffs, as this can single, good dialysis session. Severe anemia can cause them to thrombose. Acute thrombosis risks also predispose to uremic platelet dysfunction. permanent loss of the access. Severe hypotension Clotting factors or platelet number remains can also lead to access thrombosis. Blood fl ows normal. If uremic platelet dysfunction is suspected, through a well functioning dialysis access at treatment strategies include hemodialysis, 1,000–1,200 cc/min. Any leak from the access DDAVP, conjugated estrogen, cryoprecipitate, or can quickly become life-threatening. Therefore, treatment with erythropoietin or transfusions to the dialysis access should never be used to draw achieve a hemoglobin level over 10 g/dL. blood (except by a trained dialysis nurse) or to Hypercoagulability is a common problem in place an IV. ESRD. Patients on chronic hemodialysis have an 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension… 179 increased risk for venous thromboembolism. changes in blood levels of the transplant medi- Attention should be paid to appropriate DVT pro- cines, running the risk of either toxicity or rejec- phylaxis (see Medication Dosing section). tion. A formal nephrology consultation (transplant nephrology if available) is imperative any time a kidney transplant recipient is admitted. Management of the Perioperative The management of the immunosuppressive Patient on Peritoneal Dialysis medications is reviewed in the Medication Management section. Of note, a notable side The peritoneal dialysis (PD) patient presents effect of rapamycin is impaired wound healing. some slightly different issues than the hemodialy- The nephrologist may switch rapamycin to a cal- sis patient because dialysis is performed on a cineurin inhibitor before surgery and not restart it daily basis, either during the day or at night while until the wound is fully healed. Since most trans- sleeping. The dialysis is often less intense, pull- plant patients are on corticosteroids, “stress-dose ing less potassium and fl uid per hour than hemo- steroids” are commonly utilized perioperatively. dialysis. While this allows the patient’s electrolytes Transplanted kidneys are by nature dener- and volume to remain more stable over time, it is vated, decreasing responsiveness of the renin– not amenable to acutely managing electrolyte or angiotensin system to changes in volume status. volume imbalances. If a patient is volume over- As a consequence, transplanted kidneys are more loaded or precise volume management is needed, susceptible to developing prerenal azotemia than hemodialysis should be considered. native kidneys. The peritoneal catheter lies in the peritoneal cavity and exits the skin in the lower abdomen. The catheter should be protected intraoperatively Conclusion from laceration as leaks may require transition to hemodialysis until the PD catheter can be Patients with kidney disease and hypertension are replaced. Abdominal or spinal surgeries requir- at increased risk for infectious, renal, and cardio- ing an anterior approach necessitate the removal vascular complications in the perioperative of the PD catheter and transition to hemodialysis. period. If these risks are recognized, many of This should be coordinated with the patient’s them can be addressed and minimized. nephrologist before the surgery if possible. Participation of a nephrologist in the preoperative The nephrologist will order the PD treatments, planning stages will help address these risks and usually consisting of nocturnal PD using a cycling optimize the chances of a successful surgical machine. We do not recommend allowing inpa- outcome. tients to perform their own exchanges while in-house. References

Perioperative Management 1. KDOQI clinical practice guidelines for chronic kid- of the Kidney Transplant Patient ney disease: evaluation, classi fi cation, and strati fi cation. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis. 2002;39(suppl 1):S1–S246. Kidney transplant patients take immunosuppres- 2. Levey AS, Bosch JP, Lewis JB, Greene T, et al. A sion medications to prevent rejection of the trans- more accurate method to estimate glomerular fi ltration planted kidney. Correct management of transplant rate from serum creatinine: a new prediction equation. Modifi cation of Diet in Renal Disease Study Group. medications is essential to maintain good graft Ann Intern Med. 1999;130:461–70. function. Calcineurin inhibitors, commonly used 3. Levey AS, Stevens LA, Schmid CH, Zhang YL, et al. in transplantation, are metabolized through A new equation to estimate glomerular fi ltration rate. CYP450. The addition of another medication that Ann Intern Med. 2009;150:604–12. 4. Coresh J, Astor BC, Greene T, Eknoyan G, et al. is metabolized by CYP450 can lead to rapid Prevalence of chronic kidney disease and decreased 180 J.F. Simon and J.V. Nally

kidney function in the adult US population: third 19. Parfrey NEJM, Barrett BJ, Parfrey PS. Clinical prac- national health and nutrition examination survey. Am tice. Preventing nephropathy induced by contrast J Kidney Dis. 2003;41:1–12. medium. N Engl J Med. 2006;354(4):379–86. 5. US Renal Data System, USRDS 2010 annual data 20. Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, report: atlas of chronic kidney disease and end-stage Molitoris BA, Himmelfarb J, Collins AJ. Incidence renal disease in the United States. National Institutes and mortality of acute renal failure in Medicare of Health, National Institute of Diabetes and Digestive bene fi ciaries, 1992 to 2001. J Am Soc Nephrol. and Kidney Diseases, Bethesda; 2010. 2006;17:1135–42. Epub 2006 Feb 22. 6. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu 21. Myers BD, Miller C, Mehigan JT, et al. Nature of the CY. Chronic kidney disease and the risks of death, renal injury following total renal ischemia in man. J cardiovascular events, and hospitalization. N Engl J Clin Invest. 1984;73:329–41. Med. 2004;351(13):1296–305. 22. Mangano CM, Diamondstone LS, Ramsay JG, 7. Chambless LE, Folsom AR, Sharrett AR, et al. Aggarwal A, Herskowitz A, Mangano DT. Renal Coronary heart disease risk prediction in the athero- dysfunction after myocardial revascularization: risk sclerosis risk in communities (ARIC) study. J Clin factors, adverse outcomes, and hospital resource utili- Epidemiol. 2003;56:880–90. zation. The Multicenter Study of Perioperative 8. Mathew A, Devereaux PJ, O’Hare A, Tonelli M, et al. Ischemia Research Group. Ann Intern Med. Chronic kidney disease and postoperative mortality: a 1998;128:194–203. systematic review and meta-analysis. Kidney Int. 23. Chertow GM, Levy EM, Hammermeister KE, Grover 2008;73:1069–81. F, Daley J. Independent association between acute 9. Ackland GL, Moran N, Cone S, Grocott MP, et al. renal failure and mortality following cardiac surgery. Chronic kidney disease and postoperative morbidity Am J Med. 1998;104:343–8. after elective orthopedic surgery. Anesth Analg. 24. Landoni G, Zangrillo A, Franco A, Aletti G, et al. 2011;112(6):1375–81. Long-term outcome of patients who require renal 10. Lavery LA, Hunt NA, Ndip A, Lavery DC, Van Houtum replacement therapy after cardiac surgery. Eur J W, Boulton AJ. The impact of chronic kidney disease Anaesthesiol. 2006;23:17–22. on survival after amputation in persons with diabetes. 25. Abelha FJ, Botelho M, Fernandes V, Barros H. Diabetes Care. 2010;33(11):2365–9. Outcome and quality of life of patients with acute kid- 11. Chertow GM, Burdick E, Honour M, Bonventre JV, ney injury after major surgery. Nefrologia. Bates DW. Acute kidney injury, mortality, length of 2009;29:404–14. stay, and costs in hospitalized patients. J Am Soc 26. Bennet SJ, Berry OM, Goddard J, Keating JF. Acute Nephrol. 2005;16:3365–70. renal dysfunction following hip fracture Injury. Injury. 12. Ricci Z, Cruz D, Ronco C. The RIFLE criteria and 2010;41:335–8. mortality in acute kidney injury: a systematic review. 27. United States Food and Drug Administration. Kidney Int. 2008;73:538–46. Epub 2007 Dec 26. Information for healthcare professionals gadolinium- 13. Mehta RL, Kellum JA, Shah SV, Molitoris BA. Acute based contrast agents for magnetic resonance imaging kidney injury network: report of an initiative to (marketed as Magnevist, MultiHance Omniscan, improve outcomes in acute kidney injury. Crit Care. OptiMARK, ProHance), Washington. http://www.fda. 2007;11:R31. gov/Drugs/DrugSafety/PostmarketDrugSafety 14. Kheterpal S, Tremper KK, Englesbe MJ, O’Reilly M, Informationfor PatientsandProviders/ ucm142884.htm et al. Predictors of postoperative acute renal failure (2010). Accessed 25 Oct 2010. after noncardiac surgery in patients with previously 28. Li W, Shih C, Ueng SW, Shih H, et al. Uncemented normal renal function. Anesthesiology. total hip arthroplasty in chronic hemodialysis patients. 2007;107:892–902. Acta Orthop. 2010;81:178–82. 15. Kheterpal S, Tremper K, Heung M, Rosenberg A, 29. Shrader MW, Schall D, Parvizi J, McCarthy JT, et al. Englesbe M, Shanks A, et al. Development and vali- Total hip arthroplasty in patients with renal failure: a dation of an acute kidney injury risk index for patients comparison between transplant and dialysis patients. undergoing general surgery: results from a national J Arthroplasty. 2006;21:324–9. data set. Anesthesiology. 2009;110:505–15. 30. Blacha J, Kolodziej R, Karwanski M. Bipolar 16. Thakar CV, Arrigain S, Worley S, Yared JP, Paganini cemented hip hemiarthroplasty in patients with femo- EP. A clinical score to predict acute renal failure after ral neck fracture who are on hemodialysis is associ- cardiac surgery. J Am Soc Nephrol. 2005;16(1):162–8. ated with risk of stem migration. Acta Orthop. 17. Hsu CY, Chertow GM, McCulloch CE, Fan D, 2009;80:174–8. Ordonez JD, Go AS. Nonrecovery of kidney function 31. Foley RN, Murray AM, Li S, Herzog CA, McBean and death after acute on chronic renal failure. Clin J AM, Eggers PW, et al. Chronic kidney disease and the Am Soc Nephrol. 2009;4:891–8. Epub 2009 Apr 30. risk for cardiovascular disease, renal replacement, and 18. Metcalfe W, Simpson M, Khan IH, Prescott GJ, death in the United States Medicare population, 1998 Simpson K, Smith WC, MacLeod AM. Acute renal to 1999. J Am Soc Nephrol. 2005;16(2):489–95. failure requiring renal replacement therapy: incidence 32. Wolfsthal SD. Is blood pressure control necessary and outcome. QJM. 2002;95:579–83. before surgery? Med Clin North Am. 1993;77:349. 13 Perioperative Management of the Patient with Chronic Kidney Disease, Hypertension… 181

33. Dix P, Howell S. Survey of cancellation rate of hyper- 42. Gailiunas P, Dominguez-Morena M, Lazarus M, tensive patients undergoing anaesthesia and elective Lowrie E, et al. Vestibular toxicity of gentamicin. surgery. Br J Anaesth. 2001;86:789. Arch Inter Med. 1978;138:1621–4. 34. Sear JW. Perioperative control of hypertension: when 43. Hasselstrom J, Sawe J. Morphine pharmacokinetics will it adversely affect perioperative outcome? Curr and metabolism in humans. Clin Pharmacokinet. Hypertens Rep. 2008;10:480–7. 1993;24:344–54. 35. POISE study group, Devereaux PJ, Yang H, et al. Effects 44. Angst MS, Buhrer M, Lotsch J. Insidious intoxication of extended-release metoprolol succinate in patients after morphine treatment in renal failure: delayed onset undergoing non-cardiac surgery (POISE trial): a ran- of morphine-6-glucuronide action. Anesthesiology. domized controlled trial. Lancet. 2008;371:1839–47. 2000;92:1473–6. 36. Coriat P, Richer C, Douraki T, Gomez C, et al. 45. Fainsinger R, Schoeller T, Boiskin M, Bruera E. In fl uence of chronic angiotensin-converting enzyme Cognitive failure and coma after renal failure in a inhibition on anesthesia induction. Anesthesia. patient receiving captopril and hydromorphone. 1994;81:299–307. J Palliative Care. 1993;9:53–5. 37. Bertrand M, Godet G, Meersschaert K, Brun L, et al. 46. Lee MA, Leng ME, Tiernan EJ. Retrospective study Should the angiotensin II antagonists be discontinued of the use of hydromorphone in palliative care patients before surgery? Anesth Analg. 2001;92:26–30. with normal and abnormal urea and creatinine. Palliat 38. Brabant SM, Bertrand M, Eyraud D, Darmon PL, Med. 2001;15:26–34. Coriat P. The hemodynamic effects of anesthetic 47. Fitzgerald J. Narcotic analgesics in renal failure. Conn induction in vascular surgical patients chronically Med. 1991;55:701–4. treated with angiotensin II receptor antagonists. 48. Foral PA, Ineck JR, Nystrom KK. Oxycodone accu- Anesth Analg. 1999;89(6):1388–92. mulation in a hemodialysis patient. South Med J. 39. Sear JW, Jewkes C, Telles JC, Foex P. Does the choice 2007;100:212–4. of antihypertensive therapy in fl uence haemodynamic 49. Talbott GA, Lynn AM, Levy FH, Zelikov I. responses to induction, laryngoscopy and intubation? Pharmacokinetics and pharmacodynamics of codeine Br J Anaesth. 1994;73:303–8. in end-stage renal disease. Clin Pharmacol Ther. 40. Elston AC, Bayliss MK, Park GR. Effect of renal fail- 1988;43:63–71. ure on drug metabolism by the liver. Br J Anaesth. 50. Kreek MJ, Schecter AJ, Gutjahr CL, Hecht M. 1993;71:282–90. Methadone use in patients with chronic renal disease. 41. Nolin TD, Frye RF, Matzke GR. Hepatic drug metab- Drug Alcohol Depend. 1980;5:197–205. olism and transport in patients with kidney disease. 51. Dean M. Opioids in renal failure and dialysis patients. Am J Kidney Dis. 2003;42:906–25. J Pain Symptom Manage. 2004;28:497–504. Systemic Lupus Erythematosus 1 4 Elena Katzap and Richard A. Furie

acute respiratory distress syndrome, pneumotho- Introduction rax, pleural effusion, and prolonged intubation time, were reported. Patients experiencing com- Directing the care of patients with systemic lupus plications had higher oral prednisone doses, erythematosus (SLE) during the perioperative higher number of organ systems involved, and period may be no less challenging than managing more frequent renal involvement than those their disease during the nonoperative period. who did not develop complications. In a study While the team can prepare a patient for elective assessing the risk factors for operative morbid- surgery, it is the unexpected emergency proce- ity in patients with SLE by Takahashi et al., 53 dures and the unforeseen postoperative compli- patients underwent 63 surgical procedures [ 2 ] . cations that pose the most dif fi culties. Postoperative complications were seen in 15.8%, In a study of surgical outcomes in patients and four patients expired. Most of the surgical with SLE, Papa et al. described 29 patients with complications in this study were infectious. SLE who underwent a total of 36 surgical proce- Some of the preoperative variables that corre- dures [1 ] . At the time of surgical intervention, lated with the presence of operative morbidity 19 patients had active SLE. In this study, 37 were identifi ed. Upon univariate analysis, complications occurred. Wound complications, lymphopenia and hypoalbuminemia were signi- such as persistent drainage and the development fi cantly correlated and also were associated with of fi stulae accounted for 24% of the adverse higher surgical morbidity. After multivariate events, followed by respiratory (16%) and infec- logistic regression analysis, physical status, tious (16%) complications. Infectious compli- urgent indication, and blood urea nitrogen were cations, including abscess formation and sepsis, risk factors for operative morbidity. as well as respiratory complications, such as There are no guidelines for the perioperative management of patients with SLE to assist in shepherding a patient through surgery. In this E. Katzap , D.O. chapter, we will discuss some of the common Division of Rheumatology , North Shore University scenarios that may be encountered during the Hospital , 2800 Marcus Avenue, Ste. 200 , Lake Success , pre- and postoperative periods in patients with NY 11042 , USA SLE. Preparing an SLE patient for surgery R. A. Furie , M.D. () starts with an analysis of the patient’s medica- Division of Rheumatology and Allergy-Clinical Immunology , North Shore – LIJ Health System , tions as well as their preexisting manifestations; 2800 Marcus Avenue , Lake Success , NY 11030 , USA therefore, we have designed this chapter e-mail: [email protected] accordingly.

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 183 DOI 10.1007/978-1-4614-2203-7_14, © Springer Science+Business Media, LLC 2013 184 E. Katzap and R.A. Furie

SLE during prospective observation [6 ] . In their Medications series of 83 cases of major infections occurring in 249 SLE patients, use of antimalarial drugs Given the vast heterogeneity of manifestations was associated with a 16-fold reduction in infec- and disease activity, the therapeutic regimens tion rates. These observations are not surprising used to treat SLE are highly varied. In the follow- since antimalarial agents such as chloroquine ing paragraphs, drugs commonly used in the and hydroxychloroquine have a wide range of treatment of SLE are discussed; additional details antimicrobial effects [ 7] . There are no compel- are provided in Chap. 6 (“Drug Therapy”). ling reasons to stop hydroxychloroquine preop- eratively. However, if administration of this drug must be interrupted, its extremely long terminal Nonsteroidal Anti-infl ammatory Drugs half-life generally prevents the patient experi- (NSAIDs) encing any untoward effects.

Many SLE patients with musculoskeletal mani- festations use NSAIDs for control of symptoms. Glucocorticoids Traditional NSAIDs, which inhibit COX-1 and thus interfere with the formation of platelet- Glucocorticoids are the mainstay of treatment derived thromboxane A2, cause a prolongation of of SLE, but the toxicities associated with chronic the bleeding time [3 ] . The inhibition of COX-1 by use are numerous. The perioperative exposure NSAIDs other than aspirin is reversible with to corticosteroids poses yet additional hazards. enzymatic function restored upon clearance of the The increased risk of wound infections and drug [ 4 ] . Suffi cient time should elapse between delayed wound healing are attributed to imped- discontinuation of the NSAID and surgery in ing infl ammation and hindering collagen syn- order for the drug to be metabolized and platelet thesis, degradation, and fi broblast proliferation function to be restored; an adequate time interval [5, 8 ] . The threshold dose above which corticos- is usually fi ve drug half-lives. Aspirin, on the teroids signifi cantly increases the rate of post- other hand, blocks COX-1 irreversibly and inhib- operative wound complications is unknown [ 5 ] . its platelet function for the entire 10-day lifespan In addition, corticosteroids render patients more of the platelet. Therefore, aspirin should be with- susceptible to nosocomial infections, decubitus held for 7–10 days prior to surgery, whereas most ulcers, and gastric ulcers. As much as every nonaspirin NSAIDs can be continued until physician and surgeon would like to eliminate 2–5 days prior to surgery. Of all NSAIDs, ibupro- steroids during the perioperative period, most fen has one of the shortest half-lives (approxi- patients receive a boost in their steroid dose pre- mately 2 h). Selective COX-2 inhibitors, such as operatively in order to prevent vascular collapse celecoxib, have no effect on platelet function and from secondary adrenal insuf fi ciency during can therefore be taken up until surgery [3 ] . surgery or in the postoperative period. As a result, corticosteroids are typically administered to those patients deemed preoperatively to have Antimalarial Drugs hypothalamic–pituitary–adrenal (HPA) suppres- sion [9 ] . Tapering schedules and transitioning Given its pleiotropic favorable effects in patients back to oral corticosteroids must be customized with SLE, hydroxychloroquine has become according to the nature of the surgery and the widely used. Although its safety during the peri- patient’s rate of recovery. We cannot emphasize operative period in rheumatoid arthritis patients enough that the treating physician should try to has been questioned [5 ] , Ruiz-Irastorza et al. minimize steroid exposure during the periopera- reported an inverse relationship between antima- tive period and avoid prolonged tapering regi- larial use and major infections in patients with mens postprocedure. 14 Systemic Lupus Erythematosus 185

Immunosuppressive and Cytotoxic these agents, gastric intolerance that often occurs Therapies with their use and their potential for causing leu- kopenia, it is quite reasonable to withhold these Methotrexate (MTX), an inhibitor of dihydrofo- medications several days prior to high-risk sur- late reductase, is used by some rheumatologists gery. Like MTX, the clinical effects of AZA and for the treatment of patients with SLE, particu- MMF are relatively long lasting; therefore, a tem- larly those with arthritis. Several retrospective porary interruption of these medications should studies described postoperative infectious com- not provoke a fl are. plications in patients with rheumatoid arthritis (RA) as a result of exposure to MTX. However, in Cycophosphamide a prospective study by Grennan et al., there was Cyclophosphamide (CYC), an alkylating agent no increased risk of early postoperative surgical that impairs DNA replication and transcription, complications in those RA patients who contin- affects normal cellular function and can cause ued MTX (10 ] . The risk of surgery was increased, cell death [13 ] . Upon administration of this however, in those with diabetes, hypertension, cytotoxic agent, reductions in B and T cell con- ischemic heart disease, psoriasis, and asthma [10 ] . centrations and function occur [14 ] . In recent The conclusions gleaned from a cohort of patients years, intravenous CYC, which has become more with RA, may be diffi cult to extrapolate to patients popular in the United States than oral CYC for with SLE and their distinct comorbidities. It is treatment of SLE, is typically reserved for patients generally recommended to continue MTX periop- with lupus nephritis or neuropsychiatric lupus. eratively in a patient with normal renal function. Patients who have received parenteral CYC However, this recommendation may need to be develop maximal leukopenia approximately altered based on a patient’s comorbid conditions, 7–14 days after the infusion, and bone marrow such as diabetes or renal disease. recovery generally occurs by 21 days after the infusion. If a nonurgent surgical procedure is Azathioprine and Mycophenolate Mofetil planned in patients receiving cyclophosphamide, Azathioprine (AZA) is an immunosuppressive the period after the bone marrow recovery should therapy that has been used extensively in the treat- be used as a window of opportunity to perform ment of both extrarenal SLE and lupus nephritis. surgery. If need be, cyclophosphamide can Azathioprine, metabolized to 6-mercaptopurine, generally be delayed. is a potent inhibitor of purine metabolism. AZA impacts both cellular and humoral immunity as the numbers of T cells, B cells, and NK cells are Biologic Therapies reduced as a consequence of AZA therapy [11 ] . Bone marrow suppression is one of the major Rituximab is a monoclonal antibody directed toxicities of this drug. against the CD-20 antigen on B lymphocytes. Mycophenolate mofetil (MMF), also a potent While not approved for use in SLE patients, inhibitor of purine synthesis, affects T cell and B rituximab is sometimes used off-label for the cell proliferation [ 12 ] . In addition, MMF inter- treatment of autoimmune hemolytic anemia, feres with the function of adhesion molecules autoimmune thrombocytopenia, lupus nephritis, that is necessary for migration of lymphocytes. It or other serious complications. Similar to other has been successfully used in patients with SLE therapies used in SLE, there are no data available with or without renal involvement [12 ] . Side on the safety of this agent in the perioperative effects of MMF include nausea, diarrhea, and period. Upon administration of rituximab, a rapid leukopenia. and persistent depletion of peripheral B cells for There are no guidelines that address whether up to a year typically occurs [15 ] . Therefore, cli- modi fi cations to the doses of either AZA or MMF nicians may consider avoiding elective proce- are necessary during the perioperative period. dures until B cell recovery has been achieved, but Given the immunosuppressive effects of both of there are no data to support this practice. 186 E. Katzap and R.A. Furie

Belimumab (Benlysta) was approved by the United States Food and Drug Administration in Preexisting Conditions 2011 for the treatment of autoantibody positive SLE patients with persistent disease activity. Cardiopulmonary This monoclonal antibody selectively targets B Lymphocyte stimulator (BLyS), resulting in Cardiovascular manifestations of SLE, among signifi cant reductions in several B cell subpopu- which are pericarditis, premature coronary artery lations, albeit not to the degree seen with ritux- disease, conduction abnormalities, myocardial imab. In contrast to rituximab, B memory cell dysfunction, and valvular disease, may range subpopulations are preserved after treatment with from asymptomatic to life-threatening [18 ] . belimumab. Possible concerns in the periopera- Widespread availability of echocardiographic tive period that may arise include an increased studies facilitates the detection of even asymp- susceptibility to infection in someone treated tomatic valvular abnormalities. In one study, val- with belimumab or fl are of disease in the absence vular abnormalities, predominantly of the mitral of treatment. The rates of serious infections were and aortic valves, were observed in 61% of similar across treatment groups in the combined patients [ 19] . The presence of antiphospholipid BLISS-52 and BLISS-76 dataset [ 16 ] . In the antibodies is associated with an even higher prev- phase III studies, 6.6%, 2.7%, and 19.9% of study alence of valvular lesions in patients with SLE subjects had reductions in IgG, IgA, and IgM [ 20, 21 ] . Reported complications of valvular immunoglobulin levels below the lower limit of abnormalities include thromboembolic events normal, respectively, after receipt of 10 mg/kg of and bacterial endocarditis, occurring in 13% and belimumab. Only 0.2% of subjects had IgG levels 7%, respectively [ 19 ] . Of note, valvular fi ndings less than 400 mg/dL. There was no increased risk may change over time in SLE patients [ 19 ] . of infection in patients with immunoglobulin Patients with hemodynamically signifi cant val- levels below the lower limits of normal compared vular abnormalities, large vegetations, recurrent with patients with normal levels. Upon with- thromboembolic events, or persistent bacteremia drawal of belimumab in preclinical studies in may be candidates for valve surgery. cynomolgos monkeys, B cells remained depressed Prior to cardiac surgery for valve replace- one month after the last drug exposure [17 ]. ment, the patient must be evaluated for the type Belimumab is administered intravenously at of surgical treatment. One must carefully con- monthly intervals. Similar to other immunosup- sider whether anatomical repair is ideal or pressive drugs, there is no guidance regarding the whether a replacement with a bioprosthetic or administration of belimumab in the perioperative mechanical valve is preferred. In patients receiv- period. As the use of belimumab increases, indi- ing bioprosthetic porcine valves, complications vidual actions will no doubt be guided by experience. such as valvulitis may occur [ 20, 21 ] . In those Our current practice is to continue belimumab in undergoing anatomical repair, repeat surgery the perioperative period and schedule the surgery and eventual valve replacement may still need mid-way between infusions in order to reduce the to be performed. Some authors believe that the number of infusions a patient may miss. If not best choice for patients with SLE undergoing practical, we believe the drug’s prolonged pharma- valve surgery is to undergo valve replacement codynamic effect allows for a patient to miss a as opposed to repair [ 20 ] . In our institution, dose before and/or after the surgery without risk- the cardiothoracic surgeons have taken both ing a serious fl are of SLE. approaches with our SLE patients. The next portion of this chapter addresses In addition, patients with SLE are at increased specifi c preexisting conditions, some of which risk for developing coronary artery disease. While may be known to the treating physicians and oth- the overall prevalence ranges from 6% to 10%, ers unknown, and even unsuspected. Mention of young women with SLE are 50 times more likely these conditions will forewarn physicians and to develop myocardial ischemia than their healthy help them prepare a patient for surgery. counterparts [18 ] . With this in mind, patients 14 Systemic Lupus Erythematosus 187 with SLE should be screened for the presence of manifestation or during disease fl ares. Anemia, coronary artery disease prior to undergoing surgi- leukopenia, lymphopenia, and thrombocytopenia cal interventions. Predictors of the fi rst cardio- are frequently present, and a complete blood count vascular event in patients with SLE were identifi ed should be checked prior to surgical procedures. to be an antiphospolipid antibody, elevated von The frequency of autoimmune thrombocy- Willebrand factor, elevated fi brinogen levels, topenia in SLE is variable, but ranges of 7–52% arthritis, pleuritis, or previous DVT [22 ] . The have been reported [ 25 ] . Other situations in which presence of thrombocytopenia was found to be thrombocytopenia is observed include antiphos- negatively associated with cardiovascular events. pholipid syndrome, thrombotic microangiopathy, Further presurgical screening with cardiac stress drug-induced thrombocytopenia, and the rare testing may be considered in patients with the patient with amegakaryocytosis or aplastic ane- above-mentioned characteristics. mia. While physicians will tolerate platelet counts Coronary artery bypass grafting may occa- of 50,000–100,000 in a nonoperative setting, it is sionally become necessary in patients with severe desirable for the patient undergoing a surgical coronary artery disease. Chronic use of corticos- intervention to have a platelet count above this teroids and the multiorgan nature of the disease range. Preoperative treatments to normalize the make these patients challenging surgical candi- platelet count will differ according to the patho- dates. The in-hospital mortality rate has been genesis of the thrombocytopenia. For example, reported to range from 5.7% to 17% [23, 24 ] . In those with autoimmune thrombocytopenia may a study of nine patients undergoing coronary respond quite well to corticosteroids or intrave- artery bypass grafting, postoperative complica- nous gamma globulin [ 26 ] . However, this may or tions occurred in 44% of patients and included may not be the case with antiphospholipid syn- ventricular tachycardia, early graft thrombosis, drome. For those with thrombotic microangiopa- and profuse postoperative bleeding [23 ] . thy, plasmapheresis may be necessary, whereas Pulmonary involvement in SLE is quite com- for those with an inability to produce adequate mon with acute episodes of pleuritis being the numbers of platelets perhaps due to prior medica- most frequent complication. Interstitial fi brosis, tion effects, platelet transfusions will be required. pulmonary arterial hypertension, and pulmonary While important to correct quantitative abnor- thromboembolic disease, albeit less common, are malities of platelets, it is equally important to serious complications of the disease and can ensure that the platelets are functioning properly. signifi cantly impact lung function. Their detec- Therefore, as discussed previously, aspirin and tion is facilitated with pulmonary function test- NSAIDs should be discontinued in advance of ing, echocardiography, and high resolution CT. surgery in order to allow appropriate time to For the SLE patient undergoing noncardiac restore platelet function. The bleeding time has surgery, investigation of cardiac and pulmonary been a traditional method used to evaluate quan- status may be in order, depending on the nature titative and qualitative abnormalities of platelet of the surgical intervention as well as the physi- function. However, many centers no longer uti- cian’s suspicions of specifi c organ involvement. lize this test preoperatively because its predictive The patient care team must always be reminded power to assess surgical bleeding complications of the multiorgan nature of SLE and the fact that has been controversial. In the setting of uremia, SLE patients may bear a greater burden of platelet function may be improved through the disease than their age-matched counterparts with administration of desmopressin (dDAVP). other conditions. Anemia is commonly present in patients with SLE and may be due to anemia of chronic disease, vitamin de fi ciencies, autoimmune Hematology hemolysis, medications, or thrombotic microan- giopathy. When considering patients for surgery, Hematologic abnormalities are extremely common one must anticipate the amount of intraoperative in patients with SLE and may occur as an initial and postoperative blood loss that will occur. 188 E. Katzap and R.A. Furie

Treatment of signi fi cant anemia is advisable For the patient whose leukocyte count is prior to surgery, but just as in cases of thrombo- depressed because of peripheral destruction or cytopenia, there needs to be a full understanding aggregation, whether to intervene in order to cor- of the mechanism of the anemia. Different rect the laboratory abnormality is subject to opin- mechanisms require different interventions. For ion. Destruction of lymphocytes is generally the example, those patients with anemia of chronic result of antibody-dependent or complement- disease will likely respond to erythropoietin if dependent cytotoxicity. While steroids may reverse started long enough before elective surgery. this process, steroids, themselves, have lympho- Patients with autoimmune hemolytic anemia lytic effects. Therefore, despite administering cor- may require a boost in steroids, intravenous ticosteroids, the lymphocyte counts may remain gamma globulin, or rituximab, but those with depressed. In the case of neutropenia, corticoster- thrombotic microangiopathy may require plas- oids typically result in an increase in the neutro- mapheresis. Despite a restoration of hemoglo- phil concentration through demargination. bin concentrations prior to surgery, patients may However, the issue is whether the immunosup- still require transfusions during the periopera- pressive effects of corticosteroids are worth the tive period. Owing to the multiplicity of autoan- trade-off. The increase in catecholamines during tibodies synthesized by patients with SLE, either surgery will also result in higher neutrophil counts, spontaneously or because of prior transfusions, also as a result of demargination. Our practice is diffi culty in fi nding compatible blood is occa- not to administer corticosteroids solely to attempt sionally encountered. to increase leukocyte concentrations. Leukopenia stemming from lymphopenia is Recognition of a prolonged PTT during pre- quite common; neutropenia, albeit less common, surgical testing causes much consternation among may occur as well. Causes of leukopenia may be the surgical team. It is often the result of a lupus the result of inadequate production by the bone anticoagulant, but if this is not known for certain, marrow, peripheral destruction, or aggregation in an evaluation to identify a congenital absence or the periphery. As in other types of cytopenias, an acquired inhibitor of a coagulation protein understanding the mechanism underlying leuko- must be undertaken. It should be emphasized that penia is key in developing a strategy to restore a those SLE patients with antiphospholipid anti- normal count. While spontaneous cases of inade- bodies are at increased risk of a thrombotic event quate bone marrow production of leukocytes are postoperatively [28 ] . Therefore, appropriate deep occasionally encountered, the overwhelming vein thrombosis prophylaxis is recommended. majority of bone marrow-related leukopenia Catastrophic antiphospholipid syndrome is occa- occurs as a result of immunosuppressive drugs. sionally triggered by surgery as well. One should Azathioprine, mycophenolate mofetil, and cyclo- be vigilant in assessing patients postoperatively phosphamide, commonly used to treat SLE in order that appropriate and timely intervention patients, cause lymphopenia and neutropenia. occurs should a problem be identifi ed. The topic Rituximab signifi cantly depresses peripheral B of antiphospholipid syndrome is addressed in lymphocyte concentrations, and an occasional Chap. 8 (“Antiphospholipid”). patient may develop neutropenia from this drug. Particularly vulnerable to azathioprine-induced leukopenia is the patient with homozygous or Musculoskeletal heterozygous TPMT (thiopurine methyltrans- ferase) de fi ciency [27 ] . As previously discussed, it Avascular necrosis is a complication of SLE, may be prudent to discontinue immunosuppres- developing because of the disease itself or more sive therapies prior to surgery especially if leuko- likely as a result of corticosteroid therapy. Often penia is present. The effects of rituximab, however, conservative measures fail, and a joint replace- are quite long lasting. Should a patient be pro- ment procedure may be required. Since the foundly neutropenic, a therapeutic option is granu- patient with avascular necrosis has already a locyte colony-stimulating factor (e.g., fi lgrastim). proven susceptibility to this complication, even a 14 Systemic Lupus Erythematosus 189 short duration perioperative boost in corticoster- that the patient have inactive SLE prior to renal oid dose should be minimized. transplant; however, there are intercenter dif- Rheumatologists, orthopedists, and neurosur- ferences regarding how one de fi nes quiescence. geons have a heightened awareness of the poten- Some prefer a total absence of clinical and sero- tial dire consequences of myelopathy developing logical activity, whereas others are tolerant of in a patient with rheumatoid arthritis undergoing serological activity if clinical activity is absent. intubation. What is not typically appreciated is the occurrence, albeit rare, of atlantoaxial sublux- ation in patients with SLE [ 29 ] . Risk factors for Immune System the development of atlantoaxial instability reported by Babini et al. included longer disease Infections in patients with SLE are common and duration, Jaccoud’s arthropathy, patellar tendon result in signifi cant morbidity or mortality. Some elongation, and articular hypermobility. The pres- of the risk factors that increase the infection rate ence or history of arthritis failed to distinguish are the disease duration, exposure to steroids and patients with and without atlantoaxial subluxation, immunosuppressive drugs, and leukopenia [ 6 ] . In while chronic renal failure and increased serum a cohort of Chinese patients, lymphopenia was parathyroid hormone levels were signi fi cantly found to be an important risk factor for the devel- associated with the presence of atlantoaxial sub- opment of major infectious complications [ 33 ] . luxation. Although in their small series, arthritis In a recent study, lung and renal involvement was not associated with atlantoaxial subluxation, were identifi ed as additional risk factors, whereas patients who have a rheumatoid arthritis clinical treatment with antimalarial medications reduced phenotype and an SLE serological phenotype the risk of major infections [ 6 ] . While the link (rhupus) have been reported by others to develop between medication usage and infection risk atlantoaxial subluxation [30 ] . has been previously discussed, patients with SLE may have other defects in immune function that render them susceptible to infections. Renal Unfortunately, short of replacing immunoglobu- lins in those with spontaneously acquired or Renal involvement complicates the clinical drug-induced hypogammaglobulinemia, immune course of many patients with SLE. defects cannot be reversed. The issues surrounding surgery in a patient with lupus nephritis are not particularly different than those with nephritis from other causes. In the Exocrine Glands setting of uremia, platelet function may be improved through the administration of desmopressin A subset of patients with SLE may also have concur- (dDAVP). The loss of renal reserve prevents rent Sjogren’s syndrome with xerophthalmia and patients undergoing surgery to appropriately xerostomia. Lubricating eye ointments and eye drops handle fl uid, electrolytes, and properly metabolize are recommended during the hospital stay and intra- medications [ 31 ] . Patients with end-stage renal operatively to avoid corneal drying and abrasions. disease are also much more susceptible to infections and have increased morbidity or mor- tality [31 ] . The additional presence of SLE Vascular likely increases the susceptibility to infections even further. Many patients with SLE have Raynaud’s Patients with renal failure are eligible for phenomenon, which is typically exacerbated by kidney transplantation. While lupus nephritis exposure to cold temperatures or stress. Some can affect the allograft, most patients do well patients, particularly those with manifestations [ 32 ] . The majority of transplant centers require that overlap scleroderma (mixed connective 190 E. Katzap and R.A. Furie tissue disease), may have digital arterial luminal 7. Rolain JM, Colson P, Raoult D. Recycling of chloro- narrowing and fi xed obstruction as a result of sub- quine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob intimal proliferation. In order to avoid ischemic Agents. 2007;30:297–308. injury during the operative period, it is desirable 8. Anstead GM. Steroids, retinoids, and wound healing. to keep the patient’s extremities warm, restrict the Adv Wound Care. 1998;11(6):277–85. use of vasoconstrictor medications, and avoid 9. Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin placement of radial or ulnar arterial catheters. North Am. 2003;32(2):367–83. 10. Grennan DM, Gray J, Loudon J, et al. Methotrexate and early postoperative complications in patients with Conclusion rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis. 2001;60(3):214–7. 11. McCune WJ, Marder W, Riskalla M. Immunosuppressive In summary, patients with SLE are considered drug therapy. In: Wallace DJ, Hahn BH, editors. Dubois’ high risk for surgery. The complexity and variabil- lupus erythematosus. 7th ed. Philadelphia: Lippincott ity of the course of the disease may make it dif fi cult Williams &Wilkins; 2007. 12. Bandelier C, Guerne PA, Genevay S, et al. Clinical to decide when the time is optimal for a patient to experience with mycophenolate mofetil in systemic have the surgical procedure. However, it is gener- autoimmune conditions refractory to common ally agreed that patients with inactive SLE do bet- immunosuppressive therapies. Swiss Med Wkly. ter. To screen the patient for lupus activity, a 2009;139(3–4):41–6. 13. Hall AG, Tilby MJ. Mechanisms of action of, and thorough history, physical examination, and labo- modes of resistance to, alkylating agents used in the ratory evaluation need be performed. Although the treatment of haematological malignancies. Blood Rev. patient’s medication regimen may be modi fi ed 1992;6(3):163–73. perioperatively, the blanket administration of cor- 14. McCune WJ, Golbus J, Zeldes W, et al. Clinical and immunologic effects of monthly administration of ticosteroids in order to prevent disease activation intravenous cyclophosphamide in severe systemic postoperatively is not recommended. An intimate lupus erythematosus. N Engl J Med. 1988;318(22): knowledge of the patient’s prior disease and prior 1423–31. surgical experience will facilitate proper decision- 15. Breedfeld F, Agarwal S, Yin M, et al. Rituximab phar- macokinetics in patients with rheumatoid arthritis: making during this process. B-cell levels do not correlate with clinical response. J Clin Pharmacol. 2007;47(9):1119–28. 16. Wallace DJ, Navarra S, Petri M, et al. Safety profi le of belimumab, a B-lymphocyte stimulator–specifi c inhibitor, in phase 2 and 3 clinical trials of patients References with active systemic lupus erythematosus. Arthritits Rheum. 2011;63(10):S220. 1. Papa MZ, Shiloni E, Vetto JT, et al. Surgical morbid- 17. Baker KP, Edwards BM, Main SH, et al. Generation ity in patients with systemic lupus erythematosus. Am and characterization of LymphoStat-B, a human J Surg. 1989;157(3):295–8. monoclonal antibody that antagonizes the bioactivi- 2. Takahashi T, De-La-Garza L, Ponce-De-Leon S, et al. ties of B lymphocyte stimulator. Arthritis Rheum. Risk factors for operative morbidity in patients with 2003;48:3253–65. systemic lupus erythematosus: an analysis of 63 sur- 18. Doria A, Iaccarino L, Atzeni F, et al. Cardiac involve- gical procedures. Am Surg. 1995;61(3):260–4. ment in systemic lupus erythematosus. Lupus. 3. Rosandich PA, Kelley JT, Conn DL. Perioperative 2005;14(9):683–6. management of patients with rheumatoid arthritis in 19. Roldan C, Shively BK, Crawford MH. An echoradio- the era of biologic response modifi ers. Curr Opin graphic study of valvular heart disease associated Rheumatol. 2004;16(3):192–8. with systemic lupus erythematosus. N Engl J Med. 4. Schafer AI. Effects of nonsteroid anti-in fl ammatory 1996;335:1424–30. drugs on platelet function and systemic hemostasis. 20. Hakim JP, Mehta A, Jain AC, et al. Mitral valve J Clin Pharmacol. 1995;35(3):209–19. replacement and repair. Tex Heart Inst J. 2001;28: 5. Härle P, Straub RH, Fleck M. Perioperative manage- 47–52. ment of immunosuppression in rheumatic diseases– 21. Bouma W, Klinkenberg TJ, van der Horst I, et al. what to do? Rheumatol Int. 2010;30(8):999–1004. Mitral valve surgery for mitral regurgitation caused 6. Ruiz-Irastorza G, Olivares N, Ruiz-Arruza I, et al. by Libman-Sacks endocarditis: a report of four cases Predictors of major infections in systemic lupus and a systematic review of the literature. J Cardiothorac erythematosus. Arthritis Res Ther. 2009;11(4):R109. Surg. 2010;5:13. 14 Systemic Lupus Erythematosus 191

22. Gustafsson J, Gunnarsson I, Börjesson O, et al. 28. Girón-González JA, García del Río E, Rodríguez C, Predictors of the fi rst cardiovascular event in patients et al. Antiphospholipid syndrome and asymptomatic with systemic lupus erythematosus – a prospective carriers of antiphospholipid antibody: prospective cohort study. Arthritis Res Ther. 2009;11:R186. analysis of 404 individuals. J Rheumatol. 23. Lin CH, Lee ML, Hsu RB. Cardiac surgery in patients 2004;31:1560–7. with systemic lupus erythematosus. Interact 29. Babini SM, Cocco JA, Babini JC, et al. Atlantoaxial Cardiovasc Thorac Surg. 2005;4(6):618–21. subluxation in systemic lupus erythematosus: further 24. Ward MM. Outcomes of hospitalizations for myocar- evidence of tendinous alterations. J Rheumatol. dial infarctions and cerebrovascular accidents in 1990;17(2):173–7. patients with systemic lupus erythematosus. Arthritis 30. Isenberg DA, Tookman A, White AG, et al. Erosive Rheum. 2004;50(10):3170–6. rheumatoid arthritis co-existing with systemic lupus 25. Quismorio FP. Hematologic and lymphoid abnor- erythematosus. A report of a case, also showing atlanto- malities in systemic lupus erythematosus. In: axial subluxation. Clin Rheumatol. 1982;1(3):216–20. Wallace DJ, Hahn BH, editors. Dubois’ lupus ery- 31. Joseph AJ, Cohn SL. Perioperative care of the patient thematosus. 7th ed. Philadelphia: Lippincott with renal failure. Med Clin North Am. 2003;87(1): Williams &Wilkins; 2007. 193–210. 26. Maier WP, Gordon DS, Howard RF, et al. Intravenous 32. Burgos PI, Perkins EL, Pons-Estel GJ, et al. Risk fac- immunoglobulin therapy in systemic lupus erythema- tors and impact of recurrent lupus nephritis in patients tosus-associated thrombocytopenia. Arthritis Rheum. with systemic lupus erythematosus undergoing renal 1990;33(8):1233–9. transplantation: data from a single US institution. 27. Lennard L, Van Loon JA, Weinshilboum RM. Arthritis Rheum. 2009;60(9):2757–66. Pharmacogenetics of acute azathioprine toxicity: 33. Ng WL, Chu CM, Wu AK, et al. Lymphopenia at relationship to thiopurine methyltransferase genetic presentation is associated with increased risk of infec- polymorphism. Clin Pharmacol Ther. 1989;46 tions in patients with systemic lupus erythematosus. (2):149–54. QJM. 2006;99(1):37–47. Scleroderma and Raynaud Phenomenon 1 5

Corey M. Hat fi eld and Richard M. Silver

To avoid these complications, one should Introduction make every effort to keep the patient warm. This sounds simple but may prove dif fi cult when The surgical patient who suffers from Raynaud undergoing a surgical procedure that requires the phenomenon or systemic sclerosis (SSc, sclero- patient be in the operating room and exposed for derma) presents many challenges that often prolonged periods of time. The main objective require a multidisciplinary approach to manage- should be to keep the patient’s extremities and ment. In this chapter, we will discuss the aspects core body temperature warm. Cover as much pertinent to the peri-/intraoperative management body surface area as feasible for a given surgery. of such patients. Warm blankets may be helpful. Be mindful of the IV fl uids and blood products that may need to be administered. Avoid giving cold IV fl uids and Raynaud Phenomenon blood products which might lower the core body temperature and induce vasospasm/ischemia. The stress of surgery and/or conditions in the Whenever the situation allows, warm all IV solu- operating room might exacerbate digital ischemia tions and blood products. There are commercially in the patient predisposed to cold-induced vasos- available in-line blood/solution warmers which pasm, i.e., Raynaud phenomenon. When the isch- would be particularly benefi cial for the surgical emic phase is prolonged, tissue death/necrosis patient with Raynaud phenomenon. can ensue, starting with the distal aspect of the It is common practice in OR and ICU settings digits and potentially ranging from digital pitted for patients to undergo arterial line placement, scars to digital ulceration and even to gangrene. usually of the radial artery. This allows for accu- rate hemodynamic monitoring which has obvious advantages. In most patients, this procedure has a C. M. Hat fi eld , D.O. Division of Rheumatology and Immunology , low risk of complications [1 ] , but patients who Medical University of South Carolina , 96 Jonathan Lucas have Raynaud phenomenon and patients who have Street CSB 912 , Charleston , SC 29425 , USA systemic sclerosis are different in this regard. R. M. Silver , M.D. (*) There are several reports of systemic sclerosis Division of Rheumatology and Immunology, patients having adverse outcomes related to arterial Medical University of South Carolina , line placement, and such reports likely represent 96 Jonathan Lucas Street CSB 912 , Charleston , SC 29425, USA only a fraction of such complications. One case e-mail: [email protected] report describes a patient who preoperatively had

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 193 DOI 10.1007/978-1-4614-2203-7_15, © Springer Science+Business Media, LLC 2013 194 C.M. Hat fi eld and R.M. Silver an arterial catheter placed in the radial artery. The ¥ Angiotensin receptor inhibitors Ð e.g., losartan catheter was removed in the postoperative period, ¥ Prostaglandins both oral and parenteral and initially, no issues were observed. Within ¥ Endothelin receptor antagonists (ERA) Ð e.g., 48 h, however, the patient developed pain and bosentan and ambrisentan digital ischemia of the hand where the catheter Since increased sympathetic tone is thought had been placed and later went on to require digi- to play in a role in the pathogenesis of Raynaud tal amputation [2 ] . We strongly advise avoiding phenomenon, sympathectomy is sometimes used radial and other arterial cannulation/trauma, if at when digital ulcers/ischemia are refractory to all possible, at any time for the patient who has medical management. The goals are to reverse systemic sclerosis. Arterial blood gases (ABGs) vasoconstriction and to relieve pain. A tempo- are routinely obtained intraoperatively to assess rary chemical sympathectomy may be tried ini- the patient’s oxygenation status. Again, in most tially by infi ltration of a local anesthetic patients, this will have no negative consequences, (lidocaine or bupivacaine without epinephrine) but for the reasons stated above as well as the fact locally (e.g., digital or wrist block), regionally, that many scleroderma patients actually have or near the appropriate cervical or lumbar sym- ulnar artery occlusion [3 ] , one should avoid upper pathetic ganglia. The anesthetic can be delivered extremity arterial puncture in the patient as it may by repeated injections or by placement of a cath- lead to severe ischemia with potentially cata- eter into the region of the cervical or lumbar strophic consequences including loss of digits or sympathetic ganglia. Some studies have reported even limbs. that cervical sympathectomy may be more use- In lieu of ABG determination, pulse oximeters to ful in patients with primary Raynaud phenome- assess oxygenation status are often applied to fi ngers non compared to those with the secondary form; or earlobes of patients in the operating and recovery however, in our experience, individuals with pri- room settings. With Raynaud phenomenon/vasos- mary Raynaud phenomenon rarely if ever require pasm, it can be dif fi cult to get precise readings when such intervention [ 3, 5Ð 7 ] . the oximeter is applied to any of these areas. There Surgical sympathectomy may be either proxi- are pulse oximeters which can be placed on the fore- mal or distal and should only be considered in head, and in the patient with scleroderma/Raynaud cases of severe, refractory Raynaud phenomenon phenomenon, this location is preferred as it is thought when irreversible ischemia threatens the involved to provide more accurate data [4 ] . fi ngers/toes. One or more of the medications Although primary Raynaud phenomenon listed above and a trial of a chemical sympathec- often does not require any treatment, pharmaco- tomy should be tried fi rst. logic therapy is often necessary in the manage- Vascular reconstruction may be an option for ment of Raynaud phenomenon/digital ulcers in some patients who suffer from refractory isch- scleroderma patients. Many different classes of emia. Surgical revascularization of the hand and drugs (oral, topical, and parenteral) have been arterial reconstruction may improve digital perfu- tried with varying degrees of success, including: sion and hasten the healing of digital ulcers when ¥ Aspirin there is bypassable proximal artery occlusion ¥ Calcium channel blockers Ð e.g., amlodipine associated with digital artery vasospasm. Ulnar and nifedipine artery occlusion is common in systemic sclerosis, ¥ Topical nitroglycerin (applied to the web and revascularization of ulnar artery occlusive spaces between digits) disease in this setting may improve Raynaud phe- ¥ Alpha-1 antagonists Ð e.g., prazosin nomenon and help to heal digital ulcers [ 8 ] . Surgical ¥ Phosphodiesterase inhibitors Ð e.g., sildena fi l amputation of the involved digits is a last resort and and pentoxifylline should only be done in the settings of wet gangrene ¥ Statins (infection) and/or intractable pain. In the absence of 15 Scleroderma and Raynaud Phenomenon 195 such surgical indications, autoamputation usually infections occur, treatment with antibiotics and results in less tissue loss and greater preservation in some cases surgical debridement may be of function. required [ 10 ] .

Skin Pulmonary

Intravenous (IV) access is essential for Pulmonary disease is now the leading cause of patients going to the OR for a surgical proce- mortality in patients with SSc. Interstitial lung dure. Depending on the distribution and sever- disease (ILD) characterized by basilar pulmonary ity of skin thickening/ fi brosis in a patient with fi brosis occurs in both the limited (lSSc) and dif- scleroderma, IV access sites may be limited fuse (dSSc) cutaneous phenotypes. At autopsy, and/or not easily obtained. In such cases, pre- 80% of patients with SSc will have evidence of operative central line placement would be pulmonary fi brosis [11 ] . ILD is thought to occur advisable. more frequently in patients with antitopoisomerase Wound healing may be impaired in some I (Scl-70) antibody and diffuse skin disease [12 ] . patients with systemic sclerosis, although in Patients usually develop ILD within 4 years of the general, such patients overproduce collagen and onset of disease. African American males in the other extracellular matrix proteins which should fi fth and sixth decades of life have the highest risk allow for adequate wound healing. Skin ulcers of developing severe lung disease [13 ] . may be a signifi cant complication in some We recommend preoperative pulmonary func- patients. According to one study, major risk fac- tion testing in all scleroderma patients. A reduc- tors for the development of skin ulcers include tion in the diffusion capacity for carbon monoxide the diffuse cutaneous phenotype (dSSc), avas- (DLco ) is the earliest and most sensitive abnor- cular areas demonstrated on capillaroscopy, mality, but is not specifi c for ILD in these patients thrombophilia, and elevated plasma levels of [ 14 ] . A reduced DLCO may also suggest pulmo- IL-6. Infection was associated with poor wound nary hypertension. Reduction in the total lung healing. Avascular areas on capillaroscopy and capacity (TLC) with reduced FVC and a normal infection were the main determinants for ulcer FEV1/FVC ratio is indicative of the restrictive healing. To optimize ulcer healing, therapy pattern one expects to see in ILD patients, includ- should be directed at improving blood fl ow and ing scleroderma patients. PFT abnormalities may controlling infection and, if possible, the course occur prior to the onset of respiratory symptoms. of the disease [ 9 ] . If the PFT are abnormal, HRCT scan of the chest Calcinosis is another skin complication seen is recommended. HRCT of the chest may reveal in some patients with systemic sclerosis. The eti- ground glass opacifi cation indicative of an ology of calcinosis in connective tissue diseases in fl ammatory alveolitis and/or fi ne fi brosis. is not known. Deposits of calcium hydroxyapa- HRCT scan may also show thickening of inter- tite crystals can occur in the digital pads (calci- lobular septa, subpleural nodules, honeycomb nosis cutis), periarticular tissues, sites of repeated appearance, and traction bronchiectasis [ 15 ] . pressure or trauma (e.g., olecranon bursa), exten- Together, PFT and HRCT provide important sor surfaces of the forearms, prepatellar and information about the presence and extent of infrapatellar bursal areas, and in the buttocks. ILD, data essential for proper perioperative care The size of these calcium deposits varies from of such patients. tiny punctuate lesions to large masses (tumoral Scleroderma patients are at increased risk for calcinosis). Calcinosis may cause the overlying the development of pulmonary arterial hyperten- skin to ulcerate, and white/milky drainage may sion (PAH), most often in the setting of limited exude from these lesions. If secondary bacterial cutaneous disease (lSSc) with little or no ILD. 196 C.M. Hat fi eld and R.M. Silver

Pulmonary hypertension regardless of type or ¥ Pulmonary hypertension is unlikely if the etiology is considered to be a signifi cant preop- pulmonary artery systolic pressure is less erative risk factor and is associated with consid- than or equal to 36 mmHg, the tricuspid erable risk of perioperative mortality [16 ] . Thus, regurgitant jet velocity is less than or equal to preoperative assessment is vital in patients 2.8 m/s, and there are no other suggestive thought to have or to be at risk of having SSc- fi ndings (pulmonic insuffi ciency, midsystolic

PAH, e.g., the patient whose DLCO is low, particu- closure of the pulmonic valve, right ventricu- larly when it is low out of proportion to the FVC lar hypertrophy, paradoxical septal motion,

(e.g., FVC/DLCO ratio >1.8). The 6-min walk test right atrial enlargement, right ventricular (6MWT) has been used as a primary outcome enlargement, etc.). measure in many PAH clinical trials. It is a simple When suspected, right heart catheterization test to evaluate exercise capacity. Oxygen desatu- must be done to confi rm pulmonary arterial hyper- ration during a 6MWT is predictive of mortality tension. The diagnosis of PAH requires a mean in patients with idiopathic pulmonary arterial pulmonary artery pressure greater than 25 mmHg hypertension. The 6MWT may provide additional at rest with a pulmonary capillary wedge pressure information as to the severity of pulmonary less than or equal to 15 mmHg [20 ] . The right involvement in patients with systemic sclerosis heart catheterization is considered the diagnostic [17 ] , e.g., oxygen desaturation with exercise, but gold standard for diagnosing PAH. A right heart it lacks speci fi city [18 ] . The importance of recog- catheterization will also be helpful in ruling out nizing patients with PAH cannot be overempha- other causes of pulmonary HTN including left sized, especially so one might avoid, if at all ventricular diastolic dysfunction, which occurs possible, surgery in such cases. not infrequently in scleroderma patients. Other cardiac manifestations of scleroderma that could impact perioperative management include heart Cardiovascular failure, conduction block, and arrhythmias, all resulting from fi brosis and myocardial ischemia Pulmonary arterial hypertension (PAH) is more due to nonepicardial coronary artery disease. common in patients with the limited cutaneous Arterial vasospasm of different vascular beds, phenotype of scleroderma (lSSc) but may occur in such as coronary, renal, and intestinal arteries, anyone with systemic sclerosis. Symptoms of PAH may also be observed. An EKG prior to the surgi- include dyspnea, fatigue, syncope, light-headed cal procedure to evaluate for ischemic changes sensation, atypical chest pain, and/or lower extrem- and conduction abnormalities is advised. Many ity swelling. PFT may be normal and/or show a patients with scleroderma also have in fl ammatory reduced diffusion capacity. A preoperative myositis. Creatine kinase (CK) should be checked echocardiogram is recommended for screening in the preoperative period to evaluate for a myosi- patients for pulmonary hypertension. Keep in mind tis overlap syndrome. that the echocardiogram may either under- or over- estimate the peak right ventricular pressure. Sometimes the interpreting cardiologist cannot Gastrointestinal comment on the right-sided pressures because of a lack of tricuspid regurgitation. When a TR jet is Gastrointestinal motility is delayed in nearly all detected on a Doppler echocardiographic study, it patients with scleroderma, and the entire GI tract can often be determined whether pulmonary may be affected. An estimated 30Ð40% of patients hypertension is likely or unlikely [19 ] : will have subclinical esophageal dysmotility [21 ] . ¥ Pulmonary hypertension is likely if the pul- The lower esophageal sphincter (LES) pressure is monary artery systolic pressure is >50 mmHg also reduced. An incompetent LES combined and the tricuspid regurgitant jet velocity is with the esophageal dysmotility leads to re fl ux >3.4 m/s. and subsequently increases the risk of aspiration 15 Scleroderma and Raynaud Phenomenon 197 and the development of pneumonitis and/or pneu- A small oral aperture may also make intubation monia. Aspiration precautions should be observed more challenging. before, during, and after any surgical procedure. Keep the head of the bed elevated 30Ð45¡. The Trendelenburg position should be avoided. Tragic Renal outcomes have been reported in scleroderma patients who were put in Trendelenburg position Prior to the introduction of ACE inhibitors, renal at the time of surgery and who subsequently aspi- crisis was the leading cause of mortality in rated and went on to develop aspiration pneumo- patients with scleroderma. Scleroderma renal cri- nia and fatal respiratory complications. sis still occurs but is being recognized sooner and Intestinal dysmotility may lead to constipation treated aggressively with ACE inhibitors, and and can result in a pseudoobstruction. These thus, outcomes have improved. Approximately issues can be exacerbated in the perioperative 10% of patients with SSc will develop renal cri- period by opioid analgesics administered for pain sis, usually within 3 years of disease onset [ 22 ] . control. Pseudoobstruction is a very serious issue Risk factors include [23 ] : in which patients develop nausea/vomiting, ¥ Diffuse cutaneous phenotype (dSSc) bloating, obstipation, and abdominal pain. ¥ Tendon friction rubs Pseudoobstruction may be diffi cult to distinguish ¥ RNA polymerase III antibody from a true anatomical obstruction, particularly ¥ Pericardial effusion in patients who have undergone previous abdom- ¥ New anemia inal or pelvic surgery, but the former is due to a ¥ Steroid therapy functional ileus, and conservative management is Patients with scleroderma renal crisis typi- strongly recommended when at all possible. cally present with new-onset hypertension. Even Occult or overt GI bleeding may occur. Blood a mild elevation of BP in someone who is usually loss may be the result of erosive esophagitis, gas- normotensive or traditionally has had “low blood tritis, mucosal telangiectasias, Mallory-Weiss pressure” should raise clinical suspicion . A vari- tear, or gastric antral vascular ectasia (GAVE), ant known as normotensive scleroderma renal also known as the “watermelon stomach.” Be crisis is thought to occur more often in patients cautious when considering anticoagulation/DVT who have been treated with 15 mg/day or more of prophylaxis in patients with systemic sclerosis. prednisone or its equivalent [ 24 ] . Symptoms of GAVE can lead to profound blood loss requiring renal crisis might include shortness of breath, multiple blood transfusions. Fatal outcomes have pulmonary edema, lower extremity edema, occurred. Patients anticoagulated for presumed headaches, seizures, and visual disturbances with DVT/PE who, unbeknownst to the treating physi- fundoscopic changes similar to what is seen in cians, had GAVE have later died as a result of malignant hypertension. Lab abnormalities of uncontrollable bleeding. An EGD to evaluate for renal crisis may include: these vascular lesions prior to starting an antico- ¥ Microangiopathic anemia (schistocytes on agulant would be prudent. peripheral blood smear) Malnourishment and weight loss, the etiology ¥ Thrombocytopenia of which may be multifactorial, can adversely affect ¥ Renal insuf fi ciency surgical outcomes/wound healing. Scleroderma ¥ Proteinuria (usually mild) patients may experience early satiety, bloating, ¥ Active urinary sediment with RBCs and RBC and delayed gastric emptying, each of which may casts (or bland microhematuria) diminish caloric intake. Gastroparesis and The important point here is to closely follow delayed intestinal motility can reduce the absorp- the blood pressure of all patients with sclero- tion of medications administered by mouth. The derma. Evaluate even small increases in blood oral aperture may be reduced due to the skin pressure thoroughly. Immediately start ACE tightening, contributing to inadequate PO intake. inhibitors whenever “renal crisis” is suspected. 198 C.M. Hat fi eld and R.M. Silver

which can be profound and life-threatening. Musculoskeletal These mucosal telangiectasias can be diffi cult to detect even with endoscopy, which should be The progressive skin thickening/fi brosis can considered prior to anticoagulation. If anticoagu- lead to joint fl exion contractures. The proximal lation is deemed medically necessary, do so interphalangeal (PIP), elbow, and knee joints cautiously and monitor blood counts closely. are commonly affected. Physical and occupa- Please refer to Table 15.1 , which highlights tional therapy should be utilized in the postop- the main points to consider regarding the periop- erative period. Therapists can work with the erative management of the patient with Raynaud patient on range of motion exercises and when phenomenon/systemic sclerosis. appropriate use splints to help prevent joint contractures which can be painful and lead to disability. References

1. Slogoff S, Keats AS, Arlund C. On the safety of radial Hematology artery cannulation. Anesthesiology. 1983;59:42047. 2. Rose SH. Ischemic complications of radial artery can- nulation: an Association with a calcinosis, Raynaud’s Postoperatively, patients are often immobilized phenomenon, esophageal dysmotility, sclerodactyly, for prolonged periods. This immobilization and telangiectasia variant of scleroderma. increases the risk of developing deep venous Anesthesiology. 1993;78(3):587Ð9. 3. Taylor MH, McFaddden JA, Bolster MB, Silver R. thromboses (DVTs) and/or pulmonary emboli Ulnar artery involvement in systemic sclerosis (scle- (PE). To prevent thrombotic complications, anti- roderma). J Rheumatol. 2002;29(1):102Ð6. coagulation is often considered. Anticoagulation 4. Schallom L, Sona C, McSweeney M, Mazuski J. can be dangerous in patients with scleroderma. Comparison of forehead and digit oximetry in surgi- cal/trauma patients at risk for decreased peripheral As mentioned above, patients may have occult perfusion. Heart Lung. 2007;36(3):188Ð94. gastrointestinal lesions, e.g., erosive esophagitis/ 5. Gifford Jr RW, Hines Jr EA, Craig WM. gastritis and mucosal telangiectasias (GAVE). Sympathectomy for Raynaud’s phenomenon; follow Anticoagulation can be associated with bleeding up study of 70 women with Raynaud’s disease and 54 women with secondary Raynaud’s phenomenon. Circulation. 1958;17:5. Table 15.1 Key points to remember 6. Johnston EN, Summerly R, Birnstingl M. Prognosis in Raynaud’s phenomenon after sympathectomy. Br Keep patient warm/avoid cold exposure Med J. 1965;54440:962. Do not cannulate the radial artery 7. De Takats G, Fowler EF. Raynaud’s phenomenon. Preoperative PFTs, 6-min walk, EKG, echocardiogram, JAMA. 1962;179:1. and CK 8. Montorsi W, Ghiringhelli C, Annoni F. Indications and If suspected, right heart catheterization to con fi rm results of the surgical treatment in Raynaud’s phenom- presence of PAH enon. J Cardiovasc Surg (Torino). 1980;21:203. Have anesthesiologist assess oral aperture 9. Alivernini S, De Santis M, Tolusso B, et al. Skin preoperatively ulcers in systemic sclerosis: determinants of presence Aspiration precautions in the pre-, intra-, and predictive factors of healing. J Am Acad Dermatol. and postoperative periods 2009;60(3):426Ð35. 10. Clements Phillip J, Daniel EFurst, editors. Systemic Avoid Trendelenburg position sclerosis. Baltimore: Williams and Wilkins; 1996. p. Delayed GI motility pseudoobstruction/may be 389Ð407. Ch. 18, Phillip J. Clements & Thomas A. exacerbated by narcotics Medsger Jr. Monitor blood pressure closely. ACE inhibitor for 11. D’Angelo JF, Masi AT, Shulman LE. Pathological hypertension/renal crisis observations in systemic sclerosis (scleroderma). A Physical/occupational therapy for range of motion study of 58 autopsy cases and 58 matched controls. exercises/splints to prevent joint contractions Am J Med. 1969;46:428Ð40. Anticoagulate with caution. Be mindful of GI blood 12. Steen VD, Powell DL, Medsger Jr TA. Clinical cor- loss relations and prognosis based on serum autoantibod- ies in patients with systemic sclerosis. Arthritis PFTs pulmonary function tests, ACE angiotensin convert- Rheum. 1988;31:196Ð203. ing enzyme, PAH pulmonary arterial hypertension 15 Scleroderma and Raynaud Phenomenon 199

13. Steen VD, et al. Severe restrictive lung disease in 19. Badesch DB, Champion HC, Sanchez MA, Hoeper systemic sclerosis. Arthritis Rheum. 1994;37:1283Ð9. MM, Loyd JE, Manes A, McGoon M, Naeije R, 14. Catterall M, Rowell NR. Respiratory function in pro- Olschewski H, Oudiz RJ, Torbicki A. Diagnosis and gressive systemic sclerosis. Thorax. 1963;18:10Ð5. assessment of pulmonary arterial hypertension. J Am 15. Warrick JH, et al. High resolution computed tomography Coll Cardiol. 2009;54(1 suppl):S55Ð66. in early scleroderma lung disease. J Rheumatol. 20. Galie N, Hoeper MM, Humbert M, et al. Guidelines 1991;18:1520Ð8. for the diagnosis and treatment of pulmonary hyper- 16. Ramakrishna G, Sprung J, Ravi BS, Chandrasekaran tension. Eur Respir J. 2009;34:1219. K, McGoon MD. Impact of pulmonary hypertension 21. Clements PJ, Becvar R, Drosos AA, et al. Assessment on the outcomes of noncardiac surgery: predictors of of gastrointestinal involvement. Clin Exp Rheumatol. perioperative morbidity and mortality. J Am Coll 2003;21:S15Ð8. Cardiol. 2005;45(10):1691Ð9. 22. Steen VD, Medsger Jr TA. Severe organ involvement 17. Villalba WO, Sampaio-Barros PD, Pereira MC, in systemic sclerosis with diffuse scleroderma. Cerqueira EM, Leme Jr CA, Marques-Neto JF, Arthritis Rheum. 2000;43:2437Ð44. Paschoal IA. Six-minute walk test for the evaluation 23. Steen VD, et al. Factors predicting development of of pulmonary disease severity in scleroderma patients. renal involvement in progressive systemic sclerosis. Chest. 2007;131(1):217Ð22. Am J Med. 1984;76:779Ð86. 18. Garin MC, Highland KB, Silver RM, Strange C. 24. Steen VD, Medsger Jr TA. Case-control study of cor- Limitations to the 6-minute walk test in interstitial ticosteroids and other drugs that either precipitate or lung disease and pulmonary hypertension in sclero- protect from the development of scleroderma renal derma. J Rheumatol. 2009;36(2):330Ð6. crisis. Arthritis Rheum. 1998;41:1613Ð9. Perioperative Management of the Patient with Idiopathic 1 6 Infl ammatory Myopathy

Rohit Aggarwal and Chester V. Oddis

and joints [3 ] . Patients with myositis undergo sur- Introduction gical procedures, both emergent and routine, that may present challenging issues to their managing The idiopathic infl ammatory myopathies (IIM) physicians. Attention to detail during the periop- are chronic, acquired, autoimmune disorders erative period may prevent serious complications. characterized by proximal muscle weakness, ele- Many common perioperative issues in myositis vation of serum muscle enzymes (most commonly are shared by other CTD patients include manage- the creatine kinase [CK]), electromyographic fea- ment of corticosteroids and other immunosup- tures of myopathy, in fl ammatory cell in fi ltrates in pressive drugs or addressing the risk of infection, muscle tissue, and speci fi c rashes in the case of but there are unique perioperative issues exclusive dermatomyositis (DM) [1, 2 ] . Based on clinical, to myositis that should be addressed. histopathologic, and immunologic features, the Muscle weakness in the myositis patient can IIM have been classi fi ed into three general sub- re fl ect an active, in fl ammatory process or damage types including polymyositis (PM), adult and from chronic disease. Disease activity is reversible juvenile dermatomyositis, and inclusion body with treatment, but damage is generally an myositis (IBM). Myositis also occurs in overlap irreversible change in anatomy, physiology, or with other connective tissue diseases (CTD) as function, accumulated over time from the disease well as in association with malignancy. Although itself, comorbid conditions, or therapy. In myositis, muscle involvement is the hallmark of IIM, these it is important to distinguish whether weakness are systemic diseases affecting many organs re fl ects activity or damage, and the same concept including the lungs, heart, gastrointestinal tract, applies to concomitant extramuscular organ involvement. The aforementioned factors not only impact surgical outcome but may require R. Aggarwal , M.D., M.S. preoperative intervention. In general, elective UPMC Arthritis and Autoimmunity Clinic, Assistant surgery should be deferred in a myositis patient Professor of Medicine, Division of Rheumatology and with active disease, and better surgical outcomes Clinical Immunology, University of Pittsburgh Falk Medical Building , 3601 5th avenue , Suite 2B Pittsburgh , will occur in patients with quiescent or controlled PA 15213 , USA disease with good muscle strength on the lowest e-mail: [email protected] doses of corticosteroids or other immunosuppres- C. V. Oddis , M.D. () sive therapy. Although the extent of muscle Division of Rheumatology and Clinical Immunology , involvement is most often assessed through manual University of Pittsburgh School of Medicine , muscle testing (MMT) and muscle enzyme 3500 Terrace Street South 705, Biomedical Science Tower , Pittsburgh , PA 15261 , USA measurements, assessment may not reliably e-mail: [email protected] differentiate between activity and damage.

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 201 DOI 10.1007/978-1-4614-2203-7_16, © Springer Science+Business Media, LLC 2013 202 R. Aggarwal and C.V. Oddis

Improvement with an empiric trial of therapy over essential in patients with ILD. An isolated reduc- 1Ð2 months may be used to assess reversible tion in the DLCO related to other pulmonary active infl ammation. Signifi cant elevation of function test (PFT) fi ndings may be a harbinger serum CK generally implies active disease, but of pulmonary hypertension necessitating at least CK may be normal in some adults despite active echocardiography to assess pulmonary pressures disease (more often DM), and magnetic resonance and possibly cardiology consultation (see chapter imaging (MRI) musclemay help to identify on pulmonary hypertension). in fl ammation particularly when T-2-weighted fat-suppressed STIR imaging is employed. Respiratory Muscle Weakness Myositis patients with cardiac, respiratory, Clinically signifi cant respiratory muscle weak- cutaneous, skeletal, and/or gastrointestinal ness is rare (<5%) but an important consideration involvement must be carefully assessed for active in the preoperative assessment of IIM [7 ] . disease and damage in these organ systems prior Compromised ventilation in myositis is due to to major surgery. The disease activity and dam- weakness of respiratory muscles including the age in extramuscular organs may not necessarily diaphragm, external intercostal, scalene, sterno- be synchronous with the muscle involvement. cleidomastoid, and trapezius muscles and may be not be clinically obvious. This has generally been described in patients with advanced myositis and Preoperative Considerations dysphagia and may occur without obvious paren- in Myositis chymal lung involvement or respiratory com- plaints [ 8 ] . Patients may complain of insomnia, Extramuscular Organ Assessment: Lung day time hypersomnolence, morning headache, and fatigue, while an ineffective cough increases Interstitial Lung Disease the risk for aspiration pneumonia. A study on IIM The lung is the most common extramuscular patients showed subclinical diaphragmatic weak- organ involved in PM and DM, and ILD occurs in ness in more than 70% of IIM patients, even with at least 20Ð40% of patients, causing signi fi cant normal PFTs [9 ] . Subclinical disease should be morbidity and mortality [ 4, 5 ] . In myositis considered in any myositis patients undergoing patients with antisynthetase autoantibodies (most major surgery to prevent delay or inability to commonly anti-Jo-1), ILD may be present in up wean after postoperative mechanical ventilation. to 80% of these patients [6 ] . ILD is an important Diaphragmatic dysfunction reduces the ability of prognostic factor for patients with IIM and may the respiratory system to face sudden increases in cause serious problems like prolonged intubation ventilatory demand which is crucial in postopera- and dif fi culty in maintaining oxygenation, with tive patients after extubation. Thus, all myositis any major surgery requiring general anesthesia. patients with any suspicion of respiratory muscle Myositis-associated ILD can precede, occur con- weakness should have preoperative PFTs includ- comitantly with, or present after the diagnosis of ing an evaluation for diaphragmatic weakness. IIM. The clinical presentation is quite variable as Reduced inspiratory or expiratory pressures with some patients may be asymptomatic or have sub- restrictive physiology on PFTs generally suggest acute disease, while others present acutely with respiratory muscle weakness [10 ] . Supine respira- rapidly progressive respiratory failure. All newly tory function tests are useful for clinical diagnosis diagnosed myositis patients with antisynthetase and respiratory risk stratifi cation as forced vital antibodies should have baseline/preoperative pul- capacity (FVC) and vital capacity (VC) are more monary function testing (PFT) including an than 10% higher in upright compared with supine assessment of diffusion capacity (DLCO) along testing. Once respiratory muscle weakness is with high-resolution computed tomography noted, patients should be followed with serial max- (HRCT) of the lungs to determine the presence imal inspiratory pressure (MIP), maximal expira- and extent of ILD. Pulmonary consultation is tory pressure (MEP), and VC. Poor prognostic 16 Perioperative Management of the Patient with Idiopathic Infl ammatory Myopathy 203 factors for severe respiratory failure include an myocardial disease is uncommon [ 3 ] . It is important MIP and MEP less than 30% of predicted and/or to remember that patients with myositis may have vital capacity less than 55% predicted [11 ] . an elevated serum CK-MB fraction or cardiac tro- ponin T in the absence of myocarditis or coronary Pneumothorax and Pneumomediastinum artery disease [19 ] . This relates to increased expres- These two complications are rare in IIM except sion of CK-MB and troponin T in regenerating in DM (less than 5% cases). In one study, 80% of muscle [19 ] . Hence, if acute cardiac syndromes are myositis patients with pneumomediastinum had being considered in myositis, investigations other DM, half of whom also had amyopathic DM [12 ] . than troponins should be done. Myocarditis can be Risk factors include ILD, cutaneous vasculopa- evaluated by an echocardiogram, and/or cardiac thy, mild or absent muscle weakness or CK eleva- MRI may show infl ammation. Coronary artery dis- tion, a younger age, and a history of previous ease, which may be more common than in the gen- systemic corticosteroid treatment [ 13, 14 ] . eral population given the in fl ammatory nature of Pneumomediastinum in DM is a poor prognostic CTDs and chronic corticosteroid use, should be sign, but this is likely driven by the severity of the evaluated with cardiac catheterization or less inva- concomitant ILD [15, 16 ] . Pneumomediastinum sive studies. Cardiac troponin I, a more specifi c and is usually treated conservatively, but pneumotho- sensitive marker of cardiac damage than CK-MB rax may require chest tube placement and pleural and cardiac troponin T, is helpful in myositis drainage followed by pleurectomy [ 12 ] . Attention patients as a normal plasma troponin I provides to these complications is necessary in any patients some reassurance against cardiac involvement [ 19 ] . having surgery, especially if mechanical ventila- Other subclinical cardiac manifestations of myosi- tion is contemplated. However, due to rarity of tis include various conduction blocks and atrial or these complications, there is no de fi nite data to ventricular arrhythmias [ 20 ] . suggest that pressure damage from ventilation is more common in DM. Gastrointestinal Aspiration Pneumonia Infectious complications have been reported in up Oropharyngeal Dysmotility to 26% of myositis patients, resulting in an Dysphagia has been reported in 30Ð60% of myo- increased mortality rate [ 17 ] . Risk factors include sitis patients and can be present at any time dur- dysphagia, immunosuppressive medication, respi- ing the disease process [ 21 ] . The severity of ratory muscle weakness, malignancy, and lym- dysphagia may not be related to weakness in phopenia [17 ] . Aspiration pneumonia (17%) is the other proximal muscles [ 22 ] and may even most common infection with pseudomonas and precede weakness of the extremities or rarely staphylococcus as the most common offending present as the sole symptom. Primarily, the organisms [ 17 ] . This has important implications in skeletal muscleÐactivated oropharyngeal phase surgical patients as postoperative infections, espe- of swallowing is affected, leading to aspiration cially aspiration pneumonia, are common even in pneumonia and postoperative complications otherwise healthy individuals. The risk for aspira- that prolong the hospital course [21, 23] . The tion in myositis must be assessed preoperatively. management of dysphagia involves multiple disciplines to prevent aspiration pneumonia and to address nutritional de fi cits. Many differ- Cardiac ent medical and rehabilitative interventions are used to treat in fl ammatory myopathyÐassociated Cardiomyopathy dysphagia. Medications include immunosuppres- Although cardiac involvement with histologic evi- sive drugs and intravenous immunoglobulin (IVIg) dence of myocarditis is well described in up to [ 24] . Cricopharyngeal or esophageal dilation, cri- 30% of DM and PM [ 18 ] , clinically signi fi cant copharyngeal myotomy, and botulinum injections 204 R. Aggarwal and C.V. Oddis of the upper esophageal sphincter have also been utilized. Various rehabilitative interventions Intraoperative Considerations include diet modi fi cation (semisolid or pureed in Myositis foods, thickening liquids), postural changes (neck fl exion and chin tuck), and compensatory Anesthesia/Neuromuscular Blockade swallowing techniques (breath holding, voli- tional throat clearing, or coughing followed by There is no evidence that myositis affects the multiple swallows) to protect the airway [ 21 ] . In neuromuscular junction, and neuromuscular severe cases, a gastrostomy tube may be neces- responses to depolarizing (succinylcholine) or sary to protect the airway; however, there are no nondepolarizing (atracurium, vecuronium, etc.) speci fi c recommendations/data on use of feeding agents are normal even in IIM patients with or gastrostomy tube in myositis patients. active disease [ 27, 28] . Complete recovery from Preoperative evaluation to gauge the degree and anesthesia may be prolonged due to overall mus- severity of dysphagia is necessary in myositis cle weakness from active disease itself, but gen- patients and often includes a speech therapist erally not due to neuromuscular blockade. observing a barium swallow to assess for aspira- However, patients on prednisone and cyclosporine tion risk. may have medication-related prolonged recovery from neuromuscular blockade during anesthesia. Patients with adrenocortical insuf fi ciency, due to Medications chronic corticosteroid use, appear to have a defect in neuromuscular transmission which is A careful preoperative history of medication use is reversed by steroids [ 29] . Thus, stress dose ste- necessary in myositis patients particularly regarding roids may be necessary in patients chronically corticosteroids and other immunosuppressive medi- treated with steroids. Although patients receiv- cations. Most of these issues are adequately addressed ing cyclosporine are sensitive to the effects of in other chapters. However, one important therapeu- vecuronium-induced neuromuscular blockade, a tic intervention to consider in myositis patients direct effect of cyclosporine on the neuromuscu- undergoing surgical procedures is the known ef fi cacy lar junction has not been demonstrated [30 ] . Any of IVIg in treating many manifestations of therapy (including cyclosporine and potentially in fl ammatory myopathy, speci fi cally the dysphagia other agents) leading to a deterioration in renal of myositis [ 24 ] as well as the cutaneous and pulmo- function may increase the duration of nondepo- nary manifestations [ 25, 26 ] . Administering IVIg larizing neuromuscular blockade. Although a will mitigate the immunosuppressive properties that theoretical concern involving the administration so many other regimens have yet provide a mecha- of succinylcholine in a patient with myositis nism of immunomodulation that is effective in treat- is the excessive release of potassium secondary ing the underlying immune-mediated in fl ammatory to depolarization of abnormal muscle cells, process. Steroids may, of course, need to be contin- this problem has not been documented in IIM ued in the pre- and perioperative period, but an effort patients. One report noted a mild and transient should be made to taper steroids to the lowest effec- rise in the serum potassium concentration fol- tive dose if time permits. Steroid myopathy may lowing the administration of succinylcholine in hamper perioperative rehabilitation and should be IIM patients consistent with increases seen considered in patients on any dose of long-term cor- in normal patients [31 ] . In summary, there are a ticosteroids. This entity is suggested by continued or normal onset, peak effect, and recovery from the worsening (predominantly lower extremity) proximal neuromuscular blocking actions of polarizing as muscle weakness at a time when muscle enzymes well as depolarizing agents in patients with active are improving or normal. Fortunately, steroid myositis. This is probably related to the fact that myopathy does not cause diaphragm or respiratory the immunologic target of PM and DM is distal muscle weakness. to the neuromuscular junction. 16 Perioperative Management of the Patient with Idiopathic Infl ammatory Myopathy 205

In the patient with myositis (predominantly period is essential. Many studies in the last DM) in overlap with malignancy, a paraneoplas- 10 years have clearly demonstrated the benefi cial tic myasthenic syndrome may occur. Similarly, effect of exercise on clinical outcomes in PM and elderly myositis patients may have several comor- DM [32 ] even in patients with active disease. bidities and/or medications that may adversely Exercise prevents muscle loss, reducing chronic affect neuromuscular junction. Thus, the anesthe- features such as weakness due to muscle damage. siologist should exercise caution in using neuro- The severity and extent of muscle weakness and muscular blockers in some high-risk myositis endurance in patients with myositis are variable patients (patients with profound weakness includ- and should be individually assessed preopera- ing respiratory muscle involvement or ILD) and tively in order to devise a postoperative plan. consider the use of a peripheral nerve stimulator Different rehabilitation strategies are required for while titrating the medication. different phases of muscle disease activity. During phases of higher disease activity, adaptive strategies are needed to maximize function and Other Considerations independence and include stretching exercises to preserve range of motion and reduce contrac- There are no reports of malignant hyperthermia tures. In the recovery phase of myositis, an active (MH) in IIM patients exposed to agents known to strengthening program to improve muscle be associated with MH. Some anesthesiologists strength and endurance has been demonstrated to may still prefer such medications (e.g., succinyl- be both safe and ef fi cacious. choline and halogenated hydrocarbons) particu- larly in patients with active myositis and an elevated CK. Disease Flare Patients with impaired airway re fl exes and a higher risk of aspiration as described above Since immunosuppression may be temporarily should be carefully assessed by the anesthesiolo- held for surgery, the risk of a disease fl are exists gist regarding perioperative care and specifi c especially if treatment is held for more than safeguards regarding the aforementioned risks of 4Ð8 weeks. The earliest possible time for rein- pharyngeal dysphagia. stitution of stable immunosuppressive medica- tion is variable and dependent on many factors. Careful monitoring of muscle enzymes and Postoperative Considerations muscle strength is recommended realizing that (1) muscle enzymes may predate a clinical fl are Rehabilitative Challenges of myositis and (2) muscle enzymes may be “falsely” elevated due to renal failure, cardiac Postoperative rehabilitation is necessary in any complications, and trauma to muscle during the surgical patient but is especially important in surgical procedure. those with myositis. During the perioperative period, bed rest may worsen muscle atrophy and compromise function beyond that which already Special Considerations exists in the myositis patient. Corticosteroids may also exacerbate the catabolic effects of major Calcinosis and Surgery surgery contributing to worsening atrophy (par- ticularly in type II fi bers) further deteriorating Dystrophic calci fi cation is seen in up to 30% of muscle function. As stated earlier, control of patients with JDM and is much rarer in adult DM. active disease should precede surgery whenever It most commonly affects sites overlying pressure possible, but introduction of an exercise program points such as the elbows, knees, digits, and but- by a physical therapist early in the postoperative tocks. No pharmacological treatment is accepted 206 R. Aggarwal and C.V. Oddis as standard treatment to prevent or reduce calcinosis, particularly relevant for patients with IBM where but some believe that early, aggressive immuno- profound atrophy of the quadriceps muscle may suppression may prevent or ameliorate calcium actually preclude TKR due to the inability to deposition in patients with DM. The soft tissue strengthen the quadriceps musculature pre- and in fl ammatory response to subcutaneous calcium postoperatively. In fact, concern for subluxation may respond to oral colchicine (0.6Ð1.2 mg daily of the replaced joint is high due to the lack of for 7Ð14 days). Other agents anecdotally reported stabilizing forces around the knee joint. However, to bene fi t calcinosis include low-dose warfarin, this does not preclude joint replacement in the aluminum hydroxide, probenecid, and diltiazem. PM or DM patient where the response to pharma- However, the pharmacological therapy response of cologic therapy is completely different than that calcinosis, whether in the adult or pediatric DM of IBM patients and rehabilitation is possible (see patient, remains poor. Smaller super fi cial lesions III.A. above). Consultation among the rheuma- can be treated with CO2 laser. Large calcium tologist, orthopedic surgeon, and postoperative deposits may be the source of considerable mor- rehabilitative team is necessary in such instances bidity secondary to tumor tenderness and func- to (1) decide if the prosthesis can indeed be toler- tional disability. Surgical excision is often required ated, (2) prepare the patient for surgery with an for painful, infected, or localized calcifi c deposits appropriate preoperative muscle strengthening that interfere with joint function. Some authors program, and (3) design an appropriate postop- believe surgical removal of the calcifi cations not erative rehabilitative regimen. only relieves pain and improves function but also results in wound healing by primary intention without further local recurrence. If surgical inter- Muscle Biopsy vention is decided upon, removal of the complete calci fi c deposit and the surrounding necrotic tissue The role of muscle biopsy is critical in IIM patients and curettage are recommended. Rarely, this may to establish the diagnosis. This is particularly true result in a superfi cial skin defect that may be closed in the case of PM where many myositis mimics using a full-thickness skin graft. In cases of incom- can present similarly [33 ] . The selection of the plete debridement of necrotic tissue, the risk of muscle biopsy site is important, and the surgeon further infection, wound healing complications, should discuss this with the treating rheumatolo- and subsequent functional disability is increased. gist or neurologist. In general, a proximal muscle Even after surgery, recurrences of calcinosis may (e.g., deltoid or quadriceps) is selected based on occur. the fi ndings from electromyography done on the contralateral side. The muscle should be weak but not end-stage so as to minimize fi ndings of chronic Arthritis and Joint Replacement fatty replacement or fi brous atrophy. Although an open surgical biopsy is most frequently done, Joint replacement in patients with myositis most needle muscle biopsy or CT-guided muscle biopsy commonly occurs due to avascular necrosis from is being increasingly utilized with good results chronic corticosteroid use or concomitant osteoar- [34 ] . Regardless of the technique, muscle biopsy thritis. However, some patients have myositis in is a minor procedure which is very well tolerated overlap with other CTDs like rheumatoid arthritis even by the patient with advanced disease and or systemic lupus erythematosus and may have a extramuscular manifestations; however, good deforming arthropathy that necessitates arthro- local wound care should be done postbiopsy. The plasty. The unique operative issues in myositis muscle biopsy sample should be partitioned into patients are those associated with muscle weak- three samples for (1) frozen section for biochemi- ness around the joint of interest. This most com- cal and enzymatic studies, (2) paraffi n section for monly involves quadriceps atrophy or weakness histology and immunohistochemistry, and (3) related to total knee replacement (TKR). This is plastic section for electron microscopy. 16 Perioperative Management of the Patient with Idiopathic Infl ammatory Myopathy 207

Malignancy-Associated Myositis 4. Selva-O’Callaghan A, Labrador-Horrillo M, Munoz- Gall X, Martinez-Gomez X, Majo-Masferrer J, Solans-Laque R, et al. Polymyositis/dermatomyositis- The association between cancer and IIM is well associated lung disease: analysis of a series of 81 established and more common after the age of 50. patients. Lupus. 2005;14(7):534Ð42. Malignancy is seen in approximately 30% of DM 5. Marie I, Hachulla E, Cherin P, Dominique S, Hatron and 15% of PM patients with half the cancers PY, Hellot MF, et al. Interstitial lung disease in polymyositis and dermatomyositis. Arthritis Rheum. being detected after the diagnosis of IIM [1, 2 ] . 2002;47(6):614Ð22. Cancers most commonly develop within 1 year of 6. Richards TJ, Eggebeen A, Gibson K, Yousem S, the onset of myositis, but the risk is heightened Fuhrman C, Gochuico BR, et al. Characterization and for up to 5 years [1, 2 ] . The most common cancer peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis types are adenocarcinomas of ovarian, breast, Rheum. 2009;60(7):2183Ð92. uterine, lung, gastrointestinal, nasopharyngeal, 7. Dickey BF, Myers AR. Pulmonary disease in poly- and prostate origin along with lymphomas [ 35 ] . myositis/dermatomyositis. Semin Arthritis Rheum. Many patients are at their peak severity and activ- 1984;14(1):60Ð76. 8. Selva-O’Callaghan A, Sanchez-Sitjes L, Munoz-Gall ity of myositis at the time the cancer is diagnosed X, Mijares-Boeckh-Behrens T, Solans-Laque R, and at a time when surgery is necessary. This Angel Bosch-Gil J, et al. Respiratory failure due to poses a serious problem for the surgeon as the muscle weakness in in fl ammatory myopathies: main- outcome of surgery is dependent on the overall tenance therapy with home mechanical ventilation. Rheumatology (Oxford). 2000;39(8):914Ð6. health of the patient, and in a debilitated patient 9. Teixeira A, Cherin P, Demoule A, Levy-Soussan M, with severe weakness, the outcome may be less Straus C, Verin E, et al. Diaphragmatic dysfunction in than ideal. Surgeons often request rheumatologic patients with idiopathic infl ammatory myopathies. consultation for medical treatment of the myosi- Neuromuscul Disord. 2005;15(1):32Ð9. 10. Martin L, Chalmers IM, Dhingra S, McCarthy D, tis, but immunosuppressive therapy may fail to Hunter T. Measurements of maximum respiratory improve the disease, and further recovery may pressures in polymyositis and dermatomyositis. only be possible after removal and treatment of J Rheumatol. 1985;12(1):104Ð7. the underlying malignancy. In fact, patients may 11. Braun NM, Arora NS, Rochester DF. Respiratory mus- cle and pulmonary function in polymyositis and other respond to resection of the tumor and treatment of proximal myopathies. Thorax. 1983;38(8): 616Ð23. the malignancy as the paraneoplastic effect of the 12. Le Goff B, Cherin P, Cantagrel A, Gayraud M, Hachulla tumor is eliminated. Providing guidelines in such E, Laborde F, et al. Pneumomediastinum in interstitial instances is diffi cult, and the timing of surgery lung disease associated with dermatomyositis and polymyositis. Arthritis Rheum. 2009;61(1):108Ð18. relative to preoperative immunosuppressive ther- 13. Korkmaz C, Ozkan R, Akay M, Hakan T. apy must be examined on a case-by-case basis. Pneumomediastinum and subcutaneous emphysema The general treatment recommendation in an associated with dermatomyositis. Rheumatology overlap of myositis and cancer is the simultane- (Oxford). 2001;40(4):476Ð8. 14. Kono H, Inokuma S, Nakayama H, Suzuki M. ous treatment of both the cancer with surgery or Pneumomediastinum in dermatomyositis: association chemoradiation and immunosuppressive interven- with cutaneous vasculopathy. Ann Rheum Dis. tion in the case of the myositis. 2000;59(5):372Ð6. 15. Yoshida K, Kurosaka D, Kingetsu I, Hirai K, Yamada A. Pneumomediastinum in dermatomyositis itself is not a poor prognostic factor: report of a case and review References of the literature. Rheumatol Int. 2008;28(9):913Ð7. 16. Terao M, Ozawa K, Inui S, Murota H, Yokomi A, 1. Bohan A, Peter JB. Polymyositis and dermatomyositis Itami S. A case of dermatomyositis complicated with (second of two parts). N Engl J Med. 1975;292(8): pneumomediastinum. Mod Rheumatol. 2007;17(2): 403Ð7. 156Ð9. 2. Bohan A, Peter JB. Polymyositis and dermatomyositis 17. Marie I, Hachulla E, Cherin P, Hellot MF, Herson S, ( fi rst of two parts). N Engl J Med. 1975;292(7): 344Ð7. Levesque H, et al. Opportunistic infections in poly- 3. Bohan A, Peter JB, Bowman RL, Pearson CM. myositis and dermatomyositis. Arthritis Rheum. Computer-assisted analysis of 153 patients with poly- 2005;53(2):155Ð65. myositis and dermatomyositis. Medicine (Baltimore). 18. Denbow CE, Lie JT, Tancredi RG, Bunch TW. Cardiac 1977;56(4):255Ð86. involvement in polymyositis: a clinicopathologic 208 R. Aggarwal and C.V. Oddis

study of 20 autopsied patients. Arthritis Rheum. for refractory interstitial lung disease associated 1979;22(10):1088Ð92. with polymyositis/dermatomyositis. Lung. 2009;187: 19. Aggarwal R, Lebiedz-Odrobina D, Sinha A, Manadan 201Ð6. A, Case JP. Serum cardiac troponin T, but not troponin 27. Brown S, Shupak RC, Patel C, Calkins JM. I, is elevated in idiopathic infl ammatory myopathies. Neuromuscular blockade in a patient with active der- J Rheumatol. 2009;36(12):2711Ð4. matomyositis. Anesthesiology. 1992;77(5):1031Ð3. 20. Stern R, Godbold JH, Chess Q, Kagen LJ. ECG 28. Saarnivaara LH. Anesthesia for a patient with poly- abnormalities in polymyositis. Arch Intern Med. myositis undergoing myectomy of the cricopharyngeal 1984;144(11):2185Ð9. muscle. Anesth Analg. 1988;67(7):701Ð2. 21. Oh TH, Brum fi eld KA, Hoskin TL, Stolp KA, Murray 29. Meyers EF. Partial recovery from pancuronium JA, Bassford JR. Dysphagia in in fl ammatory myopathy: neuromuscular blockade following hydrocortisone clinical characteristics, treatment strategies, and outcome administration. Anesthesiology. 1977;46(2):148Ð50. in 62 patients. Mayo Clin Proc. 2007;82(4):441Ð7. 30. Wood GG. Cyclosporine-vecuronium interaction. Can 22. Kim SJ, Han TR, Jeong SJ, Beom JW. Comparison J Anaesth. 1989;36(3 Pt 1):358. between swallowing-related and limb muscle involve- 31. Johns RA, Finholt DA, Stirt JA. Anaesthetic manage- ment in dermatomyositis patients. Scand J Rheumatol. ment of a child with dermatomyositis. Can Anaesth 2010;39(4):336Ð40. Soc J. 1986;33(1):71Ð4. 23. Williams RB, Grehan MJ, Hersch M, Andre J, Cook 32. Alexanderson H. Exercise effects in patients with IJ. Biomechanics, diagnosis, and treatment outcome adult idiopathic infl ammatory myopathies. Curr Opin in in fl ammatory myopathy presenting as oropharyn- Rheumatol. 2009;21(2):158Ð63. geal dysphagia. Gut. 2003;52(4):471Ð8. 33. Nirmalananthan N, Holton JL, Hanna MG. Is it really 24. Marie I, Hachulla E, Levesque H, Reumont G, myositis? A consideration of the differential diagnosis. Ducrotte P, Cailleux N, et al. Intravenous immuno- Curr Opin Rheumatol. 2004;16:684Ð91. globulins as treatment of life threatening esophageal 34. Campellone JV, Lacomis D, Giuliani MJ, Oddis CV. involvement in polymyositis and dermatomyositis. Percutaneous needle muscle biopsy in the evaluation J Rheumatol. 1999;26(12):2706Ð9. of patients with suspected in fl ammatory myopathy. 25. Dalakas MC, Illa I, Dambrosia JM, et al. A controlled Arthritis Rheum. 1997;40(10):1886Ð91. trial of high-dose intravenous immune globulin infu- 35. Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, sions as treatment for dermatomyositis. N Engl J Med. Mellemkjaer L, Airio A, et al. Frequency of specifi c 1993;329:1993Ð2000. cancer types in dermatomyositis and polymyositis: 26. Suzuki Y, Hayakawa H, Miwa S, Shirai M, Fujii M, a population-based study. Lancet. 2001;357(9250): Gemma H, et al. Intravenous immunoglobulin therapy 96Ð100. Perioperative Management of Patients with Rheumatoid 1 7 Arthritis

Lisa L. Schroeder and Mary Chester M. Wasko

patients undergoing surgery [ 3 ] . Goals of any Introduction preoperative medical evaluation should include identifying patient factors that increase surgical Rheumatoid arthritis (RA) is a common chronic risk, attempting to quantify the risk, providing systemic in fl ammatory condition, affecting roughly recommendations to minimize the risk, and man- 1% of the population worldwide [1, 2 ] . Advancing aging comorbid medical conditions and their age, chronic in fl ammation, and side effects from therapy [3, 4 ] . A multidisciplinary team should antirheumatic medications increase the likelihood be involved, including the primary care provider, of other medical comorbidities and therefore rheumatologist, surgeon, anesthesiologist, and increase perioperative risk among these persons. other subspecialists as necessary (e.g., cardiolo- They require a coordinated, comprehensive periop- gist, pulmonologist, or otolaryngologist). Fluid erative evaluation and management plan to mini- communication between the team members, be it mize complications. We will discuss general and through the electronic medical record, paper RA-speci fi c preoperative, operative day, and post- documentation, or records and fi lms hand-carried operative medical and anesthetic considerations. by the patient to and from providers, is critical to the optimal perioperative course. Conveying the importance of this team approach to the patient Preoperative Considerations ahead of time will engage the patient in the com- munication process. Preoperative General Medical For elective procedures, a thorough periopera- Evaluation Goals tive medical evaluation ideally will be done several weeks prior to the procedure to allow time for Primary care physicians and rheumatologists testing and adjustment of medications, further have an important role in the management of RA consultation, and communication [4 ] .

L. L. Schroeder , M.D. General Medical Risk Assessment Internal Medicine, Rheumatology , Geisinger Medical and Risk Reduction Center , 100 North Academy Avenue , Danville , PA 17822 , USA A complete preoperative history and physical M. C. M. Wasko , M.D., M.Sc. () exam leads the physician to an accurate assessment Lupus Center of Excellence, Internal Medicine , West Penn/ of perioperative risk in most cases. In general, Allegheny Health System , 4800 Friendship Ave. NT-2600 , Pittsburgh , PA 15224 , USA nonselective testing does not decrease periopera- e-mail: [email protected] tive complications unless the history and/or

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 209 DOI 10.1007/978-1-4614-2203-7_17, © Springer Science+Business Media, LLC 2013 210 L.L. Schroeder and M.C.M. Wasko

Table 17.1 Preoperative lab testing in the RA patient Test Indication Comments Hemoglobin >500 cc blood loss anticipated Large joint replacements; spine surgeries WBC Use of immunosuppressive drugs Will apply to virtually all RA patients Creatinine >50Ð65-year-old patient With prevalent NSAID use, this applies to Use of NSAID or renally excreted drug most RA patients Hypertension or diabetes Risk of postoperative acute renal injury Glucose Diabetes Indicated in steroid users Current steroid use Urinalysis See creatinine indications Indicated for joint replacements Orthopedic implant planned Bladder catheter planned PT, PTT, platelets Planned perioperative anticoagulation Applies for TKR/THR where empiric warfarin for DVT prophylaxis is planned Pregnancy test Women of childbearing age Adapted from Nierman and Zakrzewski [3 ] , Copyright 1999, with permission from Elsevier

physical exam points to a specifi c problem [ 5 ] . In the general population, the most common Nierman (1999) provides general recommendations serious complications of noncardiac surgery are for preoperative screening tests based on patient cardiac events [ 3] . Data regarding optimal evalu- age, comorbidities, and procedure type [ 3 ] . ation and management of perioperative cardiac Recommendations are in Table 17.1 . risk in the RA patient is lacking. However, The preoperative medical evaluation should also assessing likelihood and extent of coronary be used to optimize the patient’s general medical artery disease in the preoperative RA patient condition before elective surgery. Escalante and must be undertaken before elective procedures, Beardmore’s work (1997) suggests that this may be particularly in patients with considerable func- particularly true for rheumatoid patients [ 6 ] . Of tional limitation. A careful history to elicit vague 137 RA patients undergoing total knee or hip exertion-related symptoms that might indicate arthroplasty, those that were over 55 years of age occult angina is essential. Importantly, the patient and with poor functional status had a signi fi cantly with RA may not provide a classic history of longer length of stay in the rehabilitation hospital; angina, and a history suggestive of angina may other characteristics associated with a prolonged re fl ect severe coronary disease because exertion rehabilitation stay were a positive rheumatoid fac- is limited by arthritis-related physical activity tor, use of bone cement, longer operating time, and limitations. female gender. This study emphasizes the impor- In addition to traditional cardiovascular risk tance of improving preoperative functional and factors, excess cardiovascular risk has been medical status in RA patients so that they can found in RA patients with two of the following bene fi t from postoperative rehabilitation. three criteria: disease duration greater than 10 years, rheumatoid factor or anticyclic citrulli- nated peptide positivity, or presence of extra- RA-Speci fi c Medical Risk Assessment articular manifestations of RA. European and Risk Reduction guidelines recommend multiplying these RA patients’ cardiovascular disease risk by a factor RA patients undergoing surgery may need addi- of 1.5 when using traditional risk models. tional preoperative testing, guided by speci fi c Evidence suggests that RA is a diabetes equiva- extra-articular disease manifestations and lent with regard to cardiovascular risk; therefore, RA-related comorbidities. we suggest that general recommendations for 17 Perioperative Management of Patients with Rheumatoid Arthritis 211 preoperative cardiovascular screening be fol- that is comparable to diabetes. However, given the lowed with this equivalence in mind [ 7 ] . limited amount of information available on this In the non-RA population, preoperative ECGs topic, we suggest a preoperative evaluation similar are recommended for males >45 years of age, to patients with diabetes, pending further reassur- females >55 years for cardiovascular procedures, ing reports. or any patient with known cardiovascular dis- The pulmonary system is often affected by RA, ease, hypertension, or diabetes [ 3 ] . If the planned with manifestations ranging from asymptomatic procedure is low risk and the patient has adequate pleural effusions to small airway disease [10, 11 ] . functional capacity without any symptoms sug- Antirheumatic medications, such as methotrexate gesting underlying cardiac disease, a preopera- can cause occult pulmonary toxicity as well [11 ] . tive ECG usually will suf fi ce [5 ] . However, since Pulmonary disease is usually mild and slowly pro- many of the orthopedic or intra-abdominal proce- gressive, and many patients do not volunteer dures required by RA patients are intermediate symptoms, even though they frequently have risk, we favor further risk assessment with an abnormal pulmonary function tests. Physicians exercise or adenosine stress test for those with can consider a baseline chest radiograph for two or more Goldman risk factors. Given the fi brosis or effusions that could compromise venti- similarities in cardiovascular risk seen with RA lation and oxygenation during surgery [10, 12 ] , patients and those with diabetes, we advocate this though we do not consider this necessary in an conservative approach and favor considering RA asymptomatic patient with good functional status. a diabetes equivalent when calculating Goldman A preoperative chest X-ray should be considered criteria for preoperative stress testing (Peters in a patient with severe functional limitations in Mike JI et al., Arth Care Res. 2009; 61(11): whom exertional dyspnea is an unreliable indica- 1571Ð79). These recommendations are in keep- tor of pulmonary disease, as signi fi cant interstitial ing with ACC/AHA guidelines, which propose lung disease may be documented. that noninvasive stress testing be considered for Many patients with RA use corticosteroids patients with poor functional capacity and at least chronically. While the detrimental effects of one or two of the Goldman risk criteria. Many long-term low-dose steroids on skin and integu- RA patients with long-standing seropositive dis- mentary fragility cannot be reversed in the brief ease fall into this category [8 ] . preoperative period, special attention to any skin This being said, the only currently available data and soft tissue ulcerations or open wounds should suggests that the perioperative risk for RA patients be paid and every effort made to heal these pre- may not be as great as that for patients with diabe- operatively, as they serve as a route for infec- tes. Yazdanyar et al. reported on the relationship tion postoperatively. Long-term use of between RA and perioperative composite cardio- corticosteroids also may predispose them to the vascular events and death in an observational data- development of diabetes. Increased risk of wound base of nearly 8 million individuals undergoing infections in RA patients with diabetes (33% vs. elective noncardiac surgery between 1998 and 3.3%) undergoing hand and wrist surgery has 2002 [9 ] . Elective surgical procedures were catego- been described elsewhere [13 ] . rized as minor, intermediate or high risk. Compared Treatment with recombinant erythropoietin with patients with diabetes, RA patients were less may correct anemia in patients with rheumatoid likely to have a cardiovascular event when under- arthritis and allow them to donate blood preop- going a low or intermediate risk procedure. For eratively for postoperative transfusions [ 14 ] . those undergoing an intermediate risk procedure, However, RA patients with active disease have a risk of death was less in RA patients than in diabe- poorer response to treatment with erythropoietin tes patients (p < 0.001), though difference among and are often unable to do autologous blood those having low or high risk procedures was not transfusions before surgery [ 15 ] . A recent statistically signi fi cant. Overall, these data do not randomized controlled trial showed that RA and support a preoperative evaluation in RA patients non-RA patients bene fi tted equally from epoetin 212 L.L. Schroeder and M.C.M. Wasko

40,000 IU once weekly for 3 weeks before postoperatively. For example, patients getting elective orthopedic surgery [ 16] . In the treated total knee replacements, but with signifi cant wrist group, hemoglobin levels were higher on the day or hand deformities, may recover better after sur- of surgery until hospital discharge, and only 10% gery with a platform walker instead of a tradi- required transfusion, compared to 40% in the tional walker. These evaluations also help patients untreated groups [ 17] . All epoetin- a-treated plan with the surgeon and therapist whether they patients in this study also received iron supple- will need a postoperative stay in a rehabilitation mentation. While this data is a post hoc analysis, facility or if the home needs any modifi cations it provides some preliminary support for preop- before discharge to home. Social workers or case erative epoetin-a treatment coupled with iron managers can provide invaluable assistance in supplementation in the weeks preceding elective this process before any planned procedure [10 ] . surgery in RA patients with anemia (hemoglo- The surgeon typically advises RA patients to bin < 10Ð11 mg/dL) when signifi cant intraopera- discontinue use of traditional nonsteroidal anti- tive blood loss is anticipated. infl ammatory drugs (NSAIDs) 5Ð10 days preop- Patients with RA suffer up to two times more eratively to reduce the risk of operative bleeding. infections than patients with osteoarthritis (OA) This brief cessation of analgesia may cause the after total joint arthroplasty [18, 19 ] . An immuno- patient to experience an exacerbation in joint dis- suppressive drug regimen for RA puts them at risk comfort before elective procedures. An excellent for infection, and uncontrolled infl ammation from alternative is the prescription of celecoxib, as this the disease itself may render the RA patient more speci fi c cyclooxygenase-2 inhibitor has no anti- prone to infections [ 18 ] . Particularly for those platelet effects and may be used safely up until patients undergoing elective orthopedic procedures the day of surgery. It also may be considered in or valve replacement, preoperative control of and the postoperative patient on warfarin therapy, recovery from dental, cutaneous, and other infec- when traditional NSAIDs are contraindicated tions are essential to minimize the risk of hematog- because of bleeding risk. enous seeding of a prosthesis postoperatively. White blood cell counts preoperatively should be checked to verify that patients do not have iatro- RA-Speci fi c Anesthetic Preoperative genic neutropenia [20 ] . While increasingly rare, Risk Assessment and Risk Reduction Felty’s syndrome (RA, neutropenia, and splenom- egaly) may increase the risk of infection; in those Cervical Spine patients with a history of recurrent infections, Cervical spine disease should be suspected in G-CSF treatment to maintain a normal neutrophil rheumatoid patients with hand and foot synovi- count perioperatively is appropriate [10 ] . tis [11 ] . Symptomatic cervical disease is more common in patients with RA >10 years and those with seropositive disease, but asymptom- Comprehensive Rehabilitation Planning atic disease is far more common [ 10 ] . Any part of the cervical spine can be involved, but atlan- Patients with longstanding or erosive RA may toaxial subluxation (anterior, posterior, vertical, have painful hand and foot deformities [10 ] . and rotatory) of C1 and C2 is most common Deformities make it uncomfortable to walk and [10Ð 12, 21 ] . do activities of daily living in the early postopera- Cervical spine disease in RA has implications tive period and could delay hospital discharge. for preoperative radiographic testing and for A physical therapy and occupational therapy intubation technique. The traditional “snif fi ng” referral before orthopedic surgeries will facilitate position (head is hyperextended on a fl exed neck) postoperative rehabilitation. The therapists can used for endotracheal intubation can worsen instruct patients on any exercises and select or subluxation and compress the cervical cord in review any adaptive devices that may be needed patients with atlantoaxial involvement because 17 Perioperative Management of Patients with Rheumatoid Arthritis 213 increased neck fl exion could cause cord com- poorly controlled aggressive disease of shorter pression [21 ] . A 2004 case report illustrated the duration, and for those patients with symptoms effect of the sniffi ng position on anterior atlanto- of subluxation [21, 23 ] . The likelihood of axial subluxation (AAS) [22 ] . A woman with detecting clinically signi fi cant subluxation in long-standing RA and asymptomatic AAS had other RA patients seems exceedingly small X-rays in the sniffi ng position, with the head fl at, [25, 26 ] . and with extension of the entire cervical spine by the exam table. The X-ray in the sniffi ng posi- TMJ tion showed marked AAS anteriorly and posteri- More than 50% of RA patients have jaw symp- orly as compared to the other two positions. This toms during their disease course, and changes in patient underwent fi beroptic intubation with the temporomandibular joints (TMJ) are seen in manual in-line stabilization for a radioulnar joint 78% of joints that are examined radiographically reconstruction procedure. She did well without [ 11, 12, 21 ] . This should be assessed carefully any airway or neurologic complications after preoperatively by both medical specialists and surgery [ 22] . Traditional intubation risk is even particularly anesthesiologists, as TMJ disease higher with cephalad migration of the odontoid. can have implications for airway management [ 4, Those patients with subaxial subluxation are at 10] . The oral aperture should be assessed and risk for cord compression with neck extension TMJ palpated for tenderness and/or crepitus with [ 21 ] . The best option is to maintain the head in a jaw opening. TMJ arthritis can reduce the mouth neutral position if the cervical anatomy is not ori fi ce and make endotracheal intubation more known at the time of surgery. dif fi cult. Severe TMJ involvement in juvenile Optimal preoperative cervical spine imaging idiopathic arthritis can also cause micrognathia, in RA patients is controversial. Some authors which makes routine intubation almost impossi- recommend fl exion and extension cervical spine ble. These patients may need fi beroptic or radiographs in only those with pain or abnormal nasotracheal intubation to prevent postoperative physical exam fi ndings [4, 21 ] , while others laryngeal edema [12 ] . advocate for routine imaging of all patients with Successful anesthetic techniques have been RA [23 ] . Kwek et al. (1998) found that preopera- described to manage bilateral total TMJ replace- tive cervical spine X-rays changed anesthetic ment surgery in RA patients [ 27 ] . This situation management [24 ] . Fifteen to twenty percent of is especially challenging, as signi fi cant postop- the patients in their study had no available previ- erative facial and jaw swelling can occur. ous cervical spine X-rays. Flexion and extension However, nasotracheal intubation with fi beroptic views improved the detection of instability, and technique has been effectively used in four these authors recommend these views, plus fron- patients with advanced RA who had preoperative tal neck and odontoid view to improve detection dysphagia from cricoarytenoid arthritis. The of lateral atlantoaxial subluxation [ 24 ] . patients were awake during intubation with topi- Interestingly, a signifi cant number of patients cal anesthetic applied to the larynx. Because three (25%) in this study had progression of their cer- of the four patients developed laryngospasm and vical spine involvement on new X-rays as com- the authors anticipated postextubation diffi culty, pared to previous C-spine X-rays. They therefore the patients remained intubated overnight. These recommend imaging before every surgery. techniques can help to make for a smooth transi- Routine imaging in every rheumatoid patient tion from the operating room to recovery room in exposes some to possibly unnecessary radiation. patients with TMJ arthritis. It can be expensive and utilizes health-care resources. As suggested by others, we favor Cricoarytenoid Arthritis preoperative fl exion and extension views of the Rheumatoid involvement of the cricoarytenoid joint cervical spine for any preoperative patient with is found in between 45% and 88% of postmortem RA for at least 10 years, for those patients with examinations and is recognized in 30% of patients 214 L.L. Schroeder and M.C.M. Wasko in clinical studies [10, 11, 21, 28] . It narrows the patient with cervical spine instability developed glottis and can cause fi xed adduction of the vocal upper airway obstruction after extubation and, cords. Physicians often do not pay attention to after several extubation attempts, required tracheo- symptoms of cricoarytenoid disease, and dire post- stomy placement [ 31 ] . Her obstruction was fi rst operative consequences can result. A discerning thought due to pharyngeal edema, but after revi- preoperative history is imperative. Patients with cri- sion of the upper cervical angle done in the initial coarytenoid arthritis may describe sore throat or full surgery, the obstruction resolved. sensation in the throat and sudden onset of exer- The common theme in the above cases is that tional dyspnea, dysphagia, choking, hoarseness, these patients had a combination of the airway aspiration, or stridor, sometimes associated with problems of concern to the anesthesiologist (cer- upper respiratory tract infections [10, 21] . However, vical spine instability, TMJ, and cricoarytenoid sore throat and dif fi culty during inspiration seem to arthritis). They also show that the underlying be the only clinical symptoms predictive of abnor- pathology causing obstruction is not always clear malities on indirect laryngoscopy [26 ] . Patients with and requires a thorough consideration of differ- cricoarytenoid arthritis also may be more prone to ential diagnoses. Preoperative indirect laryngos- obstructive sleep apnea [21 ] . copy is a simple diagnostic tool that should be Endotracheal intubation, especially if multiple considered in all patients with these characteris- attempts are required to successfully place the tics. In severe cases, prophylactic minitracheos- tube, can produce cricoarytenoid edema. Patients tomy may be considered if surgical intervention may have stridor and airway obstruction after is truly warranted. extubation. This can even lead to emergent tra- Some have suggested that use of a laryngeal cheostomy, as in the case reported by Kolman mask airway (LMA), in lieu of endotracheal intu- and Morris (2002) [29 ] . They reported a female bation, can prevent laryngeal edema by eliminat- patient with RA for 17 years who developed mul- ing the risk of intubation trauma. LMA has been tiple episodes of stridor and desaturation shortly used successfully in RA patients with cervical after extubation. She required an emergent tra- spine disease [ 32 ] . However, also in a recent case cheostomy after fi beroptic laryngoscopy showed report, a patient developed hoarseness due to vocal cord fi xation. Methotrexate therapy was vocal cord immobility after use of a LMA for resumed, and she was discharged from the hospi- elective surgery; postoperative steroid therapy tal 10 days later. Her tracheostomy was removed was necessary, though the patient was asymp- 4 weeks after placement and vocal cord function tomatic at 40-day follow-up [ 33 ] . While the had normalized. Segebarth and Limbird (2007) patient’s preoperative stridor was recognized on describe a similar case that required emergent physical exam, it was incorrectly attributed to tracheostomy and steroid treatment in a patient asthma and treated with an inhaler. LMA use with severe RA [30 ] . should also be approached with caution and used Lehmann et al. report a case of acute cri- by those with signi fi cant experience in the proce- coarytenoid arthritis that led to fatal postoperative dure and ability to transition to fi beroptic intuba- airway obstruction in a woman with long-standing tion if needed. erosive RA, neck pain, odynophagia, TMJ tender- In patients with a combination of potential ness, and limited oral aperture mobility [ 28 ] . She airway issues, a formal dialogue with the anes- had elective cervical spine surgery for severe thesiologist is indicated, and an otolaryngolo- cervical spine disease. Shortly after extubation, gist should be consulted before if a preoperative she developed acute upper airway obstruction tracheostomy is necessary [ 10 ] . The introduc- from hypopharyngeal edema likely related to tion of regional anesthesia for extremity surgery cricoarytenoid arthritis, and cardiopulmonary and fi beroptic intubation practices has been resuscitation was required. Even though she had credited with a signi fi cant decrease in in-hospi- an emergent tracheostomy, the patient suffered tal mortality in RA patients having hip or knee cerebral death and expired [28 ] . Another RA arthroplasty [21 ] . 17 Perioperative Management of Patients with Rheumatoid Arthritis 215

Sjogren syndrome are at increased risk of Operative Day Considerations postoperative ocular complications, such as corneal melting, ulcerative keratitis, or necro- Positioning tizing scleritis [17, 34 ] . For the anesthesiolo- gist, he/she may be able to minimize use of Joint deformities in RA patients may make it drugs with anticholinergic side effects that more dif fi cult to obtain optimal positioning for might worsen sicca symptoms. good surgical exposure [23 ] . This can also affect access for the anesthesiologist to perform regional anesthetic techniques, such as nerve plexus Surgical Site-Specifi c Considerations blocks. While hard collars are not recommended to prevent spinal cord damage during surgery, the When a patient is positioned for musculoskeletal use of a soft cervical collar before entering the procedures, special care by the anesthesiologist operating room may remind the operating room and surgeon should be taken to avoid undue stress staff to take extra safety measures the patient’s on arthritic joints. The rheumatologist should neck [4, 10 ] . Sedation coupled with anesthesia encourage the patient to ask about body position- may aid in maintaining required surgical posi- ing at the preoperative assessment with the sur- tions [ 21] . Heavy padding should be applied to geon and the anesthesiologist, and there should prevent pain in other joints not involved in the be open dialogue about minimizing inadvertent surgical procedure to minimize the chance of trauma to painful, deformed joints and rheuma- injury and to reduce postoperative pain from toid nodules. awkward positioning. Cervical Spine Vigilance for unusual complications after cervi- Intraoperative Monitoring cal spine surgery is imperative. Cervical spine surgery in the RA patient is fraught with a spec- Continuous ECG and pulse oximetry monitoring trum of adverse events postoperatively. Aside intraoperatively is used for moderate and major from complications related to screw placement, surgical procedures [4 ] . More invasive arterial or patients also may suffer from poor wound heal- venous catheter monitoring is at the discretion of ing, wound infection, spinal fl uid leak, and air- the anesthesiologist. Temperature regulation is way complications associated with dif fi cult particularly important in the RA patient with sec- intubation [35, 36] . In one retrospective study of ondary Raynaud’s phenomenon [12 ] . 86 RA patients undergoing cervical spine surgery who were followed for 7.5 years, the authors found a mean survival of 7.2 years after surgery. Ophthalmologic/Mucosa Predictors of mortality included the occurrence of postoperative complications [ 37 ] . Of the seven Dry mouth and eyes associated with Sjogren serious postoperative complications they syndrome can be particularly problematic in the described, one patient had a dif fi cult intubation operative patient with RA [ 10, 11 ] . Corneal and postoperative respiratory arrest that required drying or abrasions should be prevented by a new fi beroptic intubation. Two patients had using lubricating ointment during anesthesia unplanned ICU stays because of inspiratory stri- and after surgery [ 4 ] . Sips of liquid, humidi fi ed dor after extubation (presumed due to cri- oxygen, and arti fi cial saliva can help patients coarytenoid arthritis) and a coronary event with dry mouth after surgery [ 10 ] . Certain sur- intraoperatively. One patient had a dif fi cult intu- gical procedures such as eye surgery require bation, developed an airway obstruction because vigilant postoperative monitoring in this popu- of hematoma in the airway tube, and the opera- lation. After eye surgery, patients with RA and tion had to be rescheduled. 216 L.L. Schroeder and M.C.M. Wasko

Elbow the literature suggests a higher rate of postopera- Regional anesthetic techniques are commonly tive complications in those patients having the used for elbow replacement surgeries [21 ] . bilateral single-session procedure [ 44] . Because Brachial plexus blocks with continuous anes- many RA patients may fall into the higher risk thetic infusion via catheter after surgery can be category of ASA III, most patients with RA helpful in pain management and postoperative should be offered a staged procedure. early mobilization. Possible complications of elbow joint replacement include distal humerus Ankle and Foot fracture during surgery, delayed wound healing, Ninety percent of RA patients have forefoot and ulnar nerve de fi cits [38 ] . In a large review of involvement, and deformities are common [45 ] . 888 patients with RA with elbow replacement Correction of deformities can help with shoe fi t retrospectively matched to patients without RA, and ambulation. The surgeon must balance the the rate of early postoperative complications was bene fi ts of correcting a deformity with the risk of low, with respiratory complications and renal perioperative complications [ 46 ] . Advanced age failure occurring signi fi cantly more in patients with impaired circulation can affect wound heal- without RA [39 ] . ing, and in the distal ankle and foot, it is particu- larly important to assess arterial and venous fl ow Hip and Knee preoperatively. RA patients with multiple defor- Alterations in bone mechanics and biologic mities (those most likely to undergo ankle and behavior in rheumatoid patients may result in foot surgery) are more likely to have peripheral more complications and decreased survival of arterial disease in the lower extremities than age- joint arthroplasty compared with patients with and sex-matched controls without RA [ 47 ] . osteoarthritis (OA) [40, 41 ] . In a study of 64 Deformities in the toes with associated changes in patients with RA and 120 OA with total hip arterial anatomy place the patient at a higher risk arthroplasty, arthroplasty survival was compara- of vascular injury and resultant ischemic compli- ble in the two groups, but there were more nonin- cations to the toes after surgery [46 ] . A thorough fectious complications in the RA group [ 40 ] . exam, looking for changes of venous insuf fi ciency Others have found more long-term arthroplasty such as hyperpigmentation, also is important, as complications in an infl ammatory arthritis group the foot seems to be particularly vulnerable to compared with OA group [41 ] . edema, poor wound healing, and infection post- Postoperative infection rates also are increased operatively [ 46 ] . Because of this postoperative in patients with RA having joint replacement. In risk, we typically hold immunosuppressive two large series of patients undergoing hip or medications for up to 4 weeks postoperatively knee replacement followed for 4Ð10 years after when extensive foot surgery is done, and dialogue surgery, deep wound and prosthesis infections regularly with the surgeon to optimize medication were found more often in RA patients than non- management in this vulnerable period. Rheumatoid RA patients; RA patients had an infection rate of patients who smoke, drink alcohol, or have poorly approximately 1% per year and had a fourfold controlled diabetes require more frequent postop- increase in risk of infection compared with OA erative follow-up to monitor for evidence of post- patients [42, 43] . Both a history of previous operative wound complications. prosthetic joint infection and undergoing a revi- sion arthroplasty were risk factors for a septic prosthetic joint [43 ] . Postoperative Considerations The data on unilateral knee versus one-stage bilateral versus bilateral staged arthroplasty is Analgesic Management in RA virtually nonexistent in patients with RA, prob- ably because they are considered poor candidates Optimizing analgesia via intravenous, intramus- for one-stage bilateral replacements. However, cular, or epidural route is imperative in the 17 Perioperative Management of Patients with Rheumatoid Arthritis 217

postoperative period. Patient-controlled analgesia may mask infection-induced CRP increase and can facilitate physical therapy, as it optimizes minimize fever. postoperative pain management [4, 12 ] . Unfortunately, patients with severe hand defor- mities may not be able to use these patient-con- VTE Prophylaxis trolled devices. Preoperative pain medication use must be taken into account when postoperative RA patients undergo a signi fi cant number of analgesia dosing regimens are ordered. In rheu- orthopedic procedures, and the incidence of matoid patients taking oral narcotics before sur- deep venous thrombosis in patients not on pro- gery, narcotic requirements may be higher than phylaxis is signi fi cant. Documented incidence narcotic-naïve patients. Unless the patient is of deep vein thrombosis for joint replacement placed on warfarin to prevent postoperative deep surgery is 45Ð57% for total hip replacement, venous thrombosis, NSAIDs should be restarted 36Ð60% for hip fracture, and 40Ð84% for knee promptly to aid in pain management. replacement [50 ] . In RA patients and OA Hydroxychloroquine can be safely resumed as patients, early ambulation after total knee arthro- well without drug-associated risk of infection. plasty decreases the level of D-dimer on postop- erative day 7 similarly [ 51 ] . The D-dimer test has a high negative predictive value in ruling out Recognizing Postoperative Infection deep vein thrombosis, and studies have shown it in the RA Patient to be reliable as a screening test in the rehabili- tation setting [51 ] . It is unknown whether the Patients on certain DMARDs may not exhibit the risk of developing a venous thromboembolism same responses in the setting of postoperative (VTE) is different for rheumatoid patients, as infectious complications as patients not on compared to those with OA, with some indica- DMARD therapy. Research of RA patients under- tion in one study that the risk is less in RA going hip and knee replacements (not on TNF-a patients [52 ] . We found no literature addressing blockers) has shown the normal postoperative the magnitude of increased bleeding risk in CRP response is a rapid rise with peak level on those RA patients on NSAIDs and prophylactic postoperative day 1 or 2 approximately seven anticoagulation after surgery. However, we do times greater than preoperative levels. By postop- not favor the concomitant use of NSAIDs with erative week one, the level is back to preoperative warfarin due to the risk of gastrointestinal bleed- values [48 ] . A retrospective 1:1 pair-matched ing. We refer the reader to the chapter on VTE case-control study compared 22 RA patients prophylaxis in this volume. treated with tocilizumab to 22 patients without tocilizumab but conventional DMARD therapy who had orthopedic procedures [ 49 ] . They fol- Postoperative RA Flare lowed patients’ temperature, complete blood count, and CRP levels on the day before surgery, While withholding immunosuppressive medica- postoperative day 1, day 3, week 1, and week 2. tions in the postoperative RA patient will opti- Tocilizumab completely suppressed the increase mize surgical outcomes, this practice places the in CRP seen after surgery on day 1 and partially patient at risk for a disease fl are. A fi ne balance is suppressed the increase in body temperature on often necessary between a return to the preopera- postoperative days 1 and 2. White blood cell, tive medication regimen and the withholding of neutrophil, and lymphocyte counts showed no these medications to reduce the risk of postopera- signifi cant changes in either group after surgery. tive complications. In general, we favor with- There were no infectious or wound healing com- holding immunosuppressive medications for plications in either group in this short follow-up. 4Ð7 days preoperatively and 2 weeks postopera- The results of this study suggest that tocilizumab tively, unless the patient has foot/ankle surgery, 218 L.L. Schroeder and M.C.M. Wasko in which case we would hold these medications history and physical exam to evaluate for extra- for at least 4 weeks postoperatively. Nonsteroidal articular symptoms of RA that may increase peri- anti-infl ammatory drugs are resumed as soon as operative risk, such as occult coronary disease, possible after surgery. cervical spine, TMJ, and cricoarytenoid disease, Most patients will not experience a signifi cant with additional testing and treatment in response to fl are with a 3-week “holiday” from immunosup- abnormal fi ndings. Multidisciplinary involvement pressive drugs, particularly if their NSAID has with physical therapy, occupational therapy, and been restarted postoperatively. However, the foot/ social work before surgery facilitates a smoother ankle patient and those patients remaining off recovery for these patients. Additionally, it is cru- immunosuppressive drugs because of a postop- cial to balance the side effects of antirheumatic erative infection or wound dehiscence are likely medications with the risk of postoperative disease to fl are. The fl are adversely affects quality of life fl are. The odds of a successful surgical outcome for and interferes with rehabilitation; therefore, con- patients with RA are increased with coordinated trol of symptoms is imperative. effort, communication, and planning by the pri- There are two basic approaches to management mary care physician, rheumatologist, and surgeon. of the postoperative fl are. One is to reinstitute an immunosuppressive drug that is acceptable to the surgeon and reasonable in the context of the postop- References erative scenario, provided the patient is not infected. Methotrexate, even at a low dose, may serve as an 1. Spector T. Rheumatoid arthritis. Epidemiology of rheu- effective anti-infl ammatory agent and, in the opin- matic disease. Rheum Dis Clin North Am. 1990;16:513Ð37. ion of the authors, is less risky than adding or adjust- 2. Cotran R, Kumar V, Collins T. Robbins pathologic ing steroids. However, many surgeons are resistant basis of disease. 6th ed. Philadelphia: W.B. Saunders; to this plan, and an intramuscular injection of a cor- 1999. p. 1248Ð51. ticosteroid, selected intra-articular injections, or a 3. Nierman E, Zakrzewski K. Recognition and manage- ment of preoperative risk. Rheum Dis Clin North Am. short course of prednisone with a taper over 1999;25:585Ð622. 2Ð3 weeks may be required. Because biologics are 4. MacKenzie C, Sharrock N. Perioperative medical such potent immunosuppressive agents and carry a considerations with patients with rheumatoid arthritis. signi fi cant risk of infection, these agents are reserved Rheum Dis Clin North Am. 1998;24(1):1Ð17. 5. Fleisher L, Beckman J, Brown K, et al. 2009 ACCF/ for the patient who is healing well, has no evidence AHA focused update on perioperative beta blockade of infection, and is ready to resume a routine immu- incorporated into the ACC/AHA 2007 guidelines on nosuppressive regimen. perioperative cardiovascular evaluation and care for non- Pain control is imperative in the rehabilitating cardiac surgery: a report of the American College of Cardiology Foundation/American Heart Association postoperative RA patient. Analgesic management Task Force on Practice Guidelines. Circulation. without immunosuppressive drugs appropriate for 2009;120:e169. the patient with an active infection. Use of long- 6. Escalante A, Beardmore T. Predicting length of stay acting oral opioids or an analgesic patch will pro- after hip or knee replacement for rheumatoid arthritis. J Rheumatol. 1997;24(1):146Ð52. vide sustained relief. We favor use of longer acting 7. Peters M, Symmons D, McCarey D, et al. EULAR agents in the patient likely to remain off immuno- evidence-based recommendations for cardiovascular suppressive for weeks or months, with short-acting risk management in patients with rheumatoid arthritis pain medications for breakthrough pain. and other forms of infl ammatory arthritis. Ann Rheum Dis. 2010;69:325Ð31. 8. Fleischer L, Beckman J, Brown K, et al. 2009 ACCF/ AHA Focused update on perioperative beta blockage Conclusion incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College Many patients with rheumatoid arthritis undergo of Cardiology Foundation/American Heart Association surgical procedures. The patient’s medical status Task Force on Practice Guidelines. Circulation. should be optimized before surgery with a thorough 2009;120:e169Ð276. 17 Perioperative Management of Patients with Rheumatoid Arthritis 219

9. Yazdanyar A et al. Perioperative all-cause mortality 26. Campbell R, Wou P, Watt I. A continuing role for and cardiovascular events in patients with rheumatoid preoperative cervical spine radiography in rheumatoid arthritis: comparison with unaffected controls and arthritis? Clin Radiol. 1995;50:157Ð9. persons with diabetes mellitus. Arthritis Rheum. 2012 27. Kohjitani A, Miyawaki T, Kasuya K, et al. Anesthetic Epub ahead of print. management for advanced rheumatoid arthritis 10. Lyssy K, Escalante A. Perioperative management of patients with acquired micrognathia undergoing rheumatoid arthritis. Areas of concern for primary temporomandibular joint replacement. J Oral care physicians. Postgrad Med. 1996;99(2):191Ð4. Maxillofac Surg. 2002;60(5):559Ð66. 11. Harris E, Firestein G. Clinical features of rheumatoid 28. Lehmann T, Nef W, Stalder B, et al. Fatal postopera- arthritis. In: Kelly’s textbook of rheumatology. 8th ed. tive airway obstruction in a patient with rheumatoid Maryland Heights: W.B. Saunders; 2008. arthritis. Ann Rheum Dis. 1997;56(9):512Ð3. 12. Reddy D, Trost L, Lee T, et al. Rheumatoid arthritis: 29. Kolman J, Morris I. Cricoarytenoid arthritis: a cause current pharmacologic treatment and anesthetic con- of acute upper airway obstruction in rheumatoid siderations. Middle East J Anesthesiol. 2007;19(2): arthritis. Can J Anaesth. 2002;49(7):729Ð32. 311Ð33. 30. Segebarth P, Limbird T. Perioperative acute upper air- 13. Jain A, Witbreuk M, Ball C, et al. Infl uence of steroids way obstruction secondary to severe rheumatoid and methotrexate on wound complications after elec- arthritis. J Arthroplasty. 2007;22(6):916Ð9. tive rheumatoid hand and wrist surgery. J Hand Surg. 31. Yoshida M, Neo M, Fujibayashi S, et al. Upper-airway 2002;27(3):449Ð55. obstruction after short posterior occipitocervical 14. Shaw M, Mandell B. Perioperative management of fusion in a fl exed position. Spine. 2007;32(8): selected problems in patients with rheumatic diseases. E267Ð70. Rheum Dis Clin North Am. 1999;25(3):623Ð38. 32. Parnell J, Mills J. Awake intubation using fast-track 15. Tanaka N, Ito K, Ishii S, et al. Autologous blood laryngeal mask airway as an alternative to fi beroptic transfusion with recombinant erythropoietin treatment bronchoscopy: a case report. AANA J. 2006;74(6): in anaemic patients with rheumatoid arthritis. Clin 429Ð31. Rheumatol. 1999;18(4):293Ð8. 33. Miyanohara T, Igarashi T, Suzuki H, et al. Aggravation 16. Slappendel R, Weber E, Hemon Y, et al. Patients with of laryngeal rheumatoid arthritis after use of a laryngeal and without rheumatoid arthritis bene fi t equally from mask airway. J Clin Rheumatol. 2006;12(3): 142Ð4. preoperative epoetin-alpha treatment. Acta Orthop. 34. Papaconstantinou D, Georgopoulos G, Kalantzis G, 2006;77(4):677Ð83. et al. Peripheral ulcerative keratitis after trabeculec- 17. Perez V, Azar D, Foster C. Sterile corneal melting and tomy in a patient with rheumatoid arthritis. Cornea. necrotizing scleritis after cataract surgery in patients 2009;28(1):111Ð3. with rheumatoid arthritis and collagen vascular dis- 35. Munro R, Duncan M, Capell H, et al. Unusual ease. Semin Ophthalmol. 2002;17:124Ð30. complications of cervical spine surgery for cervical 18. Howe C, Gardner G, Kadel N. Perioperative medica- myelopathy in rheumatoid arthritis. Br J Rheumatol. tion management for the patient with rheumatoid 1996;35:682Ð5. arthritis. J Am Acad Orthop Surg. 2006;14(9):544Ð51. 36. Nannapaneni R, Behari S, Todd N. Surgical outcome 19. Luessenhop C, Higgins LD, Brause B, Ranawat C. in rheumatoid Ranawat class IIIb myelopathy. Multiple prosthetic infections after total joint arthroplasty: Neurosurgery. 2005;56(4):706Ð15. risk factor analysis. J Arthroplasty. 1996;11:862Ð8. 37. Ronkainen A, Niskanen M, Auvinen A, et al. Cervical 20. Litaker D. Preoperative evaluation of a woman with spine surgery in patients with rheumatoid arthritis: rheumatoid arthritis. Cleveland Clin J Med. long-term mortality and its determinants. J Rheum. 1997;64(3): 133Ð5. 2006;33(3):517Ð22. 21. Matti M, Sharrock N. Anesthesia on the rheumatoid 38. Cook C, Hawkins R, Aldridge J. Comparison of peri- patient. Rheum Dis Clin North Am. 1998;24(1): operative complications in patients with and without 19Ð34. rheumatoid arthritis who receive total elbow replace- 22. Takenaka I, Urakami Y, Aoyama K, et al. Severe sub- ment. J Shoulder Elbow Surg. 2009;18(1):21Ð6. luxation in the sniffi ng position in a rheumatoid 39. Talwalkar S, Givissis P, Trail I, et al. Survivorship of patient with anterior atlantoaxial subluxation. the Souter-Strathclyde elbow replacement in the Anesthesiology. 2004;101:1235Ð7. young infl ammatory arthritis elbow. J Bone Joint 23. Lisowkska B, Rutkowska-Sak L, Maldyk P, et al. Surg. 2005;87(7):946Ð9. Anaesthesiological problems in patients with rheuma- 40. Zwartele R, Peters A, Brouwers J, et al. Long-term toid arthritis undergoing orthopaedic surgeries. Clin results of cementless primary total hip arthroplasty Rheumatol. 2008;27(5):553Ð6. with a threaded cup and a tapered, rectangular tita- 24. Kwek T, Lew T, Thoo F. The role of preoperative cer- nium stem in rheumatoid arthritis and osteoarthritis. vical spine X-rays in rheumatoid arthritis. Anaesth Int Orthop. 2008;32(5):581Ð7. Intensive Care. 1998;26(6):636Ð41. 41. Zwartele R, Olsthoorn P, Poll R, et al. Primary total 25. Arawwawala D, Morgan P. Preoperative cervical hip arthroplasty with a fl attened press- fi t acetabular spine X-rays for patients with rheumatoid arthritis. Br component in osteoarthritis and infl ammatory arthri- J Hosp Med. 2007;68(1):56. tis: a prospective study on 416 hips with 6Ð10 years 220 L.L. Schroeder and M.C.M. Wasko

follow-up. Arch Orthop Trauma Surg. 2008;128(12): 48. Laiho K, Maenpaa H, Kautiainen H, et al. Rise in 1379Ð86. serum C reactive protein after hip and knee arthro- 42. Grogan T, Dorey F, Rollins J, et al. Deep sepsis fol- plasties in patients with rheumatoid arthritis. Ann lowing total knee arthroplasty. J Bone Joint Surg. Rheum Dis. 2001;60(3):275Ð7. 1986;68(2):226Ð34. 49. Hirao M, Hashimoto J, Tsuboi H, et al. Laboratory 43. Bongartz T, Halligan C, Osmon D, et al. Incidence and febrile features after joint surgery in patients with and risk factors of prosthetic joint infection after total rheumatoid arthritis treated with tocilizumab. Ann hip or knee replacement in patients with rheumatoid Rheum Dis. 2009;68:654Ð7. arthritis. Arthritis Rheum. 2008;59(12):1713Ð20. 50. Merli G. Deep vein thrombosis and pulmonary embo- 44. Yoon H, Han C, Yang I. Comparison of simultaneous lism prophylaxis in joint replacement surgery. Rheum bilateral and staged bilateral total knee arthroplasty in Dis Clin North Am. 1999;25(3):639Ð56. terms of perioperative complications. J Arthroplasty. 51. Nakao S, Takata S, Uemura H. Early ambulation after 2010;25(2):179Ð85. total knee arthroplasty prevents patients with osteoar- 45. Nassar J, Cracchiolo A. Complications in surgery of thritis and rheumatoid arthritis from developing the foot and ankle in patients with rheumatoid arthri- postoperative higher levels of D-dimer. J Med Invest. tis. Clin Orthop. 2001;391:140Ð52. 2010;57:146Ð51. 46. Bibbo C. Wound healing complications and infection 52. Nurmohamed M, Lems W, Dijkmans B. Risk of post- following surgery for rheumatoid arthritis. Foot Ankle discharge venous thromboembolism in patients with Clin. 2007;12(3):509Ð24. rheumatoid arthritis undergoing knee or hip arthro- 47. Del Rincón I, Haas R, Pogosian S, et al. Lower limb plasty. Is prolonged thromboprophylaxis warranted arterial incompressibility and obstruction in rheuma- or dangerous? Ann Rheum Dis. 1999;58(7): toid arthritis. Ann Rheum Dis. 2005;64:425Ð32. 392Ð5. Perioperative Management of the Patient with Takayasu’s 1 8 Arteritis

Patrick Liang

especially if it is the presenting symptom [ 2 ] . Introduction Patients may not have any constitutional features at the time that they experience ischemic Takayasu’s arteritis (TA) is an idiopathic granu- symptoms. lomatous in fl ammatory disease of large and In fl ammatory components of TA are treated medium vessels. It may involve the aorta, its main with systemic corticosteroid and other immuno- branches, and the pulmonary arteries, resulting in suppressive agents with the aim of reversing stenosis, occlusion, or aneurysm formation of existing in fl ammatory lesions and preventing diseased vessels. People of Asian descent are their occurrence. Remission can be induced in proportionally more affected although TA occurs approximately 80% of patients [3– 5 ] . In a minor- in patients of all ethnicity. The onset of disease ity of patients [ 1, 3] , TA follows a one-time, peaks during the second and third decade of life; monophasic course. In the remaining majority, however, children and patients over 40 years of however, a progressive or relapsing/remitting age may also be affected [1 ] . outcome is to be expected. At diagnosis, most Patients may present with nonspecifi c symp- patients have well-established vascular lesions toms such arthralgias, myalgias, fever, and weight [ 1 ] . These vessel injuries are frequently not loss. Stenotic lesions develop in over 95% of reversible by immunosuppressive drugs [6 ] . patients; hence, the majority of symptoms refl ect Furthermore, medical treatment may not succeed ischemia to organs supplied by diseased vessels in preventing the emergence of new lesions [ 1 ] , [1 ] . Clinical features include transient ischemic and stenotic lesions may progress due to fi brotic attacks or strokes, visual disturbance, limb clau- remodeling or persistent in fl ammation. Aneurysm dication, angina, renovascular hypertension, formation can be the consequence of fragilization abdominal pain caused by mesenteric ischemia, caused by the panarteritic process. or aneurysm. Involvement of the aortic root may Thus, in the event of unsatisfactory outcomes lead to aortic regurgitation. Pulmonary artery of medical treatments, revascularization interven- involvement may cause respiratory distress tions may become necessary. In preparation for and can be confused with pulmonary embolism, these procedures, several issues need to be addressed in order to optimize both the patient’s and the procedure’s outcome. They include de fi ning the indications for intervention, choos-  P. Liang , M.D ( ) ing the type of revascularization procedure, Rheumatology Division , University of Sherbrooke, 3001 12th Avenue N , Sherbrooke , QC J1H 5N4 , Canada timing the procedure during a period of remis- e-mail: [email protected] sion (low disease activity), measuring disease

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 221 DOI 10.1007/978-1-4614-2203-7_18, © Springer Science+Business Media, LLC 2013 222 P. Liang activity and extension, immunosuppressive drug brain by way of the circle of Willis, or by management during the perioperative period, collateral vessels that have developed over the role for anticoagulation therapy, and other time. On the other hand, incapacitating symp- concomitant therapy. A discussion of each of toms might occur as a result of extensive these aspects follows. disease or because of subclavian steal. Such lesions could put patients at risk of severe neurologic events should further impairment Indications for Revascularization of brain blood supply occur. Some authors Interventions recommend reserving surgery for symptom- atic patients [ 9 ] , while others advocate for Revascularization interventions may be required prophylactic revascularization of cervicocra- for patients with: nial vessels for patients with two or more than 1. Severely stenosed vessels responsible for isch- two involved vessels [ 10 ] . A case-by-case emic symptoms, for example, upper or lower evaluation does seem prudent, and in this extremity claudication or pain, and central ner- regard, requirement for revascularization vous system manifestations. Mesenteric isch- may be aided by assessing for adequate cere- emia may require revascularization, but is bral blood fl ow by nuclear medicine exams seldom performed due to the extensive net- [ 11, 12 ] or transcranial Doppler [13 ] . work of collateral blood vessels [ 7 ] . Although 2. Severe hypertension not amenable to adequate established stenoses may not be improved by control by medical therapy. This is most medical therapy, less advanced lesions can be. frequently caused by stenosis of one or both Consequently, immunosuppressive agents renal arteries, or by suprarenal aortic stenosis. should be prescribed prior to revascularization, It is worth emphasizing that given the high unless critical ischemia or impending compli- prevalence of subclavian artery involvement cations are present. Subsequent proliferation in TA, hypertension may be underrecognized of collateral blood vessels may compensate for if blood pressure assessment is limited to the diseased vessels, to the point that even in measurements in the upper extremities. the event of a severely stenosed or occluded Therefore, blood pressure measurements subclavian or axillary artery, for example, should be taken from all four limbs; a search ischemic symptoms to the upper limb may not for evidence of hypertension should also be present. Unlike with critical peripheral ath- include fundoscopic examination, EKG, and erosclerosis, thrombosis and embolic events echocardiogram at the time of diagnosis, dur- are less common in TA so that acute ischemia ing follow-up, and in preparation for revascu- and gangrenous changes to extremities seldom larization. Catheterization is routinely done occur. Hence, prophylactic revascularization as part of the prerevascularization work-up; it interventions are usually not required. may also be performed at diagnosis. In these One possible exception to this recommenda- circumstances, and whenever central hyper- tion concerns diseased vessels that irrigate the tension is suspected, central blood pressure brain. The brain is supplied by four vessels: readings should be obtained. two vertebral arteries, which originate from 3. Severe aortic regurgitation, usually as a result the subclavian arteries, and two carotids. At of aortitis. the base of the brain, these arteries join to 4. Congestive heart failure, which may be the form the circle of Willis. In TA, vessels that consequence of hypertension, aortic coarcta- originate from the aortic arch are involved in tion, or aortic regurgitation. the majority of patients [ 1, 4, 8 ] . Patients may 5. Aneurysms. These develop in 27–40% of have multiple stenosed or occluded cervico- patients [1, 4] . They most typically develop in cranial vessels yet have little or no symptoms, the thoracic or abdominal aorta, though other because of maintained blood supply to the vessels such as the innominate, carotids, and 18 Perioperative Management of the Patient with Takayasu’s Arteritis 223

celiac artery may be involved. Although the better patency rates, compared to bare metal stents incidence of rupture is low [ 14 ] , aneurysms [ 20 ] . Interesting results have recently been reported should be monitored longitudinally to screen for coronary artery stenoses with the use of drug- for enlargement, and in the absence of evi- eluting stents, although the true value of these dence specifi c to TA, recommendations for devices awaits further con fi rmation [21, 22 ] . repair should follow those that exist for ath- Publications that report on long-term out- erosclerotic aneurysms. comes suggest that bypass graft procedures pro- vide the best vessel patency rates [ 1, 7, 15, 16 ] . Postoperative and long-term mortality and mor- Choice of Intervention bidity are consistently reported as low. Several principles may be suggested in attempt Revascularization interventions for stenoses or to achieve lasting success from surgery. (a) Bypass occlusions can be done by percutaneous endovas- grafts for involved cervicobrachial vessels should cular procedures or by open surgical techniques originate from the ascending aorta, inasmuch as such as bypass grafts. Patch angioplasty and this segment of the aorta essentially never becomes endarterectomy do not consistently provide good stenotic or occluded [ 1 ] . On the other hand, the results and are thus best avoided in the majority subclavian and carotid vessels are so frequently of cases. involved by TA that they should be avoided as Mixed results have been reported with percu- potential in fl ow graft sites. It is important to be taneous transluminal angioplasty (PTA) with or reminded that although medical management of without concomitant stenting procedures [ 3, 15, this disease may induce remission in the majority 16 ] . Features of TA that may explain poor out- of patients, relapses are frequent [ 3 ] and new comes of endovascular procedures include: lesions may still occur despite treatment. Thus, • The length of stenotic or occlusive lesions: arch vessels may not be suitable infl ow sites for these typically extend for several centimeters bypass grafts [ 14 ] . (b) When possible, grafts should and may thus be less amenable to satisfactory extend to uninvolved arterial segments [ 9, 23 ] . (c) dilatation. Best outcomes can be expected when surgery is • Fibrosis: in TA, the infl ammatory process usu- performed during a period of inactive disease [24– ally extends through all layers of the vessel 26] . In this regard, Fields and colleagues reported wall, eventually leading to the replacement of their experience with 60 operations involving 42 muscle and adventitial layers by noncompli- patients. They subdivided patients into four catego- ant, fi brotic tissue. ries according to whether they had (1) inactive dis- • In fl ammation: proceeding with revasculariza- ease and without corticosteroid treatment, (2) tion in a segment with ongoing disease activ- inactive disease but taking steroids, (3) active dis- ity may exacerbate the in fl ammatory process. ease treated with steroids, and (4) active disease but Although several authors have had disappoint- no long-term steroid treatment. Interestingly, free- ing results, others have met with good outcomes, dom from surgical revision at 10 years was 100%, with vessel patency rates that are comparable to 81%, 57%, and 33% in groups 1, 2, 3, and 4, respec- those obtained with bypass grafts [17– 19 ] , espe- tively. Similarly, a group from Turkey described cially for short, focal, nonostial, and nonocclusive their experience in 53 patients who underwent 69 lesions. Thus, for such lesions, PTA could be a rea- vascular interventions for stenotic lesions. Patients sonable alternative to open surgical procedures. with active disease at the time of intervention were Follow-up time is on average shorter, however, more than twice as likely as those in remission to seldom longer than a few years. The role of stents suffer from vessel restenosis [ 24 ] . An important remains unsettled, as long-term outcomes with caveat to the above comments, however, is that the large case series are lacking. Similar to the experi- cited studies used various methods of activity ence with PTA, mixed results have been published. assessment with some relying solely on erythrocyte The use of stent grafts may be associated with sedimentation rate (ESR) or C-reactive protein 224 P. Liang

(CRP) as a measure of in fl ammation. These markers volunteers and patients with active disease [28 ] . have been found to correlate poorly with disease Encouraging results using matrix metalloprotei- activity [1 ] . Thus, true disease activity may not have nase (MMP) 2, 3, and 9 levels have been pub- been accurately assessed. Regardless of disease activ- lished and deserve further inquiry [29 ] . ity, some patients with severe manifestations will not Angiography has traditionally been the imaging be able to have their vascular intervention delayed. In modality of choice to evaluate for TA activity. It such circumstances, visualization of blood vessels at provides excellent image resolution of dilated or the time of surgery may enable the surgeon to select stenosed vessels and as such is the preferred an uninvolved arterial segment for graft anastomosis method of assessment to plan for revasculariza- with excellent long-term outcomes [15 ] . tion. Catheterization also enables the measurement of central blood pressure and endovascular revas- cularization techniques. However, it is invasive Determining Disease Activity and requires the utilization of iodinated contrast dye and high doses of radiation. In addition, it does Timing revascularization procedures to a period not allow proper assessment of blood vessel walls, of disease quiescence is thus recommended for where the initial prestenosis infl ammatory changes optimal outcomes [ 27 ] . De fi ning disease activity, take place. For these reasons, angiography is not however, is challenging, as tissue specimens of ideally suited for evaluation of TA activity and diseased vessels are usually not available prior to extent with routine longitudinal follow-up. surgery. In an attempt to palliate for this short- Publications that describe experience with other coming, various strategies have been proposed. imaging modalities, including ultrasonography, Guidelines from the National Institutes of Health CT scanning and CT angiography, magnetic reso- require the presence of new or worsening of two nance imaging and MR angiography, and positron of the following features in order to decide on the emission tomography (PET), suggest they may presence of unequivocal active disease [1 ] : have a role in disease activity assessment. • Systemic features such as fever, arthralgias, CT angiography and MRI/MR angiography and myalgias tests have the ability to detect luminal anomalies in • Features that relate to worsening of vessel large vessels with a sensitivity that approaches that involvement: claudication, diminished pulse, of standard angiography [30– 34 ] . They allow non- bruit, asymmetric blood pressure, and vascu- invasive evaluation of the entire aorta, proximal lar pain branch vessels, and pulmonary circulation within • Elevated erythrocyte sedimentation rate the same imaging session; furthermore, vessel wall • Typical angiographic features (new or wors- anomalies can be visualized as thickening and/or ening fi ndings) enhancement following contrast injection. Implicit of this system is the recognition of the Ultrasonography has been found to be a sensitive importance of combining clinical information method of evaluating the carotid, axillary, brachial, with imaging fi ndings in order to properly evalu- and femoral arteries [35 ] . Evaluation of the subcla- ate for disease activity. It is, however, not as reli- vian arteries, the aorta, and abdominal branch ves- able as one would hope, as approximately 45% of sels is, however, less reliable. All these imaging patients thought to be in remission have evidence modalities can evaluate blood vessel wall and may of active vasculitis on specimens obtained during thus detect active disease prior to the occurrence of surgery [1, 7] . More than 60% of patients thought irreversible stenosis or aneurysm formation. to be in remission may, nevertheless, go on to Reversibility of vessel wall anomalies has been develop new vessel lesions, by angiographic reported following treatment with immunosuppres- assessment. sive drugs [33, 36 ] . None of these techniques, how- Several serological markers besides CRP and ever, have consistently showed by itself a good ESR have been examined and have not proven correlation with disease activity. Tso and colleagues of value to reliably distinguish between healthy reported their experience with MR in 24 patients 18 Perioperative Management of the Patient with Takayasu’s Arteritis 225 with TA. MR revealed vessel wall edema in 94% of asymmetry in pulse or blood pressure, or patients with unequivocally active disease (by NIH bruits, etc.) is compatible with active disease criteria listed above). Conversely, vessel wall but should ideally be corroborated by imaging edema was also demonstrated in 56% of patients features; conversely, imaging fi ndings showing thought to be in clinical remission and did not pre- new luminal changes and vessel wall anoma- dict new anatomic changes on follow-up studies. lies are highly suggestive of active disease, Furthermore, three out of ten patients with a posi- and thus, consideration should be given to tive MR who later had surgical revascularization treat such patients with immunosuppresants. did not have anatomopathological evidence of dis- However, these changes could also represent ease activity [37 ] . chronic fi brotic disease. Once again, correla- Fluorodexyglucose (18FDG) is a radionuclide tion with other clinical or laboratory features analogous to glucose that is taken up in tissues with suggestive of disease activity will comfort the increased metabolism. In TA, PET scanning with clinician’s opinion and strengthen the thera- 18FDG (18FDG-PET) has been reported as useful peutic decision. to determine areas of active disease and may there- • Isolated vessel wall anomalies such as thick- fore also be useful to de fi ne its extension [38– 40 ] . ening, edema, or enhancement after contrast Its use is limited to evaluation of the aorta and injection in the absence of luminal anomalies proximal branch vessels, however. Some investiga- or other features of active disease may or may tors have found 18FDG-PET useful for monitoring not represent active disease [37 ] . If of recent response to treatment (see above) although others onset, the possibility of active disease should have not [ 41 ] . PET does not provide good spatial be entertained. In such a case, I would argue resolution. Its performance can be improved by that a reasonable option could be to treat with coregistering fi ndings with those of a simultane- immunosuppressants especially if the anoma- ously performed CT scan (PET/CT). lies are located in the area of intended revas- Thus, noninvasive imaging modalities have cularization, provided that the patient’s become essential means of evaluation of patients condition allows the delay. Control imaging with TA, as they have many advantages over con- several months later to assess for reversibility ventional angiography, in particular their ability to could then follow. In the event of persistent detect vessel wall anomalies before the occurrence vessel wall anomalies without evidence of of luminal changes such as stenosis or dilatation. In progression, I would then favor the hypothesis some circumstances, results correlate with disease that the anomalies on imaging represent pro- activity although their true effectiveness for that cesses other than active infl ammation, such as purpose awaits further study [ 42 ] . Characteristics remodeling, fi brosis, and repair process. of each are summarized in Table 18.1 . • The optimal use or combination of use of the In the absence of solid guidelines, the follow- various imaging modalities to assess for ing thoughts may be of use when assessing for disease activity remains to be determined. disease activity: Computed tomography/CTA and MRI/MRA • As no single marker can on its own reliably pre- stand out as the modalities of choice for dict disease activity, a combination of various assessing disease extension and may also be modalities that take into consideration clinical of use in defi ning disease activity. 18FDG- characteristics, biochemical markers of PET also appears helpful for these indica- infl ammation, and noninvasive imaging proce- tions, but as it does not provide adequate dures such as MRI, CT, or PET is needed. In this anatomical defi nition, it would seem best to gray area, clinical judgment is essential, and one correlate results obtained with this imaging must accept that despite our best effort, certainty technique with those of a simultaneously done about disease status may not be possible. CT (PET/CT) or recently performed MRI. • The appearance of new clinical fi ndings sug- An algorithm for disease activity assessment gestive of vascular involvement (claudication, is proposed in Fig. 18.1 . 226 P. Liang PET–CT May provide the best measure May provide of disease activity Enables imaging of vessel Enables imaging of vessel anomalies wall Uptake intensity higher than Uptake in atherosclerosis (useful for the two differentiating of conditions), distribution than in different uptake atherosclerosis, smooth and linear lesions, compared to of atheroscle- patchy uptakes rosis; Luminal features similar to angiography (with CT) High-dose radiation, cost, lack of availability Best resolution for carotid, distal subclavian, axillary, and brachial artery imaging Enables imaging of vessel Enables imaging of vessel anomalies wall Edema, thickening, stenoses, Edema, thickening, wall occlusions, vessel elasticity Operator dependent, cannot aorta, or abdominal evaluate vessels Diagnostic sensitivity comparable to angiography Enables imaging of vessel Enables imaging of vessel anomalies; visualiza- wall tion of pulmonary circulation Vessel wall thickening and thickening wall Vessel edema, postcontrast enhancement; luminal features similar to angiography Poor visulation of calci fi cations; may stenoses overestimate especially at branch points Diagnostic sensitivity comparable to angiography Enables imaging of vessel Enables imaging of vessel anomalies; visualiza- wall tion of pulmonary circulation Vessel wall thickening, thickening, wall Vessel mural enhancement contrast, low following attenuation ring on delayed of active images: suggestive disease; calci fi cations, high attenuation on precontrast images, and slight or no enhancement postcontrast: of inactive suggestive disease; luminal features similar to angiography Iodinated contrast, high dose radiation; limited to aorta and proximal branch vessels Angiography CT/CT angiography MRI/MR angiography Ultrasonography Best image resolution, preferred method of in planning for evaluation procedures revascularization Enables central pressure measurement; permits revasculariza- endovascular tion procedures Vessel narrowing, irregulari- narrowing, Vessel ties, occlusion, dilatation, aneurysm Invasive, iodinated contrast, Invasive, high dose radiation

Characteristics of imaging modalities for Takayasu’s arteritis arteritis Characteristics of imaging modalities for Takayasu’s

Table 18.1 Overall Overall performance Strengths Expected fi ndings Limitations 18 Perioperative Management of the Patient with Takayasu’s Arteritis 227

Asymptomatic New onset or worsening New onset or worsening patient systemic symptoms OR systemic symptoms AND vascular symptoms vascular symptoms otherwise unexplained

CT / CT angiography or MR / MR angiography or PET-CT

+ - - + + -

New lesion(s) / Persistent/unchanged progression of findings from prior existing lesions imaging exam

Disease could be Consider that Consider Disease could be active; consider disease may not be disease Active disease; active; consider Rx treatment active inactive Rx treatment Rx treatment

Reassess Reassess several months several months later later Proceed to revascularization

Fig. 18.1 Proposed algorithm for disease activity assessment in Takayasu’s arteritis

Disease Extension Medications

General management of steroids and other In preparing for revascularization and periopera- immunosuppressants is discussed elsewhere in this tive monitoring, proper identifi cation of disease volume. Some remarks about corticosteroid therapy distribution is essential. For example, the knowl- should, nevertheless, be made. Best outcomes of edge that cervicocranial vessels are stenosed or revascularization procedures are achieved when occluded in a given patient not necessarily under- these are performed during a period of low going revascularization of these vessels will, nev- disease activity or remission (see above). In a ertheless, serve as a reminder of the importance majority of patients, interventions can be done on of maintaining hemodynamic stability through- a nonurgent basis. Thus, if in an active phase, TA out the procedure. Likewise, proper blood pres- should be treated with steroids and other immuno- sure monitoring will be compromised if measured suppressants if required, to achieve a state of low from a limb supplied by a vessel with a hemody- disease activity. These may then be tapered to the namically signi fi cant stenosis. Hence, imaging of lowest possible dose prior to revascularization. the aortic arch vessels and of the aorta down to Patients with active disease at the time of revascu- and including the iliac arteries should be per- larization will bene fi t from treatment with corti- formed for proper planning of the revasculariza- costeroids and other immunosuppressive agents, tion intervention. as reported by Park et al. [ 43 ] . This study looked 228 P. Liang at patients with newly diagnosed TA who under- patency has been demonstrated in atherosclerosis went endovascular or surgical revascularization trials in patients receiving antiplatelet agents and who had not previously received immuno- compared to patients without [ 49 ] ; thus, given the suppressive therapy. In this set of patients with possibility that TA is a prothrombotic condition, presumed active disease, best outcomes in terms this author feels strongly about starting aspirin in of vessel patency were achieved in those for the postoperative period for patient not already whom immunosuppressive drugs were started in treated antiplatelets prior to surgery. the perioperative period. The presence of steroids and immunosuppres- sive drugs at the time of surgery holds the poten- tial for postoperative adverse events such as Cardiac Assessment delayed wound healing and infectious complica- tions. Thus, for the patient not taking immuno- When in need for a revascularization procedure, suppressive agents, when uncertain about disease many patients with TA are at an age when the activity status prior to revascularization, a rea- prevalence of coronary heart disease (CHD) sonable option would be to wait for the anatomo- is expected to be low. However, many have pathological report (if tissue sample is available) prevalent cardiovascular disease risk factors [48 ] before deciding on the need for corticosteroid in addition to other nontraditional risk factors therapy. However, it should be stressed that good such as chronic infl ammation and long-term ste- surgical outcomes can be achieved in patients roid treatment [ 50, 51 ] . Plus, coronary artery under steroid treatment at the time of interven- involvement has been shown to occur in 10–30% tion and that steroid use in itself does not corre- of patients with TA [52, 53 ] . late with increased risk of revision [25 ] . Similarly, Hence, these young patients could be at risk infections and delays in wound healing appear to for cardiac events during the perioperative period, be few, despite ongoing steroid treatment [ 6 ] . and screening for CHD should be done, follow- ing the American College of Cardiology/ American Heart Association 2007 guidelines on Antithrombotic Therapy perioperative cardiovascular evaluation for non- cardiac surgery [ 54 ] . In the case of major vascular As a chronic in fl ammatory condition, TA could be surgery, these mention that: associated with an increased risk of thrombotic 1. Patients with active cardiac disease such as events. Flow-obstructing thrombi have been unstable angina, acute myocardial infarction described in case reports and imaging studies [44– in the last 30 days with persistent signs of 46 ] . Hypercoagulability has also been reported in ischemia, uncontrolled congestive heart fail- TA [ 47 ] . In a recently published retrospective study, ure, signifi cant arrhythmias, or severe valvular de Souza and colleagues report that TA patients disease should have their condition controlled treated with antiplatelet therapy, mostly aspirin, prior to surgery. Cardiac revascularization suffered less acute ischemic events compared to should be performed only if already indicated those who did not take aspirin [ 48 ] . Interestingly, for reasons other than vascular surgery. over 90% of patients had at least one risk factor for 2. For patients with good functional capacity cardiovascular disease (CVD), and mean age at the ( ³ 4 Mets), surgery can proceed. time of ischemic events was approximately 40. 3. For patients with poor functional capacity, Aspirin may thus be a useful adjunct to corticos- risk factors according to the revised Lee index teroid and other immunosuppressive drugs in TA. should be evaluated: With the consent of the surgeon, patients treated (a) High-risk surgery with aspirin prior to bypass procedures can (b) Prevalent ischemic heart disease usually safely undergo the operation without (c) Congestive heart failure necessity for stopping the drug. Improved graft (d) Cerebrovascular disease 18 Perioperative Management of the Patient with Takayasu’s Arteritis 229

(e) Diabetes mellitus fl ow through narrowed cervical vessels could (f ) Renal insuf fi ciency (creatinine levels > 177 lead to a stroke, for example. Conversely, hyper- umol/L; 2 mg/dl) tensive fl ares may occur during the postoperative Patients without risk factors can proceed to period of patients undergoing cervical vessel surgery. Patients with 1–2 risk factors should revascularization, due to altered baroreceptor consider starting beta blockers [ 55 ] . Patients mechanisms [59 ] . with ³ 3 risk factors should start beta blocker therapy aiming at a heart rate of 55–65/min and consider noninvasive evaluation such as a stress Cerebral Revascularization test or radionuclide scan. According to the results, in Takayasu’s Arteritis the surgeon could choose to reconsider the inva- siveness of the proposed surgical procedure [56 ] . Cerebral edema and hemorrhage (hyperperfu- Also, surgery should be delayed 30 days while sion syndrome): In patients with chronic global medical treatment is optimized and beta blocker cerebral hypoperfusion resulting from multiple treatment is titrated. cervical vessel involvement, revascularization As mentioned above, CHD is relatively frequent procedures expectedly result in an increase in in patients with TA; the Lee criteria may not re fl ect cerebral blood fl ow, to which the brain may not their true risk, as nontraditional risk factors are not be able to respond, due to altered autoregulation taken into account. As such, my threshold for order- ability caused by dysfunction of the carotid ing noninvasive cardiac assessment would be low, sinuses [ 11] . Edema, bleeding, and death may although operative and perioperative mortality rates ensue. In order to prevent the occurrence of this for revascularization interventions in TA patients syndrome, some authors have proposed different are consistently low [7, 14, 15, 27, 57 ] . strategies: (1) evaluating cerebral perfusion prior Echocardiography has many uses as it can screen to revascularization. Patients with severe hypop- for pulmonary artery pressure, aortic root dilatation, erfusion are the most at risk. Assessment can be aortic valve competence, and left ventricular hyper- done with transcranial Doppler or xenon com- trophy (LVH). LVH re fl ects the presence of chronic puted tomography or SPECT scans [ 11 ] ; (2) pro- hypertension, which may be unrecognized in the ceeding to revascularization by stages to help event of bilateral subclavian artery involvement. intracranial vessel progressively accommodate Four limb blood pressures should therefore be mea- to the improved cerebral perfusion, (3) proceed- sured, and central blood pressure should be assessed ing to PTA with or without concomitant stenting. at the time of preoperative angiography. It is thought that the incidence of the hyperperfu- sion syndrome may be diminished with endovas- cular procedures as cerebral blood fl ow may be Other Issues less increased compared to bypass grafts. Long- term outcomes have yet to be reported, however Although anesthesiologic considerations are [ 60 ] ; (4) the use of subarachnoid catheter for beyond the scope of this chapter, it is important monitoring the spinal pressure [ 61] ; and (5) to mention that an essential objective for the using smaller grafts [ 12 ] . anesthesiologist will be to select an anesthetic technique that takes into consideration the main- tenance of blood pressure in the intraoperative Conclusion and postoperative periods [ 58 ] . Epidural analge- sia combined with general anesthesia may be A signi fi cant proportion of TA patients [1, 4 ] useful in maintaining hemodynamic stability. require revascularization interventions during Hypotension is to be avoided, as TA patients fre- long-term follow-up, with good short-term out- quently have critical stenotic lesions. Brain comes being achieved in the majority. Best long- hypoperfusion as a result of diminished blood term outcomes have been reported with surgical 230 P. Liang procedures, and according to many, vascular sur- immunogenetic features in Greece. Clin Exp gery remains the procedure of choice. For best Rheumatol. 2009;27 Suppl 52:S33–9. 5. Park MC, Lee SW, Park YB, et al. Clinical character- outcomes, vessels prone to be involved by TA, istics and outcomes of Takayasu’s arteritis: analysis of such as the subclavian and common carotid arter- 108 patients using standardized criteria for diagnosis, ies, should be avoided as sites of graft origin, activity assessment, and angiographic classifi cation. when technically feasible. Endovascular proce- Scand J Rheumatol. 2005;34:284–92. 6. Weaver FA, Yellin AE, Campen DH. Surgical proce- dures are evolving and despite mixed results may dures in the management of Takayasu’s arteritis. J Vasc be a good alternative to surgery for short, focal, Surg. 1990;12:429–39. and nonostial, nonocclusive stenotic lesions. 7. Lagneau P, Michel JB, Vuong PN. Surgical treatment Improved vessel patency rates and a decrease in of Takayasu’s disease. Ann Surg. 1987;205:157–66. 8. Sato EI, Lima DNS, Esperito SB, et al. Takaysu arteri- the need for reintervention are achieved when tis: treatment and prognosis in a university center in revascularization is performed during a time of Brazil. Int J Cardiol. 2000;75:S163–6. disease quiescence. It is thus of utmost impor- 9. Mwipatayi BP, Jeffery PC, Benin fi eld SJ, et al. tance to adequately screen every patient for the Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg. 2005;75:110–7. presence of active disease while taking into 10. Giordano JM. Surgical management of Takayasu’s consideration the limitations of our means of disease. Cleve Clin J Med. 2002;69(Suppl II):SII 146–8. assessment. Nevertheless, signifi cant advances in 11. Stoodley MA, Thompson RC, Mitchell RS, et al. imaging modalities are now making it easier for Neurosurgical and neuroendovascular management of Takayasu’s arteritis. Neurosurgery. 2000;46: clinicians to reach this goal. Cardiovascular risk 841–52. factors must be taken into account as they are 12. Hosaka A, Miyata T, Momose T, et al. Evaluation of prevalent in TA patients. Physicians should cerebral hypoperfusion by nuclear medicine imaging ensure that blood pressure measurements are in a patient with Takayasu’s arteritis. Ann Vasc Surg. 2005;19:917–20. accurate and otherwise proceed to central pres- 13. Lee YS, Yoon BW, Roh JK. Non pulsatile cerebral sure readings especially when peripheral mea- perfusion in Takayasu’s arteritis. J Neuroimaging. surements are unreliable. 2003;13:169–71. Despite improved comprehension of disease 14. Giordano J, Leavitt RY, Hoffman GS, et al. Experience with surgical treatment of Takayasu’s disease. Surgery. process and better understanding of factors associ- 1991;109:252–8. ated with improved outcomes from revasculariza- 15. Weaver FA, Kumar SR, Yellin AE, et al. Renal revas- tion interventions, TA remains a complex disease; cularization in Takayasu arteritis-induced renal artery thus, optimal management can be achieved only stenosis. J Vasc Surg. 2004;39:749–57. 16. Liang P, Tan-Ong M, Hoffman GS. Takayasu’s arteritis: by close collaboration between the vascular team vascular interventions and outcomes. J Rheumatol. (surgery and medicine), interventional radiolo- 2004;31:102–6. gists, anesthesiologists, rheumatologists, patients 17. Tyagi S, Singh B, Kaul UA, et al. Balloon angioplasty themselves, and all o thers involved in their care. for renovascular hypertension in Takayasu’s arteritis. Am Heart J. 1993;125:1386–93. 18. Tyagi S, Verma PK, Gambhir DS, et al. Early and long- term results of subclavian angioplasty in aortoarteritis (Takayasu disease): comparison with atherosclerosis. References Cardiovasc Intervent Radiol. 1998;21:219–24. 19. Sharma BK, Jain S, Bali HK, et al. A follow-up of 1. Kerr GS, Hallahan CW, Giordano J, et al. Takayasu balloon angioplasty and de novo stenting in Takayasu arteritis. Ann Intern Med. 1994;120:919–29. arteritis. Int J Cardiol. 2000;75:S147–52. 2. Shlomai A, Hershko AY, Gabbay E, Ben-Chetrit E. 20. Qureshi MA, Martin A, Greenberg RK. Endovascular Clinical and radiographic features mimicking pulmo- management of patients with Takayasu arteritis. Sem nary embolism as the fi rst manifestation of Takayasu’s Vasc Surgery. 2011;24:44–52. arteritis. Clin Rheumatol. 2004;23:470–2. 21. Katayama y, Sato H, Kitajima S, et al. Aortitis syn- 3. Maksimowicz-McKinnon K, Clark TM, Hoffman GS. drome with repeated restenoses of a drug eluting stent. Limitations of therapy and a guarded prognosis in an Japan J Thorac Surg. 2009;62:364–8. American cohort of Takayasu arteritis patients. 22. Terasawa A, Kondo K, Ishikawa S. Sirolimus-eluting Arthritis Rheum. 2007;56:1000–9. stent implantation for ostial stenosis of left main coro- 4. Karageorgaki ZT, Bertsias GK, Mavragani CP, nary artery after Bentall operation in aortitis syn- et al. Takayasu arteritis: epidemiological, clinical and drome. J Cardiol. 2010;55:147–50. 18 Perioperative Management of the Patient with Takayasu’s Arteritis 231

23. Rits Y, Oderich GS, Bower TC, et al. Interventions for 41. Arnaud L, Haroche J, Malek Z, Archambaud F, et al. mesenteric vasculitis. J Vasc Surg. 2010;51:392–400. Is 18F- fl uorodeoxyglucose positron emission tomog- 24. Bicakcigil M, Aksu K, Kamali S, et al. Long term out- raphy scanning a reliable way to assess disease activ- come in Takayasu’s arteritis: vascular procedures ity in Takayasu arteritis? Arthritis Rheum. 2009;60: performed in active or untreated patients have a poor 1193–200. outcome. APMIS. 2009;117 Suppl 127:85. 42. Use of magnetic resonance and positron emission 25. Fields CE, Bower TC, Cooper LT, et al. Takayasu’s tomography for assessing disease activity in people arteritis: operative results and in fl uence of disease with large vessel vasculitis (Takayasu’s arteritis) activity. J Vasc Surg. 2006;43:64–71. NCT00744952. 26. Pajari R, Hekali P, Harjola PT. Treatment of Takayasu’s 43. Park MC, Lee SW, Park YB, et al. Post interventional arteritis: an analysis of 29 operated patients. Thorac immunosuppressive treatment and vascular restenosis in Cardiovasc Surg. 1986;34:176–81. Takayasu’s arteritis. Rheumatology. 2006;45: 600–5. 27. Mukhtyar C, Guillevin L, Cid MC, et al. EULAR rec- 44. Hulusi M, Basaran M, Yilmaz AT. Carotid and coro- ommendations for the management of large vessel nary artery occlusion in a patient with Takayasu vasculitis. Ann Rheum Dis. 2009;68:318–23. arteritis. J Card Surg. 2007;22:352–5. 28. Hoffman GS, Ahmed AE. Surrogate markers of dis- 45. Purkayastha S, Jayadevan ER, Kapilamoorthy TR, ease activity in patients with Takayasu arteritis. Int J et al. Suction thrombectomy of thrombotic occlusion Cardiol. 1998;66 Suppl 1:S191–4. of the subclavian artery in a case of Takayasu’s arteri- 29. Matsuyama A, Sakai N, Ishigami M, et al. Matrix tis. Cardiovasc Intervent Radiol. 2006;29:289–93. metalloproteinases as novel disease markers in 46. Sharma S, Taneja K, Gupta AK, Rajani M. Morphologic Takayasu arteritis. Circulation. 2003;108:1469–73. mural changes in the aorta revealed by CT in patients 30. Park JH. Conventional and CT angiographic diagno- with nonspeci fi c aortoarteritis (Takayasu’s arteritis). sis of Takayasu arteritis. Int J Cardiol. 1996;54(Suppl): AJR Am J Roentgenol. 1996;167:1321–5. S165–71. 47. Akazawa H, Ikeda U, Yamamoto K, Kuroda T, et al. 31. Sharma S, Sharma S, Taneja K, et al. Morphologic Hypercoagulable state in patients with Takayasu’s Mural changes in the aorta revealed by CT I patients arteritis. Thromb Haemost. 1996;75:712–6. with nonspeci fi c aortoarteritis (Takayasu’s arteritis). 48. de Souza AWS, Machado NP, Pereira VM, Arraes Am J Roentgenol. 1996;167:1321–5. AED, et al. Antiplatelet therapy for the prevention of 32. Yamada I, Nakagawa T, Himeno Y, Numano F, et al. arterial ischemic events in Takayasu arteritis. Circ J. Takayasu arteritis: evaluation of the thoracic aorta 2010;74:1236–41. with CT angiography. Radiology. 1998;209:103–9. 49. Antiplatelet Trialists’ Collaboration. Collaborative 33. Andrews J, Al-Hahhas A, Pennell DJ. Non invasive overview of randomised trials of antiplatelet therapy imaging in the diagnosis and management of Takayasu’s - II: maintenance of vascular graft or arterial patency arteritis. Ann Rheum Dis. 2004;63:995–1000. by antiplatelet therapy. BMJ. 1994;308:159–68. 34. Desai MY, Stone JH, Foo TK, et al. Delayed contrast- 50. Numano F, Kishi Y, Tanaka A, et al. Atherosclerotic enhanced MRI of the aortic wall in Takayasu’s arteri- Lesions in Takayasu arteritis. Ann N Y Acad Sci. tis: initial experience. Am J Roentgenol. 2005;184: 2000;902:65–76. 1427–31. 51. Filer A, Nicholls D, Corston R, et al. Takayasu arteri- 35. Schmidt WA. Use of imaging studies in the diagnosis tis and atherosclerosis: illustrating the consequences of vasculitis. Curr Rheumatol Rep. 2004;6:203–11. of endothelial damage. J Rheumatol. 2001;28: 36. Aluquin VPR, Albano SA, Chan F, et al. Magnetic 2752–3. resonance imaging in the diagnosis and follow up of 52. Amano J, Suzuki A. Coronary artery involvement in Takayasu’s arteritis in children. Ann Rheum Dis. Takayasu’sarteritis. Collective review and guideline 2002;61:526–9. for surgical treatment. J Thorac Cardiovasc Surg. 37. Tso E, Flamm SD, White RD, et al. Takayasu arteritis; 1991;102:554–60. utility and limitations of magnetic resonance imaging 53. Endo M, Tomizawa Y, Nishida H, et al. Angiographic in diagnosis and treatment. Arthritis Rheum. 2002;46: fi ndings and surgical treatments of coronary artery 1634–42. involvement in Takayasu arteritis. J Thorac Cardiovasc 38. Lavogiez C, Guyéméneur T, Hachulla E, Huglo D, Surg. 2003;125:570–7. et al. 18FDG PET: a new criterion for disease activity 54. Fleisher LA, Beckman JA, Brown KA, et al. ACC/ in Takayasu arteritis. Rev Med Interne. 2006;27: AHA 2007 guidelines on perioperative cardiovascular 478–81. evaluation and care for noncardiac surgery: a report of 39. Webb M, Chambers A, AL-Nahhas A, Mason JC, et al. the American Colleg of Cardiology/American Heart The role of 18FDG PET in characterizing disease Association Task Force on Practive guidelines. J Am activity in Takayau arteritis. Eur J Nucl Med Mol Coll Cardiol. 2007;50:1707–32. Imaging. 2004;31:627–34. 55. Poldermans D, Devereaux PJ. The experts debate: 40. Lee SG, Ryu JS, Kim HO, Oh JS, et al. Evaluation of perioperative beta-blockade for non cardiac surgery – disease activity using F-18 FDG PET-CT in patients with proven safe or not? Cleve Clin J Med. 2009;76 Suppl Takayasu arteritis. Clin Nucl Med. 2009;34: 749–52. 4:S84–92. 232 P. Liang

56. Bauer SM, Cayne NS, Veith FJ. New developments in 59. Mesnaoui AEl, Sedki N, Bouarhroum A, et al. the preoperative evaluation and perioperative manage- Revascularisation cérébrale dans la maladie de ment of coronary artery disease in patients undergo- Takayasu. Ann Cardiol Angeiol. 2007;56:130–6. ing vascular surgery. J Vasc Surg. 2010;51:242–51. 60. Tyagi S, Gupta MD, Singh P, et al. Percutaneous 57. Ogino H, Matsuda H, Minatoya K, et al. Overview of revascularization of sole arch artery for severe cerebral late outcome of medical and surgical treatment for ischemia resulting from Takayasu arteritis. J Vasc Takayasu arteritis. Circulation. 2008;118:2738–47. Interv Radiol. 2008;19:1699–703. 58. Kathirvel S, Chavan S, Arya VK, et al. Anesthetic 61. Gu YQ, Wang ZG. Surgical treatment of cerebral management of patients with Takayasu’s arteritis: a ischaemia caused by cervical arterial lesions due to case series and review. Anesth Analg. 2001;93: Takayasu’s arteritis: preliminary results of 49 cases. 60–5. ANZ J Surg. 2001;71:89–92. Medical Issues in Osteoporotic Hip Fractures 1 9

Christopher M. Whinney

Introduction Timing of Surgery

Osteoporosis affects approximately 10 million The optimal timing for hip fracture repair has Americans and contributes to over 1.5 million been debated extensively in the literature. fractures annually. Annual costs related to osteo- Patients who sustain fractures of the hip often porosis care reach 17–20 billion dollars, most of experience a delay in operative repair greater which is related to acute and postacute care of than 24 h after admission, either due to medical fracture patients, especially hip fractures [ 1 ] . It is “clearance” issues or lack of surgeon availability expected that the Medicare population will dou- or operating room time. Some authors advocate ble by 2030; this population undoubtedly will expeditious (i.e., within 24 h of presentation) come with an increasing incidence of osteoporo- operative repair of fractures, due to reported sis and consequent fractures. In the USA, approx- lower incidence of nonunion of fracture [5 ] and imately 250,000 people suffer hip fractures avascular necrosis of the femoral head [6 ] , annually, with projections of this number dou- improved long-term functional status [ 7 ] , and bling by the year 2040 [ 2 ] . Costs related to hip decreased rates of urinary tract infections [ 8 ] , fractures including post-hospitalization care decubitus formation, pneumonia, and venous exceed $5 billion annually, and this number is thromboembolism [9– 11 ] . projected to triple by 2040 [ 3, 4 ] . With the Earlier studies suggested an increase in mor- fi nancial strain this will put on the already strained tality with delay in operative repair greater than Medicare and Medicaid systems, it is critical for 24–48 h; however, most of these studies were ret- clinicians to attend to the task of reducing the rospective and did not factor in medical delays. prevalence of osteoporosis and the incidence of In fact, some studies (including Zagrodnick et al. costly fragility fractures as well as minimizing [ 12 ] and Kenzora et al. [13 ] ) found a lower mor- complications in the perioperative period during tality with operative delays. hip fracture repair. Patients with hip fractures often have pre- fracture comorbidities such as diabetes, conges- tive heart failure, coronary artery disease, anemia, malnutrition, dehydration, and electrolyte distur- bances. After a low-energy fall and fracture, C. M. Whinney , M.D., F.A.C.P., F.H.M. () common sequelae include dehydration, electro- Department of Hospital Medicine , Cleveland Clinic lyte disturbances, and rhabdomyolysis with renal Foundation , 9500 Euclid Avenue, M2 Annex , Cleveland , OH 44121 , USA failure. These conditions, if not assessed and e-mail: [email protected] treated preoperatively, may lead to perioperative

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 233 DOI 10.1007/978-1-4614-2203-7_19, © Springer Science+Business Media, LLC 2013 234 C.M. Whinney complications such as myocardial ischemia and factors [16 ] . Table 19.1 highlights risk factors infarction, delirium, and nutritional compromise. that contribute to the development of osteoporo- These conditions both increase in-hospital and sis and fractures overall mortality, leading to a delay in weight Other indications for BMD testing [15 ] bearing and rehabilitation [5, 14 ] . A delay in sur- include: gical intervention from 24 to 48 h after admission • Women in the menopausal transition if there is has been advocated by some authors to optimize a speci fi c risk factor associated with increased these medical comorbidities. The largest study to fracture risk such as low body weight, prior date regarding the timing of surgery was done by low-trauma fracture, or high-risk medication Grimes et al. [ 10 ] . They retrospectively evaluated • Adults who have a fracture after age 50 8,383 patients with hip fractures operatively • Adults with a condition (e.g., rheumatoid repaired between 1983 and 1993. A delay in sur- arthritis) or taking a medication (e.g., gluco- gery less than 24 h from admission was associated corticoids in a daily dose ³ 5 mg prednisone or with greater long-term mortality in unadjusted equivalent for ³ 3 months) associated with low analyses as compared with delays of 24–72 h ; bone mass or bone loss however, when adjusted for demographic vari- • Anyone being considered for pharmacologic ables and for severity of underlying medical prob- therapy for osteoporosis lems, no signifi cant association was found. • Anyone being treated for osteoporosis to mon- Mortality at 30 days and postoperative morbidity itor treatment effect measures were similar, although longer time-to- • Anyone not receiving therapy in whom evi- surgery was associated with a higher incidence of dence of bone loss would lead to treatment decubitus ulcers. • Postmenopausal women discontinuing estrogen Given that patients who sustain hip fractures should be considered for bone density testing often are frail elders with multiple comorbidities Medicare covers BMD testing for many indi- as noted above, a delay in surgical intervention viduals age 65 and older, including but not lim- from 24 to 48 h after admission is a reasonable ited to: practice to correct metabolic disturbances, opti- • Estrogen-de fi cient women at clinical risk for mize chronic medical conditions, and minimize osteoporosis the risk of postoperative complications. • Individuals with vertebral abnormalities • Individuals receiving, or planning to receive, long-term glucocorticoid therapy in a daily Testing for Osteoporosis dose ³ 5 mg prednisone or equivalent for ³ 3 months The common fi rst step in assessing patients for • Individuals with primary hyperparathyroidism osteoporosis is to ascertain the presence of clini- • Individuals being monitored to assess the cal risk factors. The National Osteoporosis response or ef fi cacy of an approved osteopo- Foundation (NOF) recommends that all post- rosis drug therapy menopausal women and men age 50 and older Another consideration is the potential for falls. should be evaluated clinically for osteoporosis Risk factors for falls include a prior personal his- risk in order to determine the need for bone min- tory of falling, along with muscle weakness; gait, eral density (BMD) testing [ 15 ] . More recently, balance, and visual de fi cits; and dehydration [17 ] . the United States Preventive Services Task Force Several models exist to help determine frac- (USPSTF) published guidelines that recommend ture risk. The World Health Organization (WHO) all women over age 65 be screened using either 10-year fracture risk model consists of a set of dual energy X-ray absorptiometry (DXA) or risk factors (Table 19.2 ) that have been shown to ultrasound. Women between the ages of 50 and additively increase risk for fracture independent 65 should be screened if they have clinical risk of bone mineral density [18 ] . 19 Medical Issues in Osteoporotic Hip Fractures 235

Table 19.1 Risk factors for the development of osteoporosis Lifestyle factors Low calcium intake Vitamin D insuf fi ciency Excess vitamin A High caffeine intake High salt intake Aluminum (in antacids) Alcohol (3 or more drinks/day) Inadequate physical activity Immobilization Smoking (active or passive) Falling Thinness Genetic factors Cystic fi brosis Homocystinuria Osteogenesis imperfecta Ehlers-Danlos Hypophosphatasia Parental history of hip fracture Gaucher’s disease Idiopathic hypercalciuria Porphyria Glycogen storage diseases Marfan’s syndrome Riley-Day syndrome Hemochromatosis Menkes steely hair syndrome Hypogonadal states Androgen insensitivity Hyperprolactinemia Turner’s and Klinefelter’s syndromes Anorexia nervosa and bulimia Panhypopituitarism Athletic amenorrhea Premature ovarian failure Endocrine disorders Adrenal insuf fi ciency Diabetes mellitus Thyrotoxicosis Cushing’s syndrome Hyperparathyroidism Gastrointestinal disorders Celiac disease In fl ammatory bowel disease Primary biliary cirrhosis Gastric bypass Malabsorption GI surgery Pancreatic disease Hematologic disorders Hemophilia Multiple myeloma Systemic mastocytosis Leukemia and lymphomas Sickle cell disease Thalassemia Rheumatic and autoimmune diseases Ankylosing spondylitis Lupus Rheumatoid arthritis Miscellaneous conditions and diseases Alcoholism Emphysema Muscular dystrophy Amyloidosis End stage renal disease Parenteral nutrition Chronic metabolic acidosis Epilepsy Posttransplant bone disease Congestive heart failure Idiopathic scoliosis Prior fracture as an adult Depression Multiple sclerosis Sarcoidosis Medications Anticoagulants (heparin) Cancer chemotherapeutic drugs Gonadotropin-releasing hormone agonists Anticonvulsants Cyclosporine A and tacrolimus Lithium Aromatase inhibitors Depo-medroxyprogesterone Barbiturates Glucocorticoids (³ 5 mg/day of prednisone or equivalent for ³ 3 month)

The next step in assessing fracture risk is to bone density to the average bone density for determine bone density. The most common means young, healthy persons of the same sex, whereas of doing so involves dual energy X-ray absorpti- a Z-score compares this bone density to the ometry (DXA) scanning at the hip and spine. It is expected bone density for persons of the same measured in grams of mineral (bone) per square age and sex as the patient. The difference between centimeter scanned (g/cm2) and converted into the patient’s score and the norm is expressed in two types of scores. A T-score compares this standard deviations (SD) above or below the 236 C.M. Whinney

Table 19.2 Risk factors included in the WHO fracture onstrate a correlation with fracture risk, and can risk assessment model indicate whether disease states are responding to Current age Rheumatoid arthritis antiresorptive and anabolic drug therapy. They Gender Secondary osteoporosis also may be useful to the clinician to provide A prior osteoporotic Parental history of hip feedback to patients about drug activity and thus fracture (including fracture facilitate compliance and adherence, thus reduc- morphometric vertebral fracture) ing fracture risk [20, 21 ] . Femoral neck BMD Current smoking Low body mass index Alcohol intake (3 or more (kg/m2) drinks/day) Formation Oral glucocorticoids ³ 5 mg/day of prednisone for ³ 3 month (ever) Bone formation is the role of the osteoblast, which produces type I collagen and matrix com- ponents of osteoid and facilitates mineralization. mean, with one SD representing approximately These markers are measured in serum and are 15% of the BMD value in g/cm2. The WHO [ 18 ] osteoblast-secreted enzymes or are by-products has defi ned osteoporosis and osteopenia as of collagen deposition. Alkaline phosphatase is follows: the fi rst marker discovered and is the most widely Normal BMD within one SD of a “young used in practice; however, its speci fi city for bone normal” adult (T-score −1.0 or less) is low, as it is found in cells from the kidney, Osteopenia BMD is between 1 and 2.5 SD liver, intestine, spleen, and placenta. Newer below normal (T-score −1 to −2.5) immunoassays for bone specifi c alkaline phos- Osteoporosis BMD is greater than 2.5 SD below phatase have been developed, although some normal (T-score <−2.5) cross-reactivity still occurs with hepatic alkaline Clinicians should realize that these criteria do phosphatase. not apply to premenopausal women, men under Osteocalcin is a large protein thought to be a the age of 50, and children. hormone infl uencing energy metabolism by mod- Other modalities used for assessment of bone ulating insulin activity. Although it is classically density include peripheral DXA scanning of the known as a marker of bone formation as it is syn- forearm; this modality has similar predictive thesized by osteoblasts, it appears to refl ect both value in women for fracture risk but has not been bone formation and bone resorption as its frag- validated in men. Quantitative CT and ultrasound ments are released into serum during resorption, modalities (especially of the heel) are used as and in most disease states, bone resorption and well; both predict fracture risk in women, but formation are coupled. only ultrasound has been validated for use in Procollagen type I propeptides are cleavage fracture risk assessment in men [19 ] . products from the amino- and carboxy-terminal ends of the procollagen molecule; they are thought to re fl ect amount of newly synthesized Biochemical Markers of Bone collagen [20 ] . Turnover

A variety of assays have been developed that Resorption measure factors related to bone turnover, includ- ing the activities of osteoblasts (bone formation) Bone resorption is the role of the osteoclast, and osteoclasts (bone resorption). No specifi c which initiate bone remodeling and liberate skel- guidelines currently exist that direct the clinical etal calcium to maintain serum calcium concen- use of these markers; however, they have been tration. Markers of resorption can be measured in shown useful in assessing skeletal activity, dem- serum or in urine. 19 Medical Issues in Osteoporotic Hip Fractures 237

Hydroxyproline measurement in urine is the resorption, rather than an increase in bone den- oldest test of bone resorption; it is an amino acid sity. Thus, it makes intuitive sense to utilize ubiquitous to all forms of collagen. However, it is markers of bone resorption to document antire- nonspeci fi c as a signi fi cant amount can be mani- sorptive agent activity. As bone density may not fest due to skin collagen turnover and from change much in the fi rst year, these markers dietary collagen and gelatin. appear to have substantial clinical utility in docu- Urinary pyridinoline and deoxypyridinoline menting ef fi cacy of therapy. Bone resorption have more specifi city for bone resorption. They markers decrease by 30–70% with 3–6 months of are amino acids that cross-link and strengthen col- antiresorptive agent use [19, 25 ] . Patients using lagen fi brils in the extracellular matrix. The two alendronate who had a greater than 30% reduc- well-studied markers of this class are the amino- tion in bone alkaline phosphatase had the greatest terminal telopeptide of collagen type I (NTx) and risk reduction in both vertebral and nonvertebral the carboxy-terminal telopeptide (CTx). Other fractures [26 ] . markers include serum tartrate-resistant acid phosphatase (TRAP-5b) and cathepsin K, recep- tor activator of nuclear factor kappa (RANK) Timing for Antiresorptive or Anabolic ligand, although none of these have clear utility in Therapy in the Perioperative Period clinical practice at the present time [ 19, 20 ] . Compliance with treatment guidelines for osteo- porosis, including calcium, vitamin D, and anti- Limitations of Bone Turnover Assays resorptive agents, can reduce subsequent fracture risk by up to 50%; however, rates of treatment Typically markers of bone turnover are highest in after sustaining a hip fracture are quite low. the early morning and lowest in the late afternoon Hospitalization for hip fracture is an ideal win- and evening and can vary around 18–19% in urine dow of opportunity to identify patients at risk for [ 21 ] ; serum markers demonstrate a similar diurnal subsequent fracture and initiate appropriate treat- pattern but less in degree, with the exception of ment. Jennings et al. [ 28 ] retrospectively evalu- serum CTx which can vary up to 60% throughout ated over 50,000 patients over age 65 who the day. Serum measurements should be done in underwent osteoporotic hip fracture repair for the morning after overnight fasting [ 19, 22, 23 ] . rates of initiation of medical osteoporotic thera- pies. Only 2% of patients received calcium, vita- min D, and antiresorptive therapy; 6.6% received Clinical Applications calcium and vitamin D; and 7.3% received antire- sorptive therapy. These rates were similar regard- Garnero et al. found that the combination of BMD less of patient, provider, or hospital characteristics. assessment and high levels of CTx and high free Factors suggested as contributors to this low rate deoxypyridinoline levels predicted fracture risk of compliance include the perception of osteopo- more accurately than either modality alone [24 ] . rosis as an “outpatient” disease that is the respon- Seibel et al. [25 ] noted that urinary pyridinoline sibility of the PCP after discharge, lack of levels at baseline predicted new vertebral frac- recognition by patients and providers of osteopo- tures in women over 1 year of follow-up. Serum rosis as a contributor to the fracture, and the rela- levels of markers of bone formation typically tive lack of evidence that calcium and vitamin D vary less than do levels of bone resorption. alone reduce fracture risk (despite the fact that Antiresorptive agents such as estrogen and antiresorptive and anabolic therapies rely on ade- bisphosphonates reduce fracture risk by increas- quate calcium and vitamin D intake) [27 ] . Medical ing bone density and decreasing the rate of bone societies are taking note of this noncompliance; resorption. The reduction in fracture risk is felt to the American Orthopedic Association has devel- be predominantly due to a reduction in bone oped the “Own the Bone” program, which is a 238 C.M. Whinney

Web-based quality improvement program However, a case control study of patients under- designed to identify, evaluate, and initiate evi- going elective hip and knee arthroplasty found no dence-based care in fragility fracture patients and association between perioperative hormone encourages orthopedic surgeons to take a leader- replacement and postoperative deep vein throm- ship role in osteoporosis care [28 ] . bosis [33 ] . Hormone replacement continuation Several concerns have been postulated about thus is reasonable and safe, as long as patients the timing of initiation of antiresorptive or ana- receive appropriate pharmacologic antithrom- bolic therapy [ 27 ] . First, older agents such as botic prophylaxis. However, the feasibility and alendronate or risendronate require the patient to safety of starting an estrogen-based therapy in the remain upright for 30 min after a dose to avoid immediate postoperative period following hip esophageal irritation; after a fracture repair, this fracture is still unclear. In conclusion, the initia- upright position is dif fi cult to achieve. The more tion of bisphosphonate therapy after hip fracture recent development of parenteral agents such as repair appears safe and effective, and evidence zoledronic acid makes immediate postoperative suggests a signifi cant reduction in subsequent dosing more feasible. Another concern is that fracture risk. Prompt initiation in the hospital may bisphosphonates may interfere with fracture heal- not provide additional benefi t; current literature ing by disrupting the bone remodeling process; a suggests that a dose given 2 weeks or more after case control study found a potentially higher rate operative repair may provide optimal fracture risk of fracture nonunion with outpatient bisphospho- reduction and mortality benefi ts. Estrogen ther- nate use [ 29 ] . However, the HORIZON Recurrent apy if otherwise indicated can be deferred to the Fracture Trial, a randomized controlled trial of outpatient setting once mobility is restored and zoledronic acid administration post hip fracture thromboembolic risk is back to baseline. repair did not demonstrate differences in fracture healing or nonunion between the drug and pla- cebo groups [30 ] . However, a subgroup analysis Cemented Versus Noncemented Hip of this data set looking at time to fi rst treatment of Arthroplasty zoledronic acid after fracture repair suggested that the most ef fi cacious time frame to treat is at In displaced intracapsular fractures of the femo- 2 weeks or more after surgery [31 ] . One proposed ral neck, hemiarthroplasty is commonly per- explanation for this fi nding was increased drug formed as a more defi nitive repair technique. concentration at the fracture site during healing, Several studies cite the improvement in pain con- leading to less available drug to the rest of the trol and functional outcome with the use of skeleton; as no continued trend over time in BMD cement; however, the concern for increased peri- after fracture repair was seen, this was not felt to operative complications and cardiovascular col- represent bisphosphonate “trapping” at the frac- lapse with cement introduction has created a ture site. A more likely explanation was that the division of opinion among orthopedic surgeons. cohort of patients dosed at the less than 2-week A Cochrane review of six small trials involv- mark had more comorbidities such as hyperten- ing 549 patients noted the consistent fi nding of sion, coronary artery disease, diabetes, atrial improved pain control and better mobility [34 ] . fi brillation, and stroke, potentially accounting for A prospective randomized trial of 400 patients in higher response variability and diminished treat- the United Kingdom found signifi cantly less ment response [ 32 ] . residual pain in patients treated with a cemented Finally, the association of estrogen therapy Thomson prosthesis at 3 months after surgery, and venous thromboembolism may be more pro- compared to a noncemented Austin-Moore pros- nounced in a thrombogenic states such as hip thesis. No differences were noted in mortality, fracture and its subsequent repair. In fact, some reoperation, medical, or orthopedic complica- authors advocate withholding estrogen therapy tions [35 ] . Thus, the weight of evidence suggests up to 30 days in advance of elective surgeries. cement use has more bene fi t than harm; however 19 Medical Issues in Osteoporotic Hip Fractures 239

LaVelle [36 ] advocates avoiding signi fi cant surgery to 160 mg of enteric-coated aspirin or cement pressurization, especially in patients who placebo for 35 days after surgery. Symptomatic have compromised cardiopulmonary reserve. VTE rates were signi fi cantly reduced (2.5% vs. 1.6%, p = 0.003); no differences in mortality was noted. Bleeding rates, especially wound and GI Perioperative Anticoagulation bleeding, were higher in the patients receiving aspirin. Also, the study allowed for other prophy- Hip fracture and subsequent operative repair are laxis methods to be used; low-dose unfraction- categorized by the American College of Chest ated heparin (LDUH) and low molecular weight Physicians (ACCP) in the highest risk category heparin (LMWH) were used in 26% and 30% of for deep vein thrombosis (DVT) and pulmonary patients. A subgroup analysis of the 3,424 patients embolism (PE), with rates of DVT in the absence who received LMWH found no difference in of prophylaxis as high as 60% and PE up to 11% rates of symptomatic DVT between aspirin and [37 ] . Appropriate methods of prophylaxis reduce placebo [42 ] . this risk signifi cantly. However, many clinicians A Cochrane review of 31 trials involving fear potential bleeding complications with the 2,958 patients found comparable ef fi cacy in use of pharmacologic prophylaxis. Thus, the con- reduction of risk of VTE in hip fracture surgery sideration of the use of these agents centers on with LDUH (TID dosed), LMWH, and warfarin, the assessment of risk of bleeding and the risk of with comparable bleeding rates compared to thrombosis. placebo [43 ] . Fondaparinux, a synthetic selec- Grant and Jaffer [ 38 ] advocate immediate ini- tive Factor Xa inhibitor, was studied in 1,711 tiation of prophylactic dose anticoagulation, as patients undergoing hip fracture repair. patients often do not undergo operative repair Fondaparinux 2.5 mg dose SC starting 4–8 h until 24–48 h after sustaining a fracture. As noted after surgery was compared to enoxaparin at previously, time for assessment and stabilization 40 mg SC qd starting 12–24 h after surgery. The of decompensated medical comorbidities may be rates of VTE by postoperative day 11 were needed. Several studies suggest that delay in sur- 19.1% and 8.3% ( p < 0.001), respectively, with gery greater than 48 h, whether due to a delay in no difference in bleeding risk noted [ 44 ] . presentation to the hospital or to a delay in the When to initiate anticoagulant prophylaxis is a procedure, is associated with a markedly increased subject of considerable debate [ 37 ] . In Europe, risk of DVT, suggesting that the thrombogenic many clinicians elect to start prophylaxis ~12 h state starts with the fracture event itself, not the prior to surgery, often the evening prior to the operative repair [39, 40 ] . procedure. In the United States, clinicians typi- Some advocate the use of mechanical prophy- cally start prophylaxis 12–24 h after surgery. This laxis such as intermittent pneumatic compression serves several purposes: to minimize the risk of (IPC) devices when bleeding risk is high; how- intraoperative and postoperative bleeding, to ever, only a limited number of high-quality ran- facilitate same-day hospital admission for elec- domized trials exist. One trial of 231 patients tive surgery, and to simplify decisions related to undergoing hip fracture repair found a DVT rate choice of anesthetic methods (especially since the using serial Duplex ultrasound screening of 4% use of epidural anesthesia poses the risk of spinal of patients using IPCs versus 12% in patients who or epidural hematoma with LMWH administra- received no thromboprophylaxis ( p = 0.03) [41 ] . tion). A systematic review reported a large risk Aspirin is used for thromboprophylaxis in reduction in venographic DVT when LMWH was several orthopedic populations; however, it pro- initiated between 2 h preoperatively to 6–8 h vides a lesser degree of protection than other postoperatively in patients undergoing total hip pharmacologic methods. The Pulmonary replacement [45 ] . However, starting LMWH just Embolism Prevention (PEP) trial [42 ] random- before THR was associated with an increased risk ized over 13,000 patients undergoing hip fracture of major bleeding. 240 C.M. Whinney

As VTE risk is decreased but bleeding risk 12. Zagrodnick J, Kaufner HK. Decreasing risk by indi- appears increased with preoperative LMWH, the vidual timing of surgery of para-articular femoral fractures of the hip in the elderly. Unfallchirurgie. ACCP guidelines recommend starting either 12 1990;16:139–43. h or more preoperatively or 12 h or more postop- 13. Kenzora JE, McCarthy RE, Lowell JD, Sledge CB. eratively rather than within 4 h or less preopera- Hip fracture mortality. Relation to age, treatment, pre- tively or 4 h or less postoperatively (Grade 1B). operative illness, time of surgery, and complications. Clin Orthop. 1984;186:45–56. Given that hip fracture carries a higher risk for 14. Morrison RS. The medical consultant’s role in caring VTE, the current ACCP guidelines recommend use for patients with hip fracture. Ann Intern Med. of one of the following for a minimum of 10 to 14 1998;128:1010–20. days: LMWH, fondaparinux, LDUH, adjusted-dose 15. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Washington, VKA, aspirin (all Grade 1B), or an IPCD (Grade DC: National Osteoporosis Foundation; 2010. 1C). They also suggest the use of LMWH in prefer- 16. U.S. Preventive Services Task Force Recommendation ence to the other agents we have recommended as Statement. Screening for osteoporosis. Ann Intern alternatives: fondaparinux, LDUH (Grade 2B), Med. 2011;154:356–64. 17. Anonymous. Guideline for the prevention of falls in adjusted-dose VKA, or aspirin (all Grade 2C) [37 ] . older persons. J Am Geriatr Soc. 2001;49:664–72. 18. Kanis JA on behalf of the World Health Organization Scientifi c Group. Assessment of osteoporosis at the pri- References mary health care level. 2008 Technical report. University of Sheffi eld, UK: WHO Collaborating Center; 2008. 19. Lane NE. Metabolic Bone Disease. In: Firestein GS 1. Becker DL, Kilgore ML, Morrisey MA. The societal et al, editors. Kelley’s Textbook of Rheumatology. 8th burden of osteoporosis. Curr Rheumatol Rep. 2010; ed. Philadelphia, PA: Elsevier; 2008. 12:186–91. 20. Singer FR, Eyre DR. Using biochemical markers of 2. Zuckerman JD. Hip fracture. N Engl J Med. bone turnover in clinical practice. Cleve Clin J Med. 1996;334:1519–25. 2008;75(10):739–50. 3. Cummings SR, Melton LJ. Epidemiology and out- 21. Orwoll ES, Bell NH, Nanes MS, et al. Collagen comes of osteoporotic fractures. Lancet. 2002; N-telopeptide excretion in men: the effects of age and 359(9319):1761–7. intrasubject variability. J Clin Endocrinol Metab. 4. Haentjens P, Lamraski G, Boonen S. Costs and conse- 1998;83:3930–5. quences of hip fracture occurrence in old age: an eco- 22. Licata AA. Biochemical markers of bone turnover: nomic perspective. Disabil Rehabil. 2005; useful but underused. Cleve Clin J Med. 27(18–19):1129–41. 2008;75(10):751–2. 5. Manninger J, Kazar G, Fekete G, et al. Signi fi cance of 23. Garnero P, Delmas PD. Biochemical markers of bone urgent (within 6h) internal fi xation in the management turnover in osteoporosis. In: Marcus M, Feldman D, of fractures of the neck of the femur. Injury. 1989; Kelsey J, editors. Osteoporosis, vol. 2. 2nd ed. San 20:101–5. Diego: Academic; 2001. p. 459–77. 6. Jain R, Koo M, Kreder HJ, Schemitsch EH, Davey JR, 24. Garnero P, Hausherr E, Chapuy MC, et al. Markers of Mahomed NN. Comparison of early and delayed fi xation bone resorption predict hip fracture in elderly women: of subcapital hip fractures in patients sixty years of age the EPIDOS Prospective Study. J Bone Miner Res. or less. J Bone Joint Surg Am. 2002;84:1605–12. 1996;11:1531–8. 7. Perez JV, Warwick DJ, Case CP, Bannister GC. Death 25. Seibel MJ, Naganathan V, Barton I, et al. Relationship after proximal femoral fracture—an autopsy study. between pretreatment bone resorption and vertebral Injury. 1995;26:237–40. fracture incidence in postmenopausal osteoporotic 8. Johnstone DJ, Morgan NH, Wilkinson MC, Chissell women treated with risedronate. J Bone Miner Res. HR. Urinary tract infection and hip fracture. Injury. 2004;19(2):323–9. 1995;26:89–91. 26. Kress BC, et al. Use of bone alkaline phosphatase to 9. Parker MJ, Pryor GA. The timing of surgery for prox- monitor alendronate therapy in individual postmeno- imal femoral fractures. J Bone Joint Surg Br. pausal osteoporotic women. Clin Chem. 1992;74:203–5. 1999;45:1009–17. 10. Grimes JP, Gregory PM, Noveck H, Butler MS, 27. Bauer DC, Black DM, Garnero P, et al. Change in Carson JL. The effects of time-to-surgery on mortality bone turnover and hip, non-spine, and vertebral frac- and morbidity in patients following hip fracture. Am J ture in alendronate-treated women: the fracture inter- Med. 2002;112:702–9. vention trial. J Bone Miner Res. 2004;19(8):1250–8. 11. Villar RN, Allen SM, Barnes SJ. Hip fractures in 28. Jennings LA, Auerbach AD, Masselli J, et al. Missed healthy patients: operative delay versus prognosis. Br opportunities for osteoporosis treatment in patients Med J (Clin Res Ed). 1986;293:1203–4. 19 Medical Issues in Osteoporotic Hip Fractures 241

hospitalized for hip fracture. J Am Geriatr Soc. prevalence of deep-vein thrombosis associated with 2010;58:650–7. fractures about the hip. J Bone Joint Surg Am. 29. http://www.ownthebone.org/. Accessed 31 Jan 2011. 1996;78:581–3. 30. Solomon DH, Hochberg MC, Mogun H, et al. The 40. Zahn HR, Skinner JA, Porteous MJ. The preoperative relation between bisphosphonate use and non-union prevalence of deep vein thrombosis in patients with of fractures of the humerus in older adults. Osteoporos femoral neck fractures and delayed operation. Injury. Int. 2009;20:895–901. 1999;30:605–7. 31. Lyles KW, Colon-Emeric CS, Magaziner JS, et al. 41. Fisher CG, Blachut PA, Salvian AJ, Meek RN, Zoledronic acid in reducing clinical fracture and mortality O’Brien PJ. Effectiveness of pneumatic leg com- after hip fracture. N Engl J Med. 2007;357:1799–809. pression devices for the prevention of thromboem- 32. Eriksen EF, Lyles KW, Colon-Emeric CS, et al. bolic disease in orthopaedic trauma patients: a Antifracture ef fi cacy and reduction of mortality in prospective, randomized study of compression relation to timing of the fi rst dose of zoledronic acid. alone versus no prophylaxis. J Orthop Trauma. J Bone Miner Res. 2009;24:1308–13. 1995;9:1–7. 33. Hurbanek JG, Jaffer AK, Morra N, et al. 42. Pulmonary Embolism Prevention (PEP) Trial Postmenopausal hormone replacement and venous Collaborative Group. Prevention of pulmonary embo- thromboembolism following hip and knee arthro- lism and deep vein thrombosis with low dose aspirin: plasty. Thromb Haemost. 2004;92(2):337–43. pulmonary embolism prevention (PEP) trial. Lancet. 34. Parker MJ, Gurusamy K. Arthroplasties (with and 2000;355:1295–302. without bone cement) for proximal femoral fractures 43. Handoll HH, Farrar MJ, McBirnie J, et al. Heparin, in adults. (Cochrane review). In: The Cochrane low molecular weight heparin and physical methods Library. Chichester: Wiley; 2006. for preventing deep vein thrombosis and pulmonary 35. Parker MJ, Pryor G, Gurusamy K. Cemented versus embolism following surgery for hip fractures. uncemented hemiarthroplasty for intracapsular hip Cochrane Database Syst Rev. 2002; issue 4: article fractures: a randomised controlled trial in 400 patients. No. CD000305. J Bone Joint Surg Br. 2010;92-B:116–22. 44. Eriksson BI, Bauer KA, Lassen MR, Turpie AG, 36. LaVelle DG. Fractures and dislocations of the hip. In: Steering Committee of the Pentasaccharide in Hip- Canale ST, Beaty JH, editors. Campbell’s operative Fracture Surgery Study. Fondaparinux compared with orthopaedics. 11th ed. Philadelphia: Elsevier; 2007. enoxaparin for the prevention of venous thromboem- 37. Prevention of VTE in Orthopedic Surgical Patients. bolism after hip-fracture surgery. N Engl J Med. Falck-Ytter Y et al. Chest 2012; 141(2 Suppl); 2001;345:1298–304. e278S–e325S. 45. Hull RD, Pineo GF, Stein PD, et al. Timing of 38. Grant PJ, Jaffer AK. When should prophylactic anti- initial administration of low-molecular-weight coagulation begin after a hip fracture? Cleve Clin J heparin prophylaxis against deep vein thrombosis Med. 2006;73(9):785–92. in patients following elective hip arthroplasty: 39. He fl ey Jr FG, Nelson CL, Puskarich-May CL. Effect of a systematic review. Arch Intern Med. 2001;161: delayed admission to the hospital on the preoperative 1952–60. Total Joint Arthroplasty in the Patient with Connective 2 0 Tissue Disease

C. Ronald MacKenzie and Edwin P. Su

Introduction Epidemiologic Observations

This chapter reviews the practice of total joint The epidemiologic observations of Mentsoudis arthroplasty in patients with connective tissue et al. provide a context from which to examine disease, emphasizing the common postoperative trends in the performance and outcomes of ortho- outcomes and medical complications of this pedic surgery [1Ð 6 ] . Observations concerning the type of surgery. Recent studies of an epidemio- outcome of orthopedic surgery, speci fi cally lower logic nature have further expanded our under- extremity total joint arthroplasty, are drawn from standing of the clinical course and outcome two large national data sets. These include the experienced by patients undergoing total joint National Hospital Discharge Survey (NHDS), an arthroplasty of the lower extremity. Although this inpatient database having to do with hospital work is not speci fi cally focused on the connec- utilization collected annually since 1965 by the tive tissue disease patient, this chapter begins National Center for Health Statistics, and the with a brief review of this work as these observa- National Inpatient Sample (NIS), the largest tions are relevant to all patients undergoing such annual all payer database in the United States. surgery and they may not be widely known to The power of these studies is derived from the rheumatologists and other physicians involved in enormous size of the databases employed which, the perioperative care of these patients. A section in the case of one study, involves nearly seven dealing with total joint arthroplasty in the con- million patient discharges [4 ] . nective tissue disease patient follows, and the To date, this work has focused on lower chapter concludes with a discussion of the more extremity arthroplasty, speci fi cally the outcomes, common postoperative complications arising complications, and mortality, after total hip and after total joint arthroplasty. knee replacement (unilateral, bilateral, revision). While patients with connective tissue diseases are not speci fi cally studied, the preoperative charac- teristics, comorbidities, postoperative outcomes, C. R. MacKenzie , M.D. () and data pertaining to discharge considerations Department of Rheumatology Ð Medicine , are relevant across the span of patients undergo- Hospital for Special Surgery , 535 East 70th Street , New York , NY 10021 , USA ing such surgery. Several broad themes have e-mail: [email protected] emerged from this work. First, the use of total E. P. Su , M.D. joint arthroplasty has increased over time concur- Adult Reconstruction and Joint Replacement Service , rent with an increase in the frequency of hyper- Hospital for Special Surgery , New York , NY 10021 , USA tension, diabetes mellitus, hypercholesterolemia,

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 243 DOI 10.1007/978-1-4614-2203-7_20, © Springer Science+Business Media, LLC 2013 244 C.R. MacKenzie and E.P. Su obesity, pulmonary disease, and coronary artery arthritis (RA), psoriatic arthritis (PsA), and the disease [1, 5 ] . Despite the increasing complexity spondyloarthropathies (SpA) may account for of patients undergoing such surgery and a decreas- the preponderance of such conditions for which ing length of stay, overall postoperative complica- total joint arthroplasty might be indicated, tion rates have decreased except in the case of patients with systemic lupus erythematosus fre- bilateral procedures. Indeed, procedure-related quently require such surgical intervention, par- complication rates were higher in the bilateral ticularly total hip replacement. Several studies total joint arthroplasty patients as compared to support a general clinical impression that, in the unilateral procedures despite the younger average modern therapeutic era, the rate of surgical inter- age and lower comorbidity burden in the patients vention in patients with rheumatoid arthritis subjected to such surgery [ 2 ] . Patient selection for (RA), the most prevalent condition, has been the bilateral procedures is critical with decision declining [7Ð 11 ] . Nonetheless, joint damage, making taking into account such considerations resulting from a number of pathological mecha- as patient age (< 70 years), ASA class (< class nisms, remains an unsolved problem in the con- III), ischemic heart disease (angina pectoris or nective tissue diseases, and surgical intervention, positive stress test), depressed left ventricular most often total joint arthroplasty, is often the function (LVEF <50%), chronic pulmonary dis- fi nal solution. While not widely discussed in the ease, morbid obesity (BMI >40), renal perioperative literature, these patients not only insuf fi ciency, poorly controlled diabetes, history require surgery frequently, they are amongst the of stroke, peripheral vascular disease, and other most complex and challenging patients to care medical comorbidities, the risk of which must be for in the perioperative setting [ 12 ] . Functional balanced against those associated with two surgi- limitations compromise their cardiovascular cal procedures over time and, in the patient func- fi tness and capacity for postoperative rehabilita- tionally compromised by their symptomatic tion, the in fl ammatory process promotes the contralateral joint, their capacity to tolerate the development of (often occult) coronary artery postoperative rehabilitation after a unilateral pro- disease, and the multisystem nature of their con- cedure. This is often a complex decision. dition may compromise other organ systems Mortality after total joint arthroplasty of the (pulmonary, renal), all of which are vital to hip and knee are strongly correlated with postop- successful surgery. erative pulmonary embolism and stroke [ 3, 4 ] . Amongst patients with connective tissue dis- Preoperative risk factors for inhospital mortality ease, those suffering from infl ammatory arthritis were revision total joint arthroplasty, advanced are the most frequent candidates for total joint age (> 85 yrs), and the presence of specifi c arthroplasty. In a population-based study from comorbidities, predominately dementia, renal, the Mayo Clinic, the incidence of all joint surgery and cerebrovascular disease. Nonetheless a at 30 years was 33.7%, 17.8% of which was total steady decrease in the mortality occurred over the joint arthroplasty [7 ] . Similarly, Wolfe and time period of the study (1990Ð2004). Zwillich have reported that 33.8% of patients with RA underwent some type of orthopedic intervention in a 23-year prospective follow-up Arthroplasty in the Patient period; 25% of these were total joint replace- with Connective Tissue Disease ments [13 ] . Relatively, similar rates of joint replacement surgery have been reported in other The connective tissue diseases (CTD) are a countries as well [ 14, 15] . Only the British reports disparate group of systemic disorders whose lower rates (17%), though the follow-up period in symptomology is dominated by musculoskeletal this study was short (5 years) [ 16 ] . Postoperative manifestations. Joint pain, sometimes with joint relief of pain is generally comparable to that of destruction, is a frequent symptom. While the patients with OA but, owing to more generalized overtly infl ammatory diseases such as rheumatoid joint involvement, outcomes are less consistent 20 Total Joint Arthroplasty in the Patient with Connective Tissue Disease 245 with respect to the restoration of functional possibility of more options down the line. capacity [17 ] . In a study of 255 patients with a However, the incidence of complications after range of infl ammatory conditions, the conse- hip resurfacing is higher than for THR, and thus, quences of orthopedic surgery was assessed the procedure is not indicated for all young utilizing a comprehensive range of outcome patients. measures including functional status as judged Although a large proportion of SLE patients by the Arthritis Impact Measurement Scale develop an infl ammatory process involving their (AIMS) and Health Assessment Questionnaire joints, the arthritis is rarely erosive and thus an (HAQ). Similar improvements in upper and lower infrequent indication for Total Joint Arthroplasty extremity surgery were noted with the largest (TJA). In contrast, avascular necrosis (AVN), gains experienced by patients undergoing total whether arising in the setting of corticosteroids joint arthroplasty. Improvement varied across all or not, is a common cause of joint destruction in outcomes with the greatest impact on pain. the patient with SLE and accounts for the majority Clinical characteristics predictive of patients who of SLE patients who require TJA [24Ð 26] . For will ultimately require joint replacement include example, in a cohort of 500 patients with SLE, markers of disease activity (low hemoglobin, 3.8% ultimately required joint replacement; AVN high ESR/CRP) HAQ score, and early radio- was the most common indication in this popula- graphic signs of the disease [18 ] . tion though patients with an SLE-RA overlap In fl ammatory joint disease is also a frequent disease also made a signifi cant contribution [ 26 ] . accompaniment to the other infl ammatory con- The postoperative results of TJA, particularly THA nective tissue diseases. In a cohort of patients the most common procedure, are generally excel- with PsA, a signi fi cant proportion developed lent [ 27Ð 29] . As these patients tend to be younger erosive disease over time; those with multiple ( ³ 5) than patients requiring TJA for degenerative and active joints at disease onset and those with per- infl ammatory indications, implant survival is sistent in fl ammation were the most likely to shorter. While metal-on-metal hip resurfacing progress [19, 20] . In patients with ankylosing may seem to be an alternative to total hip replace- spondylitis (AS) and undifferentiated spondy- ment for the younger lupus patients, some experts loarthropathies (SpA), hip arthritis occurs in feel it should be avoided due to the potential for 30Ð50% of patients; both total hip and knee renal injury arising from an inadequate clearance arthroplasty are often required [21Ð 23 ] . The pro- of metal ions from the bloodstream. nounced lordosis accompanying the spinal arthri- The femoral head is the anatomic region most tis associated with these conditions may have commonly affected by AVN, followed by the more far-reaching consequences, namely, com- humeral head, the lateral femoral condyle, and pensatory fl exion of the hips and knees further the talus. Joint arthroplasty is typically the stressing these joints and structures that may be treatment of choice in the SLE patient, as core independently affected by the in fl ammatory pro- decompression procedures have had poor results cess. Patients with AS respond exceptionally well [30 ] . As in patients with other etiologies of to TJA experiencing results approaching that seen arthritis, the best results are achieved with the in patients undergoing these procedures for hip, followed by the knee, shoulder, and ankle. degenerative disease indications [21Ð 23 ] . Patients with arthritis associated with connec- tive tissue disorders are generally younger than Postoperative Complications of Total patients with osteoarthritis. As such, they may Joint Arthroplasty face multiple procedures throughout their life, beginning with a primary joint replacement Following total hip or knee arthroplasty, the clini- followed by revision procedures. Hip resurfacing cian must be aware of the potential complications is an alternative to traditional THR that allows of each procedure in order to facilitate diagnosis the preservation of femoral bone, leading to the and treatment. Prosthetic infections are covered 246 C.R. MacKenzie and E.P. Su elsewhere in this text and will not be discussed on the immediate horizon. Indeed, a multimodal here. This section will attempt to provide an over- approach combining several of these methodolo- view of the most common complications after gies is preferred by many orthopedic surgeons arthroplasty surgery. [ 35, 36] . A meta-analysis comparing the use of potent anticoagulants (LMW and factor Xa inhib- itors) vs. a multimodal approach vs. warfarin Venous Thromboembolism found the rate of all-cause mortality to be higher in the potent anticoagulation group when com- V enous thromboembolism is the most studied of pared to the other groups, lending support to this the potential postoperative complications of total preference [37 ] . joint arthroplasty. Despite the extensive literature pertaining to this subject, pulmonary embolism is still an important cause of mortality after ortho- Hematoma pedic surgery and remains a feared postoperative adverse outcome. Consensus guidelines from As just discussed, prophylaxis for venous throm- infl uential professional organizations have been boembolism (VTE) is standard practice in patients published as have numerous studies performed who have undergone total joint arthroplasty. by experienced arthroplasty surgeons with an However, a balance must be achieved between interest in this area [31, 32 ] . excessive bleeding from the anticoagulation and In the setting of orthopedic surgery, a par- the therapeutic prevention of VTE. In some cases, ticularly tenuous balance exists between a when the balance is tipped in favor of bleeding, the possible life-threatening thromboembolic event result may be the formation of joint hemarthroses and a postoperative bleeding complication that and wound hematomas. A joint hemarthrosis is could signifi cantly compromise the surgical frequently encountered when anticoagulation is result. As a consequence of these tensions, initiated rapidly and aggressively. It has been there has been considerable interest in nonphar- seen more with low-molecular heparin therapy as macological methodologies directed at the pre- compared to warfarin or aspirin usage [ 38 ] . vention of postoperative thrombosis. Such Clinically, the occurrence of hemarthrosis is considerations include the importance of expe- usually heralded by a sensation of fullness around ditious surgery (short intraoperative time), the the involved joint, limiting the range of motion. antithrombotic effects of epidural vs. general Patients will often experience pain as the collec- anesthesia (20% reduction in venous thrombo- tion of blood places tension upon the joint capsule. sis with epidural anesthesia) [33 ] , the use of Fortunately, hemarthroses are generally self-limited various pneumatic compression devices (boots, with the accumulation of blood abating once pumps, compression) [ 34 ] , and the role of early enough pressure accumulates to tamponade the ambulation. bleeding vessels. It may help to apply a compres- Virtually, every surgical procedure results in a sive dressing around the joint in order to facilitate prothrombotic state. Thus, the question is not the cessation of bleeding. Wound hematomas are whether prophylaxis will be considered but, generally more superfi cial but can also cause pain rather, which one. Prevention begins at the time by virtue of swelling and restriction of motion. of the procedure employing each of the method- Again, such collections are also self-limited and ologies just mentioned. Nonetheless, the main- generally resorb within 3Ð4 weeks. stay of treatment remains some form of A hemarthrosis may lead to the development anticoagulation. Prophylaxis should begin imme- of fevers in the postoperative period. While a diately following surgery. Regimens include common fi nding, a fever workup is necessary to aspirin alone, coumadin, and low molecular ensure there are no other sources of pyrexia. weight (LMW) heparin, with newer medications Aspirating blood via a large-gauge needle may 20 Total Joint Arthroplasty in the Patient with Connective Tissue Disease 247 temporarily alleviate a patient’s discomfort, but Dislocation unfortunately, the collection may re-accumulate. Rarely, it is necessary to return to the operat- After total hip replacement, dislocation is one of ing room for evacuation of hematoma. This is the most common complications. This is due to warranted in instances of expanding hematomas the fact that the ligamentum teres is removed refractory to compression and reversal of antico- during the surgery and the femoral implant ball agulation. Further surgical decompression may size is smaller than the removed ball size, leading be required in cases where the hematoma is to a less stable construct. Coupled with the viola- impeding physical therapy or causing wound tion of the supporting capsule around the hip joint problems such as persistent drainage or severe and inadequate early muscle control, it is not nerve compression. In these cases, an evacuation surprising that dislocation rates range from 1% to of the hematoma mass and exploration for active 5% in some studies. Risk factors for dislocation bleeders may help. include impaired cognition, female gender, taller individuals, and a history of prior surgery. A dislocated total hip replacement is typically Fat Embolism Syndrome quite painful; indeed, patients often are in such severe pain that they cannot move the affected Fat embolization is a well-known complication hip. Furthermore, they are unable to bear weight of skeletal trauma and procedures involving on the leg because of the fact that the head and instrumentation of the medullary canal [ 39 ] . socket are not articulating properly. The clinical While this phenomenon likely occurs in virtually presentation is that of a severely painful, short- all patients who sustain hip or femoral fractures, ened, rotated leg. An anterior dislocation presents the fat embolism syndrome (FES) develops in with an externally rotated lower limb, while a relatively few. Five to ten percent of patients who posterior dislocation is internally rotated. have sustained multiple long bone fractures [ 40 ] Dislocations of a total knee replacement are and 1Ð3% of patients undergoing total joint much less common and typically do not happen arthroplasty develop FES. in the acute setting. When they do occur, the The syndrome presents with a variety of clas- usual scenario is that of a hyper fl exed knee, the sic manifestations involving the respiratory, neu- leg locks and can not be straightened. rologic, hematologic systems, and the skin [41 ] . Reduction of a dislocated prosthetic joint must Hemodynamic instability may develop immedi- be carried out immediately to reduce the risks ately or insidiously over 2Ð3 days. Patients are associated with immobilization as well as to often hypotensive, become progressively hypox- decrease the tension upon the surrounding nerves. emic, and particularly in the elderly, may be con- Sedation or complete anesthesia is necessary in fused. In association with the low oxygen levels, order to relax the musculature to the point of radiographic changes including bilateral alveolar being able to effect a relocation. Following relo- infi ltrates may progress to frank respiratory cation, confi rmatory radiographs are obtained failure (ARDS). Transient thrombocytopenia is and rigid enforcement of dislocation precautions often seen. The skin eruption, which is unusual in is carried out. the total joint replacement patient, presents as a petechial rash involving the conjunctiva and oral mucosa and may become distributed over the Neuropraxias neck and axillae. Retinal changes, namely, edema and hemorrhage, may also develop. Although The inadvertent injury to a nerve in the area such patients require careful monitoring, most surrounding a joint replacement can be a devas- respond to conservative therapy (fl uid restriction, tating and frustrating complication to both the diuretics, venodilators); corticosteroids are of no patient and surgeon, often resulting in malprac- benefi t. In the majority of cases, the condition tice litigation. The nerves most commonly injured resolves within 3Ð7 days [42 ] . after total hip replacement are the sciatic or 248 C.R. MacKenzie and E.P. Su femoral nerves. The mechanism of injury to the surgery (i.e., hematoma). In addition, an MRI of nerve is unknown, but is postulated to be due to the lumbar spine is performed to assess for stretching of the nerve during the procedure, concomitant pathology that may place stress compression of the nerve from retractors or upon the nerves. Initially, all compressive dress- surgical instruments, or a vascular etiology. In ings are removed, and the limb is placed in a general, the nerve remains in continuity but is manner to avoid stretch upon the nerve. A full affected in such a way that demyelination occurs neurologic examination is performed by a neu- at the level of the insult and extends distally. rologist, and the patient is entered into a nerve The most common nerve injury after total hip injury registry. An EMG is generally not per- replacement is sciatic nerve palsy. Typically, the formed at presentation because it is too early to peroneal branch is affected, leading to a foot see electrophysiologic changes. Despite an drop; less commonly, the tibial branch is injured, uncertain predictive value, a study at about 3 leading to weakness in plantar fl exion. A foot months post-injury is performed by some clini- drop results in diffi culties in rehabilitation. An cians. A nerve-stabilizing agent such as gabapen- ankle-foot orthosis is usually needed while tin may be used if there is dysesthetic pain. ambulating in order to prevent the patient from Recovery from a nerve injury is generally slow, tripping over the foot; a resting splint is also limited by the regenerative capacity of nerve necessary so that the ankle does not contract into tissue. Further, not all injuries recover fully, and a plantar- fl exed position. In addition, therapy to patients may have persistent weakness, hypoes- keep the ankle mobile is essential. The femoral thesias, or dysesthesias. nerve may also be injured after total hip arthro- plasty. This nerve injury results in quadriceps and hip fl exor weakness as well as diminished sensa- Vascular Compromise tion in the thigh region. A nerve injury following TKR is a less com- Unintended injury to the vasculature of the lower mon event than after THR, though again the com- limbs is a rare complication after THR or TKR. It mon peroneal branch is the most common nerve may occur from the embolization of calcifi ed affected. Such injury leads to weakness in ankle plaques that break off during limb manipulation dorsifl exion and diminished sensation in the fi rst resulting in distal extremity compromise. For web space. Studies have shown this injury to be example, if a vascular calci fi cation were to break particularly associated with correction of a val- off during manipulation of the knee during TKR, gus knee with a fi xed fl exion contracture. The the calci fi c plaques may lodge distally and cause mechanism is thought to be a stretching of the ischemia to one or more of the toes. If calci fi ed common peroneal nerve at the fi bular head [43 ] . vessels are noted on a preoperative radiograph of A recent study examined the risk factors for the knee, surgeons should exercise extreme care nerve injury after total hip replacement [44 ] . not to disrupt these plaques and may want to Overall, the incidence of nerve injury was 0.3% avoid the use of a tourniquet. This complication in the years 1995Ð2009. Patient factors associ- has also been reported during THR. ated with a higher risk of nerve injury were Surgical injury to the vessels around the joints younger age, history of concomitant lumbar may also occur, especially in the setting of aber- disease, and female gender. Unfortunately, only a rant anatomy. Direct repair or bypass grafting of few of the relevant risk factors were found to be the injured vessel may be necessary. Thus, it is a amenable to modifi cation, and the incidence of good practice to have vascular surgical support nerve injury is likely to persist despite attempts to should such a complication occur. A review of understand its etiology. acute arterial injuries occurring after THR and Our protocol following a nerve injury is to TKR demonstrated an incidence of 0.13%, image the area with MRI, in order to evaluate for including diagnoses such as ischemia, bleeding, compressive lesions that can be recti fi ed by and pseudoaneurysm [45 ] . 20 Total Joint Arthroplasty in the Patient with Connective Tissue Disease 249

Periprosthetic Fracture the patient is unable to comply with protected weight-bearing, surgical correction is warranted. Fractures of the bone around a THR, TKR, or Surgical correction can be carried out with open TSR may occur at the time of surgery or during reduction internal fi xation of the fracture if the the postoperative healing phase. Periprosthetic implants remain stable or revision of the implants fractures are associated with osteoporosis and may also be necessary. the use of uncemented implants. Falls however are the most common antecedent; thus, fall prevention protocols are also imperative in the Heterotopic Bone Formation perioperative period. Periprosthetic fracture may manifest only with Heterotopic ossifi cation (HO) has been reported an increase in pain during the recovery period, or in patients after both THR and TKR and is with pain out of proportion to what is expected thought to be due to muscular trauma associated during normal recovery. Imaging studies are nec- with the surgical procedure. There is an estimated essary to make the diagnosis of a periprosthetic incidence of up to 40% of minor bone formation fracture (Fig. 20.1 ). Radiographs are the initial after THR, which in general does not result in study obtained; occasionally, a CT or MRI scan any functional compromise and is an incidental is necessary to assess for nondisplaced fractures. radiographic fi nding. Severe HO that leads to Depending upon the location, amount of dis- stiffness and functional limitations is much less placement, and the type of implants used, surgi- common, estimated to occur in 1Ð10% of THR cal correction of the periprosthetic fracture may [ 46, 47 ] . Heterotopic ossi fi cation occurring after or may not be needed. If nondisplaced, a period TKR is less well studied, with symptomatic HO of protected weight-bearing for 2Ð3 months may occurring in <1% of patients [ 48 ] . On rare occa- allow the fracture to heal nonsurgically. If displaced, sions, if the HO results in severe functional limi- if the fracture compromises implant stability, or if tations, surgical excision of the extra-articular

Fig. 20.1 ( a ) Radiograph demonstrating a completely reduction internal fi xation of fracture using a plate, and displaced femur fracture between a total hip and knee bone allograft replacement. (b ) Postoperative radiograph following open 250 C.R. MacKenzie and E.P. Su

frequency varies widely, the variance appears a function of inconsistent de fi nitions and the patient population studied [50, 51 ] . Nonetheless, that a febrile response may arise as a consequence of surgery is not surprising. Fever, as a response to injury, is well known and a predictable conse- quence of the release of various pyrogenic cytok- ines, particularly interleukins (IL) 1 and 6, tumor necrosis factor (TNF), and interferon-y . Acting on the anterior hypothalamus, these mediators cause the release of prostaglandins which are postulated to medicate the febrile response [50 ] . In one study of patient undergoing total joint arthroplasty (hip and knee), postoperative fever was virtually universal; most febrile episodes occurred early and had normalized by the fourth postoperative day [52 ] . Almost one- fi fth of these patients developed temperatures above 39.0¡C with almost none a consequence of infection. The time of onset of postoperative fever does appear important with late febrile responses (³ day 3) Fig. 20.2 Radiograph demonstrating severe bilateral heterotopic ossi fi cation following hip resurfacing associated with a higher incidence of infection [ 53] . A widely held misconception is that postop- erative fever is caused by atelectasis [ 50 ] . Studies bone may be performed; however, the risk of in patients after cardiac [ 54 ] and abdominal [ 55 ] recurrence is high. surgery have shown a poor correlation between There is an increased incidence of HO in these phenomena. patients with osteoarthritis associated with hyper- Some fi nd the “four W” pneumonic helpful in trophic bone spurs, as well as patients with the evaluation of postoperative fever: w ind ankylosing spondylitis and those with conditions (pulmonary causes), w ater (urinary tract infec- known to produce exuberant bone formation in tion), w ound (surgical site infection), and what response to surgical manipulation (DISH) did we do? (iatrogenic causes such as drug fever, (Fig. 20.2 ) [49 ] . Revision surgeries and acetabu- blood product reaction, infection due to intrave- lar fractures also place the patients at higher risk nous lines) [ 50 ] . It is always worth remembering for this additional bone formation. Prophylaxis that thromboembolic disease is also associated post-total hip replacement low-dose external with fever. beam radiation (XRT Ð 700 centigray), aspirin, or indomethacin may decrease the rate and magni- tude of extra-articular bone formation. Due to the References low incidence of HO after TKR, few studies have examined the bene fi ts of prophylaxis and such 1. Memtsoudis SG, Besculides MC, Reid S, Lager- measures are not generally employed. Baylis LK, Gonzalez Della Valle A. Trends in bilateral total knee arthroplasties. 153,259 discharges between 1990 and 2004. Clinc Orthop Relat Res. 2009;467: 1568Ð76. Postoperative Fever 2. Memtsourdis SG, Gonzalez Dela Valle A, Besculides MC, Gaber L, Sculco TP. In-hospital complications and mortality of unilateral, bilateral, and revision Fever is a common clinical phenomenon in the TKA. Based on an estimate of 4,159,661 discharges. postoperative setting. Although its reported Clin Orthop Relat Res. 2008;466:2617Ð27. 20 Total Joint Arthroplasty in the Patient with Connective Tissue Disease 251

3. Liu SS, Gonzalez Della Valle A, Besculides MC, 17. Osnes-Ringen H, Kvien TK, Henriksen LB, et al. Gaber LK, Memtsoudis SG. Trends in mortality, com- Orthopaedic surgery in 255 patients with in fl ammatory plications, and demographics for primary hip arthro- arthropathies: longitudinal effects on pain, physical plasty in the United States. Int Orthop. 2008;33: function and health-related quality of life. Ann Rheum 643Ð51. Dis. 2009;68(10):697Ð703. 4. Memtsoudis SG, Gonzalez Della Valle A, Besculides 18. Kapetanovic MC, Lindqvist E, Saxne T, Eberhardt K. MC, Esposito MA, Koulouvaris P, Salvati EA. Risk Orthopaedic surgery in patients with rheumatoid Factors for perioperative mortality after lower extrem- arthritis over 20 years: prevalence and predictive ity arthroplasty; a population-based study of 6,901,324 factors of larger joint replacement. Ann Rheum Dis. patient discharges. J Arthroplasty. 2009;25:19Ð26. 2008;67:1412Ð6. 5. Memtsoudis SG, Gonzalez Della Valle A, Besculides 19. Gladman DD, Mease PJ, Choy EH, et al. Risk factors MC, Gaber L, Laskin R. Trends in Demographics, for radiographic progression in psoriatic arthritis: Comorbidity Profi les, In-Hospital Complications and subanalysis of the randomized controlled trial ADEPT. Mortality Associated with Primary Knee Arthroplasty. Arthritis Res Ther. 2010;12(3):R113. 3,830,420 Hospital Discharges in the United States 20. Gladman DD, Chandran V. Observational cohort between 1990 and 2004. J Arthroplasty . 2008 April studies: Lessons learnt from the University of Toronto 14. [Epub ahead of print]. Psoriatic Arthritis Program, Rheumatology (Oxford) 6. Memtsoudis SG, Yan Ma, Gonzalez Della Valle A, 6 Aug 2010. Gaber-Baylis L, MacKenzie CR, Sculco TP. 21. Sochart DH, Porter ML. Long-term results of total hip Perioperative outcomes after unilateral and bilateral replacement in young patients who had ankylosing total knee arthroplasty. Anesthesiology. 2009;111: spondylitis, eighteen to thirty-year results with survi- 1206. Accepted for publication. vorship analysis. J Bone Joint Surg Am. 1997;79(8): 7. Da Silva E, Doran MF, Crowson CS, et al. Declining 1181Ð9. use of orthopedic surgery in patients with rheumatoid 22. Sweeney S, Gupta R, Taylor G, et al. Total hip arthro- arthritis? Results of a long-tem, population-based plasty in ankylosing spondylitis: outcome in 340 assessment. Arthritis Rheum. 2003;49:216Ð20. patients. J Rheumatol. 2001;28(8):1862Ð6. 8. Fevang BTS, Havelin LI, Engesaeter B, Furness O. 23. Parvizi J, Duffy GP, Tousdale RT. Total knee arthro- Reduction in orthopedic surgery among patients with plasty in patient with ankylosing spondylitis. J Bone chronic infl ammatory joint disease in Norway, 1994- Joint Surg. 2001;83:1312Ð6. 2004. Arthritis Rheum. 2007;57:529Ð32. 24. Gladman DD, Chaudhry-Ahluwalia V, Ibanez D, et al. 9. Pereira L, De Piano A, Prado Golmia R, Scheinberg Outcomes of symptomatic osteonecrosis in 95 patients MA. Decreased need of large joint replacement in with systemic lupus erythematosus. J Rheumatol. patients with rheumatoid arthritis in a specialized 2001;28(10):2226Ð9. Brazilian center. Clin Rheumatol. 2010;30:549Ð50. 25. Gladman DD, Urowitz MB, Chaudhry-Ahluwalia V, 10. Momohara S, Ikari K, Mochizuki T, et al. Ann Rheum et al. Predictive factors for symptomatic osteonecrosis Dis. 2009;68:291Ð2. in patients with systemic lupus erythematosus. 11. Weiss RJ, Ehlin A, Montgomery SM, et al. Decrease J Rheumatol. 2001;28(4):761Ð5. in RA-related orthopaedic surgery of the upper limbs 26. Mouroa AF, Amaral M, Caetano-Lopes J, Isenberg D. between 1998 and 2004: data from 54579 Swedish An analysis of joint replacement in patients with sys- RA inpatients. Rheumatology. 2008;47:491Ð4. temic lupus erythematosus. Lupus. 2009;18(14): 12. Goodman SM, Figgie MP, MacKenzie CR. 1298Ð302. Perioperative management of patients with connec- 27. Ito H, Matsuno T, Hirayama T, et al. Health-related tive tissue disease. HSS J. 2011;7:72Ð9. quality of life in patients with systemic lupus erythe- 13. Wolfe F, Zwillich SH. The long-term outcomes of matosus after medium to long-term follow-up of hip rheumatoid arthritis. Athritis Rheum. 1998;41: arthroplasty. Lupus. 2007;18(12):318Ð23. 1072Ð82. 28. Huo MH, Salvati EA, Browne MG, et al. Primary total 14. Verstappen SM, Hoes JN, Ter Borg EJ, et al. Joint hip arthroplasty in systemic lupus erythematosus. surgery in the utrecht rheumatoid arthritis cohort; J Arthroplasty. 1992;7(1):51Ð6. the effect of treatment strategy. Ann Rheum Dis. 29. Zangger P, Gladman DD, Urowitz MB, et al. Outcome 2006;65:1506Ð11. of total hip replacement for avascular necrosis in sys- 15. Palm TM, Kaarela K, Hakala MS, et al. Need and temic lupus erythematosus. J Rheumatol. 2000;27(4): sequence of large joint replacements in rheumatoid 919Ð23. arthritis. A 25-year follow-up study. Clin Exp 30. Mont MA, Fairbank AC, Petri M, Hungerford DS. Rheumatol. 2002;20:392Ð4. Core decompression for osteonecrosis of the femoral 16. James D, Young A, Kulinskaya E, et al. Orthopaedic head in systemic lupus erythemotosus. COOR. intervention in early rheumatoid arthritis. Occurrence 1997;334:91Ð7. and predictive factors in an inception cohort of 1064 31. Geerts WH, Pineo GF, Heti JA, et al. Prevention of patients followed for 5 years. Rheumatology. 2004;43: venous thromboembolism. Chest. 2004;126: 369Ð76. 338SÐ400. 252 C.R. MacKenzie and E.P. Su

32. AAOS guidelines. http://www.aaos.org/Research/ the hospital for special surgery experience. J Bone guidelines/PE_guideline.pdf . Joint Surg Am. 1982;64:347. 33. Prins MH, Hirsh J. A comparison of general anesthe- 44. Lyman S, Wu A, E Su. AAOS annual meeting, New sia and regional anesthesia as a risk factor for deep Orleans; 2010 vein thrombosis following total hip surgery: a critical 45. Calligro KD, Dougherty MJ, Ryan S, et al. Acute arte- review. Thromb Haemost. 1990;64:497Ð500. rial complications associated with total hip and knee 34. Lieberman JR, Geerts WH. Prevention of venous arthroplasty. J Vasc Surg. 2003;38(6):1170Ð7. thromboembolism after total hip and knee arthro- 46. Neal B, Gray H, MacMahon S, et al. Incidence of het- plasty. J Bone Joint Surg. 1994;76:1239Ð50. erotopic bone after major hip surgery. ANZ J Surg. 35. Della Valle AG, Serota A, Go G, et al. VTE is rare 2002;72(11):808Ð21. with a multimodal prophylaxis protocol after THA. 47. Higo, Matawari, Shigematsu, et al. Then incidence of HO Clin Orthop Relat Res. 2006;444:146Ð53. after cementless THA. J Arthroplasty 2006;21(6): 36. Beksac B, Della Valle GA, Anderson J, et al. 852-56. Symptomatic thromboembolism after one-stage bilat- 48. Austin KS, Siliski JM. Symptomatic Heterotopic eral THA with a multimodal prophylaxis protocol. Ossi fi cation Following Total Knee Arthroplasty. Clin Orthop Relat Res. 2007;463:114Ð9. J Arthroplasty. 1995;10:695Ð8. 37. Sharrock NE, Gonzalez Della Valle A, Go G, et al. 49. Iorio R, Healy WL. Heterotopic ossi fi cation after hip Potent anticoagulants are associated with higher all- and knee arthroplasty: risk factors, prevention, and treat- cause mortality rate after hip and knee arthroplasty. ment. J Am Acad Orthop Surg. 2002;10(6):581Ð95. Clin Orthop Relat Res. 2008;466(3):714Ð21. 50. Pile JC. Evaluating postoperative fever. Cleve Clin 38. Barrack RL. Failure of the American College of Chest J Med. 2006;73(1):S62Ð6. Physicians-1A protocol for lovenox in clinical out- 51. Dellinger EP. Approach to the patient with postopera- comes for thromboembolic prophylaxis. J Arthroplasty. tive fever. In: Gorbach SL, Barlett JG, Blacklow NR, 2007;22(3):317Ð24. editors. Infectious diseases. 3rd ed. Philadelphia: 39. Parisi MD, Koval K, Egoi K. Fat embolism syndrome. Lippincott Williams Wilkins; 2004. p. 817. Am J Orthop. 2002;31:505Ð12. 52. Shaw JA, Chung R. Febrile response after knee and hip 40. Levy D. The fat embolism: a review. Clin Orthop. arthroplasty. Clin Orthop Relat Res. 1999;367:181Ð9. 1990;261:281Ð6. 53. Garibaldi RA, Brodine S, Matsumiya S, et al. Evidence 41. Johnson MJ, Lucas GI. Fat embolism syndrome: a for the non-infectious etiology of early postoperative review of the pathophysiology and physiological basis fever. Infect Control. 1985;6:273Ð7. of treatment. Clin Orthop. 1982;19:48Ð9. 54. Engoren M. Lack of association between atelectasis 42. Nazon D, Abergel G, Hatem CM. Critical care in and fever. Chest. 1995;107:81Ð4. orthopedic and spine surgery. Crit Care Clin. 55. Roberts J, Barnes W, Pennock M, et al. Diagnostic 2003;19:33Ð53. accuracy of fever as a measure of postoperative pul- 43. Rose HA, Hood RW, Otis JC, et al. Peroneal nerve monary complications. Heart Lung. 1988;17: palsy following total knee arthroplasty: a review of 166Ð70. Postoperative Fever and Infection in Immunosuppressed Patients 2 1

David van Duin

pared to many other surgeries. However, the Introduction morbidity associated with infection in a joint space is substantial. Especially in the presence of Postoperative infections remain an important a foreign body like a total joint prosthesis, these source of perioperative morbidity and mortality. infections may require additional surgical proce- These infections include surgical site infections dures as well as prolonged parenteral antibiotic but also intravenous catheter-associated blood- courses. Colonization with pathogens may be stream infections and Foley catheter–associated increased secondary to immunosuppression or urinary tract infections. local factors such as skin disease. In any patient, the risk of postoperative infec- Furthermore, classic symptoms of postopera- tion results from the interplay between factors tive infections, such as fever and an elevated relating to the procedure, the host, and colonizing peripheral blood white cell count, may be blunted pathogens. With this interaction in mind, it is not or absent in immunocompromised patients. surprising that patients with rheumatologic disor- A high index of suspicion is required for timely ders on immunomodulating medications are at recognition and treatment. increased risk for this complication. Several host factors may be altered in the patient with rheumatologic disease who undergoes a surgical Immunosuppressive Medications procedure, including changes in the immune sys- and Postoperative Infection tem related to the underlying disease as well as related to medications used to treat this disease. The perioperative use of corticosteroids is esti- Surgical intervention in patients with rheumato- mated to increase the risk of incisional wound logic disorders often includes joint and spine complications two- to fi vefold. These complica- surgery, including total joint replacement proce- tions include dehiscence of primary closed dures. As these surgeries do not invade nonsterile wounds and delay of closure of open wounds. In compartments, and prophylactic perioperative addition to the effects on the immune system, antibiotics are generally given, the risk of postop- these effects are thought to be mediated by direct erative surgical site infection is lower when com- effects of corticosteroids on collagen synthesis and processing [1– 3 ] . However, low-dose corti- D. van Duin , M.D., Ph.D. () costeroids, de fi ned as <10 mg/day of prednisone Department of Infectious Disease , Cleveland Clinic , or equivalent corticosteroids, likely have a lim- Mail Code G21 9500 Euclid Avenue , Cleveland , OH 44195 , USA ited impact on both wound healing and risk of e-mail: [email protected] postoperative infections [4 ] . Similarly, patients

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 253 DOI 10.1007/978-1-4614-2203-7_21, © Springer Science+Business Media, LLC 2013 254 D. van Duin on methotrexate in the perioperative period have reoperation, when compared to primary osteoar- comparable postoperative infection rates to other thritis (hazard ratio 1.86, 95% CI 1.31–2.63) rheumatologic patients [ 5– 8 ] . Also, preoperative [ 17 ] . Similarly, in a cohort study of patients discontinuation of methotrexate does not result in undergoing primary total hip replacement in lower infection rates [ 9 ] . A single prospective California, rheumatoid arthritis was associated cohort study was reported of 201 patients with with a higher rate of complications (OR 1.88, rheumatoid or psoriatic arthritis, who underwent 95% CI 1.17–3.03) [ 18 ] . In the same study, a elective orthopedic surgery. In this study, nonsignifi cant trend towards more infections in lefl unomide was associated with increased early patients with rheumatoid arthritis was observed healing complications [10 ] . (OR 1.47, 95% CI 0.90–2.41) [ 18 ] . Also, the Therapeutic blockade of the binding of TNF- a duration of disease appears to be linked to infec- to its receptor is one of the most remarkable tion risk; patients who have a longer duration advances in the treatment of autoimmune disor- seem to be at an increased risk. ders. Several antibodies and FC fragments are Total hip replacement in ankylosing spon- currently available, including etanercept, dylitis appears to be associated with acceptable infl iximab, adalimumab, golimumab, and certoli- outcomes. A small series of 46 patients who zumab. Therapeutic TNF-a blockade is clearly underwent total hip replacement for ankylosing associated with an increased risk of severe infec- spondylitis revealed three deep infections; how- tions – a recent meta-analysis estimated this risk ever, no control group was included in this study increase at about 40% in rheumatoid arthritis [19 ] . In a larger study of 166 patients with anky- patients treated with TNF-a inhibitors [ 11 ] . In losing spondylitis who underwent total hip general, it is recommended to stop TNF-a inhibi- replacement, 44 patients required revision sur- tors prior to surgery, with many experts recom- gery; in four of these, the self-reported reason mending discontinuing the agent for 2 half-lives for revision was infection [ 20] . However, neither prior to sterile surgeries and 4–5 half-lives prior of these studies evaluated superfi cial postopera- to high-risk surgeries, such as colorectal or joint tive infections. replacement surgery [12– 15 ] .

Colonization in Common Underlying Rheumatologic Disorder Rheumatologic Disorders and Postoperative Infection An increasingly recognized risk factor for postop- All rheumatologic disorders probably carry some erative infections is preoperative colonization with degree of increased infection risk in the postop- pathogens. The likelihood of colonization with erative period, either through the primary pathogens depends on a multitude of factors, most mechanism of the disease or through the immu- of which remain incompletely understood. It is nosuppressive treatment. For example, in a series clear, however, that local immunity plays an impor- on total ankle arthroplasty, the presence of any tant role, as does the overall composition of the in fl ammatory connective-tissue disease was microbial fl ora, the so-called microbiota or micro- associated with a substantially increased risk of biome. Both these factors are infl uenced by rheu- a major wound complication (de fi ned as any matic diseases. In a study on fecal microbiota in complication which resulted in reoperation, OR rheumatoid arthritis, even in early disease, substan- 14, 95% CI 2.35–83.83) [ 16] . However, limited tial differences between patients and controls were data are available to quantify this increased risk found [21 ] . An interesting speculation regarding for various underlying conditions. In a large reg- these data is whether alterations in the microbiome istry-based study of knee arthroplasty, rheuma- may contribute to risk of rheumatic disorders. In toid arthritis was associated with a signi fi cantly addition, a number of studies indicate that patients higher risk of postoperative infections requiring with rheumatoid arthritis, as well as Wegener’s 21 Postoperative Fever and Infection in Immunosuppressed Patients 255 granulomatosis, are at increased risk of S. aureus subsequent treatment. However, in some wound colonization [22– 24 ] . S. aureus is the most impor- infections, no cultures or only limited super fi cial tant pathogen in postoperative infections, and most cultures can be obtained, the results of which do people who are infected with S. aureus get infected not correlate well with underlying microbiologic with strains that they were previously colonized causes. In limited infections, starting empiric treat- with. Screening and targeted decolonization efforts ment with an agent which covers methicillin-resis- have shown to be effective in decreasing infections tant S. aureus (MRSA) is a reasonable approach in a number of perioperative settings. while awaiting culture results. In patients who are more ill, gram-negative coverage should be added as well. The erythema should be marked and the Common Causes of Postoperative response to antibiotic therapy closely monitored. Fevers If there is no response, empiric broadening of anti- biotic therapy and/or surgical intervention should Wound Infection be considered. This stepwise approach can be used for patients with rheumatologic diseases in the Surgical site infection is the most common post- same way as for other patients, as long as close operative infection. The diagnosis is usually observation is provided. straightforward and can be made at the bedside. Erythema and warmth are the hallmark features. In addition, wound drainage may increase or Bloodstream Infection change from serosanguinous to purulent in appear- ance. Wounds which were previously closed may Line-related bloodstream infections are a com- dehisce, whereas open wounds may fail to close. mon cause of fever in hospitalized and postsurgical Systemic signs such as fever and leukocytosis patients. Classically, a patient will develop may be present or absent depending on the extent acute fevers, often with chills and/or rigors, fol- of the infection. It is important to note that all lowed by profuse diaphoresis. These symptoms these signs may be diminished in patients who are occasionally can follow infusion through the immunosuppressed. For instance, infection needs infected line; however, more often, there is no to be considered if wound healing is delayed, even temporal relationship. Strict antisepsis during if local signs such as erythema and systemic signs line placement, using an infection control bundle such as fevers are limited or absent. approach, has been shown to decrease the inci- The microbiology of surgical site infections is dence of catheter-related bloodstream infections. fairly predictable. Staphylococci are the most The diagnosis is made through blood cultures commonly encountered isolates; however, a sub- and/or culturing the tip of the line after removal. stantial subset of patients will present with gram- Various methods are available to attempt to diag- negative infection as well. In general, patients get nose a line infection while it is still in place, infected with organisms which were previously including differential time to positivity between colonizing fl ora. As noted, S. aureus colonization cultures drawn from the periphery and cultures is more common in immunocompromised hosts. drawn from the line. Another method is quantita- In addition, colonizing fl ora is in fl uenced by the tive blood cultures, in which the number of colony- antibiotic and health-care exposure of a given forming units of pathogens is compared between patient. Patients with rheumatologic disorders cultures from the line and from the periphery. may have a substantial burden of both. In sus- In the postoperative setting, however, the most pected infection, evaluating prior culture results practical approach in most cases is to remove for evidence of multidrug-resistant organisms the line. may yield valuable clues to the etiology. If a line-related infection is found, the line Culture of wound drainage when feasible is should be removed, except perhaps in the case of imperative for the microbiological diagnosis and coagulase-negative staphylococci [25 ] . In the 256 D. van Duin absence of any signs of sepsis, salvaging a line ally describe urinary symptoms which may infected with coagulase-negative staphylococci include urinary frequency, dysuria, stranguria, can be safely attempted in patients with rheuma- hematuria, or the feeling of incomplete empty- tologic diseases . In general, this is only a good ing. However, some of these symptoms are com- option if long-term access is required or if alter- monly seen in patients after urinary catheter native access options are associated with an removal in the absence of infection. In the pres- increased risk of complications. After prosthetic ence of a urinary catheter, the only symptom of a joint surgery, however, most experts would opt to urinary tract infection may be fever. If a urinary remove a possibly infected line even with less tract infection is suspected, the catheter should virulent organisms such as coagulase-negative be removed and if possible not replaced. In men, staphylococci. digital examination of the prostate should be per- Targeted intravenous antibiotic therapy should formed to rule out acute prostatitis. In most be given for a period of at least 2 weeks after the cases, imaging of the kidneys is not required, fi rst negative blood culture. If S. aureus is the unless signs and symptoms suggest pyelonephri- offending pathogen, most experts recommend tis (e.g., back pain or costovertebral angle ten- duration of treatment to be at least 4 weeks. Also, derness). However, if the patient is more severely for S. aureus bloodstream infections, infective ill than would be expected with cystitis, and endocarditis should be ruled out. This generally other causes are unlikely, ruling out pyelonephri- requires transesophageal echocardiography, espe- tis and/or a perinephric abscess is imperative. cially in patients with preexisting valvulopathy, Diabetes mellitus – including corticosteroid- for instance, from systemic lupus erythematosus. induced diabetes mellitus – is the most common Sometimes, even after transesophageal echo- risk factor for complications of urinary tract cardiography, infective endocarditis cannot be infections. In these patients, the threshold for ruled out. In those cases, most experts would treat imaging should be reduced. for at least 6 weeks and consider repeat echocar- Antibiotics should be selected, based on the diography at the end of treatment. Besides deter- urine culture results and the predicted urinary mination of treatment duration, cardiac imaging levels. Funguria can be a particularly diffi cult is essential to establish a potential need for problem, especially in the immunocompromised surgical intervention. host. The interpretation of clinical signi fi cance of funguria in a postoperative patient with fever is diffi cult, and treatment can be challenging as well. Urinary Tract Infection In most cases, treatment beyond catheter removal is not indicated. If after catheter removal urine Urinary tract infections are notoriously dif fi cult to continues to grow Candida species and no other accurately diagnose. The incidence of asymptom- source for fever is found, specifi c antifungal treat- atic bacteriuria increases with age, and for this ment may be indicated. Fluconazole is a reliable condition, antibiotic treatment has never been agent for the treatment of susceptible isolates, but shown to improve outcomes. In addition, most non-Candida albicans isolates are increasingly patients with urinary catheters will eventually common in the hospitalized setting. In these iso- develop bacteriuria and/or funguria. Prevention of lates, either partial or complete in vitro resistance urinary tract infections by early removal of urinary to fl uconazole may be observed. Uncomplicated catheters can have a substantial impact on morbid- fungal cystitis with dose-dependent resistant iso- ity. The clinical relevance of positive urine cul- lates usually can be treated effectively with higher- tures must be carefully assessed on an individual dose fl uconazole. For isolates which are fully basis. It is especially important to rule out other resistant in vitro, therapeutic choices are limited. sources of fever in the postoperative patient. Echinocandins may be tried, but urinary levels are In the absence of a urinary catheter, alert low. For serious infections, an amphotericin B patients with urinary tract infections will gener- preparation is usually preferred. 21 Postoperative Fever and Infection in Immunosuppressed Patients 257

Treatment of isolated pyuria seen on urinalysis Clostridium diffi cile–Associated Disease without obtaining a urine culture is in general not recommended, based on the unpredictable antimi- C. dif fi cile diarrhea and/or colitis is associated crobial susceptibility of pathogens causing uri- with the use of antibiotics and may follow even nary tract infections in the postoperative setting. the use of limited perioperative antibiotics. It has a wide spectrum of disease, varying from mild self-limited diarrhea to severe life-threatening Pneumonia colitis and toxic megacolon. The presence of leu- kocytosis, which may be quite pronounced, sug- Hospital-acquired or ventilator-associated pneu- gests the diagnosis as well. A test for C. dif fi cile monia are serious causes of postoperative fevers. should be sent on any patient with diarrhea in the The diagnosis can be quite obvious, but on occa- postoperative setting. When using ELISA-based sion may be dif fi cult to establish. In particular, toxin detection tests with limited sensitivity, test- pulmonary embolic disease can present in an ing at least two separate samples is recommended. identical fashion with fevers, increased oxygen Newer PCR-based methods probably do not have requirements, and chest pains. Patients with pre- that limitation. It remains important to send the existing lung conditions, such as rheumatoid lung right sample, i.e., liquid stool. Empiric treatment disease, have preexisting radiological abnormali- with oral metronidazole or vancomycin is indi- ties, which may complicate early recognition of cated if suspicion is high or if the patient is new pulmonary infi ltrates. In addition, patients acutely ill. Surgical consultation should be with cardiac disease may have signi fi cant fl uid obtained if colonic dilatation, ileus, or systemic retention, which can manifest as pulmonary disease is present, as severe cases require colec- infi ltrates as well. In addition, similar to other tomy for control of disease. A fi rst, uncomplicated infectious complications, immunosuppressed episode should be treated with oral metronidazole, patients with pneumonia may present in a more recurrences in general with oral vancomycin. In subtle fashion. severe disease combination, therapy of intrave- Classically, patients present with fevers, acute nous metronidazole, oral vancomycin, and rectal onset of cough, productive of yellow or green vancomycin should be started. Strict contact pre- sputum, increasing shortness of breath, and chest cautions should be maintained, as this pathogen pains. Chest radiology typically shows an evolv- may spread very easily from patient to patient. ing in fi ltrate. In ventilated patients, oxygen Patients on corticosteroids were recently found requirements increase, and weaning efforts are to have an increased risk for mortality after unsuccessful. Tracheal secretions increase and C. dif fi cile disease [ 26] . In addition, higher peak change in appearance. Culturing respiratory sam- peripheral white blood counts were found in this ples, either from spontaneously expectorated group as well. sputum or through samples obtained through bronchoscopy, is of the utmost importance to guide therapy. If a large pulmonary effusion Noninfectious Causes of Fever develops, this fl uid should be sampled to rule out a developing empyema. A number of noninfectious causes must be consid- Broad-spectrum treatment which includes an ered in any patient presenting with fevers in the agent with antipseudomonas activity, as well as postoperative setting. After joint replacement sur- an agent with pulmonary MRSA coverage, should gery, elevated temperatures <39.0°C are common be started if pneumonia is suspected. Antibiotics and, without other clinical signs, should lead to a should subsequently be tailored based on culture limited clinical work-up only (i.e., blood cultures results. A treatment duration of 8 days generally from two separate sites) [ 27 ] . Deep venous throm- suf fi ces for ventilator-associated pneumonia. bosis (DVT) is a common complication after 258 D. van Duin surgery and may present with fevers. Con fl icting with rheumatoid arthritis undergoing elective ortho- data have been reported on the incidence of DVT pedic surgery. Mod Rheumatol. 2006;16(1):14–9. 7. Perhala RS, Wilke WS, Clough JD, Segal AM. Local in patients with rheumatoid arthritis; it may be infectious complications following large joint replace- increased, or similar to patients with osteoarthritis. ment in rheumatoid arthritis patients treated with In addition, recent data suggest that therapeutic methotrexate versus those not treated with methotrex- TNF-a blockade may be associated with increased ate. Arthritis Rheum. 1991;34(2):146–52. 8. Wessels JA, Huizinga TW, Guchelaar HJ. Recent risk for DVT [ 28 ] . Classically, lower extremity insights in the pharmacological actions of metho- DVT presents as a swollen red leg; however, more trexate in the treatment of rheumatoid arthritis. commonly slight swelling or no observable signs Rheumatology (Oxford). 2008;47(3):249–55. are seen. Therefore, a low threshold for diagnostic 9. Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with testing is indicated. Treatment with anticoagula- rheumatoid arthritis undergoing elective orthopaedic tion is generally indicated. surgery. Ann Rheum Dis. 2001;60(3):214–7. Medication-induced fevers represent another 10. Fuerst M, Mohl H, Baumgartel K, Ruther W. common etiology of fevers in the postoperative Le fl unomide increases the risk of early healing com- plications in patients with rheumatoid arthritis under- patient. A rash, eosinophilia, or other manifesta- going elective orthopedic surgery. Rheumatol Int. tions of drug reactions may suggest the diagno- 2006;26(12):1138–42. sis. Many medications have been implicated as 11. Bernatsky S, Habel Y, Rahme E. Observational stud- a cause of fevers. Antibiotics, especially beta- ies of infections in rheumatoid arthritis: a metaanaly- sis of tumor necrosis factor antagonists. J Rheumatol. lactams, are a common cause of medication- 2010;37(5):928–31. induced fevers and are often included in 12. den Broeder AA, Creemers MC, Fransen J, de Jong E, perioperative regimens. Methotrexate pulmo- de Rooij DJ, Wymenga A, de Waal-Malefi jt M, van nary toxicity is a subacute syndrome of cough, den Hoogen FH. Risk factors for surgical site infec- tions and other complications in elective surgery in dyspnea, and fevers, which may be confused patients with rheumatoid arthritis with special atten- with pneumonia. If a medication-induced fever tion for anti-tumor necrosis factor: a large retrospec- is suspected, the possible offending agents tive study. J Rheumatol. 2007;34(4):689–95. should be withdrawn one by one, if possible. 13. Giles JT, Bartlett SJ, Gelber AC, Nanda S, Fontaine K, Ruffi ng V, Bathon JM. Tumor necrosis factor inhibitor therapy and risk of serious postoperative orthopedic infection in rheumatoid arthritis. Arthritis References Rheum. 2006;55(2):333–7. 14. Lee MA, Mason LW, Dodds AL. The perioperative 1. Anstead GM. Steroids, retinoids, and wound healing. use of disease-modifying and biologic therapies in Adv Wound Care. 1998;11(6):277–85. patients with rheumatoid arthritis undergoing elective 2. Busti AJ, Hooper JS, Amaya CJ, Kazi S. Effects of peri- orthopedic surgery. Orthopedics. 2010;33(4):257–62. operative antiinfl ammatory and immunomodulating 15. Pieringer H, Stuby U, Biesenbach G. Patients with therapy on surgical wound healing. Pharmacotherapy. rheumatoid arthritis undergoing surgery: how should 2005;25(11):1566–91. we deal with antirheumatic treatment? Semin Arthritis 3. Franchimont D. Overview of the actions of glucocorti- Rheum. 2007;36(5):278–86. coids on the immune response: a good model to char- 16. Raikin SM, Kane J, Ciminiello ME. Risk factors for acterize new pathways of immunosuppression for new incision-healing complications following total ankle treatment strategies. Ann N Y Acad Sci. 2004;1024: arthroplasty. J Bone Joint Surg Am. 2010;92(12): 124–37. 2150–5. 4. Ruyssen-Witrand A, Fautrel B, Saraux A, Le-Loet X, 17. Jamsen E, Huhtala H, Puolakka T, Moilanen T. Risk Pham T. Infections induced by low-dose corticoster- factors for infection after knee arthroplasty. A regis- oids in rheumatoid arthritis: a systematic literature ter-based analysis of 43,149 cases. J Bone Joint Surg review. Joint Bone Spine. 2010;77(3):246–51. Am. 2009;91(1):38–47. 5. Jain A, Witbreuk M, Ball C, Nanchahal J. Infl uence of 18. Soohoo NF, Farng E, Lieberman JR, Chambers L, steroids and methotrexate on wound complications Zingmond DS. Factors that predict short-term compli- after elective rheumatoid hand and wrist surgery. cation rates after total hip arthroplasty. Clin Orthop J Hand Surg Am. 2002;27(3):449–55. Relat Res. 2010;468(9):2363–71. 6. Murata K, Yasuda T, Ito H, Yoshida M, Shimizu M, 19. Shih LY, Chen TH, Lo WH, Yang DJ. Total hip arthro- Nakamura T. Lack of increase in postoperative compli- plasty in patients with ankylosing spondylitis: long- cations with low-dose methotrexate therapy in patients term followup. J Rheumatol. 1995;22(9):1704–9. 21 Postoperative Fever and Infection in Immunosuppressed Patients 259

20. Sweeney S, Gupta R, Taylor G, Calin A. Total hip 25. Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, arthroplasty in ankylosing spondylitis: outcome in O’Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren 340 patients. J Rheumatol. 2001;28(8):1862–6. DK. Clinical practice guidelines for the diagnosis and 21. Vaahtovuo J, Munukka E, Korkeamaki M, Luukkainen management of intravascular catheter-related infection: R, Toivanen P. Fecal microbiota in early rheumatoid 2009 update by the infectious diseases society of arthritis. J Rheumatol. 2008;35(8):1500–5. America. Clin Infect Dis. 2009;49(1):1–45. 22. Bassetti S, Wasmer S, Hasler P, Vogt T, Nogarth D, 26. Das R, Feuerstadt P, Brandt LJ. Glucocorticoids are Frei R, Widmer AF. Staphylococcus aureus in patients associated with increased risk of short-term mortality with rheumatoid arthritis under conventional and anti- in hospitalized patients with clostridium diffi cile- tumor necrosis factor-alpha treatment. J Rheumatol. associated disease. Am J Gastroenterol. 2010;105(9): 2005;32(11):2125–9. 2040–9. 23. Jackson MS, Bagg J, Gupta MN, Sturrock RD. Oral 27. Ward DT, Hansen EN, Takemoto SK, Bozic KJ. Cost carriage of staphylococci in patients with rheuma- and effectiveness of postoperative fever diagnostic toid arthritis. Rheumatology (Oxford). 1999;38(6): evaluation in total joint arthroplasty patients. 572–5. J Arthroplasty. 2010;25(6 Suppl):43–8. 24. Laudien M, Gadola SD, Podschun R, Hedderich J, 28. Kawakami K, Ikari K, Kawamura K, Tsukahara S, Paulsen J, Reinhold-Keller E, Csernok E, Ambrosch Iwamoto T, Yano K, Sakuma Y, Tokita A, Momohara P, Hellmich B, Moosig F, Gross WL, Sahly H, S. Complications and features after joint surgery in Lamprecht P. Nasal carriage of Staphylococcus aureus rheumatoid arthritis patients treated with tumour and endonasal activity in Wegener s granulomatosis necrosis factor-alpha blockers: perioperative interrup- as compared to rheumatoid arthritis and chronic tion of tumour necrosis factor-alpha blockers decreases Rhinosinusitis with nasal polyps. Clin Exp Rheumatol. complications? Rheumatology (Oxford). 2010;49(2): 2010;28(1 Suppl 57):51–5. 341–7. Diagnosis and Management of Prosthetic Joint Infection 2 2

Steven K. Schmitt

sion since it can be both a pathogen and a culture Introduction contaminant. Many authorities require isolation from two deep cultures to diagnose P. acnes PJI. Joint arthroplasty has become commonplace in Fungal and mycobacterial PJI are rare compared the United States, with more than 1,000,000 per- to bacterial PJI [4– 6 ] . Because they are much less formed per annum. Infection is one of the most common and require specifi c culture media, diag- feared complications of this procedure, occurring nosis is often delayed. Treatment of fungal and in 0.5–2.0% of episodes [ 1 ] . The estimated cost mycobacterial PJI is complex, and infectious dis- of diagnosis and treatment of prosthetic joint eases consultation should be sought. infection (PJI) is $30,000–50,000 per episode Prosthetic joint infections are polymicrobial [1 ] . Early recognition and effective management in 19% of cases [7 ] , tending to arise in older can help minimize the morbidity and cost of this patients with soft tissue defects or wound drain- feared complication. age. Methicillin-resistant Staphylococcus aureus and anaerobes occur in a higher proportion of polymicrobial infections than in monomicrobial Microbiology infections. A smaller proportion of episodes are culture negative, usually because of fastidious, A majority of PJI are caused by Gram-positive dif fi cult to culture organisms or prior antimicro- pathogens (see Table 22.1 ). Staphylococcus bial therapy [8 ] . aureus and coagulase-negative staphylococci are most commonly isolated, followed by strepto- cocci. Aerobic and anaerobic Gram-negative Diagnosis pathogens are less common, but are often severe [2 ] . Propionibacterium acnes has recently been Because no single diagnostic test reliably identi fi es identifi ed as a common cause of prosthetic shoul- prosthetic joint infection, the diagnosis usually der infection [3 ] . The isolation of this member of involves multiple modalities (see Table 22.2 ). In the normal skin fl ora from deep culture in pros- the preoperative phase, these include history and thetic joint revision surgery often causes confu- physical examination, blood testing, synovial fl uid analysis, and radiographic studies. Most prosthetic joint infections arise from S. K. Schmitt , M.D. () perioperative seeding of organisms, and the tim- Department of Infectious Disease , Cleveland Clinic ing and symptoms vary widely according to the Foundation , 9500 Euclid Avenue Desk G-21 , Cleveland , OH 44195 , USA offending microbe. A complete history and phys- e-mail: [email protected] ical examination may give clues to the pathogen.

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 261 DOI 10.1007/978-1-4614-2203-7_22, © Springer Science+Business Media, LLC 2013 262 S.K. Schmitt

Table 22.1 Microbiology of prosthetic joint infections Organism Percentage of episodes (%) Staphylococcus aureus 32 Coagulase-negative 23 staphylococcus species Streptococci 14 Gram-negative bacilli 6 Enterococci 3 Gram-positive bacilli 1 Anaerobes 1 Fungi 1 Polymicrobial 8 Culture-negative 8 Other 2 Fig. 22.1 Erythema and swelling in infected prosthetic Adapted from Marculescu et al. [29 ] knee

Table 22.2 Risk factors for prosthetic joint infection A variety of blood tests have been used in the Evidence-based risk Non-evidence-based risk diagnosis of prosthetic joint infection. A com- factors factors plete blood count with differential may show leu- 1. Prior septic arthritis of 1. Bacteremia or candi- same knee joint demia within 1 year kocytosis or may be entirely normal, depending 2. Prior super fi cial wound 2. Prior episodes of on the immune status of the host and the viru- infection overlying prosthetic joint infection lence of the pathogen. The erythrocyte sedimen- prosthesis at different sites tation rate (ESR) and C-reactive protein (CRP) 3. Obesity 3. Lack of skin integrity are commonly used to attempt to detect 4. Operative duration 4. Injection drug use infl ammation as a marker for PJI. These have >2.5 h poor overall sensitivity to detect infection at stan- 5. Immunosuppressive 5. MRSA infection within disease or treatment 3 years dard cutoff levels (ESR = 30 mm/h, CRP = 10 mg/l) 6. Active infection at [ 9] , possibly due to the prevalence of less virulent another anatomical site pathogens or prior antibiotic therapy. A recent Adapted from American Academy of Orthopaedic review of the use of WSR and CRP in PJI [10 ] Surgeons [23 ] suggests that operating characteristics can be improved with statistical optimization of cutoff Infections with more virulent pathogens such as levels for hip (ESR = 13 mm/h, CRP = 10.3 mg/l) Staphylococcus aureus and Gram-negative bacilli and knee (ESR = 19 mm/h, CRP = 14.5 mg/l) typically present within 90 days after surgery prostheses. It is important to note that ESR can with acute onset of fever, pain, and obvious local increase with normal aging; most studies of WSR signs such as swelling, warmth, and erythema in PJI do not stratify by age. Several newer (see Fig. 22.1 ). In contrast, infections with less infl ammatory markers have also been studied as virulent pathogens such as coagulase-negative potential diagnostic tools. Of these, the serum staphylococci, viridans streptococci, and IL-6 level shows promise, with improved sensi- Propionibacterium acnes tend to present with tivity and speci fi city over the ESR and CRP in delayed, less acute courses. Pain, sinus tract one recent analysis [11 ] . drainage, and prosthesis loosening predominate Synovial fl uid analysis should be obtained in these cases. Infections seeded by the hematog- when there is clinical suspicion for PJI. The syn- enous route are most commonly due to virulent ovial fl uid white blood cell count considered pathogens such as Staphylococcus aureus and diagnostic of infection is much different for pros- beta-hemolytic streptococci and may present thetic joints than for native septic arthritis, owing with severe symptoms and signs at any time after to overall less virulent organisms than in native prosthesis implant. joint infection and alterations in local immune 22 Diagnosis and Management of Prosthetic Joint Infection 263 function engendered by the prosthesis [ 12, 13 ] . staining of joint fl uid offers rapid information, but Whereas fl uid from infected native joints often poor sensitivity and specifi city [ 19, 20 ] . This has more than 50,000 WBC/mm [3 ] , prosthetic modality can be misleading and should not be used joints are considered likely infected at a cutoff of for clinical decision making. Information may be 1,700 WBC/mm [ 3 ] . Synovial fl uid differential obtained rapidly from frozen sections of peripros- may also be helpful in PJI diagnosis; more than thetic tissue. A fi nding of acute in fl ammation, 65% neutrophils is considered infected [ 12, 13 ] . defi ned as at least fi ve neutrophils in each of at Synovial fl uid for culture should be inoculated least three high-powered fi elds, suggests infection into a blood culture bottle [14 ] , which confers a [21, 22 ] . It is important to note that frozen section sensitivity of 56–75% and a specifi city approach- criteria have been adequately validated in fi rst- ing 100% [ 15, 16 ] . It must be noted that a nega- stage revision and not in second-stage reimplanta- tive preoperative synovial fl uid culture does not tion and that the pathologist’s experience and exclude infection. sampling error may in fl uence accuracy. Plain radiographs alone are inadequate for A new guideline from the American Academy diagnosis of PJI since the classic fi ndings of of Orthopaedic Surgeons on the diagnosis of pros- lucency and the osteolysis are nonspeci fi c. thetic joint infections [23 ] recommends that diag- Plain radiographs do have value in diagnosing nostic choices be dictated by whether there is a mechanical dysfunction and dislocation of pros- lower or higher probability of infection (see theses. Cross-sectional imaging modalities Fig. 22.2 ). Patients are placed in the higher-risk such as computed tomography (CT) or magnetic category based on the presence of pain or stiffness resonance imaging (MRI) are subject to scatter and either local examination fi ndings of infection, artifact. Given these limitations, nuclear studies early radiographic osteolysis or prosthesis loosen- have signi fi cant value in the preoperative diag- ing, or risk factors for infection. The authors rec- nosis of PJI. Technetium-99m bone scanning is ommend aspiration of hip or knee fl uid whenever sensitive but not speci fi c for PJI, and remains the ESR or CRP is abnormal, and deem infection positive for several months after surgery even likely when the fl uid cell count suggests infection in uninfected patients. The combination of and the culture is positive. In this scheme, if the indium-111-labeled leukocyte imaging and tech- cell count and culture give discordant results (i.e., netium-99m-labeled sulfur colloid has a 95% only one suggests infection), then nuclear imaging diagnostic accuracy [17 ] , but is expensive and or intraoperative synovial fl uid and pathology can time-consuming. Other studies suggest a role support a diagnosis of infection. for 18F- fl uorodeoxyglucose positron-emission Appropriate and effective medical and surgi- tomography (FDG-PET), which has a 95% cal management of PJI is best facilitated by cul- sensitivity and 93% speci fi city in prosthetic hip ture isolation of the offending pathogen(s). infection [13 ] . False-positive FDG-PET testing Intraoperative tissue culture is preferred to swab can arise from infl ammation in areas of aseptic culture, but suffers from a number of challenges. loosening [18 ] . Yield of intraoperative cultures is reduced by Given the potential uncertainty that exists in prior antimicrobial therapy given systemically or serologic and radiographic studies, the patient included in cement spacers, fastidious pathogens may reach the operative theater with a suspected that are diffi cult to cultivate or require prolonged but unconfi rmed diagnosis of infection. Indeed, cultivation times. Organisms may be associated patients with infections with indolent pathogens with bio fi lms, making them dif fi cult to dislodge such as P. acnes or coagulase-negative staphylo- into culture media during specimen preparation. cocci may present to surgery with pain as a surgi- In addition, single positive cultures growing cal indication, but little clinical suspicion of indolent skin fl ora often represent culture con- infection. In these circumstances, intraoperative tamination with poor correlation to clinical cir- histopathology and microbiology may assist in cumstances and histopathology [24 ] . A total of 2–3 clinical decision making. Intraoperative Gram cultures growing the same isolate are considered 264 S.K. Schmitt

History and physical examination suspicious for infection

CBC/differential Synovial fluid EST analysis and culture CRP

If fluid analysis or If both positive, culture positive but likely infection not both, reaspirate

Fluid analysis or If both negative, If both positive, culture positive likely not infection likely infection but not both

Intraoperative fluid If no surgery, analysis, pathology consider Tc-99 bone positive, likely scan and In-111 infection WBC scan

If positive, If negative, likely likely infection not infection

Fig. 22.2 Preoperative evaluation of suspected prosthetic hip or knee infection (Adapted from American Academy of Orthopaedic Surgeons [23 ] )

diagnostic of infection [19 ] . To minimize con- Finally, recent data suggest that sonication of founders, several measures can be undertaken. prosthesis components can liberate bio fi lm- First, most authorities recommend that antimi- associated organisms for culture, markedly crobial therapy should be discontinued at least increasing culture yield [15 ] . 2 weeks before surgery and that antibiotics given Microbiologic diagnosis of infectious dis- for prophylaxis of surgical site infections should eases is undergoing a dramatic, if slow, revolu- not commence until specimens are collected tion, as molecular assays are being employed to though this suggestion has been recently disputed supplement or in some cases supplant conven- [25 ] . Next, surgical specimens should include at tional culture techniques. Broad-based “univer- least 5–6 intraoperative tissue samples from vari- sal” poly merase chain reaction assays may detect ous sites [19 ] . When slow-growing or fastidious uncultured organisms, but do not identify speci fi c pathogens such as Propionibacterium acnes, classes of microbes, fully delineate antimicro- fungi, or mycobacteria are suspected, there bial susceptibility, or distinguish between viable should be advance communication between clini- and nonviable organisms [26 ] . Additional cian members of the care team, such orthopedic speci fi city may be attained by the use of more surgery and infectious diseases specialists, and speci fi c primers for classes or individual species. the microbiology and pathology laboratories. This is particularly helpful with organisms that 22 Diagnosis and Management of Prosthetic Joint Infection 265 are diffi cult or slow to cultivate, such as fungi treated with prolonged intravenous and then and mycobacteria. One of the pitfalls of PCR use chronic suppressive antimicrobial therapy. Late- in this setting is the detection of nucleic acids onset, chronic prosthetic joint infections are from nonviable organisms. The use of “live or dif fi cult to treat without prosthesis removal and dead” stains may help determine when organ- replacement. This can take place either in a one- isms detected by PCR are clinically signi fi cant stage or two-stage procedure, both with pro- [ 27] . Further development and validation of longed systemic antimicrobial therapy. molecular microbiologic techniques is needed to Debridement with retention of components fully realize their considerable potential. requires that the prosthesis remain well fi xed; a loose prosthesis requires removal and replace- ment. The former strategy is usually employed Management for postoperative infections within 1 month of surgery, for acute hematogenous infections Treatment of prosthetic joint infections requires a within 2 weeks of onset, and for low virulence combination of medical and surgical therapies. organisms such as coagulase-negative staphylo- While the goal of management is function with- cocci, Propionibacterium acnes, and viridans out pain or complication of infection, cure of streptococci. Surgical intervention is typically infection is not always possible, and aggressive followed by long-tem antibiotic suppression. The treatment is not always desirable. In addition, success of this regimen ranges from 40% among management protocols are limited by the fact that patients followed for an average of 5.7 years in there are no prospective randomized controlled one series [28 ] to 60% followed for 2 years after clinical trials comparing different surgical thera- surgery in another [ 29 ] . The infecting microor- pies or combinations of medical and surgical ganism can signifi cantly impact the likelihood of therapies. For this reason, treatment decisions are success. Debridement and retention achieved often based on case series, smaller randomized treatment success in only 16% of patients with trials, local treatment culture, case characteris- MRSA PJI treated by Bradbury et al. [ 30 ] . tics, and patient and family preferences. Among 99 patients treated by Marculsecu et al., Antibiotic choices should be driven by culture 78% of infections caused by streptococci were data. Though in-depth analysis of antimicrobial successfully treated, while only 12% success was choices for PJI is not possible within the confi nes achieved in infections due to Staphylococcus of this discussion, empiric therapy after culture aureus [ 29] . In a multivariate analysis of this collection includes broad-spectrum antibacterials. same cohort, duration of symptoms of 8 days or Common choices include vancomycin (for Gram- more and presence of a sinus tract predicted fail- positive cocci, including methicillin-resistant ure of the strategy [29 ] . staphylococci) and an agent directed at Gram- The exact type and duration of antibiotic ther- negative bacilli, such as ceftazidime, a beta- apy following debridement and retention have lactam/beta-lactamase inhibitor combination (e.g., not been adequately evaluated. Most experts piperacillin-tazobactam), or a fl uoroquinolone. advocate 6–8 weeks of parenteral antibiotic ther- From a practical perspective, the clinical tim- apy, followed by prolonged or chronic oral anti- ing of the infection and the organism can play an biotic suppression with an agent that is well important role in choice of treatment regimen. tolerated by the patient. Because the pathogenesis Early infections, either within a month of pros- of prosthetic joint infection is promoted by thesis implant or acute infections seeded by the biofi lm production, agents that enter biofi lms can hematogenous route, are most often treated by be useful adjuncts. Rifampin is an oral agent with debridement with retention of prosthesis compo- antistaphylococcal activity and penetrates nents, often with polyethylene liner exchange, biofi lms well. Use of rifampin with another agent and prolonged systemic antimicrobial therapy. improves chronic suppressive antibiotic therapy Infections discovered through unanticipated in staphylococcal PJI, with success in 12/12 intraoperative culture growth are most often patients in one prospective study [31 ] and 13/14 266 S.K. Schmitt in another [ 32 ] . Of note, resistance to rifampin develops rapidly in monotherapy, making combi- nation with a second agent essential. Reimplantation surgery offers a better chance of fully functional recovery than does debride- ment and retention. Reimplantation can be per- formed as a single-stage prosthesis exchange or a two-stage process with prosthesis removal and placement of a cement spacer, followed by anti- microbial therapy and ultimately reimplantation. Data suggest that the two-stage process has a greater rate of success [33 ] , but that one-stage replacement can be used in a selected patient population. Criteria that predict success with one-stage replacement include good overall patient health, a known, drug-susceptible patho- gen (i.e., not drug-resistant or a diffi cult to treat organism such as S. aureus , Enterococcus sp., or fungi), adequate soft tissue in the surgical fi eld (i.e., no sinus tract); adequate bone without need for bone grafting after prosthesis removal, and use of cement impregnated with an appropriate antimicrobial [34 ] . One-stage revision is less suc- cessful than two-stage revision for infection in patients with rheumatoid arthritis [33 ] . Following Fig. 22.3 Cement spacer placed after explantation of a single-stage replacement, treatment with paren- infected shoulder prosthesis teral antimicrobial therapy is indicated. In a two-stage replacement, the infected prosthesis is removed, and an antimicrobial- The optimal timing for reimplantation after impregnated cement spacer is placed (see prosthesis removal is the subject of some contro- Fig. 22.3 ). A new prosthesis is reimplanted after versy. There is concern that early reimplantation clearance of infection. Spacers can be articulating after discontinuation of systemic antimicrobials or nonarticulating, with articulating spacers may provide insuffi cient time to detect relapse of offering additional function. Vancomycin and infection, risking reimplantation of a new prosthe- tobramycin are the agents most frequently used sis into a persistently infected bed. Criteria used to in spacers. Though these are usually well tolerated, proceed with reimplantation after discontinuation there are case reports of renal toxicity and of antimicrobials have included sterile cultures signi fi cant systemic levels of these agents [35 ] . from an aspirate of the infected joint, normal eryth- Systemic antimicrobial therapy is indicated rocyte sedimentation rate, and normal C-reactive after prosthesis removal, but the optimal agent and protein. Unfortunately, all of these are fl awed since duration are unknown. Most experts recommend synovial fl uid cultures may have a low yield after at least 4–6 weeks of systemic therapy. Multiple antimicrobial therapy and acute-phase reactants combinations of parenteral and oral antimicrobials may be elevated without evidence of infection [ 37 ] . have been used with success, including some all- Studies of other in fl ammatory markers, such as parenteral and some all-oral regimens, and some interleukin-6, and molecular detection of organ- containing shorter courses of parenteral therapy isms in joint fl uid are in progress. (2 weeks) followed by oral therapy of several The outcome of staged reimplantation may be weeks to months duration [36 ] . in fl uenced by the joint involved and the infecting 22 Diagnosis and Management of Prosthetic Joint Infection 267 microorganism. Among 96 patients with staphy- markers for infection and further development lococcal PJI studied by Kurd and colleagues, and validation of molecular diagnostics to assist infections with methicillin-resistant organisms in culture-negative cases. Additional study of were more than three times more likely to fail a medical/surgical management for specifi c patient two-stage strategy than patients with methicillin- factors and organisms in PJI may help standardize susceptible organisms [38 ] . Reinfection need not treatment regimens, reduce costs, and improve always occur with the same organism: of 37 outcomes. patients with methicillin-resistant staphylococcal PJI treated by Mittal and colleagues, four relapsed with the same organism and fi ve with a different References microbe [39 ] . Though dif fi cult to treat, infections due to Candida species may be successfully man- 1. Matthews PC, Berendt AR, McNally MA, Byren I. aged by a cautious two-stage replacement; 8 of Diagnosis and management of prosthetic joint infec- tion. BMJ. 2009;338:b1773. 10 patients managed in this fashion by Phelan 2. Lentino JR. Prosthetic joint infections: bane of ortho- and colleagues achieved a favorable result [40 ] . pedists, challenge for infectious disease specialists. When the result of two-stage reimplantation is Clin Infect Dis. 2003;36(9):1157–61. not favorable and reinfection occurs, management 3. Levy PY, Fenollar F, Stein A, et al. Propionibacterium acnes postoperative shoulder arthritis: an emerging is diffi cult. Multiple approaches may be taken, clinical entity. Clin Infect Dis. 2008;46(12):1884–6. including a second two-stage revision, pseudart- 4. Azzam K, Parvizi J, Jungkind D, et al. Microbiological, hrosis, arthrodesis, and chronic oral antimicro- clinical, and surgical features of fungal prosthetic bial suppression. Amputation is usually reserved joint infections: a multi-institutional experience. J Bone Joint Surg Am. 2009;91 Suppl 6:142–9. for the case of acute or chronic infection that is 5. Marculescu CE, Berbari EF, Cockerill 3rd FR, Osmon uncontrolled. In one study of 34 infected hip DR. Fungi, mycobacteria, zoonotic and other organ- prostheses that were reinfected after two-stage isms in prosthetic joint infection. Clin Orthop Relat revision, successful treatment, de fi ned as a func- Res. 2006;451:64–72. 6. Berbari EF, Hanssen AD, Duffy MC, Steckelberg JM, tional prosthesis, occurred in only one third of Osmon DR. Prosthetic joint infection due to patients [41 ] . Hansson et al. [ 42 ] reported on 24 Mycobacterium tuberculosis: a case series and review patients with reinfected knee prostheses, who of the literature. Am J Orthop (Belle Mead NJ). required arthrodesis in ten cases, suppressive 1998;27(3):219–27. 7. Marculescu CE, Cantey JR. Polymicrobial prosthetic antibiotic therapy in fi ve cases (four unsuccess- joint infections: risk factors and outcome. Clin Orthop fully suppressed), and four above-knee amputa- Relat Res. 2008;466(6):1397–404. tions. Only one patient achieved an infection-free, 8. Berbari EF, Marculescu C, Sia I, et al. Culture-negative functional prosthesis. prosthetic joint infection. Clin Infect Dis. 2007;45(9):1113–9. Chronic oral antibiotic suppression is often 9. Piper KE, Jacobson MJ, Co fi eld RH, et al. employed when prosthesis removal is not possible Microbiologic diagnosis of prosthetic shoulder infec- or reasonable. Situations that suggest a use for tion by use of implant sonication. J Clin Microbiol. chronic suppression include a placement of new 2009;47(6):1878–84. 10. Piper KE, Fernandez-Sampedro M, Steckelberg KE, prosthesis with an unanticipated intraoperative et al. C-reactive protein, erythrocyte sedimentation culture isolate, inability to remove the prosthesis rate and orthopedic implant infection. PLoS One. for technical reasons, or a patient who is too ill to 2010;5(2):e9358. undergo replacement. Successful suppression 11. Berbari E, Mabry T, Tsaras G, et al. In fl ammatory blood laboratory levels as markers of prosthetic joint requires patient tolerance of an appropriate oral infection: a systematic review and meta-analysis. J antibiotic. Most studies addressing oral antibiotic Bone Joint Surg Am. 2010;92(11):2102–9. suppression are small and nonrandomized, yield- 12. Trampuz A, Hanssen AD, Osmon DR, Mandrekar J, ing success rates in the range of 38–86% with Steckelberg JM, Patel R. Synovial fl uid leukocyte count and differential for the diagnosis of prosthetic follow-up of at least 12 months [29, 43, 44 ] . knee infection. Am J Med. 2004;117(8):556–62. Future directions for study in diagnosis of 13. Parvizi J, Ghanem E, Menashe S, Barrack RL, Bauer PJI include more sensitive and speci fi c blood TW. Periprosthetic infection: what are the diagnostic 268 S.K. Schmitt

challenges? J Bone Joint Surg Am. 2006;88 Suppl 28. Azzam KA, Seeley M, Ghanem E, Austin MS, Purtill 4:138–47. JJ, Parvizi J. Irrigation and debridement in the man- 14. Hughes JG, Vetter EA, Patel R, et al. Culture with agement of prosthetic joint infection: traditional indi- BACTEC Peds Plus/F bottle compared with conven- cations revisited. J Arthroplasty. 2010;25:1022–7. tional methods for detection of bacteria in synovial 29. Marculescu CE, Berbari EF, Hanssen AD, et al. fl uid. J Clin Microbiol. 2001;39(12):4468–71. Outcome of prosthetic joint infections treated with 15. Trampuz A, Piper KE, Jacobson MJ, et al. Sonication debridement and retention of components. Clin Infect of removed hip and knee prostheses for diagnosis of Dis. 2006;42(4):471–8. infection. N Engl J Med. 2007;357(7):654–63. 30. Bradbury T, Fehring TK, Taunton M, et al. The fate of 16. Fink B, Makowiak C, Fuerst M, Berger I, Schafer P, acute methicillin-resistant Staphylococcus aureus Frommelt L. The value of synovial biopsy, joint aspi- periprosthetic knee infections treated by open debri- ration and C-reactive protein in the diagnosis of late dement and retention of components. J Arthroplasty. peri-prosthetic infection of total knee replacements. J 2009;24(6 Suppl):101–4. Bone Joint Surg Br. 2008;90(7):874–8. 31. Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner 17. Sampedro MF, Patel R. Infections associated with PE. Role of rifampin for treatment of orthopedic long-term prosthetic devices. Infect Dis Clin North implant-related staphylococcal infections: a random- Am. 2007;21(3):785–819. ized controlled trial. Foreign-body infection (FBI) 18. Reinartz P, Mumme T, Hermanns B, et al. Radionuclide study group. JAMA. 1998;279(19):1537–41. imaging of the painful hip arthroplasty: positron- 32. El Helou OC, Berbari EF, Lahr BD, et al. Effi cacy and emission tomography versus triple-phase bone scan- safety of rifampin containing regimen for staphylo- ning. J Bone Joint Surg Br. 2005;87(4):465–70. coccal prosthetic joint infections treated with debride- 19. Atkins BL, Athanasou N, Deeks JJ, et al. Prospective ment and retention. Eur J Clin Microbiol Infect Dis. evaluation of criteria for microbiological diagnosis of 2010;29(8):961–7. prosthetic-joint infection at revision arthroplasty. The 33. Berbari EF, Osmon DR, Duffy MC, et al. Outcome of OSIRIS collaborative study group. J Clin Microbiol. prosthetic joint infection in patients with rheumatoid 1998;36(10):2932–9. arthritis: the impact of medical and surgical therapy in 20. Della Valle CJ, Scher DM, Kim YH, et al. The role of 200 episodes. Clin Infect Dis. 2006;42(2):216–23. intraoperative gram stain in revision total joint arthro- 34. Hanssen AD, Osmon DR. Assessment of patient plasty. J Arthroplasty. 1999;14(4):500–4. selection criteria for treatment of the infected hip 21. Ko PS, Ip D, Chow KP, Cheung F, Lee OB, Lam JJ. arthroplasty. Clin Orthop Relat Res. 2000;381: The role of intraoperative frozen section in decision 91–100. making in revision hip and knee arthroplasties in a 35. Cui Q, Mihalko WM, Shields JS, Ries M, Saleh KJ. local community hospital. J Arthroplasty. 2005;20(2): Antibiotic-impregnated cement spacers for the treat- 189–95. ment of infection associated with total hip or knee 22. Wong YC, Lee QJ, Wai YL, Ng WF. Intraoperative arthroplasty. J Bone Joint Surg Am. 2007;89(4): frozen section for detecting active infection in failed 871–82. hip and knee arthroplasties. J Arthroplasty. 2005;20(8): 36. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint 1015–20. infections. N Engl J Med. 2004;351(16):1645–54. 23. American Academy of Orthopedic Surgeons. The 37. Ghanem E, Antoci Jr V, Pulido L, Joshi A, Hozack W, diagnosis of periprosthetic infections of the hip and Parvizi J. The use of receiver operating characteristics knee: guideline and evidence report. http://www.aaos. analysis in determining erythrocyte sedimentation org/research/guidelines/PJIguideline.pdf (2010). rate and C-reactive protein levels in diagnosing Accessed 30 Sept 2010. periprosthetic infection prior to revision total hip 24. Barrack RL, Aggarwal A, Burnett RS, et al. The fate arthroplasty. Int J Infect Dis. 2009;13(6):e444–9. of the unexpected positive intraoperative cultures after 38. Kurd MF, Ghanem E, Steinbrecher J, Parvizi J. Two- revision total knee arthroplasty. J Arthroplasty. stage exchange knee arthroplasty: does resistance of 2007;22(6 Suppl 2):94–9. the infecting organism in fl uence the outcome? Clin 25. Ghanem E, Parvizi J, Clohisy J, Burnett S, Sharkey Orthop Relat Res. 2010;468(8):2060–6. PF, Barrack R. Perioperative antibiotics should not be 39. Mittal Y, Fehring TK, Hanssen A, Marculescu C, withheld in proven cases of periprosthetic infection. Odum SM, Osmon D. Two-stage reimplantation for Clin Orthop Relat Res. 2007;461:44–7. periprosthetic knee infection involving resistant organ- 26. Bauer TW, Parvizi J, Kobayashi N, Krebs V. Diagnosis isms. J Bone Joint Surg Am. 2007;89(6):1227–31. of periprosthetic infection. J Bone Joint Surg Am. 40. Phelan DM, Osmon DR, Keating MR, Hanssen AD. 2006;88(4):869–82. Delayed reimplantation arthroplasty for candidal pros- 27. Kobayashi H, Oethinger M, Tuohy MJ, Hall GS, thetic joint infection: a report of 4 cases and review of Bauer TW. Distinction between intact and antibiotic- the literature. Clin Infect Dis. 2002;34(7):930–8. inactivated bacteria by real-time PCR after treatment 41. Pagnano MW, Trousdale RT, Hanssen AD. Outcome with propidium monoazide. J Orthop Res. 2010; after reinfection following reimplantation hip arthro- 28(9):1245–51. plasty. Clin Orthop Relat Res. 1997;338:192–204. 22 Diagnosis and Management of Prosthetic Joint Infection 269

42. Hanssen AD, Trousdale RT, Osmon DR. Patient out- treated with debridement and prosthesis retention. come with reinfection following reimplantation for Clin Infect Dis. 1997;24(5):914–9. the infected total knee arthroplasty. Clin Orthop Relat 44. Rao N, Crossett LS, Sinha RK, Le Frock JL. Long- Res. 1995;321:55–67. term suppression of infection in total joint 43. Brandt CM, Sistrunk WW, Duffy MC, et al. arthroplasty. Clin Orthop Relat Res. 2003;414: Staphylococcus aureus prosthetic joint infection 55–60. Perioperative Gout and Pseudogout 2 3 Brian F. Mandell

medical indications is also associated with post- Introduction admission fl ares. A gout fl are may result from fl uctuations in Postoperative fl ares in crystal-induced arthritis, the level of serum urate elicited by withholding most frequently gout, are relatively common. Yet hypouricemic therapy, altered dietary intake, or there are few studies which speci fi cally describe the addition of new medications or intravenous this clinical entity and no controlled interven- fl uids which can all alter the serum urate level. tional studies which address prophylaxis or treat- Acute increases and especially acute reductions ment in the perioperative setting. Hence, in serum urate levels are well known to elicit suggestions regarding management are by neces- attacks of acute gout [3 ] . Craig et al. noted that sity pragmatic and experience based. patients who suffered postoperative fl ares of gout had experienced a greater and more rapid change in their serum urate level compared to those with Demographics a history of gout but no postoperative fl are [1 ] . This observation is consistent with clinical expe- Patients who suffer a fl are in gout or “pseudog- rience and clinical trial data following introduc- out” (calcium pyrophosphate-associated arthritis) tion of hypouricemic therapy in the outpatient in the postoperative setting have usually had prior setting. Most patients with postsurgical gout are attacks. In two published studies which included men, paralleling the demographics in the general 119 patients with postsurgical gout [ 1, 2 ] , the population. Nonetheless, gout does occur in overwhelming majority of the postoperative gout women, and this diagnosis should not be over- fl ares occurred in patients with a history of gout. looked in the female patient with postoperative Yet this historical information is infrequently col- acute arthritis. lected from patients during the preoperative risk The explanation for perioperative fl ares in assessment process. The exact incidence of gout pseudogout is less clear; perhaps fl ares result or pseudogout attacks following general or ortho- from changes in serum ionized calcium and phos- pedic surgery is not known. Hospitalization for phate levels. Signifi cant fl uctuations in these electrolytes and attacks of pseudogout are expected following parathyroid surgery [ 4 ] , but almost 50% cases of postsurgical pseudogout in  B. F. Mandell , M.D., Ph.D., F.A.C.R., M.A.C.P. ( ) one series occurred in patients having had ortho- Department of Rheumatic and Immunologic Disease , Cleveland Clinic , 9500 Euclid Ave , pedic surgery [ 5 ] . About a third of patients with Cleveland , OH 44195 , USA postoperative pseudogout did not have a prior e-mail: [email protected] history of these attacks.

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 271 DOI 10.1007/978-1-4614-2203-7_23, © Springer Science+Business Media, LLC 2013 272 B.F. Mandell

the cause of acute arthritis is not a useful approach. Clinical Presentation and Diagnosis Many patients without gouty arthritis have hype- ruricemia. In hospitalized patients with acute The few clinical series of postoperative gout indi- arthritis, approximately 50% of patients with cate that patients may present with acute onset of gout and 50% of patients with septic arthritis mono-, oligo-, or polyarticular arthritis. This is (and no synovial fl uid urate crystals) had hyper- similar to patients who experience acute gout as uricemia (Mandell, unpublished). Since a an outpatient, although multiple joints may be signi fi cant drop from an elevated preoperative more frequently involved in postsurgical attacks serum urate level to a normal level may precipi- (~44% of attacks). Attacks of gout or pseudogout tate a gout attack, the serum urate is also not a occur with a mean delay of about 4 days follow- sensitive test to diagnose gout. It is possible that ing surgery. Fever is common with both, and comparable postoperative fl uxes in the serum because temperature is regularly monitored in the calcium and phosphate levels precipitate fl ares in hospital, fever is likely to be more frequently pseudogout [6 ] . noted than in the community setting. In patients In the setting of acute arthritis, radiographs, who are intubated or unresponsive, fever may be other than suggesting the presence of soft tissue the only indication of acute crystal-induced or joint swelling, will re fl ect only the prior bone arthritis. Rigors rarely accompany an attack and architecture. Ultrasound (US) examination can should prompt an aggressive search for infection. accurately demonstrate joint effusions and A quick, but complete joint examination is an swelling of speci fi c tendons or bursae. Thus, the appropriate component of the evaluation of the US examination can be used to direct fl uid aspi- febrile patient in the postoperative setting. Special ration. Experienced musculoskeletal ultrasonog- attention should be focused on the lower extrem- raphers may also identify the characteristic ity joints, including the joints of the midfoot deposition of urate or calcium pyrophosphate which may present with diffuse foot discomfort crystals which would strongly support the diag- or tenderness and generalized warmth or swell- nosis of underlying gout or pseudogout. However, ing. These joints can be best examined by gently fi nding crystal deposition does not exclude the squeezing the midfoot. The fi rst MTP joint is not presence of coexistent infection; a joint which [1 ] invariably clinically involved in gout attacks. has been damaged from prior gout may be more Involvement of the knee joint or its periarticular likely to be “seeded” as a result of bacteremia. structures can occasionally be confused with a Additionally, it must be remembered that urate DVT, thus both possibilities should be considered crystals can be found in joint fl uids in between as a careful extremity examination is performed. acute attacks. Thus, if a patient with previous Fever can be striking in pseudogout attacks. gouty arthritis has an infected joint, crystals may The knee [5 ] and wrist are commonly involved be observed in the synovial fl uid, even though by pseudogout, as in gout. Wrist infl ammation infection has caused the acute arthritis. Since can easily mimic an infi ltrated hand IV or throm- hospitalized patients are at some risk for nosoco- bophlebitis of an intravenous line site. Meticulous mial bacteremia, I routinely send these synovial examination and ultrasound examination (if nec- in fl ammatory fl uids for culture. Nuclear scans essary) should permit distinction. and MRI will not distinguish crystalline from The standard laboratory examination and septic arthritis. radiographic imaging are not particularly helpful Gout and pseudogout are far more common in confi rming the diagnosis of acute crystal- than septic arthritis, but it is impossible on clini- induced arthritis. Leukocytosis and elevated acute cal grounds to reliably distinguish acute gout phase reactants (ESR, CRP) are frequently (pseudogout) from an acute joint infection, par- observed postoperatively and may also accom- ticularly when only a single joint is involved. pany crystal-induced or infectious arthritis. Even the fi rst MTP joint can be affected by infec- Checking for hyperuricemia to diagnose gout as tion. The diagnostic procedure required to make 23 Perioperative Gout and Pseudogout 273 a fi rm diagnosis is arthrocentesis with crystal helpful if a periarticular osteomyelitis is sus- analysis and cultures. Gram stains of synovial pected, with a “sympathetic” joint effusion. fl uids are very insensitive for bacterial infection Gout and pseudogout have been described in (likely less than 50%, even for staphylococcal patients with prosthetic joints, including newly infection). If the fl uid is infl ammatory (>7,500 placed ones. wbcs or >85% neutrophils), it should generally be sent for culture. A cell count estimate can be made immediately by viewing a drop of fresh Treatment of the Acute Attack fl uid under the microscope, but often the sample is routinely sent for total and differential cell Once gout or pseudogout is defi nitively diag- counts, crystal analysis, and culture. There is no nosed, there are a number of effective therapeutic value in obtaining synovial fl uid protein or glu- options. The choice of therapy is generally dic- cose levels. PCR is available in some medical tated by the presence of comorbidities which centers. Anaerobic cultures should be considered impose safety constraints, as well as the type of if the arthritis followed an abdominal procedure surgery which was performed (concern regarding which might have permitted seeding of anaer- any bleeding, risk of infection due to hyperglyce- obes. Routinely sending fl uid from an acutely mia, the need to avoid oral feeding) and amount in fl amed joint for mycobacterial or fungal cul- of time passed since the procedure. tures is not cost-ef fi cient, but these should be sent In patients with chronic kidney disease, acute if the patient has a known mycobacterial or postoperative renal injury, a history of severe fungal infection or if there is clinical suspicion gastritis, esophageal re fl ux, or peptic ulcer dis- for an underlying undiagnosed infection, particu- ease, NSAIDs (selective or unselective) are rela- larly in the setting of immunosuppression. If no tively strongly contraindicated. In patients who crystals are initially observed, in fl ammatory syn- are anticoagulated, have thrombocytopenia, or ovial fl uid should be cultured, and blood cultures have an increased risk of surgical or mucosal should also be obtained, even in the patient with bleeding, the nonselective NSAIDs should be a known underlying infl ammatory arthritis (i.e., avoided. The COX2 selective NSAID available rheumatoid or spondylitis) if the arthritis is acute in the United States, celecoxib, can affect kidney and mono- or oligoarticular. Empiric antibiotic function, but does not affect platelet function. It therapy should be considered or initiated depend- has not been rigorously assessed for ef fi cacy in ing upon the clinical circumstances. It must be treating acute gout. My experience using it is remembered to alert the microbiology laboratory limited, but I have seen benefi t from celecoxib if preoperative “prophylactic” antibiotics were when used short term in higher than usually pre- administered. The involved joints should be scribed doses (i.e., 400 mg twice daily initially). repeatedly aspirated, as frequently as necessary If the patient has none of the above risk factors to keep the fl uid to a minimum until infection is for complications from NSAIDs, is young and excluded by culture. The synovial fl uids should generally healthy, and there are no GI concerns also repeatedly be evaluated for the presence of related to the surgery, full dose NSAID therapy crystals (if not initially seen), since they might (i.e., indomethacin 50 mg tid, naproxen 500 mg have been missed on the fi rst fl uid analysis. If bid, etc.) can be utilized in conjunction with gas- acute arthritis is suspected on examination, but tric protection from a proton pump inhibitor. no fl uid is obtained, prompt ultrasound evalua- Although it is an empiric suggestion in this set- tion and directed joint or soft tissue aspiration ting, providing gastric protection seems reason- should be performed. If polarized microscopy is able when using high dose of an NSAID not immediately available, a sample should be following the stress of a surgical procedure. It saved in a clean syringe or red top tube for crystal should be noted that parenteral administration of analysis at a later time. Radiographs might be an NSAID (i.e., ketorolac) offers no safety 274 B.F. Mandell advantage. The NSAID should be continued the next 5Ð7 days. Some clinicians prefer initial until the response fully resolves, and then for twice daily dosing, and parenteral administration several more days if possible in order to avoid should be considered whenever absorption from return of the infl ammation. Based on clinical the GI tract is not assured. ACTH is effective and, experience [ 3] , narcotics are only partially effec- perhaps due to its direct peripheral anti- tive at relieving the pain in many patients and in fl ammatory activities in addition to its adrenal- may not be suf fi cient to enable ambulation and stimulating activity, some believe that it is more rehabilitation of the patient with lower extremity effective than prednisone. ACTH however is gout or pseudogout. expensive and should be given in high and repeat Historically, intravenous colchicine had been doses. Glucocorticoids in any form can have a used by many clinicians in the postoperative set- nonspecifi c antipyretic effect (as can NSAIDs) ting. It was cheap, easily administered, and, in a and will elicit a leukocytosis which may cause single low dose, extremely well tolerated and some diagnostic confusion. without GI side effects. But the intravenous for- Intra-articular steroid (i.e., triamcinolone, mulation is no longer available due to safety con- methylprednisolone) is quite effective at aborting cerns. Oral “low-dose” branded colchicine an attack of crystal-induced arthritis [ 7 ] and (1.8 mg) has been shown to signifi cantly reduce avoids systemic effects. However, infection the pain from acute gout in the outpatient setting, should be reasonably excluded prior to injection. with a minimum of GI side effects. However, it Not all joints are easily injected. has not been thoroughly studied in the postopera- A newer approach targets a cytokine mediator tive setting, and the amount and duration of ther- of gouty in fl ammation interleukin-1. The short-acting apy needed to achieve resolution (not just IL-1 receptor antagonist anakinra has been used and signi fi cant relief of pain) of the attack is not well is effective [ 8] , as is the long-acting monoclonal defi ned. Thus, the likelihood of GI side effects, anti-IL-1 antibody canakinumab, and the soluble which can provide a signi fi cant problem in the IL-1 receptor-FC fusion protein rilonacept given postoperative setting, is not known. Mainly for weekly. Although relatively expensive (~140$ per these reasons, at least some experienced clini- subcutaneous 100-mg dose), anakinra has been cians [3 ] avoid using oral colchicine as the pri- effective in refractory gout cases; poses none of mary therapy for postsurgical gout. The approach the metabolic, GI, or renal toxicities of the above- to treating gout attacks with one pill hourly until discussed alternatives; and thus may facilitate the patient experiences relief or the onset of GI more rapid discharge or continuation of rehabilita- symptoms is untenable in the postoperative set- tion by treating the painful arthritis. However, ting, and probably should be avoided in all there is concern regarding the risk of inability to patients. Colchicine (0.6 mg once or twice daily) deal well with low-grade postoperative infection, plays an invaluable role in the prophylaxis against and there are insuf fi cient data or experience to additional attacks. address this issue. Hence, if an anti-IL-1 strategy is Corticosteroids have long been used to treat to be used, there is theoretical preference to use a gout attacks, although older writings describe short-acting agent like anakinra. One protocol in “rebound” fl ares following steroid therapy. These using this agent is 100 mg subcutaneous injection apparent “rebounds” may have been due to an daily for 3 days. inappropriately short course of therapy with Hypouricemic therapies such as allopurinol or incomplete resolution of the attack. Thus, a dic- febuxostat do not decrease the in fl ammation of tum of steroid therapy for treating gout/pseudog- an acute gout attack and theoretically may even out is that a suf fi cient dose must be given for a prolong an attack (although this has not been suffi cient period of time. As an estimate, 0.75 mg/ clearly demonstrated to occur in the setting where kg of prednisone equivalent per dose can be given an acute attack is being otherwise appropriately until a day after the attack completely resolves, treated). Hypouricemic agents are not therapy for with subsequent tapering to discontinuation over acute gout, but as discussed below, must be 23 Perioperative Gout and Pseudogout 275

considered as part of the total management of the daily should be considered (ideally suf fi ciently patient with gout. in advance of surgery in order to assure that the Hypouricemic therapy does not affect the colchicine is tolerated and not causing diarrhea). patient with pseudogout; another reason to be as Postoperatively, the colchicine dosage may need certain as possible as to the specifi c crystal caus- to be adjusted or stopped if acute renal injury, ing the acute arthritis. signifi cant ileus, or biliary obstruction develops. Attention must also be paid to coadministration of drugs (such as clarithromycin) which affect Prevention of Postsurgical Gout the metabolism and distribution of colchicine. Due to undemonstrated effi cacy and the poten- As noted above, attacks of gout can be precipitated tial adverse effects noted above, NSAIDs are by sudden fl uctuations in the serum urate level, less ideal prophylactic medications. and the majority of patients with postsurgical gout If a patient has experienced an attack of gout or have had prior attacks. Thus, it may be possible to pseudogout in the hospital, the speci fi c diagnosis identify those patients more likely to suffer a post- and the basis for that diagnosis (hopefully a syn- operative gout attack and potentially prevent it. ovial fl uid crystal analysis) should be given to the Retrospective analysis of gout patients who expe- patient in writing and transmitted to his/her pri- rienced postoperative gout fl ares suggests that pre- mary care physician. If gout is diagnosed, ideally and perioperative control of the serum urate level some patient education can take place emphasiz- and use of prophylactic anti-in fl ammatory medi- ing that gout is a chronic, potentially progressive, cation may reduce the likelihood of fl are [2 ] . but controllable disorder if the ultimate cause Although not as yet tested in a prospective (hyperuricemia) is appropriately addressed. manner, several strategies may be of value in Patients should be counseled to specifi cally preventing a postoperative gout fl are: (1) In address this with their primary physicians. Too patients with frequent gouty attacks and antici- often, patients assume that fl ares in gout were a pated elective surgery, the serum urate should be complication of surgery and not something that lowered to a target of ~6 mg/dl well in advance requires their attention after discharge. of surgery (unfortunately, not usually logistically possible). (2) If the patient with a history of gout is already on allopurinol (febuxostat), the drug References should be continued up until and including the day of surgery, and restarted as soon as possible 1. Craig MH, Poole G, Hauser CJ. Postsurgical gout. Am afterward in order to limit fl uctuations in the Surg. 1995;61:56Ð9. 2. Kang EH, Lee EY, Lee YJ, et al. Clinical features and serum urate due to stopping and starting hypou- risk factors of postsurgical gout. Ann Rheum Dis. ricemic therapy. Too frequently, these drugs are 2008;67:1271Ð5. unnecessarily stopped prior to surgery, and there 3. Mandell BF, editor. Preventing and treating acute gout is a delay in restarting them. (3) If there are no attacks across the clinical spectrum. Cle Clin J Med. 2010;77:S2-25. major contraindications (known or expected 4. Bilezikian J. Pseudogout after parathyroidectomy. signi fi cant renal dysfunction, biliary obstruction, Lancet. 1973;301:445Ð6. known intolerance), colchicine prophylaxis (0.6 5. O’Duffy JD. Pseudogout syndrome in hospital patients. daily or twice daily) should be continued at the JAMA. 1973;226:42Ð4. 6. Clowes GHA, Simeone FA. Acute hypocalcemia in same dose up until surgery and resumed as soon surgical patients. Ann Surg. 1967;146:530Ð40. as possible afterward and if the patient has expe- 7. Ho Jr G, DeNuccio M. Gout and pseudogout in hospi- rienced attacks in the past year, has tophi, has talized patients. Arch Intern Med. 1993; signi fi cant hyperuricemia, and is likely to expe- 153(24):2787Ð90. 8. So A, DeSmedt T, Revaz S, Tschopp J. A pilot study of rience wide fl uctuations in the urate level. IL1 inhibition by anakinra in acute gout. Arthritis Res Preoperative initiation of colchicine 0.6 once Ther. 2007;9:R28. Perioperative Myocardial Infarction 2 4 Benico Barzilai

However, the traditional de fi nition of an MI is Introduction diffi cult to apply to the postoperative setting as symptoms may be absent or atypical and ECG Perioperative myocardial infarction is a major changes are often subtle. Postoperative MI was cause of perioperative morbidity and mortality. often thought to occur at days 3–5 postopera- Even though orthopedic surgery is usually tively. However, recent advances in the diagnosis considered of intermediate risk with a 1–5% of acute coronary syndrome using troponin assays risk of cardiac death and/or nonfatal MI, this have revolutionized the diagnosis and manage- strati fi cation is based on all orthopedic proce- ment of perioperative myocardial infarction [5 ] . dures including those performed in young, A recent task force has rede fi ned myocardial healthy patients. However, lower extremity Infarction, emphasizing the role of new biomark- arthroplasties are frequently performed in elderly ers [6 ] . The new de fi nition includes a rise and/or patients with a high prevalence of underlying car- fall of cardiac biomarkers (preferably troponin) diovascular disease. Furthermore, many proce- with at least one value above the 99th percentile dures are performed on patients with underlying of the upper reference limit accompanied by one rheumatologic disease which predisposes patients of the following: symptoms of ischemia, isch- to cardiovascular disease [1– 4 ] . Therefore, the emic ECG changes, development of Q wave, or ability to diagnose and manage patients with imaging evidence of myocardial infarction (echo, perioperative MI is important for all individuals MRI, or nuclear studies). who take care of postoperative orthopedic patients. The preferred biomarker for the diagnosis of myocardial infarction (MI) is cardiac troponin (I or T) which has excellent sensitivity and Diagnosis of Perioperative MI specifi city. Troponin is a regulatory protein located in the myo fi bril with three protein sub- The diagnosis of acute MI as de fi ned by the units: troponin C (calcium-binding component), World Health Organization included history, troponin I (inhibitory compound), and troponin T ECG, and cardiac enzymes (usually CK-MB). (the tropomyosin-binding component). The authors of the MI defi nition emphasized that there must be a rising and/or falling pattern drawn B. Barzilai , M.D. () 6–9 h apart. One of the values must be greater Clinical Cardiology, Department of Cardiovascular than the 99th percentile. The authors required the Medicine , Cleveland Clinic Foundation , 9500 Euclid Avenue , Cleveland , OH , USA rising and/or falling pattern because some patients e-mail: [email protected] have chronic elevations (especially patients with

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 277 DOI 10.1007/978-1-4614-2203-7_24, © Springer Science+Business Media, LLC 2013 278 B. Barzilai renal failure). Several studies have suggested that increased in patients with infl ammatory myopa- false-positive troponin can be due to cross- thies. Forty-nine patients with polymyositis, reactivity of components of the assay which dermatomyositis, and myositis associated with cross-react with rheumatoid factors, heterophile connective tissue disorders were studied [12 ] . antibodies, fi brin clots, bilirubin, or products of The authors identifi ed 28 of 49 with simultaneous hemolysis [ 7] . Many troponin assays utilize CK and TnT levels. 23 patients exhibited elevated enzyme-linked immunoabsorbent assays with CK (18 with elevated troponin T). The mean level monoclonal antibodies as both the capture and of TnT in the elevated patients was 0.76 ng/mL conjugate antibodies. The rheumatoid factor anti- (less than 0.2 ng (mL) normal). Of the 41 patients bodies can bind to these monoclonal antibodies, with simultaneous CK and troponin I, 29 had causing a false-positive result. As early as 1999, elevated CK, but only 1 patient had elevated tro- there have been isolated case reports of false- ponin I. This study would suggest that some positive results (elevated troponin I) in patients patients with myositis exhibited mildly elevated with elevated rheumatoid factors. These reports troponin T. This study highlights the need for emphasize clinical correlation in these patients as serial measurement of troponin in patients with there were no concomitant ECG changes or suspected postoperative MI and the need for a ris- symptoms [8– 10] . Furthermore, the troponin lev- ing and falling pattern. els remained elevated on serial measurements Even though most troponin elevations are without a characteristic rise and fall of the related to perioperative myocardial infarction, levels. other common postoperative conditions have The best alternative to troponin assays is the been shown to cause increases in troponin. CK-MB. Serial measurements of CK-MB every Septic shock, renal failure, and pulmonary 6–9 h are required. CK-MB has a much shorter embolism are frequently associated with ele- half-life than troponin (which may remain ele- vated troponin [ 13, 14 ] . Another important con- vated for two weeks) which may be advanta- dition is Takotsubo cardiomyopathy which is a geous when trying to diagnosis reinfarction. nonischemic cardiomyopathy that is usually However, a recent study suggests that troponin triggered by emotional stress [ 15 ] . It is thought can be used for recognition of reinfarction as that this entity occurs in patients (particularly long as there is a 20% increase in value [5 ] . elderly women) with high circulating cate- CK-MB however can be increased in patients cholamines and presents immediately postop- with myositis or other chronic skeletal muscle eratively. Echocardiography shows a classic injury [5 ] . Patients with acute muscle injury pattern of apical ballooning with dyskinesis, reexpress the B chain as the skeletal muscle akinesis of the apex, but hypercontractility of tries to repair itself so that the proportion of the the base of the heart. Angiography reveals CK-MB fraction in the muscle increases mark- insignifi cant coronary artery disease. The left edly (up to 50%). Thus, postoperative orthope- ventricular dysfunction is reversible, so it is dic patients may have elevations of CK-MB important to recognize this entity postopera- related to acute muscle injury. In a recent single- tively as these patients have a good prognosis, center study of 90 patients with risk factors for but the patients must be supported aggressively CAD undergoing hip surgery, falsely elevated (may need intra-aortic balloon pulsation). CK-MB was found in 43.3% of patients [ 11 ] . Echocardiography is useful to document the Therefore, it is not recommended that CK-MB initial LV dysfunction and can be used to show alone be used for the diagnosis of postoperative the improvement over the next few weeks. MI in orthopedic patients. Serial echocardiography is useful to show the One recent study has suggested that cardiac improvement of LV function. It may be diffi cult TnT, but not cardiac TnI, may be expressed in to diagnosis this entity postoperatively as the regenerating skeletal muscle. Therefore, it is patients have diffuse T wave inversion on ECG theoretically possible that troponin T could be with minimal elevations of troponin. It may be 24 Perioperative Myocardial Infarction 279 necessary to perform coronary angiography in ture. The management of STEMI postoperatively these patients to exclude high-grade coronary is challenging since the customary use of antico- artery disease. agulants such as heparin may cause increased Patients are treated with beta-blockers and postoperative bleeding. However, since the mor- ACE inhibitors until the left ventricular function tality of acute ST elevation MI is very high, the has normalized. Since there are a few case reports patients are treated with acute intervention in the of recurrences of Takotsubo cardiomyopathy, cardiac catheterization laboratory as thrombolytic these patients must be watched carefully if they therapy is contraindicated. Coronary angiogra- undergo another procedure. phy is performed as soon as possible. High-grade lesions are treated with percutaneous intervention with placement of intracoronary stents. On rare Pathophysiology of Perioperative occasions, the patients require coronary artery Myocardial Infarction bypass grafting which is deferred as long as pos- sible to treat left main disease or multivessel Recent studies have suggested two pathophysio- disease. Aspirin and clopidogrel are prescribed in logic mechanisms of postoperative myocardial the patients treated with stents despite the infarction [16, 17 ] . Type1 ischemia/infarction is increased risk of bleeding associated with these characterized by an unstable plaque which sud- agents. denly undergoes rupture, leading to acute isch- emia. Type 2 ischemia occurs when there is prolonged supply–demand mismatch in the pres- Type 2 Perioperative MI ence of stable coronary artery disease. The importance of prolonged ischemia leading to perioperative myocardial infarction was not rec- Type 1 Perioperative MI ognized until perioperative Holter monitoring was utilized in high-risk cardiac patients. It is thought that some acute coronary syndromes Numerous studies have shown that perioperative arise when a vulnerable plaque suddenly rup- ST depression is common in the early postopera- tures. Lipid-rich plaques with relatively thin tive period (1st 48 h). Initial Holter studies used fi brous caps are thought to be unstable and prone 2-lead monitoring which had limited sensitivity to fi ssuring and rupture. More mature stable and speci fi city. With the advent of 12-lead ECG plaques have small lipid cores with thick, mature monitoring which could be used perioperatively, fi brous caps [17 ] . The high-catecholamine state investigators were better able to understand the associated with surgery may lead to increased role of “silent” ischemia in the pathogenesis of stress on the vulnerable plaque, resulting in perioperative MI. Landesberg et al. studied 185 plaque rupture. Parker and Breslow have corre- consecutive patients undergoing major vascular lated the catecholamine and cortisol response to surgery with 12-lead ECG monitoring for 72 h lower extremity surgery with surgical outcome after surgery (except for carotid patients, 48 h) including myocardial infarction [ 18 ] . Myocardial [19 ] . Cardiac troponin I was used as the marker of infarction or cardiac death occurred in those myocardial necrosis. 38 patients (20.5%) exhib- patients with markedly elevated catecholamine. ited ischemic episodes on ECG (11–629 min). It is unclear whether the elevated catecholamines Twelve of these 38 patients sustained non-Q wave were the cause or a result of these clinical events. MI. The increase in troponin correlated very Thus, Type I perioperative MI occurs when a vul- strongly with the longest episodes of ischemia nerable plaque ruptures due to the hyperdynamic and cumulative ischemia duration. All ischemic postoperative state. Plaque rupture often results events were preceded by a sustained increase in in an acute ST elevation MI (STEMI) as a plate- heart rate (mean heart rate 116 bpm). Thus, the let-rich thrombus forms at the site of plaque rup- author concluded that tachycardia caused an 280 B. Barzilai increase in myocardial demand which led to ST The overall incidence of myocardial infarction depression (ischemia) and subsequently infarc- was 0.4%. However, the incidence increased tion if the ischemia was prolonged. Furthermore, markedly with age (0.1% for ages 50–59, 0.5% most of the ischemic events (26/38) started in the for 70–79, and 1.6% for patients over the age of immediate postoperative period while the patient 80.) Urban et al. [23 ] found that the incidence of was emerging from anesthesia. A few MIs myocardial infarction was much greater (6.5%) occurred on the second or third day postopera- in a high-risk group of patients with known tively. The authors postulated that most postop- CAD (history of revascularization or positive erative myocardial infarctions occur within the stress test). They also found that 29% of the fi rst 72 h due to demand ischemia. An increase in patients with positive troponin suffered a cardiac heart rate in animal models with stable coronary complication by six months of follow-up includ- artery disease reveals a decrease of subendocar- ing four deaths. These results complement the dial blood fl ow as a result of a shortening of results found in vascular surgery patients with diastolic fi lling time [ 20 ] . Therefore, the authors postoperative troponin elevations [24 ] . Even after emphasize the need to control heart rate periop- adjustment for clinical factors such as renal dis- eratively, a concept consistent with some data ease and diabetes, the vascular surgery patients demonstrating the bene fi cial protective effect of with even a modestly elevated troponin had moderate beta-blockade in the perioperative greater than fourfold rate of events by 24 months. period. Thus, patients with postoperative troponin eleva- Pathologic studies support the concept that tion should be screened aggressively for CAD there are two mechanisms of postoperative MI with a minimum of noninvasive testing for isch- [ 21 ] . Cohen et al. analyzed 26 patients with fatal emia and cardiac catheterization in patients with postoperative MI. They found that more than signi fi cant ischemia. half of the patients (54%) did not have plaque rupture at autopsy. The patients without plaque rupture died early postoperatively (72 h). In con- Myocardial Infarction and trast, the patients with plaque rupture were Rheumatologic Disorders evenly distributed over a 17-day period. These patients died of the complications of plaque rup- In addition to the traditional risk factors for coro- ture often accompanied by thrombosis. The nary artery disease such as hypertension, hyper- pathogenesis of myocardial infarction in these lipidemia, and diabetes, recent evidence has patients was much more consistent with the suggested that infl ammation plays a signifi cant pathogenesis of acute MI in the nonoperative set- role in the pathogenesis of atherosclerosis [ 25 ] . ting (particularly STEMI). It is now recognized that there is an increased Therefore, it is important to realize that there prevalence of cardiovascular disease in general- appear to be two different pathophysiologic path- ized in fl ammatory conditions, such as psoriasis, ways which lead to an acute MI in the postopera- lupus, and rheumatoid arthritis. tive setting. As many patients have tachycardia Using the Rochester Minnesota epidemiology prior to their ischemic events, we have a potential data, the Mayo Clinic group studied patients therapeutic target in these patients. diagnosed with rheumatoid arthritis from January 1955 to January 1995. Patients were followed through January 2001 [1 ] . Out of 603 patients The Incidence of Myocardial Infarction with rheumatoid arthritis, 176 patients died from in Orthopedic Patients cardiovascular disease. Multivariate analysis revealed that the risk for cardiovascular disease The Mayo Clinic group reviewed 10,244 patients was particularly high for patients with high eryth- over a 10-year period (1986–1995) who under- rocyte sedimentation rate (over 60 mm/h), RA went primary total hip or knee arthroplasty [ 22 ] . vasculitis, and RA lung disease. In a large study 24 Perioperative Myocardial Infarction 281 of total cholesterol and triglycerides (AMORIS Beta-Blockade Study), 480,000 individuals were followed [ 26 ] . Thousand seven hundred and seventy nine The recent POISE trial highlighted the potential patients had rheumatoid arthritis with 214 with a hazards with beta-blockade used perioperatively history of myocardial infarction and 165 with (extended release metoprolol [100–200 mg]) ischemic stroke. The patients with RA had lower [ 30] . As predicted, the metoprolol groups sus- values of cholesterol and triglycerides than the tained less myocardial infarctions (0.84 hazard non-RA patients, yet there was at least a 1.6 times ratios). However, unexpectedly, there were more higher risk of MI or stroke in the RA patients, deaths in the metoprolol group (1.33 hazard ratio) con fi rming that having rheumatoid arthritis was and more strokes (2.17 hazard ratio). This study associated with a higher risk of cardiovascular established the dangers of introducing acute beta- disease. blockade, particularly at high doses. Many inves- Similarly, patients with systemic lupus ery- tigators believe that the relatively high dose of thematosus have been shown to have an increased metoprolol used in this study led to more brady- risk of cardiovascular disease [27, 28] . A study cardia and hypotension [31 ] . In patients with at the University of Pittsburgh showed that evidence of postoperative troponin elevation, we women with lupus aged 35–44 were over 50 use beta-blockers for secondary prevention. We times higher than age-matched women in the start immediate release metoprolol at 25 mg every Framingham of spring study to have sustained 8 h with careful titration in the postoperative setting an MI. Longer duration of corticosteroid use, to avoid bradycardia or hypotension. Fixed doses hypercholesterolemia, and postmenopausal sta- of extended release metoprolol are avoided. tus was associated with MI in the women with lupus. Thus, it is now recognized that patients with rheumatologic disorders are much more Statin Therapy prone for cardiovascular disease. These patients must be managed aggressively in the periopera- HMG COA reductase inhibitors have many tive period with a high vigilance for cardiovas- benefi cial effects in addition to their lipid-lower- cular events. ing effects including anti-in fl ammatory and plaque-stabilizing effects. It has been observed that cessation of statins perioperatively leads to Medical Therapy an increase in postoperative myocardial infarc- tion [ 32 ] . Therefore, it is recommended that Patients with a history of stenting of the coronary patients who were previously taking statins be arteries require special attention postoperatively. restarted as soon as possible postoperatively. In Stent thrombosis is known to occur most fre- patients with postoperative myocardial infarc- quently within the fi rst year poststent placement tion, we elect to use high doses of statins. Recent (particularly drug eluting stents), but it can occur data in patients with acute coronary syndrome as late as three years after the PCI [29 ] . Aspirin has shown that high-dose atorvastatin (80 mg) and clopidogrel should be restarted as soon as used in patients with acute coronary syndrome possible (preferably the night of surgery and ide- was associated with signifi cant reduction in ally the surgery performed with aspirin contin- death, MI, or unstable angina [ 33 ] , compared to a ued, especially if the initial reason for coronary group treated with pravastatin 40 mg. The high- stent placement was acute coronary syndrome). dose atorvastatin group achieved an LDL of Consequently, all episodes of chest pain postop- approximately 70 mg/dL compared to 100 mg/dL eratively must be investigated promptly with an in the pravastatin group. The primary end point electrocardiogram. Patients with stent thrombo- occurred in 26.3% in the pravastatin group vs. sis manifest ST elevation or marked ST depres- 22.4% in the atorvastatin group. Clinicians have sion. They should go to the catheterization lab started to apply these results to the postoperative immediately if ECG changes are present. MI patient. Thus, in patients with postoperative 282 B. Barzilai

MI without clear-cut contraindication (e.g., ele- myocardial infarction. However, the use of high- vated liver enzymes), atorvastatin 80 mg is started dose methylprednisolone in patients with myo- with careful monitoring of liver enzymes. cardial infarction resulted in increased ventricular infarct size ventricular arrhythmias and ventricu- lar rupture [39 ] . However, lower doses of predni- Aspirin sone (up to 5 mg) may be safe [ 40 ] . Patients who are taking higher doses of prednisone should The data of the use of aspirin perioperatively in have their doses tapered as quickly as possible. orthopedic patients is somewhat equivocal. The In some patients, this may not be feasible due to usual policy is to withdraw all antiplatelet agents severe underlying disease such as myositis or 7–10 days prior to orthopedic procedures. vasculitis. However, in many patients, a taper is However, there is a rebound effect with increased feasible. In addition to the increased risk for platelet adhesiveness [34– 37 ] . Studies have infarct expansion, corticosteroids have long-term shown an increased rate of bleeding and transfu- deleterious effects including increased blood sion in hip arthroplasty, but not in femoral neck pressure and abnormal lipids. Long-term studies fractures or spinal instrumentation for patients on of patients with lupus or rheumatoid arthritis on aspirin. In patients at high risk of perioperative steroids have shown the increased atherogenesis events, the benefi t of the antiplatelet agents must associated with long-term steroid use [41 ] . Thus, be weighed against the risk of increased bleed- the use of chronic steroids in patients with known ing. We would consider continuing ASA in high- arthrosclerotic coronary disease should be lim- risk patients undergoing femoral neck procedures ited to the lowest dose possible. to prevent ischemic events and to possibly reduce DVT as well. Clearly, any patient who manifests chest pain or any ischemic changes on ECG NSAIDS should be started on aspirin as soon as possible. Recent data have suggested that nonselective NSAIDs are associated with increased cardiovas- Clopidogrel cular risk particularly in patients with known car- diovascular disease [ 42 ] . Gialson et al. studied all The CURE study investigated the addition of Danish patients with fi rst-time MI discharged clopidogrel to ASA in unstable coronary syn- between 1995 and 2002. COX-2 inhibitors (rofe- drome [ 38 ] . The patients treated with clopidogrel coxib and celecoxib) were found to increase the (75 mg) and ASA were found to have signifi cantly risk of cardiovascular death in this post-MI group less events (CV death, MI, or stroke 9.3% vs. (relative risk 2.80 and 2.57). Other NSAIDs were 11.4% in the ASA group alone). The patients associated with a modest increase in risk (1.29). were given clopidogrel for 12 months in this A recent panel recommended that NSAIDs be study. It is reasonable to add clopidogrel to avoided if possible within three months of a car- patients who have a troponin elevation postopera- diovascular event [43 ] . tively for at least one year after the event. Since In conclusion, patients with rheumatologic the risk of bleeding was signi fi cant in the clopi- disorders are at increased risk for postoperative dogrel group, the clopidogrel must not be started MI, and they should be monitored closely for this until the risk of postoperative bleeding is low. complication postoperatively. Newer biomarkers have made the diagnosis of postoperative MI much easier than previously. However, there are Steroid Use still occasional false-positive results. Since most postoperative MI results from demand ischemia, Early experimental data suggested that corticos- patients are usually aggressively managed peri- teroids reduced infarct size in a canine model of operatively to reduce postoperative tachycardia 24 Perioperative Myocardial Infarction 283 and hypertension. Due to their deleterious effects, 14. Burness C, Beacock D, Channer K. Pitfalls and prob- high doses of steroids and NSAIDS should be lems of relying on serum troponin. Q J Med. 2005;98:365–71. avoided if reasonable in these patients. 15. Gianni M, Dentali F, Grandi A, Sumner G, Hiralal R, Lonn E. Apical ballooning syndrome or Takotsubo cardiomyopathy: a systematic review. Euro Heart J. 2006;27:1523–9. References 16. Landesberg G, Beattie W, Mosseri M, Jaffe A, Alpert J. Perioperative myocardial infarction. Circulation. 1. Gabriel S. Cardiovascular morbidity and mortality in 2009;119:2936–44. rheumatoid arthritis. Am J Med. Manuscript 2010; 17. Landesberg G. The pathophysiology of perioperative 1–12. myocardial infarction: facts and perspectives. 2. Maradit-Kremers H, Nicola P, Crowson C, Ballman K, J Cardiothoracic Vas Anesthesia. 2003;17:90–100. Gabriel S. Cardiovascular death in rheumatoid arthritis: 18. Parker SD, Breslow MJ, Steven M, Rosenfeld B, a population-based study. Am Coll Rheum. 2005;52: Norris EJ, Christopherson R, Rock P, et al. 722–32. Catecholamine and cortisol responses to lower 3. Maradit-Kremers H, Crowson C, Nicola P, Ballman extremity revascularization: correlation with outcome KV, Roger V, Jacobsen S, et al. Increased unrecog- variables. Critical Care Med. 1995;23(12):1954–61. nized coronary heart disease and sudden deaths in 19. Landesberg G, Mosseri M, Zahger D, Wolf Y, rheumatoid arthritis. Arth & Rheum. 2005;52(2): Perouansky M, Anner H, Drenger B, Hasin Y, 402–11. Berlatzky Y, Weissman C. Myocardial infarction after 4. Warrington K, Kent P, Frye R, Lymp J, Kopecky S, vascular surgery: the role of prolonged, stress-induced, et al. Rheumatoid arthritis is an independent risk fac- ST-depression-type ischemia. J Am Coll Cardiol. tor for multi-vessel coronary artery disease: a case 2001;37:1839–45. control study. Arth Resch & Therapy. 20. Canty JM, Giglia J, Kandath D. Effect of tachycardia 2005;7:R984–91. on regional function and transmural myocardial per- 5. Jaffe A. The evolution and revolution of necrosis fusion during graded coronary pressure reduction in markers in modern cardiology for the diagnosis of conscious dogs. Circulation. 1990;82:1815–25. acute myocardial infarction: the search for specifi city. 21. Cohen M, Aretz T. Histological analysis of coronary Card Biomark Clin Pract 1:15–45. artery lesions in fatal postoperative myocardial infarc- 6. Thygesen K, Alpert JS, White HD, for Joint ESC/ tion. Cardio Path. 1999;8(3):133–9. ACCF/AHA/WHF Task Force for the Rede fi nition 22. Mantilla C, Horlocker T, Schroeder D, Berry D, of Myocardial Infarction. Universal de fi nition of Brown D. Frequency of myocardial infarction, pul- myocardial infarction. J Am Coll Cardiol. 2007;50: monary embolism, deep venous thrombosis, and death 2173–95. following primary hip or knee arthroplasty. 7. Wu A. Biochemical and analytical laboratory issues Anesthesiology. 2002;96:1140–6. for cardiac troponin. Card Biomark Clinic Pract. 23. Urban M, Jules-Elysee K, Loughlin C, Kelsey W, 2011;3:47–62. Flynn E. The one year incidence of postoperative 8. Al-Awadhi AM, Olusi S, Hasan EA, Abdullah A. myocardial infarction in an orthopedic population. Serum concentrations of cardiac troponin-I in patients Hosp Spec Surg. 2008;4:76–80. with rheumatoid arthritis, systemic lupus erythemato- 24. Bursi F, Babuin L, Barbieri A, Politi L, Zennaro M, sus, primary Sjogren’s syndrome and Graves’ disease. Grimaldi T, Rumolo A, Gargiulo M, Stella A, Modena Singapore Med J. 2007;48(9):847–9. M, Jaffe A. Vascular surgery patients: perioperative 9. Katwa G, Komatireddy G, Walker S. False positive and long-term risk according to the ACC/AHA guide- elevation of cardiac troponin I in seropositive rheuma- lines, the additive role of post-operative troponin toid arthritis. J Rheum. 2001;28:2750–1. elevation. Euro Heart J. 2005;26:2448–56. 10. Kenny P, Finger D. Falsely elevated cardiac troponin-I 25. Libby P, Ridker P, Maseri A. In fl ammation and ath- in patients with seropositive rheumatoid arthritis. erosclerosis. Circulation. 2002;105:1135–43. J Rheum. 2005;32(7):1258–61. 26. Semb A, Kvien T, Aastveit A, et al. Lipids, myocar- 11. Monzopoulos G, Kouvaris C, Antonopoulos D, dial infarction and ischaemic stroke in patients with Stamatakos M, Tsembeli A, et al. Perioperative cre- rheumatoid arthritis in the Apolipoprotein-related atine phosphokinase (CPK) and troponin I trends after Mortality RISk (AMORIS) Study. Ann Rheumatol elective hip surgery. J Trauma. 2007;63:388–93. Dis on line 2010; doi: 10.1136/ard.2009 . 126128. 12. Aggarwal R, Lebiedz-Odrobina D, Sinha A, Manadan 27. Shah M, Shah A, Krishnan E. Poor outcomes after A, Case J. Serum cardiac troponin T, but not troponin acute myocardial infarction in systemic lupus erythe- I, is elevated in idiopathic in fl ammatory myopathies. matosus. J Rheumatol. 2009;36:570–5. J Rheum. 2009;36:2711–4. 28. Manzi S, Meilahn E, Rairie J, Conte C, et al. Age- 13. Agzew Y. Elevated serum cardiac troponin in non-acute speci fi c incidence rates of myocardial infarction and coronary syndrome. Clin Cardiol. 2009;32:15–20. angina in women with systemic lupus erythematosus: 284 B. Barzilai

comparison with the framingham study. Am J Epidem. 37. Manning BJ, O’Brien N, Aravindan S, Cahill RA, 1997;145:408–15. McGreal G, Redmond HP. The effect of aspirin on 29. Decker R, et al. Perioperative management of the blood loss and transfusion requirements in patients patient with cardiac disease. J Am Acad Orthop Surg. with femoral neck fractures. Injury. 2010;18:267–77. 2004;35:121–4. 30. POISE Study Group, Devereaux PJ, Yang H, Yusuf S, 38. Peters R, Mehta S, Fox K, Zhao F, Lewis B, et al. et al. Effects of extended-release metoprolol succinate Effects of aspirin dose when used alone or in combi- in patients undergoing non-cardiac surgery (POISE nation with clopidogrel in patients with acute coro- trail): a randomized controlled trial. Lancet. 2008; nary syndrome: observations from the clopidogrel in 371(9627):1839–47. May 31, Epub 2008 May 12. unstable angina to prevent recurrent events (CURE) 31. London M. Quo Vadis, Perioperative Beta Blockade? study. Circulation. 2003;108:1682–7. Are You “POISE’d” on the Brink? International Anes 39. Bulkley B, Roberts W. Steroid therapy during acute Resch Soc. 2008;106:1025–30. myocardial infarction. Am J of Med. 1974;56: 32. Le Manach Y, Godet G, Coriat P, Martinon C, Bertrand 244–50. M, Fléron M, Riou B. The impact of postoperative 40. Friedewald V, Ganz P, Kremer J, Mease P, O’Dell J, discontinuation or continuation of chronic statin ther- Pearson T, Venkata C, Ram S, Ridker P, Salmon J, apy on cardiac outcome after major vascular surgery. Roberts W. AJC editor’s consensus: rheumatoid Anesthesia & Analg. 2007;104:1326–33. arthritis and atherosclerotic cardiovascular disease. 33. Cannon C, Braunwald E, McCabe C, Rader D, Am J Cardiol. 2010;106:442–7. Rouleau J, et al. Intensive versus Moderate Lipid 41. Davis III J, Kremers H, Crowson C, Nicola P, Ballman Lowering with Statins after Acute Coronary K, Therneau T, Roger V, Gabriel S. Glucocorticoids Syndrome. J Shouxi.net 2006; Abstract 1–9. and cardiovascular events in rheumatoid arthritis. Am 34. Anekstein Y, Tamir E, Halperin N, Mirovsky Y. Coll Rheumatology. 2007;56:820–30. Aspirin therapy and bleeding during proximal femoral 42. Gislason G, Jacobsen S, Rasmussen J, Rasmussen S, fracture surgery. Clin Orthop. 2004;418:205–8. Buch P, Friberg J, Schramm T, et al. Risk of death or 35. Burger W, Chemnitius J, Kneissl G, Rucker G. Low- reinfarction associated with the use of selective dose aspirin for secondary cardiovascular prevention – cyclooxygenase-2 inhibitors and nonselective non- cardiovascular risks after its perioperative withdrawal steroidal antiinfl ammatory drugs after acute myocar- versus bleeding risks with its continuation – review dial infarction. Circulation. 2006;113:2906–13. and meta-analysis. J Intern Med. 2005;257:399–414. 43. Friedewald V, Bennett J, Christo J, Pool J, Scheiman 36. Chassot P, Delabays A, Spahn DR. Perioperative anti- J, Simon L, Strand V, White W, Williams G, Roberts platelet therapy: the case for continuing therapy in W. AJC editor’s consensus: selective and nonselective patients at risk of myocardial infarction. Br J Anaesth. nonsteroidal anti-infl ammatory drugs and cardiovas- 2007;99:316–28. cular risk. Am J Cardiol. 2010;106:873–84. Cervical Spine Stabilization 2 5 Christopher A. Iannotti and Gordon R. Bell

(basilar invagination or cranial settling), at the Introduction C1Ð2 atlantoaxial joint complex (atlantoaxial subluxation and atlantoaxial rotary subluxation), Rheumatoid arthritis (RA) is a chronic, relapsing, or within the subaxial cervical spine (subaxial in fl ammatory arthritis that typically affects mul- cervical subluxation). tiple diarthrodial joints with varying degrees of systemic involvement and is one of the most common disabling diseases. The number of Surgical Management of Atlantoaxial patients with RA in the USA has been estimated Instability Due to Atlantoaxial to be 2Ð2.4 million and 630Ð650,000 in the Subluxation United Kingdom. A signifi cant number of these patients will develop involvement of the cervical It should be appreciated that the OÐC1 (occipito- spine that requires attention. The prevalence of cervical) articulation is responsible for approxi- RA in adults over the age of 15 is approximately mately 50% of normal neck fl exionÐextension 1%, with a peak incidence occurring in the fourth and the C1Ð2 (atlantoaxial) joint is responsible through sixth decades of life. Studies demon- for about 50% of normal neck rotation. Therefore, strate a female predominance, with females disease or surgical stabilization (fusion) involv- affected twice as often as males [1 ] . Approximately ing these joints can result in signifi cant limitation 50% of patients are unable to work within of neck motion. The biomechanical stability of 10 years of onset, and the lifetime costs of the the atlantoaxial complex depends predominantly disease rival those of coronary artery disease and on the transverse ligament and alar ligaments stroke. Involvement of the cervical spine, and and, to a lesser degree, on the apical ligaments. more speci fi cally the craniocervical junction, is RA is an erosive synovitis causing polyarthropa- second in incidence only to that of the hands and thy and is associated with microtears in liga- feet [2 ] . Various studies estimate that 59Ð88% of ments, disruption of collagen, repair, and patients with RA develop cervical disease [ 2, 3 ] . in fi ltration of fi brous tissue. The involvement of Rheumatoid involvement of the cervical spine the transverse ligament, the alarÐapical ligament may occur at the occipitocervical junction complex, and the capsular ligaments of the lateral mass and facet joints dramatically alters the bio- mechanical stability of the craniocervical junc- tion. Pannus formation results in the narrowing of  C. A. Iannotti , M.D., Ph.D. ¥ G. R. Bell , M.D. ( ) the spinal canal, which can lead to intermittent or Center for Spine Health , Cleveland Clinic , 9500 Euclid Avenue , Cleveland , OH 44195 , USA persistent spinal cord compression as well as e-mail: [email protected] damage to structural elements (dens/ligaments),

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 285 DOI 10.1007/978-1-4614-2203-7_25, © Springer Science+Business Media, LLC 2013 286 C.A. Iannotti and G.R. Bell resulting in neurological deterioration, deformity, present in 60% of cases [ 5 ] . The pain often and/or pain. radiates into the occiput and/or vertex. In addi- There are three types of cervical instability that tion, pain associated with atlantoaxial sublux- may occur with RA: basilar invagination, also ation is usually increased with neck fl exion and known as cranial settling or superior migration of rotation, and may be accompanied by a “clunk- the odontoid, atlantoaxial subluxation, and sub- ing” sensation. Paresthesias in the C2 der- axial subluxation (Figs. 25.1 and 25.2a, b). matome, or occipital neuralgia, may also be Atlantoaxial (C1Ð2) subluxation is the most com- present and is typically felt along the lateral mon cervical spine pathology associated with RA, aspect of the scalp. Neurological symptoms are accounting for 65% of all subluxations in patients typically due to spinal cord and/or brainstem with RA (Fig. 25.2 ). Anterior subluxations com- compression or vertebral artery compromise. prise the majority of these cases, whereas lateral These patients may complain of arm or leg and posterior subluxations account for 20% and weakness or incoordination, gait dif fi culty, 10% of rheumatoid atlantoaxial subluxations, bladder and bowel problems, and Lhermitte’s respectively [4 ] . Anterior atlantoaxial subluxation phenomenon (especially with neck fl exion). may result in compression of the cervical spinal The latter is de fi ned as an electrical shock-like cord between the dens/pannus complex and the sensation radiating to one or more extremities posterior arch of atlas. Excessive pannus forma- with neck fl exion eliminate duplicate. tion dorsal to the dens may impinge upon the spi- The neurologic examination of rheumatoid nal cord, even with minimal cervical motion. The patients may be diffi cult because of associated cervical spinal cord is particularly vulnerable to musculoskeletal joint involvement, and typical compression when the neck is fl exed, as C1 trans- signs of myelopathy may therefore be masked. lates ventrally on C2 during fl exion, thereby Atlantoaxial instability is easily demonstrated on resulting in narrowing of the spinal canal. lateral plain radiographs obtained in both fl exion The most frequent complaint of patients with and extension and may be de fi ned in terms of the atlantoaxial instability is neck pain, which is anterior atlantodental interval (ADI). ADI is measured from the midposterior margin of the anterior C1 arch to the anterior surface of the dens. An ADI ³ 5 mm in adults is generally accepted as radiographic evidence of an unstable C1Ð2 articulation. The anterior ADI is generally accentuated with neck fl exion and is diminished with neck extension (Fig. 25.2 ). A more clinically important measurement may be the posterior ADI, which measures the actual space available for the spinal cord. The posterior ADI is mea- sured from the posterior aspect of the dens to the anterior aspect of the posterior C1 arch. MRI can demonstrate cord compression and visualize soft tissues such as ligaments and pannus that may contribute to canal narrowing and cord compression. A cervical CT scan with sagittal and coronal reconstruction is often used in preoperative plan- ning in these patients. Surgical fusion of the atlantoaxial motion seg- Fig. 25.1 Sagittal MRI showing proximal migration of ment is typically indicated when atlantoaxial the odontoid (dens) through the foramen magnum and compressing the brainstem. This condition is also known instability occurs as a result of transverse liga- as basilar invagination or cranial settling. ment erosion or laxity resulting from rheumatoid 25 Cervical Spine Stabilization 287

Fig. 25.2 ( a) Lateral fl exion X-ray showing increased indicated by dotted circle) and all subaxial levels except space (double-pointed arrow) between the anterior aspect C5Ð6. Note that the alignment of C5Ð6 improved of the dens (dotted vertical line) and the posterior aspect signi fi cantly with extension (c ) and anteroposterior (d ) of the anterior arch of C1 (dotted circle) consistent with X-rays showing the technique of translaminar C2 screw atlantoaxial (C1Ð2) subluxation. The distance marked by fi xation. This patient also had C4Ð6 lateral mass fusion the double-pointed arrow is known as the anterior atlan- with rods and screws because of her C4Ð5 and C5Ð6 sub- todens interval (AADI). Note the slippage (subaxial sub- axial subluxations. It was decided to try to preserve the luxation) between C4Ð5, C5Ð6, and C6Ð7. The posterior C2Ð3 and C3Ð4 segments, rather than perform a C1Ð6 aspects of vertebral bodies marked by a vertical line fi xation in order to try to preserve two additional motion should all line up with each other. ( b) Lateral extension segments. The lateral X-ray, however, seems to show pos- X-ray showing realignment of C1Ð2 (posterior aspect of terior bone across the C2Ð4 levels (arrow) indicating dens indicated by vertical dotted line; anterior ring of C1 probable fusion of those levels also pannus formation. Indications for surgical stabi- presence of neurological de fi cits from the lization in cases of rheumatoid atlantoaxial sub- atlantoaxial instability, or severe cord compres- luxation include severe or unremitting pain, the sion as a result of the C1Ð2 subluxation, even if 288 C.A. Iannotti and G.R. Bell not associated with neurological defi cit. If the consideration of fusion to those segments. Rarely, subluxation is reducible and there is no clinical or a transoral decompression with resection of the radiographic evidence of cord compression, a odontoid process may be also indicated in addi- posterior C1Ð2 fusion procedure is often per- tion to posterior atlantoaxial fusion for a nonre- formed. Over the last several decades, a number ducible atlantoaxial instability with severe spinal of posterior C1Ð2 stabilization techniques have cord/brainstem compression by the dens/pannus been developed (Fig. 25.3 ). There is some evi- complex. dence that surgical stabilization of a C1Ð2 subluxation may reduce the risk of developing occipitocervical disease (cranial settling/basilar Surgical Stabilization of the invagination). When there is any evidence of Atlantoaxial (C1–2) Joint Using early basilar invagination, or if the occipitoatlan- Transarticular Screw Fixation tal joint is severely diseased, strong consideration is typically given to performing a posterior occip- The primary goal in the surgical management of itocervical fusion (see Fig. 25.6 ). Including the atlantoaxial instability is to decompress the spi- occiput in a fusion will result in an incremental nal cord, to stabilize the C1Ð2 complex, and if 50% loss of normal neck motion. However, since possible, to restore and preserve alignment. There most rheumatoid patients with disease severe are several techniques for fusing the atlantoaxial enough to warrant surgical stabilization do not joint. Most of the current commonly used tech- have normal motion, fusion will result in less loss niques obviate the need for supplemental halo of motion compared to what would be experi- vest stabilization. Details of these techniques are enced by a normal patient. Rheumatoid patients beyond the scope of this chapter. Fixation of the should also be assessed for concomitant subaxial C1Ð2 lateral masses may be performed by insert- instability since its presence would warrant ing transarticular screws across the C1Ð2 joint

Fig. 25.3 ( a ) Lateral and anteroposterior (b ) X-rays patient with atlantoaxial subluxation. On each side, a showing lateral mass C1 screws and pars interarticularis small vertical rod connects the C1 and C2 screws C2 screws stabilizing the atlantoaxial joint (C1Ð2) in a 25 Cervical Spine Stabilization 289 and augmenting it with autograft, placed between the subluxation be reducible and dif fi culties asso- the posterior arch of C1 and the posterior spinous ciated with certain body habitus. Patients with a process of C2. This technique provides immedi- proximal cervicothoracic kyphosis (e.g., “dowa- ate stabilization and does not require the presence ger’s hump” or “buffalo hump” deformities) may of a complete or competent posterior C1 arch not be able to undergo this technique because of [6, 7 ] . This technique is technically demanding dif fi culties associated with obtaining the proper and requires careful preoperative planning with screw trajectory to cross the C1Ð2 joint. thin-cut CT scans and sagittal CT reconstruction to con fi rm the presence of adequate bone for passage of the screws and to look for aberrancies Atlantoaxial Fusion Using C1–2 in the anatomy of the adjacent vertebral arteries. Segmental Fixation Transarticular screw fi xation provides immediate rigid stabilization and is associated with high A more common method for C1Ð2 fi xation fusion rate. Disadvantages of this technique involved lateral mass C1 and pars or pedicle C2 include a signi fi cant risk of vertebral artery injury, fi xation with bilateral rod fi xation [ 15, 16 ] which has been reported to be approximately 2% (Fig. 25.3a, b). A signifi cant advantage of this risk per screw [ 8Ð 10] . A 2Ð15% incidence of technique is the ability to achieve fi xation in screw malposition has been reported following patients with an irreducible C1Ð2 subluxation C1Ð2 transarticular screw fi xation, with the inci- and in patients who have vertebral artery anoma- dence of vertebral artery injury ranging from 0% lies that preclude the safe passage of transarticu- to 8% per patient. lar screws [ 17 ] . A cancellous onlay bone graft Cadaveric studies have shown that safe tran- may be used as a supplement, or structural bone sarticular screw placement may not be feasible in grafting or wiring may be performed. An alterna- as many as 20% of patients due to an aberrant ver- tive to C2 pars/pedicle screw fi xation is the use of tebral artery. In some cases, the technique of C1Ð2 bilateral translaminar C2 screws (Fig. 25.2c, d ). transarticular screw placement may be modifi ed This technique provides rigid fi xation equivalent in patients with unilateral vertebral artery anoma- to other C1Ð2 techniques, is technically simple, lies that prevent placement of a screw across one is not affected by variations in individual anat- of the C1Ð2 facets [ 11 ] . In such cases, a single omy, and does not place the vertebral artery at contralateral transarticular screw may be placed risk [18, 19 ] . Disadvantages of C2 translaminar in conjunction with interspinous bone graft/wir- screws include the risk of neural injury from ing, thereby avoiding neural or vertebral artery breach of the ventral laminar surface, with subse- injury while providing C1Ð2 stability [ 12 ] . quent entry of the screw into the spinal canal. Postoperatively, these patients are typically placed In addition, the use of laminar screws creates less in hard cervical collar, such as a Philadelphia col- space available for supplemental fusion methods lar, for 6Ð8 weeks. Biomechanically, unilateral (e.g., sublaminar wiring). C1Ð2 facet screw fi xation with interspinous bone graft wiring is an excellent alternative in the treat- ment of atlantoaxial instability when bilateral Surgical Management of Rheumatoid screw fi xation is contraindicated. The fusion rate Basilar Invagination for C1Ð2 bilateral transarticular screw placement is 96Ð100%, with a similar fusion rate of up to Basilar impression (BI), also known as cranial set- 95% following unilateral transarticular screw tling, vertical subluxation, or atlantoaxial impac- placement supplanted with dorsal bone graft/ tion, results from bony erosion and compression wiring and postoperative bracing [13, 14 ] . of the lateral masses of the atlas (C1) with sub- Other disadvantages of the C1Ð2 transarticu- sequent cranial migration of the odontoid peg lar screw technique include the requirement that (Fig. 25.1 ). The erosive destruction of the occipital 290 C.A. Iannotti and G.R. Bell condylarÐC1 joint may be severe, and the occipital transarticular screws, by C2 pars screws, or by condyles may completely erode through the C1 translaminar screws. Titanium rods are then lateral masses. Rheumatoid BI is typically accom- attached to the suboccipital plate and upper cervi- panied by excessive proliferation of granulation cal, thereby providing immediate, rigid immobili- tissue, which, together with the invaginated odon- zation of the occipitocervical region. If additional toid process, can produce cervicomedullary com- stabilization is needed within the subaxial spine pression. BI frequently presents with occipital (e.g., in cases with associated subaxial instability), or suboccipital pain, often with radiation to the lateral mass screw fi xation may also be performed. cranial vertex. Neurological de fi cits are also fre- Bone grafting is performed with corticocancellous quently present on presentation, and these may bone grafting. Rheumatoid patients undergoing include myelopathic fi ndings of weakness, sen- posterior occipitocervical fusion should be man- sory loss, and gait imbalance. When brainstem aged postoperatively in a cervical orthosis for compression is present, vertigo, diplopia, dys- 6Ð8 weeks postoperatively. The type of bracing phagia, hoarseness, and sleep apnea may occur. used depends upon surgeon preference, stability of BI implies the presence of occipitocervical the fi xation, and patient parameters. instability, and conservative nonoperative treat- Rheumatoid patients with nonreducible BI ment in patients with signs and symptoms of may require a ventral transoral decompression neural compression carries a signi fi cant risk of procedure in order to resect the dens and decom- progressive and irreversible neurological impair- press the spinal cord. In this procedure, exposure ment and sudden death and is, therefore, usually of the anterior arch of C1 and the C2 dens is contraindicated. Patient age, severity of disease, achieved through the posterior pharynx. The nutritional status, and overall medical condition dens/pannus complex is resected, thereby providing of the patient are important factors in determin- decompression of the spinal cord and/or caudal ing whether or not surgery should be performed. brainstem. Following transoral decompression, a Preoperative workup for patients suspected of posterior occipitocervical or atlantoaxial fusion having BI includes plain cervical radiographs, procedure is required, either immediately follow- including fl exion/extension views, and MRI. ing the decompression or in staged fashion, in Preoperative halo traction, performed under careful order to provide suf fi cient. cardiac and respiratory monitoring in an inten- sive care unit, may be attempted to reduce the vertical subluxation by distracting the odontoid Surgical Management of Rheumatoid process from the within foramen magnum. Subaxial Subluxation

Subaxial subluxation (SAS) associated with RA Occipitocervical Fusion and Transoral is the second most common rheumatoid instabil- Decompression ity after atlantoaxial subluxation and may be associated with both atlantoaxial instability and In patients who are neurologically normal, basilar invagination (Fig. 25.4 ). Subaxial sublux- preoperative traction is generally unnecessary. ation may present as focal or diffuse neck pain Neurologically impaired patients, who undergo and/or cervical kyphotic deformity (e.g., “chin- traction and have reducible cranial settling, can be on-chest” deformity). If the subluxation is severe maintained in halo traction until surgery. The enough to encroach on the spinal canal and/or de fi nitive treatment for reducible BI is posterior spinal nerves, patients may present with com- occipitocervical fusion. Occipitocervical fusion plaints related to radiculopathy (arm numbness, procedures involve the placement of a Y-shaped weakness, or pain) or myelopathy (arm and hand suboccipital plate that is secured to the thick mid- weakness, gait imbalance, spasticity, and urinary line bony keel of occiput (Fig. 25.4 ). Fixation to incontinence or retention). Preoperative workup the upper cervical spine can be achieved by C1Ð2 should include plain radiographs, MRI to evaluate 25 Cervical Spine Stabilization 291

Fig. 25.4 (a ) Lateral X-ray and (b ) sagittal MRI showing suggesting instability at the C7ÐT1 level. (c ) Lateral and basilar invagination (cranial settling) with the dens protrud- (d ) anteroposterior X-rays showing an occiputÐT3 poste- ing through the foramen magnum and compressing the rior fusion. Fusion of this magnitude was required to brainstem. Note also the subaxial subluxation of C5 on address the occiputÐC1 instability (basilar invagination, C6, best appreciated on the MRI (white arrow) with mod- cranial settling), the C6Ð5 subaxial subluxation, and the erate spinal cord compression at that level. Anterior tilting instability at C6ÐT1 of C6 on C7 is noted on the lateral X-ray (short arrow), for cord compression, and sometimes cervical since it may lead to additional instability and the CT with sagittal and coronal reconstructions. development of postlaminectomy cervical kypho- The lateral radiographic appearance of multiple sis. Therefore, supplemental posterior instru- contiguous subaxial subluxations may have the mented fusion typically accompanies laminectomy appearance of a “staircase” (Fig. 25.5 ). in order to provide stabilization of the involved motion segments and possibly achieve normal spinal alignment. Fusion is achieved with a screw- Cervical Laminectomy and Posterior rod construct with bone grafting in which polyax- Instrumented Fusion ial titanium screws are inserted into the lateral masses of the cervical vertebrae (Figs. 25.4 and In cases in which spinal cord or nerve root com- 25.5). Posterior instrumentation is supplemented pression is present, cervical decompression and with bone graft material to ensure construct and stabilization may be indicated. Laminectomy fusion longevity. This is typically performed with alone, however, is generally contraindicated in the local morselized bone harvested from the spinous setting of rheumatoid subaxial cervical instability processes and laminae or by allograft bone. 292 C.A. Iannotti and G.R. Bell

Fig. 25.5 ( a) Lateral X-ray and (b ) sagittal MRI showing Fusion is generally not stopped at the C7 level for con- signifi cant subaxial subluxation between C4 and C5 and cerns about iatrogenic instability at the C1ÐT1. Therefore, smaller amount at C3 and C4. (c ) Lateral and (d ) antero- this patient was fused across the cervicothoracic junction posterior showing posterior C3ÐT2 instrumented fusion. to the proximal (T2) thoracic spine across The construct addressed the slippage at C3Ð4 and C4Ð5.

Management of Cervical Spine arthritic condition in the United States and Fractures in Patients with involves an HLA-B27 genetic predisposition in Ankylosing Spondylitis the majority of cases. AS typically develops in younger males (maleÐfemale ratio 3:1), starting Ankylosing spondylitis (AS) is a seronegative, in the third or fourth decades of life. The disease progressive, systemic, infl ammatory rheumatic is characterized by a diffuse infl ammatory reac- spondyloarthropathy, mainly affecting the spine tion resulting in ossifi cation of spinal ligaments, and sacroiliac joints. AS is the third most common joints, and intervertebral discs. AS has been 25 Cervical Spine Stabilization 293

Fig. 25.6 ( a) Sagittal T2 and (b ) sagittal T1 MRI of patient ing quadriparesis from cord compression.( c ) Sagittal CT scan with ankylosing spondylitis (AS) sustaining a C6 fracture showing the C5 vertebral body fracture (arrow). (d ) Lateral (white arrows) with epidural hematoma (black arrows) caus- X-ray showing posterior C3ÐT3 instrumented fusion 294 C.A. Iannotti and G.R. Bell

estimated to affect between 0.1% and 1.4% of the spontaneous fusion of the subaxial spine from general population, most of which are found to AS can lead to excessive dynamic loading of the be HLA-B27 positive [20 ] . AS is characterized craniovertebral junction, thereby resulting in sub- by progressive bony ankylosis and the formation luxation and basilar invagination. of marginal syndesmocytes, resulting in the classic “bamboo spine.” Ankylosis may occur within the intervertebral discs, anterior longitudi- Posterior Cervicothoracic Fusion nal ligament, posterior longitudinal ligament, and posterior elements (lateral mass facet joints and Cervical fractures in patients with AS are often spinous processes). Eventually, the spinal column highly unstable. As such, AS patients with may become osteoporotic, rigid, or deformed, Chance-type fractures are susceptible to extensive and it can be susceptible to fracture from rela- neurological injury and progressive spinal defor- tively minor forces [21Ð 24 ] . From a biomechani- mity. Routine imaging may be negative, and the cal standpoint, the motion segments immediately diagnosis depends upon a high index of suspicion. adjacent to the ankylosed segment experience When in doubt, MRI or CT is usually diagnostic. excessive loading, and fractures typically occur MRI should also be obtained, when possible, to through regions adjacent to the ankylosed seg- assess for spinal cord injury or ongoing spinal cord ment. In cases where a large segment of the spine compression, injury to the posterior ligamentous is ankylosed, fracture may occur within the anky- complex, and epidural hematoma (Fig. 25.6a, b). losed segment (Fig. 25.6c). Although these frac- Typically, AS patients with cervical fractures are tures (termed Chance fractures) are commonly surgically managed by posterior instrumented located in the thoracolumbar spine, they also fusion (Fig. 25.6d ) or a combined anterior/poste- occur in the subaxial cervical spine. In many rior approach involving anterior cervical corpec- instances, the zone of injury extends through both tomy and strut grafting followed by posterior the anterior and posterior spinal columns, thereby instrumented spinal fusion. In patients with creating a highly unstable fracture with a incomplete spinal cord injury, surgical decom- signifi cant risk of extensive neurological injury pression via laminectomy and fusion should be and spinal deformity after even minor trauma. performed urgently. From a technical standpoint, These individuals are at signi fi cant risk for cata- there is often signifi cant distortion of the anatomy, strophic neurologic sequelae, including complete with bony landmarks often obscured because of or incomplete spinal cord injury resulting from the underlying disease process, making hardware transient or persistent compression by bone frag- placement sometimes challenging. Fortunately, ments and/or epidural hematoma (Fig. 25.6a, b ). bone healing and fusion in patients with ankylos- The morbidity and mortality of AS patients expe- ing spondylitis is typically very good. riencing Chance-type fractures is signi fi cant and has been estimated to be 50% and 30%, respec- tively [25 ] . Therefore, these uniquely complex Conclusion injuries require a high index of suspicion for diagnosis and aggressive surgical management to Rheumatoid involvement of the cervical spine may provide spinal stability and optimize functional occur at the occipitocervical junction (basilar outcome. invagination or cranial settling), at the atlantoaxial AS may also be associated with signifi cant (C1Ð2) joint complex (atlantoaxial subluxation), risk of injury within the atlantoaxial region. Type or within the subaxial cervical spine (subaxial cer- II odontoid fractures, which occur within the vical subluxation). Surgical treatment of basilar midportion of the dens, and fractures of the C2 invagination without neurological de fi cit typically par interarticularis, termed Hangman’s fractures, involves in situ occipitocervical fusion, even if the may be seen in patients with AS with preexisting deformity cannot be reduced. Basilar invagination spontaneous occipitoatlantal fusion. In addition, associated with neurological de fi cit typically 25 Cervical Spine Stabilization 295 involves attempted preoperative reduction in skel- Kehr P, Weidner A, editors. Cervical spine. Berlin: etal traction (cranial tongs or halo device). If BI Springer. 1986;322Ð7. 7. Haid Jr RW. C1-C2 transarticular screw fi xation: reduces in traction, a posterior occipitocervical technical aspects. Neurosurgery. 2001;49(1):71Ð4. fusion is typically performed. In nonreducible BI 8. Grob D, Jeanneret B, Aebi M, Markwalder TM. with spinal cord or brainstem compression, an Atlanto-axial fusion with transarticular screw fi xation. anterior transoral approach may also be required J Bone Joint Surg Br. 1991;73(6):972Ð6. 9. Madawi AA, Casey AT, Solanki GA, Tuite G, Veres in order to resect the odontoid/pannus complex R, Crockard HA. Radiological and anatomical evalu- and decompress the spinal cord. Posterior occip- ation of the atlantoaxial transarticular screw fi xation itocervical fusion is also performed, usually fol- technique. J Neurosurg. 1997;86(6):961Ð8. lowing the anterior transoral approach. The 10. Wright NM, Lauryssen C. Vertebral artery injury in C1-2 transarticular screw fi xation: results of a survey surgical treatment of rheumatoid atlantoaxial sub- of the AANS/CNS section on disorders of the spine luxation involves posterior C1Ð2 arthrodesis by and peripheral nerves. American Association of one of several instrumentation techniques. Subaxial Neurological Surgeons/Congress of Neurological subluxation associated with neurological defi cit is Surgeons. J Neurosurg. 1998;88(4):634Ð40. 11. Dickman CA, Sonntag VK. Posterior C1-C2 transar- typically treated by posterior cervical laminec- ticular screw fi xation for atlantoaxial arthrodesis. tomy and instrumented fusion. In the absence of Neurosurgery. 1998;43(2):275Ð80. neurological defi cit or signifi cant cord compres- 12. Haid Jr RW, Subach BR, McLaughlin MR, Rodts Jr sion, instrumented fusion alone may suf fi ce. GE, Wahlig Jr JB. C1-C2 transarticular screw fi xation for atlantoaxial instability: a 6-year experience. Cervical fractures in patients with AS can be Neurosurgery. 2001;49(1):65Ð8. missed but often highly unstable. Patients with 13. Melcher RP, Puttlitz CM, Kleinstueck FS, Lotz JC, AS sustaining a fracture are susceptible to exten- Harms J, Bradford DS. Biomechanical testing of pos- sive neurological injury and progressive spinal terior atlantoaxial fi xation techniques. Spine. 2002; 27(22):2435Ð40. deformity and are therefore typically treated sur- 14. Claybrooks R, Kayanja M, Milks R, Benzel E. gically. Either a posterior instrumented fusion or Atlantoaxial fusion: a biomechanical analysis of two a combined anterior/posterior decompression and C1-C2 fusion techniques. Spine J. 2007;7(6):682Ð8. fusion is usually required. The latter involves 15. Goel A, Laheri VK. Plate and screw fi xation for atlanto-axial dislocation. (Technical report). Acta anterior cervical corpectomy and strut grafting fol- Neurochir (Wien). 1994;129:47Ð53. lowed by posterior instrumented spinal fusion. 16. Harms J, Melcher RP. Posterior C1-C2 fusion with polyaxial screw and rod fi xation. Spine. 2001;26: 2467Ð71. 17. Menendez JA, Wright NM. Techniques of posterior References C1-C2 stabilization. Neurosurgery. 2007;60(Supp1 1): S103Ð11. 1. Katz JN, Liang MH. Differential diagnosis and con- 18. Gorek J, Acaroglu E, Berven S, Yousef A, Puttlitz servative treatment of rheumatic disorders. In: CM. Constructs incorporating intralaminar C2 screws Fromeyer JW, editor. The adult spine: principles and provide rigid stability for atlantoaxial fi xation. Spine. practice, vol. 1. New York: Raven. 1991;699Ð718. 2005;30(13):1513Ð8. 2. Casey ATH, Crockard HA. Rheumatoid arthritis. In: 19. Wright NM. Translaminar rigid screw fi xation of Dickman CA, Spetzler RF, Sonntag VKH, editors. the axis. Technical note. J Neurosurg Spine. 2005; Surgery of the craniovertebral junction. New York: 3(5):409Ð14. Thieme. 1998;151Ð74. 20. Kubiak EN, Moskovich R, Errico TJ, Di Cesare PE. 3. Menezes AH. Rheumatogical disorders. In: Menezes Orthopaedic management of ankylosing spondylitis. AH, Sonntag VKH, editors. Principles of spinal sur- J Am Acad Orthop Surg. 2005;13:267Ð78. gery, vol. 1. New York: McGraw Hill. 1996;705Ð22. 21. Detwiler KN, Loftus CM, Godersky JC, Menezes 4. Boden SD, Clark CR. Rheumatoid arthritis of the cer- AH. Management of cervical spine injuries in patients vical spine. In: Clark CR, editor. The cervical spine. 3rd with ankylosing spondylitis. J Neurosurg. 1990;72: ed. Philadelphia: Lippincott-Raven. 1998;693Ð704. 210Ð5. 5. Menezes AH. Congenital and acquired abnormalities 22. Kanter AS, Wang MY, Mummaneni PV. A treatment of the craniovertebral junction. In: Youmans JR, edi- algorithm for the management of cervical spine frac- tor. Neurological surgery, vol. 2. 4th ed. Philadelphia: tures and deformity in patients with ankylosing spon- WB Saunders. 1996;1035Ð89. dylitis. Neurosurg Focus. 2008;24(1):E11. 6. Magerl F, Seeman PS. Stable posterior fusion of the 23. Bronson WD, Walker SE, Hillman LA, Keisler D, Hoyt atlas and axis by transarticular screw fi xation. In: T, Allen SH. Bone mineral density and biochemical 296 C.A. Iannotti and G.R. Bell

markers of bone metabolism in ankylosing spondylitis. two trauma centers. J Neurosurg Spine. 2006;5: J Rheumatol. 1998;25:929Ð35. 33Ð45. 24. Einsiedel T, Schmelz A, Arand M, Wilke HJ, Gebhard 25. Apple Jr DF, Anson C. Spinal cord injury occurring in F, Hartwig E, et al. Injuries of the cervical spine in patients with ankylosing spondylitis: a multicenter patients with ankylosing spondylitis: experience at study. Orthopedics. 1995;18:1005Ð111. Laminectomy 2 6

Fernando Techy and Gordon R. Bell

Introduction Laminectomy: Applied Anatomy

The principal goals of spine surgery are to restore The lamina forms the posterior arch of the verte- function and alleviate pain. These objectives can bral canal and is considered part of the posterior be surgically accomplished by adhering to 3 prin- elements of the vertebra. It is interposed between ciples: (1) decompression of the spinal cord and the pedicles and the spinous processes. nerve roots, (2) providing stability to an unstable Laminectomy is the technique of surgically and painful segment by fusion (arthrodesis), and removing the vertebral lamina with the main pur- (3) correction of coronal and sagittal spinal pose of decompressing the neurologic elements imbalance. In general, surgery is most reliable in (Figs. 26.1 and 26.2). Although it can be used in relieving leg pain by surgical decompression. the lumbar spine to access and decompress com- This chapter will focus on the surgical tech- pression that is both ventral and dorsal to the neu- nique of decompressive laminectomy. This pro- ral elements (cauda equina), it is generally cedure involves the surgical removal of the indicated in the cervical and thoracic spine when vertebral lamina, with the main purpose of the source of compression is located posterior to decompressing the neurologic elements, hence the neural elements (spinal cord). Laterally, the improving function and relieving leg pain. This lamina forms the superior and the inferior articu- chapter will go over the defi nitions, indications, lating processes that form the facet joints. The brief surgical technique, postoperative care and bony bridge between the superior articulating expectations, and complications of this proce- process and the remained of the lamina is called dure as it pertains to patients with rheumatic the “pars interarticularis.” This structure should conditions. be preserved when performing a decompressive laminectomy in order to maintain stability. Laminectomy is most commonly performed for degenerative conditions which cause narrow- ing of the spinal canal or the neural foramina. The most common degenerative condition resulting in leg pain in the older adult is spinal stenosis. The F. Techy , M.D. ¥ G. R. Bell , M.D. () pathophysiology of spinal stenosis involves disc Neurological Institute, Center for Spine Health , degeneration with loss of disc height resulting in Cleveland Clinic , 9500 Euclid Avenue , Cleveland , OH 44195 , USA narrowing of the neural foramina and redundancy e-mail: [email protected] and hypertrophy of the ligamentum fl avum. The

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 297 DOI 10.1007/978-1-4614-2203-7_26, © Springer Science+Business Media, LLC 2013 298 F. Techy and G.R. Bell

facet joints are secondarily involved with degeneration resulting in osteophyte formation and further canal and foraminal narrowing. The disc may also herniated and cause additional cen- tral canal narrowing. Laminectomy involves removal of the posterior lamina and associated ligamentum fl avum, thereby allowing access to the spinal canal where additional decompression can be performed. This commonly involves lim- ited removal of the facets and decompression of the neural foramen, when indicated. Surgical decompression is the standard surgical treatment for refractory lumbar degenerative stenosis and provides good intermediate and long-term success for radicular leg pain and symptoms of neurogenic claudication [ 1Ð 4] . Patients undergoing concomi- Fig. 26.1 Bilateral laminectomy (bone resection repre- tant fusion for associated back pain should be sented in red, axial cut). The decompression is performed warned that relief of back pain is unpredictable. from pedicle to pedicle, with care being taken to preserve the pars interarticularis and adjacent facet joints Laminotomy

Laminotomy involves the resection of only a por- tion of the lamina with the objective of providing surgical decompression without producing insta- bility (Figs. 26.3 and 26.4). Instability can be produced if too much of the facet joint is removed. Laminotomies are useful to access and decom- press the spinal canal for conditions such as disc herniation and focal stenosis. Decompression without fusion is indicated for radicular arm or leg pain from neural compression, particularly when mechanical back or neck pain is not one of the primary features of the patient’s symptoms. When signi fi cant axial (neck and back) pain or radiographic instability is also present, such as spondylolisthesis or lateral listhesis (abnormal alignment), an arthrodesis (fusion) can be consid- ered. In summary, symptomatic nerve compres- sion causing radicular pain that is unresponsive to conservative measures is treated with surgical decompression. The treatment for mechanical back or neck pain, whose source can be deter- mined, and symptomatic instability is spinal fusion. When refractory spinal stenosis is accom- panied by degenerative spondylolisthesis, the Fig. 26.2 Wide bilateral laminectomy. Coronal view surgical treatment generally involves both lamine- (bone resection area represented in red) ctomy and spinal fusion [5Ð 9 ] . 26 Laminectomy 299

be resected in order to avoid instability of that motion segment. To a large extent, the likelihood of developing postsurgical instability is directly proportional to the amount of the facet that is excised. Laminectomy, particularly when associ- ated with facetectomy, is more likely to produce instability in the cervical spine than in the tho- racic or lumbar spine. Cervical laminectomy is associated with complications from postopera- tive instability, kyphosis, or recurrent stenosis in up to 11Ð47% of patients [ 10, 11 ] . Accordingly, cervical laminectomy is generally accompanied by concomitant instrumented fusion. In addition, wide decompression across a transitional area, such as the cervicothoracic or thoracolumbar junction, is often accompanied by fusion in order Fig. 26.3 Left L4 laminotomy (bone resection area in to minimize the risk of postoperative instability. red ). The goal is to perform the decompression preserving the facet joint integrity ( blue area). Very frequently, a laminotomy of the upper portion of the lamina below (L5 in this case) is performed for better exposure (bone resec- Foraminotomy tion in green) Foraminotomy involves decompression when the nerve root is compressed within the neural fora- men. The primary indications for this procedure are far lateral (foraminal) disc herniations and foraminal stenosis. In many cases of diffuse stenosis, all areas of the spinal canal may be com- pressed and may require laminectomy, facetec- tomy, and foraminotomy. In the cervical spine, unilateral cervical foraminotomy can be safely performed without the likelihood of producing iatrogenic instability. To avoid postsurgical instability, caution should be taken to resect no more than 50% of the facet joint (Fig. 26.5 ) [12 ] .

Postoperative Care and Patient Expectation Fig. 26.4 Axial view of a left laminotomy

Pain control and early mobilization are very Facetectomy important in the early postoperative management. Adequate analgesics should be administered Facetectomy is the partial or complete resection (opioids, NSAIDs) to promote early mobiliza- of the facet joint. Facetectomy may be either par- tion. Mechanical deep venous thrombosis (DVT) tial or complete and is sometimes required to prophylaxis with compression stockings and achieve adequate decompression of the neural intermittent compressive devices is recom- elements. As little of the facet as possible should mended. We generally do not use routine chemical 300 F. Techy and G.R. Bell

Fig. 26.5 Patient with complaints of bilateral thigh pain with laminectomy, bilateral laminotomy, facetectomy, and neurogenic claudication who failed conservative and foraminotomy at L3-4 level. No fusion was necessary. treatment. No axial back pain or radiographic signs of ( a) Normal canal at L2-3. (b ) Severe central stenosis with instability were present. Excellent results were obtained facet hypertrophy at L3-4

DVT prophylaxis (anticoagulants) in the setting during the procedure, and most of these neu- of spinal surgery due to the risk of developing an ropraxic episodes are usually transient, lasting epidural hematoma. Incentive spirometry is up to 6Ð12 weeks. encouraged to reduce the risk of postoperative 2. Incidental durotomy occurs in 5Ð10% of pre- atelectasis. Postoperative drains to reduce the viously unoperated cases [ 3, 4 ] . The incidence likelihood of hematoma formation are usually is signi fi cantly higher in patients having prior not required for routine decompression surgery. surgery at the same level. Direct repair of the Physical therapy may be instituted during the defect is performed at the time of surgery if inpatient setting or delayed as an outpatient if the durotomy is noticed. If the repair is not needed. Most patients ambulate on the same day feasible, the defect can be sealed with a patch of surgery, and most decompression cases leave of dural substitute, fat, muscle, or fi brin seal- the hospital on the same day or on postoperative ants. A watertight closure of all layers of the day one. There are no restrictions after decom- wound should be performed in order to avoid pressive surgery besides general wound care. a CSF-cutaneous fi stula. One or two days of Patients are allowed to eat and to bear full weight bed rest may be recommended if there is con- on their spine immediately after they meet the cern about the integrity of the repair or in cases discharge criteria of the postsurgical recovery of large durotomy. Bed rest decreases the area. hydrostatic pressure at the repair site for lum- bar durotomies. In the cervical spine, the patient is treated in a semi-upright position in Complications and Their order to reduce hydrostatic forces at the repair Management site. Occasionally, a lumbar drain may be required for a few days in order to reduce the 1. Neurological injury is uncommon after hydrostatic forces at a lumbar durotomy. If the decompressive surgery. When it occurs, it can fl ow of cerebrospinal fl uid (CSF) cannot be produce new or increased leg pain, numbness stopped, revision surgery may be necessary. or tingling, and weakness. Most cases result 3. Prophylactic antibiotics are routinely given from excessive manipulation of the thecal sac perioperatively in all spinal surgery cases. 26 Laminectomy 301

Despite this, surgical site infection may occur Indications for Laminectomy after laminectomy, laminotomy, or fusion pro- in Rheumatologic Conditions cedures. Postoperative infection is more com- mon in the immunosuppressed patient, such as Rheumatoid Arthritis (RA) those with rheumatoid arthritis or other Cervical spine involvement occurs in over half of infl ammatory arthropathies. Treatment is usu- patients with rheumatoid arthritis. The most com- ally by incision and debridement with culture- mon abnormality is atlantoaxial dislocation, fol- guided antibiotic therapy. lowed by atlantooccipital arthritis with cranial 4. Postlaminectomy instability is reported in up settling and subaxial instability [ 18 ] . Cervical to 11Ð47% of cases following multilevel cer- laminectomy may be required for relief of spinal vical laminectomy [10, 11 ] . This can manifest cord compression, particularly when associated as axial pain, but it can lead to deformity with instability (subluxation). Cervical laminec- (postlaminectomy kyphosis or scoliosis) or tomy in the rheumatoid patient should nearly recurrent neurological compression. The treat- always be accompanied by arthrodesis because ment is usually surgical stabilization (fusion) of the high risk of developing postoperative insta- of the segment with further decompression as bility. This is recommended even if preexisting needed. instability is not present. The incidence of lumbar spine involvement in RA is similar to that of the general population Unique Considerations [ 19 ] . The medical and surgical treatment should in the Rheumatic Patient follow the same guidelines as for any patient with symptomatic stenosis. Special attention should Infection be paid to the risk of infection in the immunosup- pressed patient. In addition, spinal instrumenta- Postoperative infection is considered to be more tion in patients with in fl ammatory arthropathies common in patients receiving anti-tumor necro- can be diffi cult because of the higher likelihood sis factor a agent therapy (reported incidence 5.6Ð of poor fi xation of implants due to osteoporotic 20%) [13, 14] . This is especially true when bone. Finally, healing of the bone itself (fusion) metallic devices are implanted. Postoperative is more dif fi cult both because of the underlying infection after routine (noninstrumented) in fl ammatory arthropathy and because of the laminectomy is uncommon. A case of late dis- medications often used to manage the disease. citis, occurring 8 months after a laminectomy in a patient who had been on anti-tumor necrosis Ankylosing Spondylitis (AS) factor a , has been reported. In that case, the Indications for surgery in the patient with AS anti-tumor necrosis factor a agent had been include symptomatic neurological compression. stopped 4 months prior to surgery and was Additional indications include (1) surgical cor- resumed 2 months following surgery. In this rection of spinal deformity, such as severe kypho- case report, the authors emphasize that a high sis, which is relatively common in patients with index of suspicion is necessary to diagnose AS, and (2) evacuation of epidural hematoma infection in patients using these drugs, even which can occur following cervical, or other after relatively small and benign surgical proce- level, fracture. The sudden onset of axial, particu- dures [15 ] . Recent guidelines recommend that larly cervical, pain in a patient with AS following treatment with in fl iximab and etanercept be minor trauma should raise the index of suspicion withheld for 2Ð4 weeks prior to major surgical for possible spinal column fracture. In both of procedures [16, 17 ] . In patients with rheuma- these situations, wide decompression of the neu- toid arthritis, low doses of methotrexate and ral elements is required to address the underlying prednisolone were not identi fi ed as independent problem. In addition, however, both of these con- risk factors for increased risk of surgical infec- ditions require concomitant fusion to address the tion [13, 14 ] . underlying problem. 302 F. Techy and G.R. Bell

tion in the treatment of degenerative spondylolisthe- Conclusion sis with spinal stenosis. J Spinal Disord. 1993;6: 461Ð72. 7. Ghogawala Z, Benzel EC, Amin-Hanjani S, Barker Laminectomy is the technique of surgically remov- 2nd FG, Harrington JF, Magge SN, et al. Prospective ing the vertebral lamina, with the main purpose of outcomes evaluation after decompression with or decompressing the neural elements, thereby reliev- without instrumented fusion for lumbar stenosis and degenerative Grade I spondylolisthesis. J Neurosurg ing pain and hopefully improving function. Spine. 2004;1:267Ð72. Laminotomy is the partial resection of the lamina 8. Herkowitz HN, Kurz LT. Degenerative lumbar spon- with the objective of performing a more limited dylolisthesis with spinal stenosis. A prospective study decompression in order to minimize the risk of comparing decompression with decompression and intertransverse process arthrodesis. J Bone Joint Surg producing iatrogenic instability. Facet resection Am. 1991;73:802Ð8. should be limited in order to reduce the likelihood 9. Martin CR, Gruszczynski AT, Braunsfurth HA, of developing postoperative. If instability is pres- Fallatah SM, O’Neil J, Wai EK. The surgical manage- ent or anticipated, the addition of a fusion to the ment of degenerative lumbar spondylolisthesis: a sys- tematic review. Spine. 2007;32:1791Ð8. involved vertebral segments should be strongly 10. Mikawa Y, Shikata J, Yamamuro T. Spinal deformity considered. Because it is dif fi cult to precisely pin- and instability after multilevel cervical laminectomy. point the exact source of axial pain, fusion for back Spine. 1987;12:6Ð11. or neck pain is fraught with the risk of failure. If 11. Kato Y, Iwasaki M, Fuji T, Yonenobu K, Ochi T. Long-term follow-up results of laminectomy for the source of axial pain can be demonstrated, cervical myelopathy caused by ossi fi cation of the fusion may be palliative. In general, the indica- posterior longitudinal ligament. J Neurosurg. 1998; tions for decompression in the rheumatologic 89:217Ð23. patient are similar to those in the general popula- 12. O’Toole JE, Eichholz KM, Fessler RG. Posterior cer- vical foraminotomy and laminectomy. In: Ozgur B, tion. Special consideration should be given to the editor. Minimally invasive spine surgery. A practical immunosuppressed patient, to those with osteopo- guide to anatomy and techniques. New York, NY: rosis, and to patients with ankylosing spondylitis. Springer; 2009. 13. Giles JT, Bartlett SJ, Gelber AC, et al. Tumor necrosis factor inhibitor therapy and risk of serious postopera- Acknowledgment Note of appreciation to Dr. Lars tive orthopedic infection in rheumatoid arthritis. Gilbertson, Ph.D., and to Prasath Mageswaran, M.S., from Arthritis Rheum. 2006;55:333Ð7. 12. the Spine Biomechanical Laboratory at the Cleveland 14. Ruyssen-Witrand A, Gossec L, Salliot C, et al. Clinic, for helping with the illustration of this chapter. Complication rates of 127 surgical procedures performed in rheumatic patients receiving tumor necrosis factor alpha blockers. Clin Exp Rheumatol. 2007;25:430Ð6. References 15. Mori S, Tomita Y, Horikawa T, Cho I, Sugimoto M. Delayed spinal infection after laminectomy in a patient with rheumatoid arthritis interruptedly exposed 1. Amundsen T, Weber H, Nordal HJ, et al. Lumbar spi- to anti-tumor necrosis factor a agents. Clin Rheumatol. nal stenosis: conservative or surgical management?: 2008;27:937Ð9. A prospective 10-year study. Spine (Phila Pa 1976). 16. Koike R, Takeuchi T, Eguchi K, Miyasaka N. Update 2000;25(11):1424Ð35. on the Japanese guidelines for the use of in fl iximab 2. Malmivaara A, Slätis P, Heliövaara M, et al. Surgical or and etanercept in rheumatoid arthritis. Mod Rheumatol. nonoperative treatment for lumbar spinal stenosis? A ran- 2007;17(451Ð458):14. domized controlled trial. Spine. 2007;32(1):1Ð8. 17. Ledingham J, Deighton C. Update on the British soci- 3. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical ety for rheumatology guidelines for prescribing versus nonsurgical treatment for lumbar degenerative TNFalpha blockers in adults with rheumatoid arthritis spondylolisthesis. N Engl J Med. 2007;356:2257Ð70. (update of previous guidelines of April 2001). 4. Weinstein JN, Tosteson TD, Lurie JD, et al. Surgical Rheumatology (Oxford). 2005;44:157Ð63. versus nonsurgical therapy for lumbar spinal stenosis. 18. Bouchaud-Chabot A, Liote F. Cervical spine involve- N Engl J Med. 2008;358:794Ð810. ment in rheumatoid arthritis. A review. Joint Bone 5. Mardjetko SM, Connolly PJ, Shott S. Degenerative Spine. 2002;69:141Ð54. lumbar spondylolisthesis. A meta-analysis of litera- 19. Harzy T, Allali F, Bennani-Othmani M, Hajjaj- ture 1970Ð1993. Spine. 1994;19:2256SÐ65S. Hassouni N. Radiological characteristics of the lum- 6. Bridwell KH, Sedgewick TA, O’Brien MF, Lenke bar spine in patients with rheumatoid arthritis. Presse LG, Baldus C. The role of fusion and instrumenta- Med. 2007;36(10):1385Ð9. Vertebral Augmentation 2 7 Fernando Techy and R. Douglas Orr

Introduction “bone cement.” It is extremely compatible with human tissues and has been safely used in hip and Vertebroplasty and kyphoplasty are minimally knee arthroplasty for over 40 years. invasive treatment options for pathological (osteo- Vertebroplasty was fi rst developed in France, porosis or malignancy) compression fractures introduced by Galibert et al. [2 ] in 1987, and is the that are refractory to clinical management. Their simple injection of the fi ller into the vertebral excellent, almost immediate, results and extremely body. It is, of course, cheaper but requires the low rate of complications have made them uncom- cement injection to be under pressure. Kyphoplasty monly popular among treating physicians and was developed later and has two main advantages patients. Approximately one-third of osteoporotic over the fi rst procedure that, at least in theory, compression fractures evolve to become chroni- should bring a better overall outcome. In kyphop- cally symptomatic and debilitating [1 ] . Classically, lasty, before the injection of the PMMA, balloon due to elevated morbidity and high failure rate of is inserted into the vertebra. The balloon is then performing spinal surgery on patients with fi lled with fl uid, creating a cavity where the low osteoporosis, even more so in the rheumatic pressure cement injection takes place. (1) Injecting immunosuppressed person, vertebral compres- the cement in a low pressure manner diminishes sion fractures were treated conservatively unless the risk of PMMA extravasation during the proce- they presented with gross spine instability or neu- dure. (2) Infl ating the balloon also partially rological de fi cit. Both vertebroplasty and kyphop- restores the vertebral height lost with the fracture, lasty consist of injecting a bone fi ller material improving the overall sagittal balance and the (most commonly PMMA Ð polymethyl methacry- patient’s kyphosis, hence its name. The mecha- late) into the vertebral body to restore the stability nism of action of both procedures is believed to be and treat the pain associated with it in compres- due the immediate stabilization of the fracture by sion fractures. PMMA is a polymer also known as the hardened cement. Another less accepted theory is that the PMMA exothermic reaction when F. Techy , M.D. inserted would kill the nerve endings at the frac- Neurological Institute , Center for Spine Health, ture site promoting pain relief. This second theory Cleveland Clinic , 9500 Euclid Avenue , Cleveland , does not explain how pain is also promptly OH 44195 , USA relieved when other fi llers that do not cause an R. D. Orr , M.D., F.R.C.S.C. () exothermic reaction are injected into the vertebral Neuroscience Institute , Cleveland Clinic , body (Figs. 27.1 and 27.2 ). Lutheran Hospital 2C, 1730 W 25th Street , Cleveland , OH 44113 , USA It is estimated that the worldwide prevalence e-mail: [email protected] of insuf fi ciency vertebral compression fractures

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 303 DOI 10.1007/978-1-4614-2203-7_27, © Springer Science+Business Media, LLC 2013 304 F. Techy and R.D. Orr

Fig. 27.1 Intraoperative AP (a ) and lateral ( b ) in fl ation to create a cavity for the cement (Reprinted from fl uoroscopic images demonstrating balloon placement in Pateder et al. [ 3 ] , Copyright 2007, with permission from the vertebra during kyphoplasty. (c ) Subsequent balloon Elsevier)

is around 1.4 million [ 4] , while the US prevalence within expert opinion, multiple case series, and is 750,000 [ 5 ] . The exact incidence and preva- non-blinded, non-placebo-controlled prospec- lence of vertebral osteoporotic compression frac- tive studies. tures are dif fi cult to be obtained because of the heterogeneity in how vertebral fractures are de fi ned and the overall lack of diagnosis [6 ] . Patient Selection From 2001 to 2006, the number of vertebro- plasty procedures performed in the United States Identifying patients who would bene fi t from has doubled, from 4.3 to 8.9 per 1,000 persons [7 ] . these procedures requires a thorough workup There are multiple studies to date reporting incorporating the fi ndings of history, physical the good outcomes and low complications of examination, and imaging studies [ 13 ] . Physicians patients receiving vertebroplasty and kyphoplasty need to be extremely careful in correlating a for osteoporotic compression fractures. patient’s back pain with the compression frac- Recent attention was directed to the subject ture. The clinical history is usually a sudden onset when, in 2009, two prospective, randomized, of back pain that may or may not be associated placebo-controlled studies published on the same with a traumatic event. High-energy trauma is the issue of the New England Journal of Medicine exception in these cases. On physical examina- (NEJM) basically showed no difference between tion, acute compression fractures tend to have vertebroplasty and a sham operation [ 8, 9] . These tenderness directly over the fracture site. This studies have generated signifi cant controversy fi nding is very important to differentiate them around the procedure and its indications having from old compression fractures, which usually do elicited letters and statements of clarifi cation not hurt, are stable, and do not require treatment. from fi eld leaders and even national societies Posteroanterior and lateral radiographs will [10Ð 12] . These were on face well performed tri- detect most vertebral compression fractures, the als but had signifi cant limitations. Vertebral aug- overall spinal column alignment, and any focal mentation ( fi lling) procedures for the treatment kyphosis associated; however, it is often diffi cult of insuf fi ciency fractures continue to be widely to differentiate whether the fracture is acute or used with excellent results in pain control, return chronic or whether it is associated with a tumor. to function, and minimal complications Ð at least MRI is an excellent imaging modality because not 27 Vertebral Augmentation 305

Fig. 27.2 ( a , b ) After the balloon is defl ated and AP ( c) and lateral (d ) radiographs are taken to evaluate removed, cement is deposited into the cavity under live cement position and overall alignment (Reprinted from fl uoroscopic guidance in a retrograde fi ll pattern (from Pateder et al. [ 3] , Copyright 2007, with permission from the ventral aspect of the cavity to its dorsal aspect). Final Elsevier) only can it detect the edema associated with acute improvement after the procedure. For patients in fractures, but it can also show any tumorous whom MRI is contraindicated, nuclear scintigra- lesions associated. The best sequences to observe phy (bone scan) can be used to evaluate the acuity the edema of the acute changes are the sagittal of the fracture (Fig. 27.3 ). T2-weighted and fat-suppressed T2-weighted or the short tau inversion recovery (STIR) images. These images show increased signal intensity at Indications for Vertebroplasty the fracture site in patients who have acute and or Kyphoplasty subacute fractures and thus help select who will bene fi t the most from the intervention [14 ] . 1. Acute painful pathologic compression frac- Patients who demonstrate no increased signal tures (osteoporotic or tumoral) intensity on the MRI are less likely to experience 2. Painful lytic metastatic vertebral lesions 306 F. Techy and R.D. Orr

Technical Considerations

Both vertebroplasty and kyphoplasty are mini- mally invasive percutaneous procedures. Their indications are basically the same. The patient is positioned prone on the operating table. Insertion of the cement is done through a cannula placed trans- or extrapedicular into the vertebral body. Anesthesia can be local or general, and the procedure can be done in the hospital or at an out- patient surgery center, depending mostly on the general condition of the patient. Blood loss is minimal. An extremely import part of the proce- dure is obtaining a biopsy of the lesion before inserting the cement through the cannula. Biopsy should be considered for fi rst time fractures and those with any history of malignancy [15 ] . Good fl uoroscopy imaging is fundamental as for all percutaneous procedures (Fig. 27.4 ). The rheumatoid patient, especially the one that needs high steroid doses, is at a high risk for compression fractures of the spine due to the Fig. 27.3 A fat-suppressed T2-weighted MRI demon- osteoporosis caused by the disease or by the treat- strating a compression fracture (high signal) of a lumbar ment. Their risk of fracture recurrence is also vertebra (Reprinted from Pateder et al. [ 3 ] , Copyright elevated. Vertebral augmentation procedures are 2007, with permission from Elsevier) of enormous value for these patients due to its minimal invasion (keeping the infection rate 3. Painful vertebral hemangioma extremely low), excellent results, and almost 4. Posttraumatic osteonecrosis of the vertebral immediate improvement. body (Kummell’s disease)

Evidence-Based Outcomes Contraindications for Vertebroplasty or Kyphoplasty Vertebroplasty for Osteoporotic Fractures 1. Fracture associated with a neurological injury 2. Burst-type fracture (whole body of the verte- Voormolen et al. prospectively randomized 18 bra is involved as opposed to only the anterior patients to vertebroplasty and 16 patients to optimal 50% of body involvement in compression medical management. Vertebroplasty was associ- fractures) Ð relative ated with signi fi cantly greater pain reduction, less 3. Fractures that extend to the spinal canal Ð analgesic use, and greater mobility and physical relative [13 ] function when compared to optimal medical man- 4. Fractures in the presence of vertebral agement 1 day and 2 weeks after treatment [16 ] . osteomyelitis In another prospective, non-randomized study, 5. Matrix producing metastatic vertebral lesions Ð Alvarez showed that vertebroplasty was associ- relative ated with a signi fi cantly greater reduction in pain 27 Vertebral Augmentation 307

Fig. 27.4 Patient prone on the table. Minimally invasive procedure with percutaneous needle placement in both pedicles. AP and Lateral (biplanar) simultaneous fl uoroscopy imaging is very helpful if available

3 and 6 months after the intervention, when com- (total of 2,086 patients), concluding that a rapid pared with optimal medical treatment. It was also and consistent relief of the pain was achieved on associated with better functional scores and less every study. Their complications were 0.9% pain medication use at 3 months. There was no major morbidity, 0.1% cement embolism, and difference between the two methods at 1 year 0% mortality [20 ] . follow-up [ 17 ] . Diamond, in a prospective non- Hulme had a meta-analysis (69 studies and randomized trial, concluded that vertebroplasty over 4,000 patients) comparing kyphoplasty to was superior to medical management in improv- vertebroplasty and showed that both methods ing pain control and physical activity at 24 h are effi cacious for rapid pain control. The com- postprocedure. No difference was found at 1.5, 5, plications were 3.9% symptomatic complica- or 12 months [18 ] . In a different study, the same tions, 0.6% neurological decline, and 0.6% author compared vertebroplasty and medical pulmonary embolism for the vertebroplasty management and found that the vertebroplasty group and 2.2% symptomatic complications, group had better pain scores and function at 6 0.03% neurological decline, and 0.01% pulmo- weeks but no difference at 1 or 2 year follow-up. nary embolism for kyphoplasties [ 21 ] . Eck did a The incidence of adjacent vertebral fractures was similar review on 136 studies with over 9,500 the same for the two groups at 2 years [19 ] . patients comparing both methods (kyphoplasty A recent study (Vertos II) prospectively ran- and vertebroplasty). Pain improvement results domized 202 patients with acute painful fractures were the same as in the previous cited articles. confi rmed by MRI into two groups: vertebro- The complications were 1.6% symptomatic plasty and conservative treatment. There was a cement leak, 0.9% pulmonary embolus, 0.3% clear superiority in the treatment on the vertebro- hematoma, and 0.1% infection for vertebro- plasty group. No complications were reported plasty and 0.3% symptomatic cement leak, 0.4% [10 ] . Hockmuth et al. published a meta-analysis pulmonary embolus, 0.1% hematoma, and 0.3% on vertebroplasty where they analyzed 30 studies infection for kyphoplasty [ 22 ] . 308 F. Techy and R.D. Orr

Finally, multiple case series studies report a better for the kyphoplasty patients. The compli- signifi cant and rapid improvement in pain after cation rate was the same for the two groups [42 ] . vertebroplasty for osteoporotic compression fractures [ 23Ð 31 ] . Vertebral Filling Procedures for Compression Fractures Associated Kyphoplasty for Osteoporotic Fractures with Tumors

Kasperk compared kyphoplasty with optimal In a meta-analysis of 74 vertebroplasty and 35 medical management in a prospective, controlled, kyphoplasty studies, McGirt concluded that verte- non-randomized trial and found that patients who bral fi lling procedures are superior to medical underwent kyphoplasty had better pain scores treatment at 3 months with minimal complications and returned to activity at 3 and 6 months [32 ] . when used in osteoporotic compression fractures. Later, Grafe reported the outcome of these same The same review paper analyzed 18 case series patients at 12 months and concluded that the studies for tumor-associated vertebral compres- kyphoplasty group did better in regard to pain sion fractures and found that both vertebroplasty control with less visits to the doctor. and kyphoplasty are effective in pain reduction The kyphoplasty group also had less adjacent with minimal complications as well [43 ] . vertebral fractures at 1 year [33 ] . There are also In a case series of 37 patients with tumor- numerous case series studies demonstrating fast associated fractures, Weil had 94% of pain and reliable pain relief after kyphoplasty [34Ð 39 ] . improvement and 8.1% of transient radiculopa- Taylor has published a meta-analysis on kyphop- thy due to cement extravasation [44 ] . lasty showing a signi fi cant and rapid decrease in In his series on tumor-associated fractures, pain scores (35 studies/1,946 patients) [ 40 ] . Cortet had a cement leakage in 72.5% of cases, Another two meta-analyses comparing the clinical with 6.9% requiring surgery for that complication results of kyphoplasty and vertebroplasty were [45 ] . Other studies of kyphoplasty or vertebro- already mentioned in the previous section [21, 22 ] . plasty on tumor-associated fractures report asymp- In an 82-patient case series written by the tomatic cement leakage from 4% to 26% [46Ð 50 ] . junior author of this chapter, analyzing the results of kyphoplasty after osteoporotic fractures, it was found that fractures in men and in the lumbar Prospective Randomized Placebo- spine had a less favorable response to kyphop- Controlled Studies lasty when compared to fractures in women and in the thoracic spine. The recurrence rate for a Buchbinder et al. (Australian New Zealand vertebral fracture at 1 year after kyphoplasty was Clinical Trials Registry) measured pain, quality 9%. About half of the new vertebral fractures of life, and functional status at 1 week and at 1, 3, were adjacent to the kyphoplasty levels. and 6 months after a sham procedure and verte- The amount of vertebral height correction after broplasty, fi nding no signi fi cant between-group kyphoplasty did not signifi cantly correlate with differences at any time point. Patients in the two the clinical outcome. And fi nally, there were no study groups had improvement in pain [8 ] . complications to be reported on this series [41 ] . Kallmes et al. [ 9] reported that pain and dis- More recently, a prospective trial, from 21 ability outcomes at 1 month in a group of patients centers in 8 countries (FREE study), randomized who underwent vertebroplasty were similar to 300 patients into 2 groups: optimal medical man- those in a control group that underwent a sham agement vs. kyphoplasty for the treatment of procedure. In both studies, the sham procedure acute compression fractures of the spine. The consisted in injecting a short-acting anesthetic in pain improvement results were signi fi cantly the vertebral periosteum. 27 Vertebral Augmentation 309

These studies, even though well designed, had still recent and small and the results are at best numerous fl aws. In both, the majority of invited comparable with when using PMMA [55 ] . patients (approximately 70%) refused to be ran- The concept of osteoconduction is very appeal- domized and opted to be able to choose their own ing, and the property of graft reabsorption and treatment, therefore not being able to participate. bone incorporation is defi nitely the ultimate goal Arguably, those could be the patients that were in when treating fractures with bone void fi llers. a greater deal of pain and did not want to risk get- However, this concept may be more relevant to fi ll ting the sham treatment, creating a huge selection and incorporate a graft used to treat a segmental bias to start. Another problem noted was that tibial plateau fracture in a young patient that will both studies were underpowered and had poor need his knee for many years to come and not so defi nition of inclusion criteria. Buchbinder had important in patients treated for osteoporotic ver- 80% of patients from one single center. Also, in tebral fractures in whom the PMMA bone inter- both studies, patients with subacute fractures of face will most likely outlast them. One of our up to 1 year were included, what could have also recent studies shows that at 5-year follow-up, made the difference to the control sham group 57% of patients treated with kyphoplasty were not so signifi cant. MRI to assure the fractures had either deceased or unreachable, and the other 43% infl ammatory changes at the time of treatment were pleased with the treatment result using also was not a constant in these studies. PMMA as a fi ller (their SF 36 was comparable Finally, two prospective randomized trials with the age-matched controls) [41 ] . with adequate power and more controlled inclusion criteria were published at The Lancet in 2009 and 2010, clearly favoring vertebro- Conclusion plasty (Vertos II study) [10 ] and kyphoplasty (FREE study) [ 42 ] when compared to optimal Although insuf fi ciency vertebral compression medical management. These two articles repro- fractures were classically treated nonoperatively duce the great results of vertebral augmenta- due to open surgery morbidity, they can now be tion of innumerous case series and case control stabilized with reproducible good results and studies, as well as the anecdotal positive expe- minimally invasive techniques. There are cur- rience of an uncountable number of physicians rently multiple studies reporting the good out- worldwide. comes and low complication rates of patients receiving vertebroplasty and kyphoplasty for osteoporotic or tumoral compression fractures. New Filler Materials Both procedures have been shown to be quite similar in regard to bringing excellent functional Although PMMA is extremely biocompatible and pain improvement. Lastly, kyphoplasty seems and cheap, it has a few drawbacks. It hardens by to have the advantage of fewer fi ller extravasa- means of an exothermic reaction that may theo- tion-related complications and the ability to retically be harmful to surrounding tissues [ 51 ] restore vertebral height after the fracture. and does not reabsorb, not allowing bone remod- Nevertheless, the exact relation of vertebral eling to occur through it (osteoconduction). height correction after kyphoplasty and clinical Newer fi lling material like ceramic cements outcome is yet to be determined. Vertebral aug- (especially calcium phosphate) and acrylic resin/ mentation procedures are extremely relevant for ceramic composites shows good mechanical prop- the treatment of the rheumatic patient’s osteopo- erties and biocompatibility and allows for bone to rosis, especially when under immunosuppressant remodel through it (animal studies data) [52Ð 54 ] . agents that not only will contribute to the causing These new fi llers for kyphoplasty and vertebro- of osteoporotic fractures but will also elevate the plasty are expensive, and clinical data in humans is traditional surgery risks even more. 310 F. Techy and R.D. Orr

References 16. Voormolen MH, Mali WP, Lohle PN, et al. Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with 1. Riggs BL, Melton 3rd LJ. The worldwide problem of subacute or chronic painful osteoporotic vertebral osteoporosis: insights afforded by epidemiology. compression fractures. The vertos study. AJNR Am Bone. 1995;17(5):505SÐ11. J Neuroradiol. 2007;28:555Ð60. 2. Galibert P, Deramond H, Rosat P, et al. Preliminary 17. Alvarez L, Alcaraz M, Perez-Higueras A, et al. note on the treatment of vertebral angioma by percu- Percutaneous vertebroplasty: functional improvement taneous acrylic vertebroplasty. Neurochirurgie. in patients with osteoporotic compression fractures. 1987;33:166Ð8. French. Spine. 2006;31:1113Ð8. 3. Pateder DB, Khanna AJ, Lieberman IH. Vertebroplasty 18. Diamond TH, Champion B, Clark WA. Management and kyphoplasty for the management of osteoporotic of acute osteoporotic vertebral fractures: a nonran- vertebral compression fractures. Orthop Clin North domized trial comparing percutaneous vertebroplasty Am. 2007;38:409Ð18. with conservative therapy. Am J Med. 2003;114: 4. Johnell O, Kanis JA. An estimate of the worldwide 257Ð65. prevalence and disability associated with osteoporotic 19. Diamond TH, Bryant C, Browne L, Clark WA. fractures. Osteoporos Int. 2006;17:1726Ð33. Clinical outcomes after acute osteoporotic vertebral 5. Carmona RH. Of fi ce of the surgeon general. Bone fractures: a 2-year non-randomised trial comparing health and osteoporosis: a report of the Surgeon gen- percutaneous vertebroplasty with conservative ther- eral. Rockville: Department of Health and Human apy. Med J Aust. 2006;184:113Ð7. Services; 2004. 20. Hochmuth K, Proschek D, Schwarz W, et al. 6. Black DM, Cummings SR, Stone K, Hudes E, Palermo Percutaneous vertebroplasty in the therapy of osteo- L, Steiger P. A new approach to defi ning normal porotic vertebral compression fractures: a critical vertebral dimensions. J Bone Miner Res. 1991;6: review. Eur Radiol. 2006;16:998Ð1004. 883Ð92. 21. Hulme PA, Krebs J, Ferguson SJ, Berlemann U. 7. Weinstein JN. Balancing science and informed choice Vertebroplasty and kyphoplasty: a systematic review in decisions about editorial. N Engl J Med. of 69 clinical studies. Spine. 2006;31:1983Ð2001. 2009;361:619Ð21. 22. Eck JC, Nachtigall D, Humphreys SC, Hodges SD. 8. Buchbinder R, Osborne RH, Ebeling PR, et al. A ran- Comparison of vertebroplasty and balloon kyphop- domized trial of vertebroplasty for painful osteoporo- lasty for treatment of vertebral compression fractures: tic vertebral fractures. N Engl J Med. 2009;361: a meta-analysis of the literature. Spine J. 2008;8: 557Ð68. 488Ð97. 9. Kallmes DF, Comstock BA, Heagerty PJ, et al. A ran- 23. Burton AW, Mendel E. Vertebroplasty and kyphop- domized trial of vertebroplasty for osteoporotic spinal lasty. Pain Physician. 2003;6:335Ð41. fractures. N Engl J Med. 2009;361:569Ð79. 24. Carlier RY, Gordji H, Mompoint DM, et al. 10. Klazen CAH, Lohle PNM, De Vries J, et al. Osteoporotic vertebral collapse: percutaneous verte- Vertebroplasty versus conservative treatment in broplasty and local kyphosis correction. Radiology. acute osteoporotic vertebral compression fractures 2004;233:891Ð8. (Vertos II): an open-label randomised trial. Lancet. 25. Chen LH, Lai PL, Chen WJ. Unipedicle percutaneous 2010;376(9746):1085Ð92. vertebroplasty for spinal intraosseous vacuum cleft. 11. Bono CM, Haggeness MH, Mick CM, et al. North Clin Orthop Relat Res. 2005;435:148Ð53. American spine society: newly released vertebro- 26. Choe DH, Marom EM, Ahrar K, Truong MT, plasty randomized controlled trials: a tale of two tri- Madewell JE. Pulmonary embolism of polymethyl als. Spine J. 2010;10(3):238Ð40. methacrylate during percutaneous vertebroplasty and 12. Munk PL, Liu DM, Murphy KP, Baerlocher MO. kyphoplasty. AJR Am J Roentgenol. 2004;183: Effectiveness of vertebroplasty: a recent controversy. 1097Ð102. Can Assoc Radiol J. 2009;60(4):170Ð1. 27. Cohen JE, Lylyk P, Ceratto R, et al. Percutaneous ver- 13. Phillips FM, et al. Osteoporosis: surgical strategies. tebroplasty: technique and results in 192 procedures. In: Herkowitz HN, Gar fi n SR, Eismont FJ, editors. Neurol Res. 2004;26:41Ð9. Rothman-Simeone: the spine. 5th ed. Philadelphia: 28. Gar fi n SR, Yuan HA, Reiley MA. New technologies WB Saunders. 2006;1341Ð51. in spine: kyphoplasty and vertebroplasty for the treat- 14. Park SW, Lee JH, Ehara S, et al. Single shot fast spin ment of painful osteoporotic compression fractures. echo diffusion-weighted MR imaging of the spine: is Spine. 2001;26:1511Ð5. it useful in differentiating malignant metastatic tumor 29. Gaughen Jr JR, Jensen ME, Schweickert PA, et al. infi ltration from benign fracture edema? Clin Imaging. Lack of preoperative spinous process tenderness does 2004;28(2):102Ð8. not affect clinical success of percutaneous vertebro- 15. Togawa D, Lieberman IH, Bauer TW, Reinhardt MK, plasty. J Vasc Interv Radiol. 2002;13:1135Ð8. Kayanja MM. Histological evaluation of biopsies obtained 30. Gaughen Jr JR, Jensen ME, Schweickert PA, et al. from vertebral compression fractures: unsuspected Relevance of antecedent venography in percutaneous myeloma and osteomalacia. Spine. 2005;30(7):781Ð6. 27 Vertebral Augmentation 311

vertebroplasty for the treatment of osteoporotic com- tures: an evidenced-based review of the literature. pression fractures. AJNR Am J Neuroradiol. 2002;23: Spine J. 2009;9:501Ð8. 594Ð600. 44. Weill A, Chiras J, Simon JM, et al. Spinal metastases: 31. Phillips FM, Todd Wetzel F, Lieberman I, Campbell- indications for and results of percutaneous injection Hupp M. An in vivo comparison of the potential for of acrylic surgical cement. Radiology. 1996;199: extravertebral cement leak after vertebroplasty and 241Ð7. kyphoplasty. Spine. 2002;27:2173Ð8. 45. Cortet B, Cotten A, Boutry N, et al. Percutaneous ver- 32. Kasperk C, Hillmeier J, Noldge G, et al. Treatment of tebroplasty in patients with osteolytic metastases or painful vertebral fractures by kyphoplasty in patients multiple myeloma. Rev Rhum Engl Ed. 1997;64: with primary osteoporosis: a prospective nonrandom- 177Ð83. ized controlled study. J Bone Miner Res. 2005;20: 46. Fourney DR, Schomer DF, Nader R, et al. Percutaneous 604Ð12. vertebroplasty and kyphoplasty for painful vertebral 33. Grafe IA, Da Fonseca K, Hillmeier J, et al. Reduction body fractures in cancer patients. J Neurosurg. of pain and fracture incidence after kyphoplasty: 2003;98:21Ð30. 1-year outcomes of a prospective controlled trial of 47. Lane JM, Hong R, Koob J, et al. Kyphoplasty enhances patients with primary osteoporosis. Osteoporos Int. function and structural alignment in multiple 2005;16:2005Ð12. myeloma. Clin Orthop Relat Res. 2004;426:49Ð53. 34. Lieberman IH, Dudeney S, Reinhardt MK, Bell G. 48. Sun G, Cong Y, Xie Z, et al. Percutaneous vertebro- Initial outcome and ef fi cacy of “kyphoplasty” in the plasty using instruments and drugs made in china for treatment of painful osteoporotic vertebral compres- vertebral metastases. Chin Med J (Engl). 2003;116: sion fractures. Spine. 2001;26:1631Ð8. 1207Ð12. 35. Masala S, Cesaroni A, Sergiacomi G, et al. 49. Dudeney S, Lieberman IH, Reinhardt MK, Hussein Percutaneous kyphoplasty: new treatment for painful M. Kyphoplasty in the treatment of osteolytic verte- vertebral body fractures. In Vivo. 2004;18:149Ð53. bral compression fractures as a result of multiple 36. Rhyne 3rd A, Banit D, Laxer E, Odum S, Nussman D. myeloma. J Clin Oncol. 2002;20:2382Ð7. Kyphoplasty: report of eighty-two thoracolumbar 50. P fl ugmacher R, Schleicher P, Schroder RJ, Melcher I, osteoporotic vertebral fractures. J Orthop Trauma. Klostermann CK. Maintained pain reduction in fi ve 2004;18:294Ð9. patients with multiple myeloma 12 months after treat- 37. Shindle MK, Gardner MJ, Koob J, et al. Vertebral ment of the involved cervical vertebrae with vertebro- height restoration in osteoporotic compression frac- plasty. Acta Radiol. 2006;47:823Ð9. tures: kyphoplasty balloon tamp is superior to postural 51. Togawa D, Bauer TW, Lieberman IH, et al. Histologic correction alone. Osteoporos Int. 2006;17:1815Ð9. evaluation of human vertebral bodies after vertebral 38. Voggenreiter G. Balloon kyphoplasty is effective in augmentation with polymethyl methacrylate. Spine. deformity correction of osteoporotic vertebral com- 2003;28:1521Ð7. pression fractures. Spine. 2005;30:2806Ð12. 52. Verlaan JJ, van Helden WH, Oner FC, et al. Balloon 39. Wilhelm K, Stoffel M, Ringel F, et al. Preliminary vertebroplasty with calcium phosphate cement aug- experience with balloon kyphoplasty for the treatment mentation for direct restoration of traumatic thora- of painful osteoporotic compression fractures. Rofo. columbar vertebral fractures. Spine. 2002;27:543Ð8. 2003;175:1690Ð6. 53. TurnerTM, UrbanRM, LimTH, et al. Vertebroplasty 40. Taylor RS, Fritzell P, Taylor RJ. Balloon kyphop- using injectable calcium phosphate cement compared lasty in the management of vertebral compression to polymethylmethacrylate in a unique canine verte- fractures: an updated systematic review and meta- bral body large defect model. In: Transactions of the analysis. Eur Spine J. 2007;16:1085Ð100. 49th annual meeting of orthopaedic research society. 41. Techy F, Mohan V, Ryu R, Mekhail A. Demographics, New Orleans; 2003; Paper no 267. clinical and radiographic results of kyphoplasty. 54. Takikawa S, Bauer TW, Turner AS, et al. Comparison Follow up from 2 weeks to 5 years. Spine J. 2010; of injectable calcium phosphate cement and polym- 10:29S. ethylmethacrylate for use in vertebroplasty: in-vivo 42. Wardlaw D, Cummings SR, Van Meirhaeghe J, et al. evaluation using an osteopenic sheep model. Presented Ef fi cacy and safety of balloon kyphoplasty compared at the 28th Annual Meeting of the Society of with non-surgical care for vertebral compression fracture Biomaterials. Tampa, 24Ð27 Apr 2002; Paper no (FREE): a randomised controlled trial. Lancet. 231(abstract). 2009;373:1016Ð24. 55. Siemund S, Nilsson LT, Cronqvist M, Strömqvist B. 43. McGirt MJ, Parker SL, Wolinsky JP, Witham TF, Initial clinical experience with a new biointegrative Bydon A, Gokaslan ZL. Vertebroplasty and kyphop- cement for vertebroplasty in osteoporotic vertebral lasty for the treatment of vertebral compression frac- fractures. Interv Neuroradiol. 2009;15(3):335Ð40. Shoulder Arthroplasty 2 8 Jason D. Doppelt and Joseph P. Iannotti

Introduction with shoulder pain as the chief complaint. Careful patient selection is required when considering Shoulder involvement is common in patients with shoulder arthroplasty for patients with advanced rheumatic disease. In one series, 91% of patients arthritis due to rheumatic disease. reported some history of shoulder problems and 31% had “severe painful shoulder disability” [ 1 ] . Multiple joint involvement increases the risk of Presentation and Workup shoulder pathology as monoarticular rheumatic disease does not typically involve the shoulder Patients typically present with an insidious onset [2 ] . Any of the bursal or articular surfaces of the of symptoms which include pain and swelling. shoulder can be affected in addition to the gle- Loss of motion is another common occurrence; nohumeral joint, and the source of the patient’s however, this may not be noticed initially due to pain is not always clear. Kelly demonstrated that compensatory motion at adjacent joints [4 ] . 55% of patients with advanced radiographic Limited active motion secondary to discomfort is changes in the glenohumeral joint had pain relief seen early in the course of treatment; however, from either a subacromial or acromioclavicular fi xed contractures can develop over time. Atrophy injection of local anesthetic, indicating gle- of the shoulder girdle musculature may be pres- nohumeral arthritis was not the main pain genera- ent, especially in the setting of rotator cuff pathol- tor is those patients [ 3 ] . He did fi nd that when the ogy [5 ] . Physical examination can be confounded sphericity of the humeral head was compromised, by the fact that multiple bursal and articular sur- the main source of discomfort was in fact the faces are involved. Speci fi cally, tenderness to pal- glenohumeral joint. An additional confounder pation of the acromioclavicular and sternoclavicular is the high incidence of cervical spine pathology joints should be assessed as contributors to the in this patient population which can be associated patient’s pain. In addition a careful exam of the cervical spine must be performed to rule out neu- ropathy as the source of the patients symptoms. J. D. Doppelt , M.D. Radiographic workup begins with a true Department of Orthopaedic Surgery , Cleveland Clinic , anteroposterior and axillary view of the shoulder. 9500 Euclid Avenue , Cleveland , OH 44195 , USA The earliest radiographic feature of RA is J. P. Iannotti , M.D. (*) regional osteopenia. Over time, marginal ero- Orthopaedic and Rheumatologic Institute , sions will become present. Superior migration of Cleveland Clinic , 9500 Euclid Avenue , Cleveland , OH 44195 , USA the humeral head will be seen when the superior e-mail: [email protected] rotator cuff is compromised, and this must be

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 313 DOI 10.1007/978-1-4614-2203-7_28, © Springer Science+Business Media, LLC 2013 314 J.D. Doppelt and J.P. Iannotti

Candidate Selection

Prosthetic replacement is indicated in patients with advanced joint destruction who have not experienced adequate improvements despite opti- mal medical management, physical therapy, and local corticosteroid injections. Preoperative plan- ning must take the condition of the entire extrem- ity into consideration. Advanced destruction of the shoulder may be seen in the setting of ipsilat- eral elbow pathology. Typically, the most degen- erated joint is addressed fi rst. A second surgery to address the other joint should be postponed until all rehabilitation goals have been met. Due to the in fl ammatory nature of rheumatic Fig. 28.1 Loss of the superior rotator cuff is indicated by disease, there is typically pathology on both sides superior migration of the humeral head with loss of the acromiohumeral interval of the joint. Partial joint replacements, where only the humerus is addressed, have been used in the past due to concerns regarding the secure fi xation of a glenoid component. Advanced imag- appreciated as it is an important consideration in ing such as computed tomography should be surgical planning (Fig. 28.1). Magnetic reso- obtained to decide if placement of a glenoid com- nance imaging is useful in cases where the con- ponent is advisable. Prior research demonstrated dition of the rotator cuff is uncertain [ 6 ] . Some a 90% incidence of lucency around keeled gle- degree of rotator cuff involvement is present in noid component in patients with rheumatoid 75% of patients, and 20–35% have full thickness arthritis 5 years after total shoulder arthroplasty tears [7 ] . Neer found that 12 of 69 patients under- [ 10 ] . Fortunately, newer implants have demon- going total shoulder arthroplasty had “massive strated superior long-term fi xation, making place- disintegration of the rotator cuff” at the time of ment of a glenoid component advisable in most surgery [8 ] . situations (Fig. 28.2). Bell and Gschwend dem- Prior surgery and especially the presence of onstrated superior pain relief and restoration of previously placed hardware make infection a motion with total shoulder arthroplasty compared diagnosis that must be ruled out prior to place- to hemiarthroplasty [11 ] . ment of any prosthetic components. As previously mentioned, rotator cuff tears are Preoperative blood work including a complete not uncommon in the setting of rheumatic dis- blood count with differential, erythrocyte sedi- ease and should be addressed at the time of shoul- mentation rate, and C-reactive protein should der replacement. Some chronic large cuff tears be obtained. Glenohumeral aspiration should may not be reparable and can result in a poor out- be performed to culture the synovial fl uid if the come if not addressed. A functional rotator cuff is patient has had prior surgery on the affected associated with superior results in traditional shoulder. All cultures should be monitored for total shoulder arthroplasty [12 ] . In the setting of an extended period of time to rule out the pres- a massive irreparable rotator cuff tear, the sur- ence of a low virulence organism such as geon may elect to use a reverse shoulder prosthe- Propionibacterium acnes which is commonly sis where the con fi guration of the ball and socket associated with infected hardware in the shoul- is reversed [13 ] (Fig. 28.3 ). This type of arthro- der and may take up to 2 weeks to demonstrate plasty allows improved shoulder elevation in the growth on culture [ 9 ] . setting of an absent superior cuff. One problem 28 Shoulder Arthroplasty 315

predictor of paralysis [14 ] . While the incidence of radiographic instability is 41% in patients undergoing total joint arthroplasty, fortunately, only 8% of patients had radiographic fi ndings predictive of paralysis [ 15 ] . When cervical stabil- ity is compromised, fi ber-optic intubation should be considered to keep neutral cervical alignment and reduce the risk of iatrogenic injury. During surgery, the patient will be in the beach-chair position, and again cervical alignment must be carefully monitored to avoid injury. In cases where intubation is not the best option, the sur- gery can be performed with a well-placed and effective scalene block. Regional anesthesia is another important con- sideration for postoperative pain management. Prior to intubation, an interscalene block can be performed to reduce the amount of narcotic required both during and after the procedure. A single shot of long-acting local anesthetic can be administered or a catheter can be inserted to provide prolonged anesthesia over the fi rst sev- eral postoperative days. The pain reduction seen with continuous interscalene nerve blocks allows improved range of motion in the immediate postoperative period [16 ] as well as decreased Fig. 28.2 Anchor peg glenoid components provide ini- time until readiness for discharge [ 17 ] . tial fi xation as well as improved long-term stability when Postoperatively, patients may have a dense nerve bony ingrowth is present (indicated by white arrow ) block affecting the involved upper extremity, making assessment of postoperative function with this type of surgery in this particular patient impossible. Patients should be instructed to use population is loosening of the glenoid component added caution in this situation to avoid inadver- due to the combination of poor bone and the tent injury such as a rotator cuff tear, joint dislo- increased stress on the glenoid component inher- cation, or fracture due to loss of protective ent with this type of prosthesis. abilities. The pain management team should be made aware of an excess effect and decrease the local anesthetic infusion rate so that pain levels Anesthesia Considerations are minimal, yet the patient has protective motor control of the upper extremity. Patients may be Shoulder arthroplasty is typically performed discharged with the catheter in place to optimize under general endotracheal anesthesia. At the pain control at home as well. Persistent paresthe- time of intubation, the neck is positioned in sia, dysesthesia, or pain not related to surgery is extension which cannot be safely done in setting present in 14% of patients at 10 days postopera- cervical instability. The preoperative workup tively; however, long-term complaints have an must therefore include fl exion and extension lat- incidence of only 0.4% [18 ] . Serious complica- eral x-rays to assess for radiographic instability tions such as seizure due to intravascular injec- and more importantly measure the posterior tion and pneumothorax have a low incidence of atlanto-odontoid interval which is an important 0.2% each [18, 19 ] . 316 J.D. Doppelt and J.P. Iannotti

treatment for fractures below a well-fi xed and functioning stem can be treated with application of a plate designed for this purpose. Occasionally, the stem may need to be removed and treated with a long-stem prosthesis to achieve adequate stability. For fractures with a loose component, revision with a cemented long-stem implant is performed with iliac crest bone graft. Cortical strut allograft or plate fi xation can be considered if additional stability is thought to be necessary. Neurovascular complications during shoulder arthroplasty are fortunately uncommon. The axil- lary nerve is at risk as it passes below the inferior joint capsule and must be protected throughout the case. Injury to the nerve is clinically evident when there is numbness over the lateral aspect of the shoulder or deltoid muscle weakness. More extensive damage to the brachial plexus is possi- ble but rarely encountered as dissection in this area is not typically required during shoulder Fig. 28.3 A reverse shoulder arthroplasty can be per- arthroplasty. Previous surgery and the presence formed in the setting of an irreparable rotator cuff repair of a dense scar tissue do increase the risk of neu- rovascular injury. Complications Hematologic complications are encountered less frequently in the shoulder compared to hip and Due to preexisting osteopenia, patients with rheu- knee arthroplasty. The incidence of deep vein matic disease are at increased risk of intraoperative thrombosis and pulmonary embolism is 0.5% and fracture during humerus preparation and compo- 0.23%, respectively [ 21 ] . Wound hematoma requir- nent implantation. Fractures proximal to the tip of ing intervention is rare due to the thick soft tissue the prosthesis are typically managed with cerclage envelope around the glenohumeral joint. Prior wiring and a standard length prosthetic. reports have described wound hematomas requir- Intraoperative fractures at and below the tip of the ing debridement in patients receiving heparin ther- prosthetic should be managed with cerclage wiring apy for a diagnosed pulmonary embolism [22 ] . and use of a long-stem prosthetic with or without Proximal migration of the humeral component cement depending on the distal rotational stability is a common occurrence seen in 55% of patients of the fracture after cerclage fi xation and trial stem at 7.7 years after surgery [ 23 ] . This occurs due to insertion. Postoperatively, there is also a risk of tearing or poor function of the rotator cuff. It is fracture as a result of relatively minor trauma due correlated to preoperative rotator cuff status and to the stress riser at the tip of the humeral stem. length of follow-up. The incidence of loosening The treatment algorithm proposed by Kumar et al. on the humeral side is much less, although some [20 ] is based largely on the stability of the humeral authors have previously advocated cementation component. A trial of management in a fracture of the humeral stem to enhance fi xation [24 ] . brace can be attempted if fi xation of the stem is not compromised and the fracture is distal to the stem. In this circumstance, good reduction and mainte- Recovery nance of reduction in a cast brace must be demon- strated [4 ] . Operative intervention can be Patients are typically hospitalized for 2 to 4 days considered if the fracture has not progressed following surgery depending mostly on their toward union by 3 months after the injury. Operative underlying comorbidities. The rehabilitation 28 Shoulder Arthroplasty 317

program is typically broken down into four emphasized as the overall results with shoulder phases to optimize recovery [ 25 ] . Phase one is arthroplasty for rheumatoid arthritis are inferior initiated on the day following surgery where to cases of osteoarthritis [26 ] . early protected motion is emphasized. Pendulum exercises and supine passive forward elevation is performed under the supervision of the physi- References cal therapist. The integrity of the subscapularis should be protected and monitored closely. The 1. Petersson CJ. Painful shoulders in patients with rheu- maximum amount of passive external rotation matoid arthritis. Prevalence, clinical and radiological features. Scand J Rheumatol. 1986;15:275–9. that does not place unacceptable tension on the 2. Cuomo F, Greller MJ, Zuckerman JD. The rheumatoid repair is assessed prior to wound closure. The shoulder. Rheum Dis Clin North Am. 1998;24:67–82. postoperative therapy orders allow external rota- 3. Kelly IG. The source of shoulder pain in rheumatoid tion only up to approximately 20° less than this arthritis: usefulness of local anesthetic injections. J Shoulder Elbow Surg. 1994;3:62–5. maximum acceptable external rotation. If loss of 4. Chen AL, Joseph TN, Zuckerman JD. Rheumatoid subscapularis integrity is suspected, clinically, arthritis of the shoulder. J Am Acad Orthop Surg. the diagnosis should be confi rmed by plain 2003;11:12–24. radiograph in the case of a lesser tuberosity 5. Weiss JJ, Thompson GR, Doust V, Burgener F. Rotator cuff tears in rheumatoid arthritis. Arch Intern Med. osteotomy or ultrasound when a subscapularis 1975;135:521–5. tenotomy is performed. Early recognition and 6. Kieft GJ, Dijkmans BA, Bloem JL, Kroon HM. urgent surgical intervention for re-repair may Magnetic resonance imaging of the shoulder in allow for healing and achieving of a satisfactory patients with rheumatoid arthritis. Ann Rheum Dis. 1990;49:7–11. clinical result. 7. Curran JF, Ellman MH, Brown NL. Rheumatologic Phase two is initiated at 3 weeks following aspects of painful conditions affecting the shoulder. surgery where stretches focusing on shoulder Clin Orthop Relat Res. 1983;173:27–37. extension and cross-body adduction are added. 8. Neer 2nd CS, Watson KC, Stanton FJ. Recent experi- ence in total shoulder replacement. J Bone Joint Surg Internal rotation is not added until 6 weeks after Am. 1982;64:319–37. surgery. At 6 weeks, strengthening exercises 9. Lutz MF, Berthelot P, Fresard A, Cazorla C, Carricajo focusing on external rotation, internal rotation, A, Vautrin AC, et al. Arthroplastic and osteosynthetic and extension are allowed utilizing elastic bands infections due to Propionibacterium acnes: a retro- spective study of 52 cases, 1995–2002. Eur J Clin of progressive resistance. Phase three begins at Microbiol Infect Dis. 2005;24:739–44. 12 weeks where strengthening in abduction, for- 10. Trail IA, Nuttall D. The results of shoulder arthro- ward elevation, and external rotation at 45° in the plasty in patients with rheumatoid arthritis. J Bone plane of the scapula is performed. Phase four is Joint Surg Br. 2002;84:1121–5. 11. Bell SN, Gschwend N. Clinical experience with total allowed at 16 weeks where heavier strength train- arthroplasty and hemiarthroplasty of the shoulder using ing is emphasized. Return to work and sports is the Neer prosthesis. Int Orthop. 1986;10:217–22. tailored to the severity of the pathology, overall 12. Franklin JL, Barrett WP, Jackins SE, Matsen III FA. musculoskeletal limitations, and medical comor- Glenoid loosening in total shoulder arthroplasty. Association with rotator cuff de fi ciency. J Arthroplasty. bidities. Maximum benefi t from shoulder arthro- 1988;3:39–46. plasty is not realized until 9–12 months after 13. Rittmeister M, Kerschbaumer F. Grammont reverse shoulder arthroplasty [4 ] . total shoulder arthroplasty in patients with rheuma- Expectations regarding activity are based toid arthritis and nonreconstructible rotator cuff lesions. J Shoulder Elbow Surg. 2001;10:17–22. heavily on the condition of the soft tissue around 14. Boden SD, Dodge LD, Bohlman HH, Rechtine GR. the glenohumeral joint. In the presence of a func- Rheumatoid arthritis of the cervical spine. A long- tioning rotator cuff, excellent motion and strength term analysis with predictors of paralysis and recov- can be achieved. While small defects in the cuff ery. J Bone Joint Surg Am. 1993;75:1282–97. 15. Grauer JN, Tingstad EM, Rand N, Christie MJ, may not compromise the patient’s fi nal activity Hilibrand AS. Predictors of paralysis in the rheumatoid level, large cuff tears can be associated with cervical spine in patients undergoing total joint arthro- persistent dysfunction. Realistic goals should be plasty. J Bone Joint Surg Am. 2004;86-A:1420–4. 318 J.D. Doppelt and J.P. Iannotti

16. Ilfeld BM, Wright TW, Enneking FK, Morey TE. der arthroplasty. J Bone Joint Surg Am. 2004;86- Joint range of motion after total shoulder arthroplasty A:680–9. with and without a continuous interscalene nerve 21. Lyman S, Sherman S, Carter TI, Bach PB, Mandl LA, block: a retrospective, case-control study. Reg Anesth Marx RG. Prevalence and risk factors for symptom- Pain Med. 2005;30:429–33. atic thromboembolic events after shoulder arthro- 17. Ilfeld BM, Vandenborne K, Duncan PW, Sessler DI, plasty. Clin Orthop Relat Res. 2006;448:152–6. Enneking FK, Shuster JJ, et al. Ambulatory continu- 22. Sperling JW, Co fi eld RH. Pulmonary embolism fol- ous interscalene nerve blocks decrease the time to dis- lowing shoulder arthroplasty. J Bone Joint Surg Am. charge readiness after total shoulder arthroplasty: a 2002;84-A:1939–41. randomized, triple-masked, placebo-controlled study. 23. Sojbjerg JO, Frich LH, Johannsen HV, Sneppen O. Anesthesiology. 2006;105:999–1007. Late results of total shoulder replacement in patients 18. Borgeat A, Ekatodramis G, Kalberer F, Benz C. Acute with rheumatoid arthritis. Clin Orthop Relat Res. and nonacute complications associated with intersca- 1999;366:39–45. lene block and shoulder surgery: a prospective study. 24. Stewart MP, Kelly IG. Total shoulder replacement in Anesthesiology. 2001;95:875–80. rheumatoid disease: 7- to 13-year follow-up of 37 19. Brown DL, Ransom DM, Hall JA, Leicht CH, joints. J Bone Joint Surg Br. 1997;79:68–72. Schroeder DR, Offord KP. Regional anesthesia and 25. Iannotti JP, Williams GR. Disorders of the shoulder: local anesthetic-induced systemic toxicity: seizure diagnosis & management. 2nd ed. Philadelphia: frequency and accompanying cardiovascular changes. Lippincott Williams & Wilkins; 2007. Anesth Analg. 1995;81:321–8. 26. McCoy SR, Warren RF, Bade 3rd HA, Ranawat CS, 20. Kumar S, Sperling JW, Haidukewych GH, Cofi eld Inglis AE. Total shoulder arthroplasty in rheumatoid RH. Periprosthetic humeral fractures after shoul- arthritis. J Arthroplasty. 1989;4:105–13. Carpal Tunnel Surgery 2 9 Peter J. Evans and Ngozi I. Mogekwu

Introduction Presence of the latter two is referred to as double crush syndrome, while the presence of all three is Carpal tunnel syndrome (CTS) is a compressive considered a triple crush syndrome [13 ] . neuropathy of the median nerve at the wrist. It is one of the most common ailments of the hand, and thus, carpal tunnel release (CTR) is one of the Surgical Indications most common procedures performed in the upper extremity. The vast majority of CTS cases are idio- CTS is primarily a clinical diagnosis. Careful eval- pathic. Some are associated with systemic condi- uation of the sensory and motor function of the tions such as diabetes mellitus, thyroid disorders, hand is paramount to clinical diagnosis. Classic renal failure, and rheumatologic disorders. CTS is fi ndings include numbness and tingling in the a known extra-articular manifestation of rheuma- thumb, index, long, and radial half of ring fi nger; toid arthritis in the early stages of the disease and nighttime symptoms; a positive Tinel and Phalen the most common compressive neuropathy in sign; and positive median nerve compression test- rheumatoid arthritis [6, 7 ] . Cases of CTS have ing. Flexion of all fi ve fi ngers should also be eval- been reported in children with juvenile rheumatoid uated. Finger triggering, crepitus, and lack of full arthritis [19 ] . The pathogenesis of carpal tunnel active fl exion with full passive fl exion are all signs syndrome in rheumatoid arthritis was initially of fl exor tenosynovitis and/or rupture that can described and classifi ed by Chamberlain et al. in occur concurrently with CTS in the rheumatic 1970 and was further modi fi ed into three potential patient. Muscle wasting in the thenar region should etiologies as described by Taguchi and colleagues also be evaluated. Physical examination in the [ 3, 13 ] : (1) rheumatoid neuropathy caused by vas- rheumatic patient may be more challenging due to cular damage to the peripheral nerve, (2) compres- the presence of concurrent hand and fi nger dys- sion secondary to synovitis or swollen joints, and function including deformity, joint swelling, mus- (3) cervical neuropathy secondary to cervical cle atrophy, and tendon ruptures [ 13 ] . The cervical pathology such as atlantoaxial instability. [ 13 ] . spine and the remaining upper extremity should be evaluated to rule out a double or triple crush phe- nomenon. Radiographs of the wrist (anterior-pos- P. J. Evans , M.D., Ph.D., F.R.C.S.C. (*) terior, lateral, and oblique) should be obtained in ¥ N. I. Mogekwu , M.D. the rheumatic patient to assess any associated wrist Orthopaedic and Rheumatologic Institute , pathology with malalignment. MRI and ultrasound Cleveland Clinic Foundation , 9500 Euclid Avenue - A40 , Cleveland , OH 44195 , USA are not necessary but can be useful tools in assess- e-mail: [email protected] ing tenosynovitis within the carpal canal [18 ] .

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 319 DOI 10.1007/978-1-4614-2203-7_29, © Springer Science+Business Media, LLC 2013 320 P.J. Evans and N.I. Mogekwu

Electrodiagnostic studies are obtained to esti- under local or regional anesthesia such as a Bier mate the severity of injury to the median nerve. block, and this helps to avoid the need for neck These include nerve conduction studies (NCS) manipulation in the operating room. and electromyography (EMG). Based on these studies, neuropathy can be graded as mild, mod- erate, and severe. In rheumatic patients, these Disease-Associated Perioperative studies may not necessarily provide a correlation Issues to their clinical symptoms. Studies by Sivri et al. and Lanzillo et al. have shown electrophysiologi- The patient with rheumatic disease typically is on one cal changes consistent with peripheral nerve or more medications used in managing their disease. damage, even in the absence of clinical symp- These include but are not limited to disease modifying toms [ 11, 16 ] . Standard indications for surgical antirheumatic drugs (DMARDS) and anti-infl ammatory decompression for CTS include progressively medications. Unfortunately, there are no good data that worsening symptoms, symptoms refractory to strati fi es the risk of infectious complications [4, 5] in nonoperative management such as wrist splinting patients taking immunosuppressive medications to the and corticosteroid injections and severe CTS type of surgery performed. The management of immu- associated with progressive muscle atrophy. In nosuppressive therapy in the perioperative period is the rheumatic patient, earlier surgery is warranted usually patient speci fi c to balance the risks and bene fi ts for the following reasons: (1) to prevent further to that specifi c patient. For carpal tunnel surgery, the loss of function of the hand and (2) to ease com- patients can generally continue their medications pression from synovial proliferation. (except non-Cox-2 anti-in fl ammatories) in the periop- The American Academy of Orthopaedic erative period. Surgeons has an evidence-based consensus guideline on the diagnosis of carpal tunnel release that was approved in 2007 [1 ] . However, it does Procedure-Speci fi c Complications not speci fi cally address carpal tunnel syndrome in the rheumatic patient. Surgical site infection is of concern postoperatively in the patient with rheumatic disease. Prophylactic antibiotics are usually administered within one Anesthesia Considerations hour before the surgery. This is usually a fi rst- generation cephalosporin like cephazolin or clin- The cervical spine is of paramount importance to damycin if the patient has a documented allergy. the anesthesiologist in the rheumatic patient, There is no evidence that continued antibiotic ther- especially in the rheumatoid arthritis population. apy reduces the risk of infection. Cervical spine involvement has been reported in Overall, postoperative surgical site infection after 15Ð86% of patients with rheumatoid arthritis carpal tunnel surgery is exceedingly rare [ 8, 10, 14 ] . [ 15, 20] . The destruction of normal anatomy Rates have been reported from 0% to 8%. A recent leads to atlantoaxial subluxation and/or subaxial retrospective study by Harness et al. reported a subluxation [ 12 ] . Patients with poor neck mobil- 0.004% occurrence rate. Infections occurred in 11 ity may have intraoperative dif fi culty with visu- out of 3,003 patients. In addition, there was no alization of the larynx. Operative risks include signi fi cant difference in infection risk in patients neurological and/or vascular injury, even death who did not receive preoperative antibiotics, but from cervical subluxation during laryngoscopy information on patients not withholding DMARDs or neck positioning. Preoperative clinical evalua- was not given [ 9 ] . However, we still recommend pre- tion of neck range of motion and radiographic operative antibiotics in the rheumatic patient because evaluation is necessary before surgery. In cases as a group, they are more susceptible to infections. with cervical spine instability or a very rigid air- Other well-described complications not way, fi ber optic intubation may be required. specifi c to the rheumatic patient include incom- Carpal tunnel surgery is typically performed plete transverse carpal ligament release, median 29 Carpal Tunnel Surgery 321 nerve injury or scarring, ulnar nerve or artery 5. Dixon WG, Watson K, Lunt M, Hyrich KL, Silman damage, damage to the palmar arterial arch, and AJ, Symmons DP. Rates of serious infection, including site-speci fi c and bacterial intracellular infection, in sympathetically mediated chronic regional pain rheumatoid arthritis patients receiving anti-tumor syndrome. necrosis factor therapy: results from the British society Regarding surgical technique, CTR in the pres- for rheumatology biologics register. Arthritis Rheum. ence of RA is typically done as an open procedure 2006;54(8):2368Ð76. 6. Fleming A, Dodman S, Crown JM, Corbett M. Extra- versus an endoscopic procedure. This is primarily articular features in early rheumatoid disease. Br Med because synovitis within the carpal canal and sur- J. 1976;1(6020):1241Ð3. rounding the fl exor tendons will prevent adequate 7. Geoghegan JM, Clark DI, Bainbridge LC, Smith C, visualization and render the endoscopic procedure Hubbard R. Risk factors in carpal tunnel syndrome. J Hand Surg Br. 2004;29(4):315Ð20. unsafe. 8. Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic Postoperative Management surgery. Ann Rheum Dis. 2001;60(3):214Ð7. 9. Harness NG, Inacio MC, Pfeil FF, Paxton LW. Rate of and Rehabilitation infection after carpal tunnel release surgery and effect of antibiotic prophylaxis. J Hand Surg Am. 2010;35(2): Carpal tunnel release is an outpatient procedure, 189Ð96. and the vast majority of patients go home on the 10. Kremer JM, Rynes RI, Bartholomew LE. Severe fl are of rheumatoid arthritis after discontinuation of long-term day of surgery. The patient usually has a soft methotrexate therapy. double-blind study. Am J Med. dressing or splint, at the discretion of the surgeon. 1987;82(4):781Ð6. We favor a soft postoperative dressing. The 11. Lanzillo B, Pappone N, Crisci C, di Girolamo C, wound typically heals in 10Ð14 days. Hand ther- Massini R, Caruso G. Subclinical peripheral nerve involvement in patients with rheumatoid arthritis. apy can be helpful if the patient is having diffi culty Arthritis Rheum. 1998;41(7):1196Ð202. with full fi nger range of motion. On rare occa- 12. Macarthur A, Kleiman S. Rheumatoid cervical joint sions, patients may have postoperative “pillar disease a challenge to the anaesthetist. Can J Anaesth. pain” on the thenar or hypothenar side of the 1993;40(2):154Ð9. 13. Muramatsu K, Tanaka H, Taguchi T. Peripheral neu- proximal palm. They may need longer periods of ropathies of the forearm and hand in rheumatoid therapy to regain hand strength and endurance for arthritis: Diagnosis and options for treatment. activities. The overall outcomes are very positive Rheumatol Int. 2008;28(10):951Ð7. with greater than 95% good or excellent results 14. Pieringer H, Stuby U, Biesenbach G. The place of methotrexate perioperatively in elective orthopedic and patient satisfaction [2, 17 ] . surgeries in patients with rheumatoid arthritis. Clin Rheumatol. 2008;27(10):1217Ð20. 15. Sherk HH. Atlantoaxial instability and acquired basilar invagination in rheumatoid arthritis. Orthop References Clin North Am. 1978;9(4):1053Ð63. 16. Sivri A, Guler-Uysal F. The electroneurophysiological 1. American Academy of Orthopaedic Surgeons. (May fi ndings in rheumatoid arthritis patients. Electromyogr 18th, 2007). Clinical practice guidelines: Guidelines Clin Neurophysiol. 1999;39(7):387Ð91. on the diagnosis of carpal tunnel syndrome. 17. Trumble TE, Diao E, Abrams RA, Gilbert-Anderson 2. Belcher HJ, Varma S, Schonauer F. Endoscopic carpal MM. Single-portal endoscopic carpal tunnel release tunnel release in selected rheumatoid patients. J Hand compared with open release: A prospective, randomized Surg Br. 2000;25(5):451Ð2. trial. J Bone Joint Surg Am. 2002;84-A(7):1107Ð15. 3. Chamberlain MA, Bruckner F. Rheumatoid neuropa- 18. Uchiyama S, Itsubo T, Yasutomi T, Nakagawa H, thy. Clinical and electrophysiological features. Ann Kamimura M, Kato H. Quantitative MRI of the wrist Rheum Dis. 1970;29(6):609Ð16. and nerve conduction studies in patients with idio- 4. den Broeder AA, Creemers MC, Fransen J, de Jong E, pathic carpal tunnel syndrome. J Neurol Neurosurg de Rooij DJ, Wymenga A, de Waal-Male fi jt M, van den Psychiatry. 2005;76(8):1103Ð8. Hoogen FH. Risk factors for surgical site infections and 19. Unal O, Ozcakar L, Cetin A, Kaymak B. Severe other complications in elective surgery in patients with bilateral carpal tunnel syndrome in juvenile chronic rheumatoid arthritis with special attention for anti- arthritis. Pediatr Neurol. 2003;29(4):345Ð8. tumor necrosis factor: A large retrospective study. 20. Watt I, Cummins B. Management of rheumatoid neck. J Rheumatol. 2007;34(4):689Ð95. Ann Rheum Dis. 1990;49(10):805Ð7. Metacarpophalangeal Arthroplasty 3 0 Peter J. Evans and Ngozi I. Mogekwu

Introduction structures then leads to joint instability. The loose, unstable joint progresses to joint defor- The metacarpophalangeal joint is important for mity such as volar subluxation or dislocation function of the fi ngers and hand. This joint is and ulnar deviation [5 ] . Other factors that lead to frequently involved in rheumatoid arthritis, sys- MCP joint deformity include wrist deformity, temic lupus erythematosus, scleroderma, and fl exor and extensor tendon forces, intrinsic mus- psoriatic arthritis. Destruction of this joint can cle imbalance, and forces of gravity and pinch result in signi fi cant deformity and functional [6 ] . The extrinsic extensors and fl exors contrib- impairment. The MCP joint is the most com- ute to ulnar drift of the fi ngers in rheumatoid monly affected joint in the rheumatoid hand [1 ] . arthritis patients. The extensor tendons are often The MCP joint is a diarthrodial, condylar joint shifted or dislocated in an ulnar direction in rela- with synovial lining of the joint capsule. It tion to the metacarpophalangeal joint. The allows motion in the planes of fl exion/extension, stretching of the collateral ligaments which sup- radial/ulnar deviation, and circumduction. The port the fl exor tendon sheath and pulleys allows radial condyle is larger than the ulnar condyle, volar and ulna shifts of the pulleys and can con- allowing the head to lean more ulnarly [2 ] . The tribute to joint deformity [4 ] . The intrinsic mus- volar surface of the metacarpal head is broader culature contributes to further ulnar deviation than the dorsal surface, and this accounts for the and volar subluxation of the MCP joint by cam effect that tightens the collateral ligaments interossei and lumbrical muscle contractures on when the joint is fl exed [ 3 ] . The deforming the ulnar side of the joint. forces of the joint in rheumatoid arthritis are thought to begin as a proliferative synovitis that occurs in the recess between the metacarpal Surgical Indications head and the collateral ligaments. This eventu- ally causes fraying and stretching of the capsule MCP surgery in the in fl ammatory disease patient and collateral ligaments [4 ] . Loosening of these can usually be classi fi ed as preventative or reconstructive. Prophylactic measures include synovectomy and soft tissue reconstruction. P. J. Evans , M.D., Ph.D., F.R.C.S.C. () MCP arthroplasty is considered a reconstructive ¥ N. I. Mogekwu, M.D. procedure. Severe, advanced deformity of the Hand and Upper Extremity Center, Orthopaedic and MCP joint requiring surgery is generally rare Rheumatologic Institute , Cleveland Clinic Foundation , 9500 Euclid Avenue Ð A40 , Cleveland , OH 44195 , USA except in the setting of rheumatoid arthritis. The e-mail: [email protected] vast majority of the published work in MCP

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 323 DOI 10.1007/978-1-4614-2203-7_30, © Springer Science+Business Media, LLC 2013 324 P.J. Evans and N.I. Mogekwu

arthroplasty has been in rheumatoid arthritis are performed under regional nerve block and patients. In general, the indications for surgical monitored anesthesia care (MAC), the level of treatment include a painful MCP joint deformity sedation needed can vary signifi cantly depend- with destruction and/or subluxation of the joint, ing on the patient. Intraoperative changes in the or a deformity that cannot be corrected with soft need for deeper sedation may require laryngeal tissue reconstructive procedures and impairs mask airway or endotracheal intubation to secure function [2 ] . It is important to remember that the the patient’s airway. typical patient with rheumatoid arthritis has a combination of other upper extremity deformi- ties that may need to be combined or staged with Disease-Associated Perioperative the MCP arthroplasty to attain the optimal outcome Issues for each procedure and overall function. The goals of surgery are to restore functional range of Global assessment of the adjacent joints is impor- motion, restore joint stability, and resist lateral tant in evaluating potential surgical candidates for and rotational forces [ 7 ] . The patient will expect MCP joint arthroplasty. The timing of the hand pain relief, correction of deformity, improvement surgery is imperative to obtaining good functional in function, and appearance of the hand. outcome. As a general rule, any pending lower It is important to remember that MCP joint extremity and proximal upper extremity proce- deformity itself is not an automatic indication for dures, such as those involving the shoulder, elbow, surgery. Some of these patients have clinical and and wrist, should be addressed fi rst. radiographic evidence of MCP joint destruction, Disease-modifying antirheumatic drugs subluxation, etc., but are pain-free with good (DMARDs) and anti-in fl ammatory (COX-2 hand function. They should be observed as sur- inhibitors only) medication use in the periopera- gery may not improve their function and could tive period is an ongoing debate. There is no data potentially weaken their strength. Only if their that addresses the risk-bene fi t ratio of these drugs deformity and hand function progressively in patients undergoing upper extremity surgery. worsen should they be considered for surgical MCP arthroplasty has exceedingly low complica- intervention. tions which will be discussed in the next section, Contraindications to MCP arthroplasty include and the vast majority of practicing hand surgeons active skin and/or joint infection, poor skin qual- allow the continued use of DMARDS and COX-2 ity with atrophied soft tissues unlikely to heal, inhibitor anti-in fl ammatory medications in the compromised neurovascular status, nonfunc- perioperative setting. tional musculotendinous system, and active vas- culitis [ 4] . Poor bone stock with excessive loss of metacarpal head or proximal phalange, and fatty Procedure-Speci fi c Complications replacement of cancellous bone can result in an unstable prosthesis [8 ] . Potential complications associated with MCP arthroplasty include recurrent ulnar deviation, extensor lag, limited MCP joint fl exion, implant Anesthesia Considerations fracture, infection, silicone-induced particulate synovitis, and lymphadenopathy. As with all rheumatic patients, especially those Most patients will have some recurrent ulnar with long-standing disease and rheumatoid deviation and loss of extension of the MCP joint. arthritis patients, cervical spine assessment for In some of the longest follow-up studies instability should be assessed preoperatively to (5Ð8 years retrospective) of MCP joint arthro- be prepared for potential cervical manipulation plasty, patients maintained functional motion that to obtain airway access in the operating room had not deteriorated despite some recurrence of [ 9 ] . Although most MCP arthroplasty surgeries ulnar drift extensor lag [10, 11 ] . 30 Metacarpophalangeal Arthroplasty 325

Fractures of the implants are rare, and the inci- used at night to keep the MCP and IP joints in the dence has been reported to be an average of 2% of corrected position. Flexion of the MCP joints is cases [ 10, 12] . A signifi cant increase in ulnar devi- then initiated after 4 weeks during therapy ses- ation and shortening of the fi nger should increase sions only. After the fi rst 6 weeks, the daytime the index of suspicion for a fracture which can be splint can be discontinued, and the patient can confi rmed with x-rays [ 13 ] . Most patients with have unrestricted motion but still wears an MCP fractured implants have good acceptable function brace to maintain alignment during active range and do not require revision surgery. of motion. Heavy lifting or gripping should be Infections postoperatively are exceedingly avoided for 3 months. rare with reported rates of 0.6% [ 12 ] . Deep infec- There is no universal single postoperative pro- tion requiring removal of implants has been tocol. The rehabilitation plan of splinting and reported to vary from 1.6% to 9% [ 4 ] . Excision of exercise program is individualized to the patient the implant and antibiotic treatment usually con- depending on the specifi c preoperative deformity trols the infection. Millender et al. found that all and soft tissue condition. infections presented within 8 weeks of surgery, The results of MCP arthroplasty are well docu- with Staphylococcus aureus being the most com- mented in the literature. In appropriately selected mon organism [14 ] . The implants were removed patients, pain is relieved and function is improved and the patients were treated with 2 weeks of with high overall satisfaction rates [ 10, 11, 15, 16 ] . antibiotics, and their subsequent function was similar to patients with resection arthroplasty. Silicone-induced particulate synovitis and References silicone-induced lymphadenopathy have been reported in 0.06% and 0.08% of all cases, respec- 1. Abboud JA, FAUÐBeredjiklian PK, Beredjiklian PK, tively [12 ] . The synovitic changes occurred pre- FAUÐBozentka DJ, Bozentka DJ. Metacarpophalangeal dominantly in the involved MCP joint. The joint arthroplasty in rheumatoid arthritis. J Am Acad presence of giant cell reaction in axillary lymph Orthop Surg. 2003;11(3):184Ð91. 2. Bass RL, FAUÐStern PJ, Stern PJ, FAUÐNairus JG, nodes of the patients with lymphadenopathy in Nairus JG. High implant fracture incidence with sut- the Foliart et al. study determined that the pres- ter silicone metacarpophalangeal joint arthroplasty. ence of silicone implants was a concomitant J Hand Surg Am. 1996;21(5):813Ð8. fi nding and not a causal fi nding [12 ] . 3. Beckenbaugh RD. Implant arthroplasty in the rheuma- toid hand and wrist: Current state of the art in the United States. J Hand Surg Am. 1983;8(5 Pt 2):675Ð8. 4. Beckenbaugh RD, Dobyns JH, Linscheid RL, Bryan Postoperative Management RS. Review and analysis of silicone-rubber metacar- and Rehabilitation pophalangeal implants. J Bone Joint Surg Am. 1976; 58(4):483Ð7. 5. Bieber EJ, Weiland AJ, Volenec-Dowling S. Silicone- MCP arthroplasty is typically done on an outpa- rubber implant arthroplasty of the metacarpophalan- tient basis. The dressings are changed within the geal joints for rheumatoid arthritis. J Bone Joint Surg fi rst week of surgery. A static splint is used to Am. 1986;68(2):206Ð9. 6. Feldon P, Terrono A, Nalebuff EA, Millender LH. maintain the corrected position of the MCP joint Rheumatoid arthritis and other connective tissue dis- (near full extension and some radial deviation). eases. In: Green DP, Hotchkiss RN, Pederson WC, Some surgeons utilize custom dynamic splints to Wolfe SW, editors. Green’s operative hand surgery. support the MCP joints for up to 6 weeks postop- 5th ed. Philadelphia, PA: Elsevier; 2005. p. 2049. 7. Flatt AE, Fischer GW. Biomechanical factors in the eratively, but many do not allow any MCP joint replacement of rheumatoid fi nger joints. Ann Rheum motion for the fi rst 4 weeks (our preference). The Dis. 1969;28(5):36Ð41. interphalangeal (IP) joints are usually free, and 8. Foliart DE. Swanson silicone fi nger joint implants: the patient performs exercises under the supervi- A review of the literature regarding long-term compli- cations. J Hand Surg Am. 1995;20(3):445Ð9. sion of an occupational therapist several times a 9. Kirschenbaum D, Schneider LH, Adams DC, Cody day. A static forearm-based resting hand splint is RP. Arthroplasty of the metacarpophalangeal joints 326 P.J. Evans and N.I. Mogekwu

with use of silicone-rubber implants in patients who 13. Roberts WN, Daltroy LH, Anderson RJ. Stability of have rheumatoid arthritis. Long-term results. J Bone normal joint fi ndings in persistent classic rheumatoid Joint Surg Am. 1993;75(1):3Ð12. arthritis. Arthritis Rheum. 1988;31(2):267Ð71. 10. Macarthur A, Kleinman S. Rheumatoid cervical joint 14. Smith RJ, Kaplan EB. Rheumatoid deformities at the diseaseÐa challenge to the anaesthetist. Can J Anaesth. metacarpophalangeal joints of the fi ngers. J Bone 1993;40(2):154Ð9. Joint Surg Am. 1967;49(1):31Ð47. 11. Marmor L, Flatt AE. Rheumatoid hand, ulnar drift 15. Swanson AB. Flexible implant arthroplasty for and swan-neck deformities. Phys Ther. 1971;51(5): arthritic fi nger joints: rationale, technique, and results 581Ð2. of treatment. J Bone Joint Surg Am. 1972;54(3): 12. Millender LH, Nalebuff EA, Hawkins RB, Ennis R. 435Ð55. Infection after silicone prosthetic arthroplasty in the 16. Wilson RL, Carlblom ER. The rheumatoid metacar- hand. J Bone Joint Surg Am. 1975;57(6):825Ð9. pophalangeal joint. Hand Clin. 1989;5(2):223Ð3. Total Hip Arthroplasty in Rheumatic Disease and Associated 3 1 Infl ammatory Arthropathies

David M. Joyce and Michael J. Joyce

Introduction patients due to concerns of complications associ- ated with poor-quality bone. Hip arthritis, whether from in fl ammatory etiology, general wear, or posttraumatic, has been success- fully treated with total hip arthroplasty over the Components past four decades. The total hip arthroplasty (THA) is indicated primarily for pain relief from Acetabular cups come in either a cemented poly- hip arthritis and secondarily for increased range ethylene cup (Fig. 31.2b ) or a metallic bony of motion in patients with rheumatoid arthritis ingrowth cup (Fig. 31.3 ) that is impacted with (RA) or other in fl ammatory arthropathies. optional screw fi xation. Most common are Rheumatoid patients have 15% and 28% hip cementless ingrowth cups made from titanium involvement at 1 and 5 years, respectively, after and cobalt-chromium. The cementless cups have onset of disease [1 ] . About 2.4Ð3.6% of all THA a porous acetabular surface that allows for bony are performed in RA patients [2 ] . ingrowth (Fig. 31.3). Hydroxyapatite coating and supplemental screw fi xation are other augmenta- tions for fi xation to bone. Femoral stems Total Hip Arthroplasty Concept (Fig. 31.4 ), made of cobalt-chromium or tita- nium, also have been constantly modifi ed over Total hip arthroplasty (Fig. 31.1 ) consists of the years for strength and better fi xation. replacing the femoral side by placing a stem into Modularity of the total hip design can be used to the remaining femur after the head and neck are minimize the dislocation risk of the hip. The sur- removed and placing an acetabular cup with a geon can change head sizes and increase neck liner. Hemiarthroplasty, generally used for femo- length and offset. The femoral stem in some sys- ral neck fractures replacing only the femoral tems can also be adjusted by changing version, head, is contraindicated because it does not offset, and height in order to minimize the risk of address the diseased acetabular cartilage. Hip dislocation. resurfacing is generally not performed in RA

Fixation: Cement and Cementless

D. M. Joyce , M.D. ¥ M. J. Joyce , M.D. (*) Generically known as bone cement, polymethyl- Department of Orthopaedic Surgery , Cleveland Clinic , 9500 Euclid Avenue , Cleveland , OH 44195 , USA methacrylate (PMMA) can be used to cement the e-mail: [email protected] femoral and acetabular components into the bone.

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 327 DOI 10.1007/978-1-4614-2203-7_31, © Springer Science+Business Media, LLC 2013 328 D.M. Joyce and M.J. Joyce

Cemented components are mostly used for poor bone quality and bone surfaces unlikely to lead to ingrowth. Most surgeons use cementless compo- nents with or without one to two screw fi xations in the acetabulum and a bony ingrowth femoral stem when there is reasonable quality of bone. Cementless components can be used in young JIA patients [3 ] with good results. Both cemented and non-cemented cups and stems have good sur- vival results [ 2 ] in RA patients and are similar to that of OA patients [ 2, 4 ] . Cementing techniques have evolved to decrease the air bubbles in the cement that signifi cantly improves the strength and duration of the cement mantle interface. The addition of antibiotic to cement supplies a high dose of local antibiotics for a brief period of time measured in days. Determining whether or not to place antibiotics in the cement is some- what dependent on the surgeon’s judgment. The antibiotics usually chosen are broad spectrum, bactericidal, and effective against gram-positive Fig. 31.1 Basic total hip arthroplasty consisting of femoral cocci and gram-negative rods. Typical antibiotics stem, ceramic head, and bony ingrowth cup with poly- ethylene liner used in cement include vancomycin, tobramycin,

Fig. 31.2 ( a ) Uncemented constrained liner insert. (b ) Cemented polyethylene cup 31 Total Hip Arthroplasty in Rheumatic Disease and Associated In fl ammatory Arthropathies 329

Fig. 31.3 Bony ingrowth acetabular cups

Fig. 31.4 Femoral stem variety. (a Ð c ) Smooth cemented femoral stems. (d ) Uncemented bony ingrowth stem and gentamicin. With no more than a 10% detri- antibiotic cement is only consistently supported mental effect on the mechanical properties of the in use for revision cases [ 5] , but given the prob- cement due to the addition of 1 gram(g) of anti- lems in the rheumatoid population with infec- biotic to 40 g of bone cement [ 5 ] , there seems to tion, antibiotic cement can be used to reduce be no increase in THA failure rates. In fact, when infections in both primary and revision total comparing cemented arthroplasties without joints [7, 8 ] . Depending on the antibiotic, poros- antibiotic cement to antibiotic-cemented arthro- ity of the cement, and combination of antibiotics plasties, the risk of revision increased 1.5 times used, antibiotic concentrations can remain above [6 ] . There appears to be no evidence of bacterial MIC for several days to several weeks depending resistance or systemic toxicity development with on the properties of the cement and amount of manufacturer antibiotic cement [7 ] . Currently, antibiotics. 330 D.M. Joyce and M.J. Joyce

Bearing Surfaces signifi cantly manifested by the stress of surgery and lead to signifi cant complications. Forty per- The choice of articulating surfaces of a THA on the cent of RA undergoing a THA have a signifi cant femoral side consists of either metal or ceramic fem- comorbidity with the most common problems oral head component. The predominate articulation being cardiovascular, respiratory, and gastrointes- used to which all others are compared is cobalt- tinal [ 11] . Much emphasis should be placed on chromium femoral head with an ultrahigh molecular having a good dialogue between the surgeon and weight polyethylene (UHMWPE) acetabular insert. the rheumatologist in order to determine what is Femoral heads typically consist of a harder material best for the patient. compared to the cup material and are either ceramics or metal alloys such as cobalt-chromium. Ceramic heads on modular ceramic acetabular liners have Blood Loss favorable wear characteristics. However, concerns about audible squeaking with these ceramic-on- Blood loss of at least 250Ð350 ml intraoperatively ceramic components have started to limit this com- and another 350 ml postoperatively [ 12 ] can be bined use [ 9 ] . The liner generally consists of highly expected for most primary THA during surgery crossed linked UHMWPE but can also come in the with more postoperative blood loss expected in form of a ceramic. Polyethylene liners can be cementless fi xation and revision arthroplasty modi fi ed to have a lip or be constrained to reduce the [ 13 ] . The patient should be properly informed risk of dislocation (Fig. 31.2a ). and consented as to receiving blood products or the alternatives before proceeding with surgery. Alternatives to allogenic products include autolo- The Total Hip Arthroplasty Patient gous blood (no longer routinely done) donated Preoperative Assessment about a month before surgery or intraoperative red blood cell salvage. Preoperative erythropoie- Indications/Contraindications tin and iron can be used to increase the red blood cell mass prior to surgery. Indications for a THA remain relative as to age as evident in several studies with THA being per- formed in patients as young as 20 [ 3, 10 ] to older Antibiotic Prophylaxis for Surgery than 70 [ 4 ] but continue to be directed to reliev- ing pain and improving function and range of Rheumatoid patients are given prophylactic anti- motion of the hip that has failed medical and con- biotic within an hour before skin incision, with servative treatments. Absolute contraindications vancomycin requiring 2 h prior to incision (AAOS remain few but include ongoing or recent infec- guideline) [ 14] . These patients are given the same tion. Relative contraindications are many such as prophylactic antibiotic that the healthy total joint severe osteoporosis, insuffi ciency of the hip mus- patient is given, typically 1 g (2g if > 86 kg) of culature, neuropathic arthropathy (Charcot joint), cefazolin. Antibiotics are continued for 24 h after severe neurological disease, and medical prob- surgery and then discontinued. If a patient has a lems that pose a risk to the patient surviving sur- speci fi c allergy, they are given the appropriate gery, such as recent myocardial infarction or alternative. Other antibiotics used include clin- severe respiratory disease. damycin, vancomycin, and cefuroxime. Dosage amounts are adjusted for body weight and renal function [ 14 ] . There is no data supporting the Medical Considerations prolonged duration of prophylactic antibiotics for patients with prior surgical site and skin infec- Total hip arthroplasty surgery has a signifi cant tions, wound-healing problems, or for revision impact on the patient’s physiologic system. Subtle surgery. However, some surgeons will elect to disease processes, while in check, can become give antibiotics to rheumatoid joint replacement 31 Total Hip Arthroplasty in Rheumatic Disease and Associated In fl ammatory Arthropathies 331 patient until their surgical wound has stopped a cautious approach than immediately proceed draining. If a hospital system has a high nosoco- with surgery. Skin lesions should ideally be mial rate of methicillin-resistant staphylococcus, brought under control preoperatively. Many of consideration should be given to modifying the the older rheumatoid patients have thin skin with choice of prophylactic antibiotics [15 ] . poor dermal/subcutaneous support. This may lead to shearing of the skin when the limb is not handled gently intraoperatively. Hip Pain

Discomfort from hip disease is usually groin and Anesthesia Considerations anterior thigh pain. The pain may be referred to the knee. Pain described by the patient as being While the anesthesiologist will make the fi nal on the lateral aspect of the hip is generally not choice of anesthesia with the patient, the surgeon, related to the joint itself but can be due to the soft rheumatologist, primary physician, and patient tissue overlying the greater trochanter. Patients must be aware of the options and peculiarities of may describe a deep posterior buttock pain which a rheumatoid patient. JIA patients may have tem- often is spine related. Hip pain may be from an poromandibular joint problems as well as microg- infection, avascular necrosis (AVN), or fracture nathia, making intubation dif fi cult. Regional besides in fl ammatory or degenerative wear. anesthesia in the form of a spinal or epidural Steroids predispose the hip to AVN and anesthesia often is recommended in RA and JIA insuffi ciency fracture as well as making the patients [ 17 ] . However, patients suffering from patient more susceptible to infection. AVN itself ankylosing spondylitis may be unable to have can cause acute pain due to its progression in the regional anesthesia. RA involves the joints of the form of collapse and may be a common articular cervical spine. These patients can have limited disease seen in SLE patients. Given the inability motion in the cervical spine requiring general to reliably differentiate AVN without infection anesthesia via fi beroptic intubation. A preopera- compared with infection in an in fl ammatory tive anesthesia consult is important because up to arthropathy patient, septic arthritis should always 61% of rheumatoid joint replacement patients be considered [ 16 ] . Hip pain can also be an have radiographic evidence of cervical spine insuf fi ciency fracture that may not show up on a instability at C1ÐC2 [ 18 ] . These patients are plain fi lm. Insuffi ciency fractures from poor- asymptomatic on physical exam, making it quality bone due to steroids and rheumatoid dis- diffi cult to appreciate instability. Rheumatoid ease can have catastrophic consequences. patients should have current lateral fl exion and extension fi lms of their neck before surgery. If an instability pattern is discovered, the instability Skin problem should be evaluated by a spine surgeon prior to surgery. If the x-rays are normal, in the Rheumatoid patients suffer from skin manifesta- absence of neurological symptoms or fi ndings tions that may limit or complicate surgery. A and without instability, it is relatively safe to pro- rheumatoid nodule may ulcerate with minimal ceed without spine surgeon input. trauma such as bed transfers and provide an ave- nue for infection. It is therefore imperative that a full skin examination be performed. There should Potential Sources of Infection be no skin defects present or nodule drainage in the recent past. Efforts should be made to rule out Postoperative joint infections can come from some indolent infection from previously draining other total joint replacements, stasis ulcers, or nodules. With skin manifestations including areas vascular sources. Another source of potential of unexplained erythema, it is often better to take infection that should never be overlooked is the 332 D.M. Joyce and M.J. Joyce oral cavity. It has been observed that bacteremia elbow arthritis that limit the ability to use assis- from dental work may hematogenously seed a tive devices during rehabilitation. Their upper total joint arthroplasty, with the greatest risk up extremity arthritis may be so signifi cant that it to 2 years after surgery [ 19 ] . This fi nding sup- eliminates the ability to be protective weight ports that all in fl ammatory arthropathy patients bearing through these limbs. Patients undergoing should have all extensive dental work (i.e., proce- THA will require the use of a walker in the early dures other than simple cleanings) done prior to postoperative phase. This requirement often dic- having a THA due to the mouth being a signi fi cant tates a decision whether to proceed with THA source of bacteremia. Urologic and gastroentero- fi rst or proceed with some type of operative treat- logical sources provide other avenues for bacter- ment for the upper extremities trying to provide a emia through cystoscopy, prostatectomy, or even stable weight-bearing platform for rehabilitation colonoscopy [ 19 ] . Most orthopedic surgeons after a THA. A multidisciplinary (i.e., total joints, would agree that all other needed surgery and upper extremity, or spine surgeon) team approach semi-elective surgery be performed fi rst. Although should determine which joint to operate on fi rst. THA is of great benefi t for the patient, it is elec- Lower limb surgery is generally performed before tive and the increased possibility of an infection upper limb surgeries due to reliance on walking can make delaying the THA surgery a conserva- aids that may damage the upper extremity surgi- tive and prudent approach until other procedures cal reconstructions. are done. After a THA, patients should receive Joint arthroplasty must consider the anatomic some form of antibiotic prophylaxis prior to any and mechanical axis to properly balance the hip, future procedure that could lead to bacteremia. allowing a near normal walking gate. Bone deformity can require osteotomies in order to obtain proper alignment. Contractures of the Allergies hip, knee, and ankle can affect proper balance and alignment during gait. Surgery of a joint Potential allergy to the preoperative antibiotic or other than the hip may be required before the the antibiotic in the cement should be noted by a THA. Some patients with RA and most patients thorough history. Alternatives should be chosen. with ankylosing spondylitis (AS) suffer from There are also reports of patients having an hip and knee contractures compensating for the allergy or sensitivity to chromium, cobalt, and deformity of the spine. THA surgery in an AS or nickel [20 ] . This should be elicited by asking RA patient with spinal deformity must account about allergies to jewelry in the form of rashes. A for the relationship of the pelvis to the uncor- patient can have appropriate testing done to deter- rected lumbar spine in order to correctly posi- mine how sensitive the patient is to the allergen. tion the acetabular component [ 22 ] . THA is However, these tests may not totally correlate often performed before osteotomies of the spine with a true allergy. Although very unusual, as THA may relieve enough pain and improve patients can have chronic pain until implants are enough motion that negate the need of osteoto- removed and replaced with a different material. mies of the spine [ 22 ] . There are reports of allergies or sensitivities to bone cement with some having allergies to acryl- ics used in dental fi llings and arti fi cial nails [21 ] . Osteoporosis, Osteopenia, Bone Loss, and Bony Deformity

Multiple Arthropathy, Deformity, RA of the hip often leads to cysts, erosions, pro- and Contractures trusion, bone loss, and poor bone stock. Unfortunately, prolonged steroid use causes a Rheumatoid arthritis is polyarticular by nature, signifi cant impact on bone quality. These and patients often suffer from wrist, hand, and patients often have early osteoporosis. Because 31 Total Hip Arthroplasty in Rheumatic Disease and Associated In fl ammatory Arthropathies 333 of the disease process and medications, these patients are more prone to have nontraumatic insuf fi ciency fractures [17 ] . The risk of intraop- erative fracture is also increased with osteopo- rosis. If the quality of bone is poor, surgeons often elect to use cemented implants which can diminish the risk of operative fracture. Erosions and cysts pose a signifi cant source of bone loss that further reduces the bone available to pro- vide a stable foundation for implants. Deformities can be addressed through a combination of aug- mented surgical approaches and techniques which can slow the patient’s progress to a full Fig. 31.6 Failure of THA due to protrusion of the acetab- weight-bearing status. ular component

Protrusio Acetabuli

Protrusio acetabuli is the medial migration of the femoral head beyond the ilioischial or Kohler’s line on an AP pelvis x-ray (Fig. 31.5 ). The com- bination of softening of the subchondral bone of the acetabulum, often due to steroids and the in fl ammatory nature of rheumatoid process, and cyclic pressure of the femoral head can lead to progressive protrusion [23 ] . The femoral head can be intrapelvic. Protrusio occurs in the skele- tally immature adolescent and young adults as well as older adults already with THA (Fig. 31.6 ). Because protrusio acetabuli is caused by a multi- tude of causes besides in fl ammatory etiology, it Fig. 31.7 Bilateral protrusio acetabuli treated with cus- is important to rule out infection. Reconstructive tom cages and THA treatment involves restoring the joint center through a combination bone grafting, cementing, more extensive approach, such as a trochanteric and possible acetabular cage (Fig. 31.7 ). Often, a osteotomy, must be taken in order to obtain proper exposure to perform surgery in these types of patients, thus limiting the patient’s weight-

bearing ability in the early postoperative phase.

Postoperative Treatment and Considerations

Expectations and Disposition

There is no universally accepted or standard method of rehabilitation in a total hip patient. Fig. 31.5 Bilateral hip protrusio acetabuli Typical length of hospital stay for THA has 334 D.M. Joyce and M.J. Joyce changed from weeks to days, with the average Physical Therapy stay for an uncomplicated patients being 3Ð5 days barring any complications. Patients will often Physical therapy often starts that day after sur- then go to a rehabilitation facility or skilled nurs- gery with the patient being taught how to get out ing facility (SNF) depending on the physical and of bed and transfer as well as assisted to stand. medical requirements of the patient. Direct home They are trained in deep breathing, ankle and calf going requires that a caregiver (spouse or family pumps, as well as quadriceps and gluteal isomet- member) be around most of the day and be able ric exercises. Patients progress over the next sev- to provide limited care. Given that most THA eral days from standing to walking with the patients are older, the typical older family mem- ultimate goal of being able to walk up 3Ð5 steps ber does not have the ability to physically help with walking aids. Patients are often placed in an the patient often necessitating the need for a sub- abduction foam wedge and later transitioned to a acute facility before going home. pillow that prevents crossing of their legs during Patients are made weight bearing as tolerated sleeping. Patients are instructed in safe positions in the cemented fi xation group and partial to full to sit, sleep, and properly pickup objects from the weight bearing in the uncemented bony ingrowth fl oor by not completely bending over. This edu- group. Although patients are made weight bear- cation is to help prevent hip dislocations because ing as tolerated, they act functionally as partial patients are susceptible to posterior dislocation weight bearing due to pain and weakness. Their when the hip is placed in greater than 90¡ of weight bearing status can change based on intra- fl exion and internal rotation as well as being at operative complications such as fracture or based risk for anterior dislocation when the hip is in on a surgeon’s evaluation of bone quality. Weight extension and external rotation. Patients are bearing is sometimes restricted to protect the soft instructed during the fi rst 6 weeks to use a pillow tissue repair of the hip. between the legs at night, lie supine, limit hip Sutures or staples often come out at 10Ð14 days fl exion to 90¡, minimize internal rotation, and try but only after it is noted that the wound appears to avoid using low sitting chairs or toilets. Patients to be healing. Rheumatoid patients can have a are advised to minimize reaching and bending delay in wound healing that may necessitate and are given aids that allow them to place socks sutures stay in for up to 21 days. Patients are gen- on their feet. erally advised to wait to shower until after the After about 4Ð6 weeks, patients begin a phase sutures or staples are taken out. Some surgeons of therapy that involves further improvement in recommend not sitting in water (hot baths, hot motion, muscle strength, and return to functional tubs, and swimming pools) up to 4Ð6 weeks after activities including work and home activities. surgery. Occasionally, there may be patients with Patients prior to this phase were not allowed to good-quality skin in which a subcuticular closure perform resisted hip motions in order to allow the was accomplished, which requires no suture soft tissue to heal. Patients are instructed in removal. resisted hip exercises such as straight-leg raises. Unfortunately, THA often does not always Most patients can return to driving at about the relieve all the preoperative pain, but the pain is 4Ð6-week mark if the THA was performed on the improved. Patients generally describe pain in the left side; right-sided THA tend to take slightly fi rst few days being almost unbearable. After a longer. week, the pain begins to taper down substantially. After recovery, patients should be encouraged At 4Ð6 weeks, the pain is drastically reduced as is to engage in light recreational activities that limit evident from the patient’s ease of walking and par- the impact stress such as golfi ng, swimming, and ticipation in activities of daily living. Generally, biking. High-impact activities such as running or patients are no longer using walking aids at about jogging and backpacking should be discouraged. 6 weeks. Patients report that it often takes up to a Given the young age of rheumatoid patients, they year before they feel the hip is back to “normal.” usually are allowed to resume sexual activity at 31 Total Hip Arthroplasty in Rheumatic Disease and Associated In fl ammatory Arthropathies 335 about 4Ð6 weeks after being instructed in safe and 5.1% rate of prolonged hospitalization sexual positions and avoidance of positions that reported in joint replacements [ 29 ] . These studies place the hip in a fl exed, adducted, and internally emphasize the need to minimize the VTE risk rotated position. while not increasing the risk of complications that would be ampli fi ed in a chronically immuno- suppressed population. With the seriousness of Pain Control VTE and joint infection in mind, the AAOS developed a set of guidelines, founded on the pre- Pain control consists of a combination of oral and vention of clinical outcomes such as symptom- intravenous medications including narcotics. atic and fatal PE, death, and major bleeding Patients have the option of an epidural catheter episodes for their current recommendations in which can deliver anesthesia during the fi rst night VTE prophylaxis [30 ] . Joint replacement patients and is typically stopped within a day or two in are risk stratifi ed for VTE prophylaxis. Several order to begin pharmacologic venous throm- factors can increase the risk of thromboembolic boembolism prophylaxis. Patients are also given disease such as protein C and S de fi ciency and local ice to the operative area to decrease the other disorders of the coagulation cascade. There amount of swelling and pain. are also historical risk factors to keep in mind when asking a history such as previous stroke, phlebitis, previous DVT, or myocardial infarc- Venous Thromboembolism and Deep tion. Another risk factor for DVT was found in a Vein Thrombosis Prophylaxis study comparing DMARDs to TNF antagonists used in patients receiving a hip, knee, or ankle Venous thromboembolism (VTE) and deep vein prosthesis which showed that 51% of patients on thrombosis (DVT) pharmacologic prophylaxis TNF therapy versus 26% on DMARD therapy can begin the night of surgery or at the latest the developed a DVT [31 ] . morning after surgery if there is no epidural cath- The choices of pharmacologic prophylaxis are eter. Mechanical prophylaxis (mobilization/pneu- low molecular weight heparin (LMWH), fonda- matic devices) is begun during surgery on the parinux, and warfarin. The AAOS recommends nonsurgical leg and immediately after surgery on at least 10 days and up 35 days for a THA [ 32 ] . the operative leg. Currently, the American Warfarin is often started the night of surgery and Academy of Orthopaedic Surgeons and American is generally titrated to an INR of 2.0Ð2.5 and con- College of Chest Physicians differ on the method tinued 2Ð6 weeks and monitored at a minimum of prevention of DVT and PE [24 ] . The differ- weekly. The other forms of pharmacologic pro- ence in recommendations from each of these phylaxis are started the following morning. organizations stems from the difference in belief Enoxaparin is generally dosed 40 mg daily or that asymptomatic clots (very distal) are relevant. 30 mg twice a day and has been used from 14 to The AAOS position is based on the concept that 21 days. Guidelines can be seen at the AAOS prevention of symptomatic PE, with the risk of website. fatal PE reported to be 0.1Ð0.2% following a pri- DVT scans with ultrasound are not routinely mary THA regardless of the type of prophylaxis scheduled unless there is suspicion of a DVT. [25Ð 27 ] , is more clinically relevant than preven- Some surgeons continue to get these ultrasounds tion of all DVTs. Prevention of all DVTs carries before discharge although one study showed that a substantial risk of complications such as persis- inpatient surveillance duplex scans were not clin- tent drainage or wound hematoma that places the ically useful when managed with effective DVT joint replacement patient at high risk of a deep prophylaxis [33 ] . DVTs are dif fi cult to evaluate joint infection [ 28 ] . Following the ACCP guide- clinically as they can be associated with pain and lines has been associated with a 4.7% readmis- swelling that is normal with THA. Any suspicion sion rate, 3.4% irrigation and debridement rate, should prompt an ultrasound of both legs. 336 D.M. Joyce and M.J. Joyce

tions come in three forms: early (less than Complications 3 months after surgery), delayed (3Ð24 months after surgery), and late with late infections occur- Venous Thromboembolism ring more than 2 years after implantation and are believed to be from hematogenous seeding com- One of the most common complications of a pared to early infections thought to be from con- THA is deep vein thrombosis. Half of all symp- tamination during surgery [ 38 ] . Hematogenous tomatic VTE occur within the fi rst 14 days of a seeding can occur from local infection such as THA [34 ] . In the past with early forms VTE pro- pneumonia, bladder infections, and associated phylaxis, venous thrombosis occurred in about bacteremia caused by dental or surgical proce- half of the patients, fatal pulmonary emboli was dures. RA patients seem much more susceptible reported in about 2% of the THA population; to blood-borne or hematogenous prosthetic today, with current protocols, pulmonary embolus joint infections. Prosthetic joint infection is a incidence has been reported between 0.64% and devastating complication that most often 0.90% [ 35 ] . For the total hip patient, these events requires the removal of the prosthesis, place- can occur in any of the vessels of the pelvis, leg, ment of an antibiotic cement spacer, as well as and calf, with up to 90% occurring in the calf IV antibiotic treatment of at least 6 weeks. of the operative leg [ 33 ] . The main concern being propagation of the calf thrombi reported in 17Ð23% [34 ] . Neurovascular Injury

Speci fi c neurovascular injury in total hip arthro- Hematoma plasty relates to the specifi c approach used. An anterior or lateral approach can cause injury to the Hematoma represents a serious complication that femoral nerve. A posterior approach can put the can affect overall outcome. Careful history can sciatic nerve at risk. Nerve injuries happen about identify patients that are more susceptible to 1Ð2% in patients receiving a total hip [ 39 ] . Sciatic bleeding including anticoagulants, antiplatelet nerve injury is the most common injury (90% of drugs, anti-in fl ammatory therapy, herbal medica- nerve injuries) reported with overall rates reported tion affecting hemostasis, coagulopathies, and to be 0.6Ð3.7% [39, 40 ] in primary THA and as family history of bleeding problems. Hematoma high as 8% [ 40] in revision cases. Of the sciatic can cause nerve palsy and be a source for even- nerve injuries, 94% involved the peroneal division tual wound infection. while the tibial division was involved in 2% of the occurrences [ 39, 40 ] and are much more likely to occur with a posterior approach, the majority of Surgical Site and Prosthetic Infection which recover in 6 months. Vascular injuries are much less common but are possible with place- Infection can be divided up into surgical site ment of retractors in the posterior approach. Both infections (SSI) and deep or prosthetic joint the femoral nerve and artery are at risk during the infections (PJI). The overall incidence of pros- anterior approach. thetic infection in RA versus OA was reported to be 4.2% versus 1.4%, respectively, at 5 years after surgery [ 36 ] . Within the RA population, Dislocation revision arthroplasty was associated with a 5.9% infection rate compared to 2.0% in primary joints Dislocation is one of the common complications [ 36] . In revision arthroplasty for previous infec- of a THA with greater than 50% occurring within tion, the infection rate was reported to be between the fi rst 3 months of surgery [41 ] (Fig. 31.8 ). 21% [ 37] and 52.2% [ 36 ] . Prosthetic joint infec- Depending on surgical approach and surgeons 31 Total Hip Arthroplasty in Rheumatic Disease and Associated In fl ammatory Arthropathies 337

Fig. 31.8 Total hip arthroplasty dislocation preferences in component positioning, disloca- could lead to pain as well as possible impinge- tions can occur either anterior or posterior with ment and dislocation. Prevention of HO in the 75Ð90% being posterior dislocations [ 41 ] . THA consists of either single treatment 7 Gray of Posterior approaches are more susceptible to pos- radiation within 5 days of surgery [43 ] or indo- terior dislocations with a 3.23% dislocation rate methacin 25 mg TID (or other NSAIDs) with compared to a direct lateral approach incidence gastric ulcer prophylaxis. of 0.55% [ 42 ] . Dislocations require a trip to the emergency room for relocation under muscle relaxation/sedation or even possibly to the surgi- Periprosthetic Fracture cal suite for closed or open surgical reduction. There are occasions when components have to be Periprosthetic fracture can occur with both revised through surgical intervention. cementless and cemented components. With poor quality of bone, RA patients are at a higher risk of intraoperative and postoperative fractures. A Heterotopic Ossifi cation review of the Mayo Clinic Joint Registry showed that incidence of primary THA intraoperative Heterotopic ossi fi cation (HO) was thought to femoral fractures was 0.3% for cemented compo- occur frequently in patients with ankylosing nents and 5.4% for cementless components with spondylitis as well as cementless fi xation the incidence being higher for revision surgery [22, 43] . However, the use of HO prophylaxis in [ 44] . Another study showed that there were no patients with AS who are undergoing THA may intraoperative acetabular fractures in cemented not be warranted unless patients have signi fi cant devices compared to an incidence of 0.4% for risk factors including bilateral hypertrophic cementless fi xation [45 ] . osteoarthrosis, prior site surgery, bilateral sur- gery, and previous HO [ 43 ] . Although some data suggests the use of cementless components The Late Postoperative Patient (specifi cally the femoral component) increases (6 Months Out) the likelihood of HO development in the hip, this subsequently has been disputed in other studies Patients are generally seen by their surgeon at [43 ] . THA patients that develop HO can develop 2Ð4 weeks, 3 months, 6 months, and a year out problems with range of motion of the hip that from surgery. After that, visits are based on an as 338 D.M. Joyce and M.J. Joyce needed basis. Rheumatologist and generalist should expect to see total joints patients with Conclusion complaints of joint pain or erythema at some point after surgery. It is important to get a detailed Patients must understand that hip replacement is history of the complaint in order to determine if not a simple procedure that will solve all of their this is a possible infection, fracture, dislocation, hip problems. Hip arthroplasty, for the majority or component failure. After determining that the of cases, represents an elective procedure in the patient is stable and shows no evidence of sepsis, in fl ammatory arthropathy and rheumatoid popu- a stepwise approach can be taken to aid in the lations. Thought must be given to the risk and diagnosis of the problem. An x-ray can be of the benefi ts of proceeding with surgery. This popula- utmost value as it can rule out gas in the joint, tion of patients is often less healthy, with multiple which would be evidence of an aggressive infec- comorbidities, compared to the osteoarthritis tion, dislocation, fracture, or gross hardware fail- (OA) patient. Arthroplasty surgery is not without ure. If there is concern of acute infection, blood signifi cant potential complications. The decision work should be performed that includes a blood to perform a total hip replacement should be cultures, CRP, ESR, and CBC with differentia- made in conjunction with the rheumatologist, tion. If erythema is noted, it should be traced out orthopedic surgeon, and the patient. as an aid to determine progression or resolution. A joint aspiration should be performed prior to administrating antibiotics. This should be per- References formed in the most sterile aseptic method and done under fl uoroscopy in radiology or operating 1. Eberhardt K, et al. Hip involvement in early rheuma- room. Prior to placing a needle into the affected toid arthritis. Ann Rheum Dis. 1995;54(1):45Ð8. 2. Havelin LI, et al. The nordic arthroplasty register joint, communication should be had with the sur- association: a unique collaboration between 3 national geon as they may elect to evaluate the patient and hip arthroplasty registries with 280,201 THRs. Acta perform the aspiration themselves. Antibiotics Orthop. 2009;80(4):393Ð401. should be started as soon as possible after the 3. Clohisy JC, et al. Function and fi xation of total hip arthroplasty in patients 25 years of age or younger. aspiration and if septic, as soon as the antibiotics Clin Orthop Relat Res. 2010;468:3207Ð13. are available. The patient should be made NPO in 4. Rud-Sorensen C, et al. Survival of primary total hip case of urgent surgical intervention. In the case of arthroplasty in rheumatoid arthritis patients. Acta infection not located near a total joint, antibiotics Orthop. 2010;81(1):60Ð5. 5. Joseph TN, Chen AL, Di Cesare PE. Use of antibi- should be started as soon as possible to minimize otic-impregnated cement in total joint arthroplasty. J the risk of hematogenous seeding. Patients with Am Acad Orthop Surg. 2003;11(1):38Ð47. complaints of pain with fall or chronic pain 6. Engesaeter LB, et al. Does cement increase the risk of related to weight bearing may have an impending infection in primary total hip arthroplasty? Revision rates in 56,275 cemented and uncemented primary fracture if a fracture is not overtly evident on THAs followed for 0Ð16 years in the Norwegian x-ray. These patients should be made non-weight arthroplasty register. Acta Orthop. 2006;77(3):351Ð8. bearing and should have follow-up with their sur- 7. Dunbar MJ. Antibiotic bone cements: their use in rou- geon who can order other imaging to determine if tine primary total joint arthroplasty is justi fi ed. Orthopedics. 2009;32(9):660. a fracture exists. Chronic joint pain, after acute 8. Parvizi J, et al. Ef fi cacy of antibiotic-impregnated infection has been ruled out, should be seen in the cement in total hip replacement. Acta Orthop. surgeon’s of fi ce as it may represent a smoldering 2008;79(3):335Ð41. infection or aseptic loosening of the implants. 9. Schroder D, et al. Ceramic-on-ceramic total hip arthroplasty: incidence of instability and noise. Clin Any acute complaint that involves the surgical Orthop Relat Res. 2010. joint should have prompt communication and 10. Haber D, Goodman SB. Total hip arthroplasty in follow-up with the appropriate surgeon. It is juvenile chronic arthritis: a consecutive series. important to have a good dialogue between ortho- J Arthroplasty. 1998;13(3):259Ð65. 11. March LM, et al. Costs and outcomes of total hip and pedist, rheumatologist, and internist as this should knee joint replacement for rheumatoid arthritis. Clin be a team approach. Rheumatol. 2008;27(10):1235Ð42. 31 Total Hip Arthroplasty in Rheumatic Disease and Associated In fl ammatory Arthropathies 339

12. Fink B, et al. Comparison of a minimally invasive are the implications for clinicians and patients? Chest. posterior approach and the standard posterior approach 2009;135(2):513Ð20. for total hip arthroplasty a prospective and compara- 25. Freedman KB, et al. A meta-analysis of thromboem- tive study. J Orthop Surg Res. 2010;5:46. bolic prophylaxis following elective total hip 13. Mahadevan D, Challand C, Keenan J. Revision total arthroplasty. J Bone Joint Surg Am. 2000;82A(7): hip replacement: predictors of blood loss, transfusion 929Ð38. requirements, and length of hospitalisation. J Orthop 26. Douketis JD, et al. Short-duration prophylaxis against Traumatol. 2010;11(3):159Ð65. venous thromboembolism after total hip or knee 14. Prokuski L. Prophylactic antibiotics in orthopaedic replacement: a meta-analysis of prospective studies surgery. J Am Acad Orthop Surg. 2008;16(5): investigating symptomatic outcomes. Arch Intern 283Ð93. Med. 2002;162(13):1465Ð71. 15. Meehan J, Jamali AA, Nguyen H. Prophylactic antibi- 27. Sheth NP, Lieberman JR, Della Valle CJ. DVT pro- otics in hip and knee arthroplasty. J Bone Joint Surg phylaxis in total joint reconstruction. Orthop Clin Am. 2009;91(10):2480Ð90. North Am. 2010;41(2):273Ð80. 16. Huang JL, et al. Septic arthritis in patients with sys- 28. Parvizi J, et al. Does “excessive” anticoagulation pre- temic lupus erythematosus: salmonella and nonsal- dispose to periprosthetic infection? J Arthroplasty. monella infections compared. Semin Arthritis Rheum. 2007;22(6 Suppl 2):24Ð8. 2006;36(1):61Ð7. 29. Burnett RS, et al. Failure of the American college 17. Lachiewicz PF. Rheumatoid arthritis of the hip. J Am of chest physicians-1A protocol for lovenox in Acad Orthop Surg. 1997;5(6):332Ð8. clinical outcomes for thromboembolic prophylaxis. 18. Collins DN, Barnes CL, FitzRandolph RL. Cervical J Arthroplasty. 2007;22(3):317Ð24. spine instability in rheumatoid patients having total 30. Johanson NA, et al. Prevention of symptomatic hip or knee arthroplasty. Clin Orthop Relat Res. pulmonary embolism in patients undergoing total 1991;272:127Ð35. hip or knee arthroplasty. J Am Acad Orthop Surg. 19. Guay DR. Antimocrobial prophylaxis in noncardiac 2009;17(3):183Ð96. prosthetic device recipients. Hosp Pract (Minneap). 31. Kawakami K, et al. Complications and features after 2012 Feb; 40(1): 44-74. It is a review article looking joint surgery in rheumatoid arthritis patients treated at the numerous literature out there regarding with tumour necrosis factor-alpha blockers: perioper- prosthetic devices and looks specifi cally at joint ative interruption of tumour necrosis factor-alpha replacement. It states “Prosthetic joint recipients blockers decreases complications? Rheumatology should receive prophylaxis in the following 3 circum- (Oxford). 2010;49(2):341Ð7. stances: 1) patient is to undergo dental procedure(s) 32. Friedman RJ. Optimal duration of prophylaxis for capable of inducing high-level bacteremia plus either venous thromboembolism following total hip arthro- the patient is still within 2 years of device implanta- plasty and total knee arthroplasty. J Am Acad Orthop tion/revision or the patient has ≥ 1 risk factor for Surg. 2007;15(3):148Ð55. hematogenous prosthetic joint infection; 2) patient is 33. Ciccone 2nd WJ, et al. Ultrasound surveillance for to undergo genitourinary tract procedure(s) capable of asymptomatic deep venous thrombosis after total joint inducing high-level bacteremia plus the patient has ≥ replacement. J Bone Joint Surg Am. 1998;80(8): 1 risk factor for high-risk bacteriuria; and 3) patient is 1167Ð74. to undergo perforating dermatologic surgery on the 34. Pellegrini Jr VD, et al. Embolic complications of oral mucosa or at skin sites at increased risk for surgi- calf thrombosis following total hip arthroplasty. cal site infection plus patient has ≥ 1 risk factor for J Arthroplasty. 1993;8(5):449Ð57. hematogenous prosthetic joint infection.” 35. Katz JN, et al. Association between hospital and sur- 20. Carlsson A, Moller H. Implantation of orthopaedic geon procedure volume and outcomes of total hip devices in patients with metal allergy. Acta Derm replacement in the United States medicare population. Venereol. 1989;69(1):62Ð6. J Bone Joint Surg Am. 2001;83A(11):1622Ð9. 21. Kaplan K, et al. Preoperative identi fi cation of a bone- 36. Bongartz T. Elective orthopedic surgery and periop- cement allergy in a patient undergoing total knee erative DMARD management: many questions, fewer arthroplasty. J Arthroplasty. 2002;17(6):788Ð91. answers, and some opinions. J Rheumatol. 2007;34(4): 22. Kubiak EN, et al. Orthopaedic management of anky- 653Ð5. losing spondylitis. J Am Acad Orthop Surg. 37. Berbari EF, et al. Outcome of prosthetic joint infec- 2005;13(4):267Ð78. tion in patients with rheumatoid arthritis: the impact 23. Ranawat CS, Zahn MG. Role of bone grafting in cor- of medical and surgical therapy in 200 episodes. Clin rection of protrusio acetabuli by total hip arthroplasty. Infect Dis. 2006;42(2):216Ð23. J Arthroplasty. 1986;1(2):131Ð7. 38. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint 24. Eikelboom JW, et al. American association of ortho- infections. N Engl J Med. 2004;351(16): 1645Ð54. pedic surgeons and American college of chest physi- 39. DeHart MM, Riley Jr LH. Nerve injuries in total hip cians guidelines for venous thromboembolism arthroplasty. J Am Acad Orthop Surg. 1999;7(2): prevention in hip and knee arthroplasty differ: what 101Ð11. 340 D.M. Joyce and M.J. Joyce

40. Schmalzried TP, Amstutz HC, Dorey FJ. Nerve palsy 43. Iorio R, Healy WL. Heterotopic ossi fi cation after hip associated with total hip replacement. Risk factors and knee arthroplasty: risk factors, prevention, and and prognosis. J Bone Joint Surg Am. 1991;73(7): treatment. J Am Acad Orthop Surg. 2002;10(6): 1074Ð80. 409Ð16. 41. Morrey BF. Instability after total hip arthroplasty. 44. Berry DJ. Epidemiology: hip and knee. Orthop Clin Orthop Clin North Am. 1992;23(2):237Ð48. North Am. 1999;30(2):183Ð90. 42. Masonis JL, Bourne RB. Surgical approach, abductor 45. Haidukewych GJ, et al. Intraoperative fractures of the function, and total hip arthroplasty dislocation. Clin acetabulum during primary total hip arthroplasty. Orthop Relat Res. 2002;405:46Ð53. J Bone Joint Surg Am. 2006;88(9):1952Ð6. Total Knee Arthroplasty in Rheumatoid Disease and Other 3 2 Associated Infl ammatory Arthropathies

David M. Joyce and Michael J. Joyce

Introduction ligaments are preserved and balanced. All of this is usually performed through a medial parapatel- Total knee arthroplasty, the most frequently per- lar incision to enter the knee joint with the use of formed orthopedic procedure for RA, signifi cantly a tourniquet. While cementless devices seem to increases the patient’s range of motion and abil- be the norm with regard to total hip replace- ity to perform activities of daily living while ments, surgeons performing TKA usually use decreasing the pain [ 1 ] . This surgery, while able polymethylmethacrylate bone cement anchoring to change someone’s entire functional life, is not the femoral, tibial, and patella components. without its potential complications. TKA over the years have come in many designs: total condylar varus-valgus limited con- strained, posterior cruciate ligament retaining Total Knee Arthroplasty (PCL) (Fig. 32.2a), posterior cruciate substitut- ing (Fig. 32.2b), and mobile bearing and hinged Total knee arthroplasty (TKA) involves resect- prosthesis (Fig. 32.3). The majority of knees ing the arthritic surfaces of the distal femoral implanted today consist of either a PCL retaining and proximal tibia weight-bearing surfaces and or a PCL substituting component. Due to the poor under surface of the patella (Fig. 32.1). The soft tissue quality seen in in fl ammatory arthropa- resected diseased bone and cartilage are replaced thies, some surgeons routinely elect to place a with a smooth metallic femoral articular surface PCL substituting designed knee. Male and and a metal tibial tray with polyethylene insert females exhibit difference in standard width and or all polycemented tibial component. The tibial height of the distal femur. TKA systems now base plate has some type of keel or fi n that is exist that address these differences, and one sys- pushed into the bone of the proximal tibia. The tem is described as being gender speci fi c. patella undersurface is replaced with a polyeth- Implants can either be cemented or cement- ylene button. The patient’s own collateral knee less bony ingrowth surfaces. The vast majority of TKA are cemented due to the high osteolysis rate seen with some cementless implants [ 2 ] . Patients may have poor bone quality requiring the need to bone graft and the use of augments or modular D. M. Joyce , M.D. () ¥ M. J. Joyce , M.D. systems to restore the joint line. Some systems Department of Orthopaedic Surgery , Cleveland Clinic , 9500 Euclid Avenue , Cleveland , OH 44195 , USA have formal and tibial stems that insert distally in e-mail: [email protected] the canal to provide further stabilization.

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 341 DOI 10.1007/978-1-4614-2203-7_32, © Springer Science+Business Media, LLC 2013 342 D.M. Joyce and M.J. Joyce

Cement antibiotics supplies high local dose of antibiotic [3 ] that lasts in signifi cant concentrations mea- Most of the fi xation in total knees is performed sured in days. The antibiotics usually chosen are with polymethylmethacrylate (PMMA), generi- broad spectrum, bactericidal, and effective against cally known as bone cement. Preparing the cement gram-positive cocci and gram-negative rods. The is done with vacuum mixing to reduce the amount addition of 1 g of powdered antibiotic to a 40-g of porosity or bubbles in the cement (Fig. 32.4 ). bag of cement has minimal effect on the mechani- Given the problems in the rheumatoid population cal properties of the cement [ 3 ] , and there appears with infection, antibiotic cement is often used to to be no increase in failure rates with antibiotic reduce infections in both primary and revision cement. There appears to be no evidence of bacte- total joints. Determining whether or not to place rial resistance or systemic toxicity developing, antibiotics is somewhat dependent on the sur- although there appears to be one report of a geon’s judgment. Data support placing antibiotics delayed-type hypersensitivity reaction to Zosyn in cement for revision total knees. The addition of placed in bone cement [4 ] . Using antibiotic cement in TKA to reduce prosthetic joint infec- tions in RA patients is supported in the literature, and according to one author, there is no reason not to use antibiotic cement in total joints [ 5 ] .

Total Knee Arthroplasty: Patient Preoperative Assessment

Indications/Contraindications

Indications for a total knee arthroplasty in a rheu- matoid patient are generally the same for a patient in the general population. TKA is indicated for relatively older individuals to relieve arthritic pain and deformity of the knee with the second- ary goal to gain mobility with increased range of motion of full extension and fl exion greater than 90¡. While older age (> 65) used to be considered Fig. 32.1 Basic total knee arthroplasty consisting of a relative requirement for the general population, metal femoral and tibial components, polyethylene patel- younger age is less a contraindication today. JIA lar button, and polyethylene posterior stabilized tibial patients as young as 16 years old have received insert

Fig. 32.2 Tibial polyethylene inserts. ( a ) PCL retaining or CR retaining. ( b ) PCL sacri fi cing or posterior stabilizer tibial insert 32 Total Knee Arthroplasty in Rheumatoid Disease and Other Associated In fl ammatory Arthropathies 343

Fig. 32.3 Hinge total knee arthroplasty

tion and recent or recurrent septic arthritis or osteomyelitis. Recurrent infections in the same joint indicate that the infection was likely never eradicated. A relative contraindication is marked dysfunction or lack of extensor mechanism as this would negate the functional benefi t of the arthroplasty. There exist a multitude of relative contraindications that include severe medical comorbidities that place the patient in such a signifi cant risk that the survival through surgery is questionable. Several other relative contraindi- cations include neuropathic arthropathy (Charcot Fig. 32.4 Cement mixer with cement joint), recurrent uncontrollable urinary tract infection, and history of osteomyelitis in the dis- TKA. Inability of the native knee fl exing to 90¡ tal femur or proximal tibia. Another relative con- can make normal activities such as climbing traindication to a TKA is open growth plates. stairs dif fi cult. Flexion contractures of 10Ð20¡ Rheumatoid patients tend to close at a relatively can make daily walking quite tiring due to fatigue young age, making this less of an issue. in the quadriceps muscles. Relative indications to The indications and contraindications for perform TKA in younger patients include refrac- simultaneously performed bilateral total knee tory pain from arthritic changes whether from arthroplasties are much the same for the single in fl ammatory etiology or trauma. total knee arthroplasty. Several factors come into There are a few absolute contraindications account when deciding whether to proceed with which include current local and systemic infec- simultaneous bilateral TKA which include patient 344 D.M. Joyce and M.J. Joyce preference, deformity that may limit rehabilita- with surgery. These patients may suffer from skin tion, and most important being the patient health or systemic problems that are not always evident status or physiologic reserve. With the added preoperatively on physical exam or from a history. stress of two simultaneous surgeries, more scru- Subtle disease processes can become signi fi cant tiny into the patient’s physiologic reserve must be by the stress of surgery. Patients with RA have performed. Performing bilateral knee replace- increased prevalence of cardiovascular disease, ments during one surgical episode may lead to even in the absence of traditional risk factors. cost savings and not having a poorly functioning Emphasis should be placed on having a good dia- knee hinder the rehabilitation program. While it logue between the surgeon and the rheumatologist has been argued that bilateral TKA can reduce to determine what is best for the patient. acute care procedural hospital costs, the majority Rheumatoid patients undergoing elective knee of these bilateral patients require longer rehabili- replacement tend to be younger and on signi fi cant tation stays which are not fi gured in the acute immunosuppressants besides other health main- costs. Performing bilateral TKA may bene fi t the tenance medications. Medications such as non- patient in whom two anesthesia events may be steroidal anti-infl ammatory drugs (NSAIDs), more risky or detrimental to the patient’s physi- steroids, disease modifying antirheumatic drugs ologic reserve. One study stated that simultane- (DMARDs), and other biologic agents such as ous bilateral total knee arthroplasty in RA patients tumor necrosis factor antagonists (anti-TNF) are was a procedure of low cost, saving blood, used in the rheumatoid patient. Both the reduced anesthesia risk, and facilitated early in fl ammatory disease process and the medica- rehabilitation but noted a 5.6% late infection rate tions tend to make the patients signi fi cantly more [6, 7 ] . It has also been suggested that simultaneous susceptible to infection [ 10, 11 ] . Infection risk is bilateral arthroplasties increase the risk of a increased 13-fold in individuals with RA com- perioperative cardiovascular adverse event [ 8 ] . pared to the normal healthy population [ 11 ] . Within the RA total joint arthroplasty subset, infection risk is 2.6 greater than matched controls Medical Issues and Medications [ 12 ] . Besides the patient’s physiology, immuno- suppressants may make wound healing problems Total knee arthroplasty (TKA) surgery has a and drainage much more prevalent. However, signifi cant impact on the patient’s physiologic little is published with respect to total joint com- system. Sixty-one percent of RA patients under- plications such as infection and wound healing going a TKA have a signifi cant comorbidity with with the use of DMARDS and anti-TNF drugs. cardiovascular/hypertension, respiratory, and gas- Because of con fl icting data regarding medica- trointestinal being the most common problems tion and wound complications, wound healing [9 ] . While a typical osteoarthritis patient undergo- history becomes very important when deciding ing total joint replacement may undergo routine what medications should be held and which to testing including EKG, chest x-ray, and routine continue. Most importantly, consultation with a labs, rheumatoid patients represent a set of patients patient’s rheumatologist should be a requirement. that have underlying comorbidities that necessi- Discontinuation of any of these immunosuppres- tate further scrutiny into the overall health of the sants can lead to fl are-ups of disease. Disease patient. Labs and tests that should be considered fl ares can lead to poor outcomes due to pain and for a rheumatoid include nutritional evaluation inability to mobilize the patient during rehabilita- and x-ray of the entire limb in order to determine tion. A frank discussion with the patient about alignment and deformity for presurgical planning. expectations if medications are continued or held These patients must undergo an aggressive screen- must be accomplished to prepare the patient for ing process and must be evaluated not just by an all possible outcomes. orthopedic surgeon, but also require at the least a Potential allergy history to either planned pro- visit to their rheumatologist before proceeding phylactic antibiotics or antibiotic cement should 32 Total Knee Arthroplasty in Rheumatoid Disease and Other Associated In fl ammatory Arthropathies 345 be accomplished. Alternatives should be chosen. secondary infection. It is therefore imperative There are also reports of patients having an allergy that a full skin examination be performed. There or sensitivity to chromium, cobalt, and nickel should be no skin defects or nodule drainage [13 ] as well as bone cement ingredients [14 ] . One present by the knee. Skin quality is also of some should ask about allergies to jewelry or metals in concern. The skin tissue may have the quality of the form of rashes. If needed, a patient can be sent tissue paper, leading to inadvertent tearing of the to have appropriate testing done to determine how skin through grasping the extremity during sensitive the patient is to the allergen. However, surgery. these tests may not completely correlate with a true allergy. Although rare, an implant material allergic patient may have chronic pain until Sources of Infection implants are removed and replaced with some other implant made of a different material. Other sources of infection exist besides the skin. Rheumatoid patients are given the appropriate A source of possible infection is the oral cavity. prophylactic antibiotic before skin incision with The AAOS in cooperation with the American timing depending on the type of antibiotic given. Dental Association has published an advisory that These patients are given the same prophylactic noted that bacteremia from dental work may antibiotic that the healthy total joint patient is hematogenously seed a TKA with the greatest given. Antibiotics are continued for 24 h after risk up to 2 years after surgery [ 17] . Many sur- surgery and then discontinued. If a patient has an geons believe that all infl ammatory arthropathy allergy, they are given the appropriate alternative. patients and especially those on immunosuppres- There are no data supporting the prolonged dura- sants should be given prophylaxis during dental tion of prophylactic antibiotics for patients with procedures as well as having all extensive dental prior surgical site and skin infections, wound work (i.e., procedures other than simple clean- healing problems, or for revision surgery. ings) done prior to having a TKA. Urologic and However, some surgeons will elect to give antibi- gastroenterological sources can provide avenues otics to rheumatoid joint replacement patients of bacteremia through cystoscopy, prostatectomy, until their surgical wound has stopped draining. or even colonoscopy. It is therefore advisable to If a hospital has a high rate of nosocomial methi- prescribe some form of site-specifi c prophylactic cillin-resistant staphylococcal infections, consid- antibiotics during these procedures. Some ortho- eration can be given to modifying the choice of pedic surgeons would suggest that all other needed antibiotics [ 15 ] . The AAOS guidelines can be surgery/dental work and semielective pending viewed on the academy web site [16 ] . surgery be performed before the arthroplasty.

Skin and Infection Blood Loss

Rheumatoid patients suffer from skin manifesta- The possibility of blood transfusion should be tions that may limit or complicate surgery. addressed before proceeding with surgery. Rheumatoid nodules around the knee may be a A patient should be informed and properly con- source of pressure problems. A nodule both distal sented about receiving blood products and alter- to and about the operative site may erupt from the natives before entering the surgical theater. skin, providing an avenue for infection, or a nod- Cemented TKA done using a tourniquet typically ule may remain buried and still become in fl amed only lose about 150Ð200 cc in blood intraopera- and infected. With the patient on immunosup- tively. This however does not represent all the pression type drugs for the systemic rheumato- blood loss during the hospital stay. More blood is logic disease, a patient may fi nd it diffi cult to lost over the next several days as bony oozing and mount a normal infl ammatory response to a small capillary bleeding. Some studies have 346 D.M. Joyce and M.J. Joyce shown through calculations that unilateral TKA total blood loss is between 800 cc and 1200 cc [18 ] . Allogenic blood products carry some risk of infection and transfusion reaction that can never be completely eliminated. Alternatives to allo- genic products are autologous blood that is donated (not routinely done) about a month before surgery or perioperative red blood cell sal- vage. Using iron plus erythropoietin to increase the preoperative red cell mass is another option.

Order of Surgery Fig. 32.5 Rheumatoid patient with bilateral deformity of Patients undergoing TKA in one knee often have the knees similar pain and deformity with the contralateral knee. These patients can choose to have both alignment. Erosions and deformity can be knees to be done at the same time if their medical signifi cant enough to warrant augments to build condition allows. They also have other joints that up insuffi cient bone stock. These defects and are affected by rheumatoid disease. Patients suf- deformities force a surgeon to select different fering from knee arthritis also have problems in implant options as well as perform releases that their hips, wrists, elbows, ankles, and shoulders can affect rehabilitation time. The greater the that must be considered when planning the tim- amount of bone or soft tissue removed or repaired ing of a TKA. TKA patients will require the use may lead to more time in rehabilitation. It can of some walking aid in the form of a cane, walker, also affect the patients’ progress to a full weight- or crutches. These walking aids will place added bearing status. Body and knee size is an impor- stress on the joints of the upper extremity. Often tant consideration when considering a knee TKA will be performed before replacement or replacement. Very small patients may require fusion of the joints in the upper extremities due to custom components be manufactured. Patients as the added stress impact on the upper extremity young as 12 years old have had knee replace- joint while using a walker potentially causing ments performed. failure or limit their rehabilitation.

Anesthesia Considerations Bone and Soft Tissue Characteristics and Quality This decision as to type of anesthesia is made by the anesthesiologist, but the surgeon, rheumatolo- Rheumatoid patients present a somewhat unique gist, primary physician, and patient must be aware subset of patients for which bone quality and soft of the options. The disease process may involve tissue characteristics are important in planning the joints of the spine particularly the cervical what type of knee system to implant. These spine. These patients can have limited motion in patients are often on chronic steroids making the cervical spine and jaw, making general anes- their residual bone very soft and prone to intraop- thesia via intubation most diffi cult. Regional anes- erative fracture. Their destructive in fl ammatory thesia may provide the best option for patients. arthropathy tends to create signifi cant bone A preoperative anesthesia consult is most deformity, erosions, and bone loss at the joint line important. Up to 61% of these arthroplasty patients (Fig. 32.5 ). Varus and valgus deformity can be have radiographic evidence of cervical spine severe and requires correction to obtain proper instability [ 19] . Often these patients are asymp- 32 Total Knee Arthroplasty in Rheumatoid Disease and Other Associated In fl ammatory Arthropathies 347 tomatic for cervical spine problems, making it several days. No resistance or weight training is dif fi cult to discover from history or physical exam done. Rehabilitation involves instruction in that the patient has cervical instability problems. activities of daily living, gait training, and some This highlights the point that each of these rheu- minimal strengthening. During the fi rst 6 weeks matoid patients should have current lateral fl exion of the subacute phase, patients are generally only and extension fi lms of their neck before proceed- working on increasing their range of motion. ing with surgery. Prior to surgery, if an instability Between 4 and 6 weeks, patients should be pattern is discovered, the instability problem obtaining their maximal fl exion ability. Flexion should be evaluated by a spine surgeon. If the less than 90¡ at this time will often be treated x-rays are relatively normal without instability with a manipulation under anesthesia to increase and a normal neurological exam, it is relatively overall fl exion end point. A fl exion defi cit (less safe to proceed without spine surgeon input. than 90¡ of fl exion) limits a patient’s ability to ascend and descend stairs as well as sitting and rising from a chair. At about 6 weeks, patients Postoperative Treatment and begin to work on strengthening their leg. Patients Considerations are told that the most important predictor in a good outcome is what happens in the fi rst Expectations and Disposition 2Ð3 weeks of physical therapy.

Patients often go home on their third postopera- tive day. Bilateral TKA patients can expect to Pain Control stay at least 4 days and then requiring a stay in some form of rehabilitation or skilled nursing In the past, pain control consisted of only using a facility. Patients are generally made weight bear- combination of oral and IV narcotics. Patients ing as tolerated immediately after surgery with a having total knee arthroplasty often bene fi t from routine cemented TKA barring intraoperative an indwelling femoral nerve catheter. But these complications. With signifi cant bone defects and are not without potential risks. These patients revision TKA, bone grafting may be required must wear a knee immobilizer for the duration of which may limit early full weight-bearing ability. the block as their knee is unable to actively extend Postoperatively, some surgeons elect to use a due to the paresis of the quadriceps muscle group, continuous passive motion (CPM) machine peri- placing the patient at substantial risk of fall when odically that fl exes and extends the knee while getting out of bed. While the pain catheters are the patient is in bed, although CPM appears to effective in relieving anterior pain and likely provide no additional long-term bene fi t in range quadriceps spasm associated with the surgery, the of motion [20 ] . continuous femoral nerve block does not relieve pain in the posterior aspect of the knee as that is innervated by the sciatic nerve. After appropriate Physical Therapy titration, the muscles can somewhat function while still obtaining a signi fi cant amount of pain Physical therapy starts on the day after surgery. control. Patients are instructed in transfers in and out of Another option for pain control is an indwell- bed and isometric exercises for gluteal and quad- ing epidural pain catheter. This can be maintained riceps muscle groups. Patients are encouraged to for a period of time. During this time, no heparin do deep breathing and ankle pumps while in bed. anticoagulation can be given due to concern of Physical therapy will often start with passive bleeding within the epidural space with the cath- knee extension, and active assisted fl exion is eter. DVT chemical prophylaxis is begun about encouraged. Patients move to standing and walk- 12Ð24 h after the catheter comes out. During this ing with an aid of a walker or crutches in the fi rst time, a Foley catheter is maintained. 348 D.M. Joyce and M.J. Joyce

Venous Thromboembolism and Deep fondaparinux, and warfarin. This chemical pro- Vein Thrombosis Prophylaxis phylaxis is maintained from 10 to 28 days on average, although the AAOS recommends Venous thromboembolism (VTE) and deep vein 10 days at a minimum for TKA and up 35 days thrombosis (DVT) pharmacologic prophylaxis is for a THA [ 26 ] . Warfarin is often started the night often begun the morning after surgery. Mechanical of surgery and is generally titrated to an INR of sequential calf pneumatic device prophylaxis is 2.0Ð2.5 and continued 2Ð6 weeks. The other begun during surgery on the nonsurgical leg and forms of pharmacologic prophylaxis are started immediately after surgery on the operative leg. the following morning. Enoxaparin is generally Currently, the American Academy of Orthopaedic dosed 40 mg daily or 30 mg twice a day and has Surgeons (AAOS) and American College of been used from 14 to 21 days. Aspirin when used Chest Physicians (ACCP) differ on the method of for knees only is dosed 325 mg twice daily for prevention of DVT and pulmonary embolism 6 weeks and is only used when intermittent pneu- (PE) in total joint patients. This led the ACCP to matic compressions devices are used. Risk adopt a position that stated: the AAOS adopted strati fi cation of the patient in question will deter- a position that is inconsistent with evidence mine which prophylaxis is appropriate. [21, 22 ] . The difference in recommendations DVT scans with ultrasound are not routinely from each of these organizations stems from the scheduled unless there is suspicion of a DVT. difference in belief that all asymptomatic clots Inpatient surveillance duplex scans were found (very distal) are relevant. The AAOS position is not clinically useful in patients managed with based on the concept that prevention of symptom- effective DVT prophylaxis [27 ] . atic PE is more clinically relevant than prevention of all DVTs due to the risk of hematoma develop- ment and the complications associated with treat- Complications ment of a symptomatic hematoma. Patients undergoing primary TKA have been shown to Venous Thromboembolism and Deep have symptomatic rates of PE of 1.9% when no Vein Thrombosis prophylaxis was used [23 ] . The risk of fatal PE is reported up to 0.14% following a TKA regardless The most common complication following total of the type of prophylaxis [ 24 ] . Following the knee replacement remains to be deep vein throm- ACCP guidelines has been associated with per- bosis (DVT) or venous thromboembolus (VTE). sistent wound drainage and hematoma, leading to Half of all symptomatic VTE occur within the increased risk of infection [ 25 ] , a 4.7% readmis- fi rst 7 days of a TKA [28 ] . The biggest concern is sion rate, 3.4% irrigation and debridement rate, for the DVT to evolve into a PE. Symptomatic and 5.1% rate of prolonged hospitalization in VTE occurs both early and late after TKA with joint replacements [ 22 ] . Because of the serious- the average time of a VTE for TKA reported to ness of a joint infection, the AAOS developed a be 7 days [28 ] . Risk factors for DVT in a TKA set of guidelines that used prevention of clinical patient include estrogen use in the form of con- outcomes such as symptomatic and fatal PE, traceptives in younger people and hormone death, and major bleeding episodes as the basis replacement therapy, age older than 40, previous for their current recommendations [26 ] . This is DVT, stroke, cancer, prolonged immobility, even more signi fi cant given that the risk of infec- smoking, nephritic syndrome, CHF, indwelling tion is already higher in a RA patient. Patients catheter in the femoral vein, infl ammatory bowel receiving joint replacement are risk stratifi ed to disease, obesity, varicose veins, smoking, HTN, determine the best VTE prophylaxis for the DM, and MI. One study found that when compar- patient’s circumstances. ing anti-TNF and DMARDs in joint replacement The choices of pharmacologic prophylaxis are patients, the majority of which were TKA, aspirin, low molecular weight heparin (LMWH), patients were at higher risk of development of a 32 Total Knee Arthroplasty in Rheumatoid Disease and Other Associated In fl ammatory Arthropathies 349

DVT in the anti-TNF treatment group compared polyethylene insert exchange up to 2Ð4 weeks to other DMARDs group with 51% of the patients from onset of symptoms, while chronic infec- treated with anti-TNF developing DVTs, while tion requires explant and antibiotic spacer place- only 26% of the DMARDs group developed a ment [34 ] . While antibiotic suppression may be DVT [29 ] . This information should make the sur- an option for treating a chronic infection in geon and the rheumatologist more vigilant about some settings, it is not an option for a rheuma- possible DVT in an anti-TNF-treated patient toid patient on chronic immunosuppressive complaining of symptoms potentially related to a therapy. blood clot. Without mechanical or chemical VTE prophylaxis, the prevalence of DVT after TKA has been reported to be between 40% and 84% Neurovascular Injury [30 ] . Calf DVT which have been reported as being 95% [ 31 ] of the DVTs in TKA patients are Neurovascular injury can be devastating and is not as concerning as the proximal thrombi that often not noticed until the end of surgery with the occur in the popliteal vein or above. Proximal injury masked by the use of a tourniquet. Arterial venous thrombosis may occur in 9Ð20% of complications occur 0.03Ð0.17% with 25Ð43% patients and pose a more signi fi cant risk of pul- [ 35, 36] resulting in amputation. Nerve injury can monary embolism (PE) which may be asymp- occur with either the tibial nerve or peroneal tomatic [30 ] in 10Ð20% and symptomatic in nerve and has an overall incidence ranging from 0.5Ð3% with a mortality rate of 2%. The major 0% to 9.5% [ 35, 37 ] . Peroneal nerve palsy is the concern is that thrombi in the lower extremity commonly reported nerve palsy after TKA and propagate which happens in 6Ð23% of calf was seen in 1.8% of rheumatoid patients [ 38 ] . thrombi [32 ] . DVT can be very hard to determine Peroneal nerve injury has been reported as high clinically as the signs and symptoms of DVT can as 3Ð4% and even to 8Ð10% in knees requiring mimic signs of cellulitis. A patient may have a valgus deformity and fl exion contractures correc- DVT and be relatively asymptomatic. tion, respectively [39 ] . Most peroneal nerve stretch injuries recover around 6 months with the patient requiring an ankle foot orthosis to mini- Infection and Wound Issues mize fl exion contracture of the ankle. EMG is generally not performed before 3 weeks. Infection rates tend to be higher in rheumatoid patients that are on immunosuppressants. Infection of TKA was reported up to 2.6% with Patellofemoral Problems perioperative risk factors identi fi ed as RA, skin ulceration, previous knee surgery, use of the Patellofemoral complications form a spectrum hinge knee, obesity, concurrent UTI, steroid from minimally symptomatic such as patellar use, renal failure, DM, poor nutrition, cancer, clunk syndrome seen in posterior substituting and psoriasis, making rheumatoid patients much stabilized knees with patellar instability but more susceptible to infections [ 33 ] . Infection in include fracture, component failure, and loosen- a total joint replacement carries a mortality risk ing to the most devastating complication of exten- of up to 18% [ 11] . Infection comes in two forms, sor mechanism failure that renders the quadriceps super fi cial and deep. Deep joint infections often functionless. Quadriceps or patellar tendon rup- lead to removal of the implants and placement ture occurs in less than 1% of patients [35, 40 ] of an antibiotic spacer and IV antibiotics. Acute but has been reported as high as 5% with risk fac- postsurgical infections are due to contamination tors being chronic steroid use [ 35 ] . This requires from the index surgery. Acute infections, with either a direct repair or allograft reconstruction, less than 2 weeks of symptoms, can be treated making long-term rehabilitation necessary, but with an arthrotomy, washout, debridement, and may still result in dysfunction of the knee. 350 D.M. Joyce and M.J. Joyce

Periprosthetic Fractures patient is stable and shows no evidence of sepsis, a stepwise approach can be taken to aid in the Fractures can occur during surgery and after sur- diagnosis of the problem. An x-ray can be of the gery such as periprosthetic fractures. The patients utmost value as it can rule out gas in the joint generally have poor bone quality due to disease (evidence of an aggressive infection) or disloca- and medications such as steroids and methotrex- tion, fracture, or gross hardware failure. If there ate that affect bone remodeling and quality. is concern of acute infection, blood work should Fractures tend to be more on the femoral side and be performed that may include blood cultures, are associated with anterior femoral notching, CRP, ESR, and CBC with differentiation. If ery- osteoporosis, rheumatoid arthritis, steroid use, thema is noted, it should be traced out as an aid to female gender, neurological disorders, and revi- determine progression or resolution. A joint aspi- sion arthroplasty [35 ] . These periprosthetic frac- ration should be performed away from the area of tures are reported in 0.3Ð2% TKA patients. One skin erythema prior to administering antibiotics. must be suspicious of any rheumatic patient com- This should be performed as a sterile aseptic plaining of new-onset pain with or without trauma method. Prior to placing a needle into the affected and whether or not they have a TKA. Complaints joint, communication should been accomplished of chronic distal femoral pain could be an impend- with the surgeon as they may elect to evaluate the ing fracture not evident on x-ray. These fractures patient and perform the aspiration themselves. can occur within the fi rst several months to sev- Antibiotics should be started as soon as possible eral years out from surgery. after the aspiration if infection is suspected. The patient should not eat or drink in case of urgent surgical intervention. In the case of infection not Heterotopic Ossifi cation located near a total joint, antibiotics should be started as soon as possible to minimize the risk of Heterotopic ossifi cation, while mostly thought of hematogenous seeding. Patients with complaints as a complication seen in hip surgery, can occur of pain with fall or chronic pain related to weight in the TKA. While RA is not correlated with bearing may have an impending fracture if a frac- postoperative onset of HO, hypertrophic arthrosis ture is not overtly evident on x-ray. These patients has been shown to be a risk factor in development should be made non-weight bearing and should of HO after a TKA [ 41 ] . In one study of TKA have follow-up with their surgeon who can order performed in ankylosing spondylitis patients, HO other imaging to determine if a fracture exists. developed in 20% of the knees and did limit some Chronic joint pain, after acute infection has been motion [41 ] . ruled out, should be seen in the surgeon’s offi ce as it may represent a smoldering infection or aseptic loosening of the implants. Any acute The Late Postoperative Patient complaint that involves the surgical joint should (6 Months Out) have prompt communication and follow-up with the appropriate surgeon. It is important to have a Patients are generally seen by their surgeon at good dialogue between orthopedist, rheumatolo- 2Ð4 weeks, 3 months, 6 months, and a year out gist, and internist and to take a team approach from surgery. After that, visits are based on an when taking care of the rheumatoid patient. as-needed basis. Rheumatologist and generalist should expect to see total joint patients with com- plaints of joint pain or erythema at some point Conclusion after surgery. It is important to get a detailed his- tory of the complaint in order to determine if this Patients must understand that knee replacement is a possible infection, fracture, dislocation, or is not a simple procedure and, for the majority of component failure. After determining that the cases, represents an elective procedure. Thought 32 Total Knee Arthroplasty in Rheumatoid Disease and Other Associated In fl ammatory Arthropathies 351 must be given to the risk and benefi ts of proceed- 14. Kaplan K, et al. Preoperative identi fi cation of a bone- ing with surgery. Rheumatoid patients are often cement allergy in a patient undergoing total knee arthroplasty. J Arthroplasty. 2002;17(6):788Ð91. less healthy, with multiple comorbidities, com- 15. Meehan J, Jamali AA, Nguyen H. Prophylactic antibi- pared to the osteoarthritis (OA) patient. otics in hip and knee arthroplasty. J Bone Joint Surg Arthroplasty surgery is not without signi fi cant Am. 2009;91(10):2480Ð90. potential complications. The decision to perform 16. Prokuski L. Prophylactic antibiotics in orthopaedic surgery. J Am Acad Orthop Surg. 2008;16(5):283Ð93. a total knee replacement should be made in con- 17. Curry S, Phillips H. Joint arthroplasty, dental treat- junction with the rheumatologist, orthopedic sur- ment, and antibiotics: a review. J Arthroplasty. geon, and the patient. 2002;17(1):111Ð3. 18. Levy O, et al. The use of fi brin tissue adhesive to reduce blood loss and the need for blood transfusion after total knee arthroplasty. A prospective, random- References ized, multicenter study. J Bone Joint Surg Am. 1999;81(11):1580Ð8. 1. Yano K, et al. Effect of total knee arthroplasty on dis- 19. Collins DN, Barnes CL, FitzRandolph RL. Cervical ease activity in patients with established rheumatoid spine instability in rheumatoid patients having total arthritis: 3-year follow-up results of combined medi- hip or knee arthroplasty. Clin Orthop Relat Res. cal therapy and surgical intervention. Mod Rheumatol. 1991;272:127Ð35. 2010;20(5):452Ð7. 20. MacDonald SJ, et al. Prospective randomized clinical 2. Rand JA, et al. Factors affecting the durability of pri- trial of continuous passive motion after total knee mary total knee prostheses. J Bone Joint Surg Am. arthroplasty. Clin Orthop Relat Res. 2000;380:30Ð5. 2003;85-A(2):259Ð65. 21. Eikelboom JW, et al. American Association of 3. Jiranek WA, Hanssen AD, Greenwald AS. Antibiotic- Orthopedic Surgeons and American College of Chest loaded bone cement for infection prophylaxis in total Physicians guidelines for venous thromboembolism joint replacement. J Bone Joint Surg Am. prevention in hip and knee arthroplasty differ: what 2006;88(11):2487Ð500. are the implications for clinicians and patients? Chest. 4. Song EK, Seon JK, Jeong MS. Delayed-type hyper- 2009;135(2):513Ð20. sensitivity reaction to piperacillin/tazobactam in a 22. Burnett RS, et al. Failure of the American College patient with an infected total knee replacement. J of Chest Physicians-1A protocol for lovenox in Bone Joint Surg Br. 2010;92(11):1596Ð9. clinical outcomes for thromboembolic prophylaxis. 5. Dunbar MJ. Antibiotic bone cements: their use in rou- J Arthroplasty. 2007;22(3):317Ð24. tine primary total joint arthroplasty is justi fi ed. 23. Stringer MD, et al. Deep vein thrombosis after elec- Orthopedics. 2009;32(9):660. tive knee surgery. An incidence study in 312 patients. 6. Lu H, et al. Simultaneous bilateral total knee arthro- J Bone Joint Surg Br. 1989;71(3):492Ð7. plasty for rheumatoid arthritis. Chin Med J (Engl). 24. Lachiewicz PF. Comparison of ACCP and AAOS guide- 1996;109(12):937Ð40. lines for VTE prophylaxis after total hip and total knee 7. Noble J, Goodall JR, Noble DJ. Simultaneous bilat- arthroplasty. Orthopedics. 2009;32(12 Suppl):74Ð8. eral total knee replacement: a persistent controversy. 25. Parvizi J, et al. Does “excessive” anticoagulation pre- Knee. 2009;16(6):420Ð6. dispose to periprosthetic infection? J Arthroplasty. 8. Basilico FC, et al. Risk factors for cardiovascular 2007;22(6 Suppl 2):24Ð8. complications following total joint replacement sur- 26. Johanson NA, et al. Prevention of symptomatic pul- gery. Arthritis Rheum. 2008;58(7):1915Ð20. monary embolism in patients undergoing total hip or 9. March LM, et al. Costs and outcomes of total hip and knee arthroplasty. J Am Acad Orthop Surg. knee joint replacement for rheumatoid arthritis. Clin 2009;17(3):183Ð96. Rheumatol. 2008;27(10):1235Ð42. 27. Schwarcz TH, et al. Surveillance venous duplex is not 10. Doran MF, et al. Frequency of infection in patients clinically useful after total joint arthroplasty when with rheumatoid arthritis compared with controls: a effective deep venous thrombosis prophylaxis is used. population-based study. Arthritis Rheum. Ann Vasc Surg. 2004;18(2):193Ð8. 2002;46(9):2287Ð93. 28. White RH, et al. Incidence and time course of throm- 11. Mushtaq S, Goodman SM, Scanzello CR. Perioperative boembolic outcomes following total hip or knee management of biologic agents used in treatment of arthroplasty. Arch Intern Med. 1998;158(14): rheumatoid arthritis. Am J Ther 2011;18(5):426Ð34. 1525Ð31. 12. Howe CR, Gardner GC, Kadel NJ. Perioperative medi- 29. Kawakami K, et al. Complications and features after cation management for the patient with rheumatoid joint surgery in rheumatoid arthritis patients treated arthritis. J Am Acad Orthop Surg. 2006;14(9):544Ð51. with tumour necrosis factor-alpha blockers: perioper- 13. Carlsson A, Moller H. Implantation of orthopaedic ative interruption of tumour necrosis factor-alpha devices in patients with metal allergy. Acta Derm blockers decreases complications? Rheumatology Venereol. 1989;69(1):62Ð6. (Oxford). 2010;49(2):341Ð7. 352 D.M. Joyce and M.J. Joyce

30. Moser KM, LeMoine JR. Is embolic risk conditioned 36. Holmberg A, Milbrink J, Bergqvist D. Arterial com- by location of deep venous thrombosis? Ann Intern plications after knee arthroplasty: 4 cases and a review Med. 1981;94(4 pt 1):439Ð44. of the literature. Acta Orthop Scand. 1996;67(1): 31. Ciccone 2nd WJ, et al. Ultrasound surveillance for 75Ð8. asymptomatic deep venous thrombosis after total joint 37. Schinsky MF, et al. Nerve injury after primary total replacement. J Bone Joint Surg Am. 1998;80(8): knee arthroplasty. J Arthroplasty. 2001;16(8):1048Ð54. 1167Ð74. 38. Knutson K, et al. Nerve palsy after knee arthroplasty 32. Ciccone 2nd WJ, Reid JS, Pellegrini Jr VD. The role in patients with rheumatoid arthritis. Scand J of ultrasonography in thromboembolic disease man- Rheumatol. 1983;12(3):201Ð5. agement in the orthopaedic patient. Iowa Orthop J. 39. Clarke HD, et al. Anatomic risk of peroneal nerve 1999;19:18Ð25. injury with the “pie crust” technique for valgus release 33. Luessenhop CP, et al. Multiple prosthetic infections in total knee arthroplasty. J Arthroplasty. 2004;19(1): after total joint arthroplasty. Risk factor analysis. 40Ð4. J Arthroplasty. 1996;11(7):862Ð8. 40. Parker DA, Dunbar MJ, Rorabeck CH. Extensor 34. Moyad TF, Thornhill T, Estok D. Evaluation and man- mechanism failure associated with total knee arthro- agement of the infected total hip and knee. Orthopedics. plasty: prevention and management. J Am Acad 2008;31(6):581Ð8. quiz 589-90. Orthop Surg. 2003;11(4):238Ð47. 35. Lonner JH, Lotke PA. Aseptic complications after 41. Parvizi J, Duffy GP, Trousdale RT. Total knee arthro- total knee arthroplasty. J Am Acad Orthop Surg. plasty in patients with ankylosing spondylitis. J Bone 1999;7(5):311Ð24. Joint Surg Am. 2001;83-A(9):1312Ð6. Knee Arthroscopy 3 3 James S. Williams

Introduction with in fl ammatory arthritis who undergo knee arthroscopy can be expected to suffer higher Knee joint function in patients with infl ammatory complication rates, prolonged recovery times, arthritis may deteriorate over time if synovial and greater cost of care than noninfl ammatory in fl ammation is unchecked resulting in irrevers- arthritis patients undergoing the same procedure. ible damage to articular cartilage and bone. The arthroscopic surgeon, rheumatologist, and Evaluation of medications, functional ability, and anesthesiologist should work closely together to goals will facilitate development of a treatment optimize preoperative, perioperative, and postop- plan prior to arthroscopic knee surgery which erative care to minimize the patients’ risk of com- will help to maximize peri- and postoperative plications and to maximize treatment outcomes. patient care. Initially used for lavage and diagno- The patients’ list of current medications must be sis, arthroscopic knee surgery for patients with reviewed [ 1, 2 ] . A well-thought-out plan as to infl ammatory arthritis is currently also used to which medicines need to be stopped and when evaluate newer treatment responses over time and they should be restarted can help avoid or mini- to perform complete synovectomy in symptom- mize many potential complications and help to atic patients in the early stages of the disease who reassure the patient with in fl ammatory arthritis have failed standard nonoperative treatments. undergoing knee arthroscopy. The synovium has a rich blood supply and arthroscopic synovectomy causes signifi cant Preoperative Considerations bleeding and hemarthrosis. A large hemarthrosis of the Patient with RA causes more pain, slows down rehabilitation, can delay wound healing, and puts the patients at a Treatment decisions can be dif fi cult for higher risk of infection. arthroscopic surgeons and outcomes less predict- Due to the nature of the disease, patients with able due to the wide range of overall health status infl ammatory arthritis are more susceptible to in patients with in fl ammatory arthritis. Patients problems with wound healing and infection to begin with. As a result, all medicines that prolong bleeding, inhibit wound healing, or increase J. S. Williams , M.D. () chances of infection rates should all be stopped at Department of Orthopaedics , Orthopaedic and the appropriate times prior to surgery and restarted Rheumatologic Institute , 99 Northline Circle Suite #100 , Euclid , OH 44119 , USA when the risks have subsided. The patients’ list of e-mail: [email protected] current medicines and comorbidities must be

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 353 DOI 10.1007/978-1-4614-2203-7_33, © Springer Science+Business Media, LLC 2013 354 J.S. Williams reviewed preoperatively. A well-thought-out plan While no consensus exists as to the appropriate or medication changes and comorbidity maximi- volume of saline to use in arthroscopic lavage, vol- zation will help to minimize many potential com- umes of 3Ð5 L have demonstrated bene fi cial effects plications and help to reassure the patient with for patients with in fl ammatory arthritis with symp- infl ammatory arthritis undergoing knee arthros- tomatic knees [4, 6, 7 ] . In one study, the bene fi cial copy. DVT prophylaxis is not usually indicated effects of arthroscopic lavage were prolonged by with knee arthroscopy due to the low incidence intra-articular injection of both corticosteroid and unless the patient has a history of prior DVT. high molecular weight hyaluronan [9 ] . Patients Cervical spine fi lms are generally obtained pre- with infl ammatory arthritis with relapsing symp- operatively in patients with long-standing disease toms for more than six months and who have mild or in patients with complaints of neck pain. The joint destruction (Larsen grade less than III) patient with infl ammatory arthritis with milder responded best to this form of treatment. Overall forms of atlantoaxial disease can often still undergo arthroscopic lavage for patients with in fl ammatory knee arthroscopy with use of local, epidural, femo- arthritis is safe and well tolerated and allows treat- ral block, or spinal anesthesia instead of GETA. ment of concurrent intra-articular knee pathology, Contraindications to arthroscopic knee sur- in those patients with milder forms of infl ammatory gery are ongoing infection, comorbidities that arthritis of the knee. preclude surgery, and open wounds around the knee joint. Arthroscopy in Diagnosis, Staging, and Evaluation of Novel Therapies Arthroscopic Lavage for RA

Lavage of the symptomatic knee joint in RA Use of the arthroscope for visualization and patients has been used as a form of disease treat- biopsy of the knee joint in patients with ment for decades. Overtime, needle lavage gave in fl ammatory arthritis was fi rst reported in the way to arthroscopic lavage as results proved to late 1960s [10 ] . Arthroscopic synovial biopsy be better with use of the arthroscope [ 3Ð 8 ] . The had advantages over open synovial biopsy in that improvement in results is due to the ability to it provided a more complete assessment of the move the arthroscope around the joint, thereby entire knee joint and could be done under local performing a more complete irrigation of the anesthesia, through small incisions, with less knee joint over needle lavage. Symptomatic pain and complications and a shorter period of relief after knee lavage in patients with convalescence. Biopsies obtained by knee infl ammatory arthritis is thought to be related to arthroscopy in patients with in fl ammatory arthri- removal of debris and to reducing the concentra- tis have been shown to be more accurate than tion of cytokines, degradative enzymes, and needle biopsy and demonstrate less morbidity other in fl ammatory agents. than open biopsies [11 ] . Over time, use of the Standard medial and lateral portals are made, arthroscope has provided the opportunity to cor- and saline is run throughout the knee joint relate the fi ndings with stage of the disease and removing debris and infl ammatory products. long-term outcomes. Biopsies could be taken Patients with infl ammatory arthritis often have easily with use of the arthroscope with little mor- mechanical causes of knee pain on top of the bidity and repeated over time to help correlate in fl ammatory pain. Arthroscopic treatment has intra-articular fi ndings with symptoms and dis- the additional advantage over needle lavage of ease progression [12, 13 ] . not only being able to wash out the knee more Use of the arthroscope in patients with infl a- thoroughly but also treating any mechanical mmatory arthritis has evolved to the point where issues relating to meniscal tears, loose bodies, or it is increasingly being used for the evaluation of loose articular cartilage. novel therapies via synovial biopsies [14, 15 ] . 33 Knee Arthroscopy 355

appears to have a role in the treatment of patients Arthroscopic Synovectomy with infl ammatory arthritis with early symptom- atic knees that have failed 6-months of standard Synovectomy as a form of treatment for patients treatment. with infl ammatory arthritis symptomatic knee synovitis has been used since the early 1900s. Over time, open knee synovectomy gave way to Surgical Techniques arthroscopic knee synovectomy due to less pain, less morbidity, fever complications, easier reha- Setup bilitation, repeatability, and the ability to treat associated pathology. Arthroscopic synovectomy The patient is placed supine on the operating for the treatment of symptomatic knees in patients table. Once anesthesia and preoperative antibiot- with in fl ammatory arthritis has seen a decline as a ics have been given, a knee exam is performed. result of new effective nonoperative treatments. The leg is then placed in a leg holder after a tour- The best indication for arthroscopic knee synovec- niquet is placed around the thigh. A variety of tomy appears to be in those patients with portals are made so as to be able to remove all the infl ammatory arthritis with early disease who have synovium and take care of any other pathology demonstrated failure to improve over a 6-month such as meniscal tears, cartilage injury, or loose time with standard nonoperative treatments. bodies. At the conclusion of the case, the portals Open synovectomy for the treatment of are closed, a local is injected, and a sterile dress- chronic knee synovitis was fi rst performed in the ing full-length bandage, cooling unit, and knee early nineteenth century [ 16 ] . Several studies uti- immobilizers are applied. lizing open total synovectomy demonstrated good short-term results (less pain, increased mobility, and decreased infl ammation) in patients Surgical Synovectomy with infl ammatory arthritis with early disease [17Ð 39] In general, these studies demonstrated A midlateral viewing portal is made just lateral to overall radiographic worsening with time; how- the patellar tendon and just above the joint line ever, the patients with infl ammatory arthritis in (Fig. 33.1a ). Use of a triple-headed arthroscopic the early stages (1&2) did signifi cantly better canula allows for intra-articular pressure mea- than those in the later stages (3&4). Open knee surement, in fl ow of saline, and out fl ow or drain- synovectomy gave way to arthroscopic knee syn- age of fl uid, thereby eliminating the need for an ovectomy as patients with in fl ammatory arthritis outfl ow canula. Once the 4.0 arthroscope has were found to have less pain, bleeding, complica- been placed in the joint, a spinal needle can be tions, and better ROM, and it could be performed used to establish proper position of the midme- on an outpatient basis [ 18, 21, 40Ð 53 ] . Despite dial portal (Fig. 33.1b ). the lack of evidence-based studies, it is clear that A thorough exam of the knee is performed, and results of arthroscopic knee synovectomy deteri- any additional pathology such as meniscal tears, orate over time and seem to work best in the ear- loose bodies, or loose fl aps of articular cartilage lier stages of the disease. can be taken care of. Synovectomy should start In conclusion, arthroscopic knee synovectomy with the front of the knee progress to the sides and in patients with infl ammatory arthritis is safer gutters, followed by the posterior portion of the with less morbidity and results in less radio- knee and concluding with the suprapatellar area graphic evidence of OA long term than open syn- as it is the most vascular and likely to bleed, ovectomy. Newer nonoperative treatments for thereby making visualization more dif fi cult. patients with in fl ammatory arthritis with knee Accessory posteromedial and posterolateral por- involvement have resulted in fewer arthroscopic tals are necessary to perform a complete synovec- synovectomies. Arthroscopic synovectomy still tomy and should be made under direct visualization 356 J.S. Williams using a spinal needle. Care must be taken around warm, swollen joint is common due to the bleed- the cruciate ligaments so as not to damage them. ing into the knee. Temperatures over 102.5¡F Use of a 3.5-mm full radius resector works best in become more worrisome. Patients with develop- this area. Additional portals in the suprapatellar ing knee infections usually look sick. There area may also be needed. As arthroscopic fl uid should be a low threshold to aspirate the knee tends to leak readily from these portals when not and send it for culture if there is any suspicion of in use, this is another reason for saving the supra- infection. Antibiotics should never be started patellar area for last. A variety of shaved sizes prior to knee aspiration to avoid unnecessary use (3.5Ð5.5 mm) may be necessary to complete the of numerous antibiotics in individuals whose synovectomy in a timely and safe manner. While health is already compromised. working in the posterior portion of the knee, a 70¡ DVT rates in this population following arthroscope allows for more complete visualiza- arthroscopic synovectomy are not known but tions of the posterior synovium. are most likely higher than the rates of 3.5Ð 9.9% [54Ð 56] reported for knee arthroscopy in general. Postoperatively, patients need to be Post-op encouraged to do frequent ankle pumps to avoid venous stasis. For patients at moderate risk for Patients are discharged the same day. Weight DVT, enteric-coated ASA 325 mg per day for bearing as tolerated with crutches or walker is 4Ð6 weeks starting the night of surgery can be allowed, and strict ice and elevation above the considered. For patients at high risk for DVT, heart with frequent ankle pumps is encouraged. enoxaprin 30 mg SC every 12 h for 10 days Patients are given a narcotic prescription and fol- starting the night of surgery should be consid- low-up appointment for 3Ð4 days post-op. At that ered. Any form of anticoagulation therapy must visit, the dressing is removed and range of motion be weighed against the increased risk of hemar- and exercises are started by the physical therapist. throsis and the possibility of adverse interac- The knee immobilizer and crutches/walker are tions with the patients’ current medications. discontinued once the swelling is down, and Any patient that presents with calf pain should patients can walk normally (typically a couple be sent for an ultrasound as there are no reliable days to a couple weeks post-op depending on the clinical signs for DVT. Neurovascular injuries patients overall health). Formal outpatient therapy have been reported in knee arthroscopy but are is started after this fi rst visit and will continue 2 rare events. During synovectomy, numerous times per week for a minimum of 6 weeks. portals are used and some of them are very close to major nerves and vessels. While the incidence of neurovascular injury after Complications arthroscopic knee synovectomy is not known, a good neurovascular exam should be performed Hemarthrosis is the most common complication on each patient postoperatively. If any question postoperatively due to the vascularity of the syn- exists as to the vascular status of the limb ultra- ovium. Pain related to the pressure of a large sound, venogram or arteriogram should be per- effusion is also a common side effect. For formed. Suspected nerve injury can be con fi rmed patients with a large painful effusion aspiration by and EMG/NCV exam 3 weeks post-op. under sterile conditions after numbing, the area up with local anesthetic can give the patient a lot of relief. A Jones dressing is applied to limit Conclusion repeat swelling. The importance of strict ice and elevation above the heart cannot be overstated in Patients with in fl ammatory arthritis with symp- helping to prevent these complications. tomatic knees who are referred for potential Postoperative low-grade fever along with a arthroscopic surgery present unique challenges to 33 Knee Arthroscopy 357

Fig. 33.1 ( a) Medial arthroscopic portals: (D) midmedial, (E) superior medial, and (F) posterior medial. (b ) Lateral arthroscopic portals: (A) midlateral, (B) superior lateral, and (C) posterior lateral orthopedic surgeons. The high incidence of atlan- arthritis with early disease who have failed 6 toaxial instability, comorbidities, and medica- months of standard treatments. tions all must be reviewed in conjunction with the patient’s rheumatologist so as to maximize pre-, peri-, and postoperative treatment. References The advent of the use of the arthroscope to diagnose and treat patients with in fl ammatory 1. Jacobs AM. Perioperative management of the patient arthritis with symptomatic knees has helped with rheumatoid arthritis. Clin Podiatr Med Surg. expand the treatment options available to clini- 2010;27:235Ð42. cians. Use of the arthroscope in patients with 2. Scanzello CR. Perioperative management of medica- tions used in the treatment of rheumatoid arthritis. infl ammatory arthritis has led to a better under- HSSJ. 2006;2:141Ð7. standing of the disease. Arthroscopic knee 3. Fitzgerald O, Hanly J, Callan A, et al. Effects of joint biopsy has been used not only to diagnose lavage on knee synovitis in rheumatoid arthritis. Br J infl ammatory arthritis but more recently to eval- Rheumatol. 1985;24:6Ð10. 4. Sohen S, Tanakak S. Intra-articular washing. uate intra-articular and systemic treatments. Rheumatology. 1995;13:251Ð4. Synovectomy has been a long-standing treat- 5. Sharma A, Baethge BA, Acebes JC, Lisse JR. ment option for the patient with infl ammatory Arthroscopic lavage treatment in rheumatoid arthritis arthritis with symptomatic knee infl ammation. of the knee. J Rheumatol. 1996;23:1872Ð4. 6. Tanaka N, Sakahashi H, Sato E, Hirose K, Ishii S. Open treatment gave way to arthroscopic knee Effects of needle-arthroscopic lavage with different synovectomy due to less morbidity, ease of use, volumes of fl uid on knee synovitis in rheumatoid and greater patient tolerability. While the use of arthritis. Clin Rheumatol. 2002;21:4Ð9. arthroscopic knee synovectomy has declined in 7. Tsujimoto H, Sohen S, Hahanishi C, Tanaka S. The effect of arthroscopic lavage on rheumatoid arthritis recent years due to newer treatments, it is effec- knee. Clinical Rheumatology and Related Research. tive in symptomatic patients with infl ammatory 2000;12:53Ð6. 358 J.S. Williams

8. van Oosterhout M, Sont JK, van Laar JM. Superior study of 60 knees). Arthritis Rheum. 1972;15(6): effect of arthroscopic lavage compared with needle 571Ð81. aspiration in the treatment of in fl ammatory arthritis of 25. Graham J, Checketts RG. Synovectomy of the knee- the knee. Rheumatology (Oxford). 2003;42:102Ð7. joint in rheumatoid arthritis. A long term follow-up. 9. Tanaka N, Sakahashi H, Hirose K, Ishima T, Ishii S. JBJS. 1973;55:786Ð95. Volume of a wash and the other conditions for maxi- 26. Paradies LH. Synovectomy for rheumatoid arthritis of mum therapeutic effect of arthroscopic lavage in rheu- the knee. JBJS. 1975;57:95Ð100. matoid knees. Clin Rheumatol. 2005;25:65Ð9. 27. Ishikawa H, Ohno O, Hirohata K. Long term results of 10. Jayson MI, Dixon AS. Arthroscopy of the knee in rheu- synovectomy in rheumatoid patients. JBJS. matic diseases. Ann Rheumat Dis. 1968;27:503Ð11. 1986;68:198Ð205. 11. Youssef PP, Kraan M, Breedveld F. Quantitative 28. Marmor L. Surgery of the rheumatoid knee: synovec- microscopic analysis of in fl ammation in rheumatoid tomy and debridement. JBJS Am. 1973;55:535Ð44. arthritis synovial membrane samples selected at 29. Laurin CA, Desmarchais J, Daziano L, et al. Long arthroscopy compared with samples obtained blindly term results of synovectomy of the knee in rheuma- by needle biopsy. Arthritis Rheum. 1998;41:663Ð9. toid patients. JBJS Am. 1974;51:521Ð31. 12. Smeets TJ, Barg EC, Kraan MC, et al. Analysis of the 30. Geens S, Clayton ML, Leidholt JD, et al. Synovectomy cell in fi ltrate and expression of proin fl ammatory and debridement of the knee in rheumatoid arthritis. cytokines and matrix metalloproteinases in arthroscopic JBJS Am. 1969;51:626Ð42. synovial biopsies: comparison with synovial samples 31. Doets HC, Bierman B, von Soesbergen R. Synovectomy from patients with end stage, destructive rheumatoid of the rheumatoid knee does not prevent deterioration. arthritis. Ann Rheumat Dis. 2003;62:635Ð8. Acta Orthop Scand. 1989;60(5): 523Ð5. 13. Tanaka N, Sakahashi H, Sato E, Ishii S. 32. Brattstrom C, Gschwend H, et al. Long term results of Immunohistological indication for arthroscopic syn- knee synovectomy in early cases of rheumatoid arthri- ovectomy in rheumatoid knees: analysis of synovial tis. Clin Rheumatol. 1985;4(1):19Ð22. samples obtained by needle arthroscopy. Clin 33. Paus AC, Ferre O, Pahle JA, et al. A prospective clini- Rheumatol. 2002;21:46Ð51. cal fi ve year follow up study after open synovectomy 14. Kanbe K, Inoue K. Ef fi cacy of arthroscopic synovec- of the knee joint in patients with chronic infl ammatory tomy for the effect attenuation cases of in fl iximab in joint disease. The prognostic power of clinical, rheumatoid arthritis. Clin Rheumatol. 2006;25: 877Ð81. arthroscopic, histologic and immunohistologic vari- 15. Patzakis MJ, Mills DM, Bartholomew BA, et al. ables. Scand J Rheumatol. 1992;21(5):248Ð53. A visual, histological, and enzymatic study of regen- 34. Ranawat CS, Dasai K. Role of early synovectomy of erating rheumatoid synovium in synovectomized the knee joint in rheumatoid arthritis. Arthritis Rheum. knee. JBJS. 1973;55:287Ð300. 1975;18(2):117Ð21. 16. Swett PP. Synovectomy in chronic infectious arthritis. 35. Verdeck WN, McBeath AA. Knee synovectomy for JBJS. 1923;5:110Ð21. rheumatoid arthritis. Clin Orthop Relat Res. 1978;134: 17. McEwen C. Multicenter evaluation of synovectomy 168Ð72. in the treatment of rheumatoid arthritis. Report of 36. Mongan ES, Boger WM, Gilliland BC, et al. results at the end of fi ve years. J Rheumatol. Synovectomy in rheumatoid arthritis. A retrospective 1988;15:765Ð9. study. Arthritis Rheum. 1970;13(6):761Ð8. 18. Wilkes LL. Arthroscopic synovectomy in the rheuma- 37. Meijers KA, Valkenburg HA, Cats A. A synovectomy toid knee. J Med Assoc Ga. 1985;74:582Ð3. trial and the history of early knee synovitis in rheuma- 19. Cohen S, Jones R. An evaluation of the ef fi cacy of toid arthritis. Rheumatol Int. 1983;3:161Ð6. arthroscopic synovectomy of the knee in rheumatoid 38. Fowler RL, Berg E. Synovectomies in moderately to arthritis: 12Ð24 month results. J Rheumatol. 1987; severely involved rheumatoid knees: an alternative to 14:452Ð5. implant arthroplasty. South Med J. 1977;70(2):181Ð3. 20. Cleland LG, Treganza R, Dobson P. Arthroscopic 39. Barnes CG, Mason RM. Synovectomy of the knee synovectomy: a prospective study. J Rheumatol. joint in rheumatoid arthritis. Ann Phys Med. 1986;13:907Ð10. 1967;9(3):83Ð102. 21. Klein W, Jensen K. Arthroscopic synovectomy of the 40. Matsui N, Taneda Y, Ohta H, et al. Arthroscopic ver- knee joint: indication, technique and follow-up results. sus open synovectomy in the rheumatoid knee. Arthroscopy. 1988;4(2):63Ð71. International Orthopaedics (SICOT). 1989;13:17Ð20. 22. Doets HC, Bierman B, Soesbergen R. Synovectomy 41. Shibata T, Shiraoka K, Takubo N. Comparison of the rheumatoid-knee does not prevent deteriora- between arthroscopic and open synovectomy for the tion. 7-year follow-up of 83 cases. Acta Orthop Scand. knee in rheumatoid arthritis. Arch Orth Traum Surg. 1989;60(5):523Ð5. 1986;105:257Ð62. 23. Jensen CM, Poulsen S, Ostergren M, Hansen K. Early 42. Ogilvie-Harris D, Weisleder L. Arthroscopic syn- and late synovectomy of the knee in rheumatoid ovectomy of the knee: is it helpful? Arthroscopy. arthritis. Scand J Rheumatol. 1991;20:127Ð31. 1995;11:91Ð5. 24. Ranawat CS, Ecker ML, Straub LR. Synovectomy 43. Klug S, Wittman G, Weseloh G. Arthroscopic syn- and debridement of the knee in rheumatoid arthritis (a ovectomy of the knee joint in early cases of rheuma- 33 Knee Arthroscopy 359

toid arthritis: follow-up results of a multicenter study. 51. Cohen S, Jones R. An evaluation of the ef fi cacy of Arthroscopy. 2000;16:262Ð7. arthroscopic synovectomy of the knee in rheumatoid 44. Roch-Bras F, Daures J, Legouffe M, et al. Treatment of arthritis: 12Ð24 month results. J Rheumatol. 1987;13: chronic knee synovitis with arthroscopic synovectomy: 907Ð10. long term results. J Rheumatol. 2002;29:1171Ð5. 52. Latosiewicz R, Murawski J. Arthroscopic knee joint 45. Gibbons C, Gosal H, Bartlett J. Long term results of synovectomy in the treatment of early stages of rheu- arthroscopic synovectomy for seropositive rheuma- matoid arthritis. Roczniki Akudemii Medycznej W toid arthritis: 6-16 year review. International Bialymstoku. 1994;39:25Ð30. Orthopaedics (SICOT). 2002;26:98Ð100. 53. Dirienzo G, Osti L, Merlo F. Our experience in the 46. Smiley P, Wasilewski S. Arthroscopic synovectomy. treatment of rheumatoid knee by arthroscopic syn- Arthroscopy. 1990;6:18Ð23. ovectomy. Chir Organi Mov. 1997;82:275Ð8. 47. Murgo A, Paresce E, Fantini F. Arthroscopic synovec- 54. Hoppener MR, Ettema HB, Henny CP, Verheyen CC, tomy in chronic in fl ammatory rheumatism: clinical Büller HR. Low incidence of deep vein thrombosis and functional aspects. Reumatismo. 2003;55:39Ð44. after knee arthroscopy without thromboprophylaxis: a 48. Myllyla T, Peltonen L, Puranen J, et al. Consequences prospective cohort study of 335 patients. Acta Orthop. of synovectomy of the knee joint: clinical histopatho- 2006;77(5):767Ð71. logical and enzymatic changes and changes in 2 com- 55. Williams JS, Hulstyn MJ, Fadale PD, Lindy PB, ponents of complement. Ann Rheum Dis. Ehrlich MG, Cron J, Dorfman G. Incidence of deep 1983;42:28Ð35. vein thrombosis after arthroscopic knee surgery: a 49. Fiocco U, Cozzi L, Rigon C, et al. Arthroscopic syn- prospective study. Arthroscopy: The Journal of ovectomy in rheumatoid and psoriatic knee joint syn- Arthroscopic and Related Surgery. 1995;11(6): ovitis: Long term outcome. Br J Rheumatol. 701Ð5. 1996;35:463Ð70. 56. Ilahi OA, Reddy J, Ahmad I. Deep venous thrombosis 50. Ogilvie-Harris D, Basinski A. Arthroscopic synovec- after knee arthroscopy: a meta-analysis. Arthroscopy: tomy of the knee for rheumatoid arthritis. Arthroscopy. The Journal of Arthroscopic and Related Surgery. 1991;7:91Ð7. 2005;21(6):727Ð30. Surgery for Avascular Necrosis of the Femoral Head 3 4

Peter J. Brooks

Introduction Staging

Avascular necrosis (AVN) of the femoral head The natural history of AVN follows its radiological accounts for approximately 10% of reconstruc- features and dictates treatment options. Radiographic tive hip procedures [ 1 ] and is much less common fi ndings allow for staging. Multiple staging systems than osteoarthritis. However, since AVN often have been proposed, but the four-tier system of Ficat presents in younger, active, high-demand patients, and Arlet is often used [2 ] . Initially, following circu- the outcomes of reconstructive procedures such latory insult from any source, bone necrosis occurs as hip replacement are generally associated with and is accompanied by infl ammation and pain. In poorer outcomes. Failures due to loosening, wear, stage 1, plain radiographs are typically normal or component breakage, and other complications may show osteoporosis, but MRI reveals a necrotic have led surgeons to consider many other options segment and intraosseous edema. With time, patchy in the management of this dif fi cult condition. changes including areas of sclerosis may become Avascular necrosis has a large number of risk apparent on X-ray (stage 2). During stages 1 and 2, factors, both intrinsic to the individual and extrin- the femoral head remains round and may heal with- sic. Disease states such as lupus, sickle cell dis- out long-term sequelae. ease, and vasculitis predispose to AVN. Trauma More often, however, the condition pro- such as hip fracture or dislocation may damage gresses. A subchondral fracture delineating the the fragile blood supply of the femoral head. avascular region may appear on plain fi lms, Other common causes are excessive alcohol intake known as a “crescent sign.” A cartilage crack and steroid use, both associated with comorbidi- may accompany this, and joint fl uid may be seen ties. Steroid-associated AVN is often multifocal, to enter the fracture on MRI. Weight-bearing often involving the shoulder and knee, which may causes this region to fl atten and collapse to a complicate rehabilitation and crutch use. greater or lesser extent, accompanied by a marked increase in pain (stage 3). With time, secondary arthritic changes of the femoral head and acetabulum occur due to mechanical effects of a fl attened head in the socket, as well as joint space narrowing (stage 4). * P. J. Brooks , M.D., F.R.C.S(C) ( ) The results of hip arthroplasty in patients with Department of Orthopaedic Surgery , Cleveland Clinic , 9500 Euclid Avenue - A41 , Cleveland , OH 44195 , USA avascular necrosis are generally worse than for e-mail: [email protected] patients with osteoarthritis. This, together with

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 361 DOI 10.1007/978-1-4614-2203-7_34, © Springer Science+Business Media, LLC 2013 362 P. J. Brook s the fact that many patients with AVN are young, fl uoroscopic control. Once optimum position has suggests that joint replacement should be avoided been achieved, a cannulated drill is passed over if possible. Joint-preserving biologic procedures the guide pin, entering the defect. It is important are appropriate in the early stages 1 and 2, while not to penetrate the joint. the femoral head remains round. Stages 3 and 4 The pin and drill are then withdrawn. In many are associated with poorer results of biologic pro- cases, this completes the operation. Some sur- cedures, and a variety of prosthetic options are geons prefer to insert bone graft or demineralized available. bone matrix into the defect through the tunnel just created [ 4 ] . Others transfer a segment of the ipsilateral fi bula (Fig. 34.2a ) into the drill hole Biologic Procedures with microvascular anastomoses to add structure and blood supply [5 ] . Instead of joint replacement, many younger Core decompression is commonly performed patients may be considered candidates for bio- as an outpatient procedure. Patients are kept on logical procedures. These may attempt to heal the crutches with partial weight-bearing for six necrotic defect or to realign the upper femur in weeks, followed by gradual return to activities. such a way as to move the defect out of the Complications include subtrochanteric fracture weight-bearing part of the joint. through the drill hole, penetration of the joint, Core decompression (Fig. 34.1) has been and missing small defects altogether. Fibular advocated as a simple method to reintroduce transfers have the potential for donor site morbid- blood supply to the necrotic area of the femoral ity. The most common complication is failure of head [3 ] . This is thought to reduce intraosseous the procedure with progression of the disease into pressure, relieve pain, promote healing, and in stages 3 and 4, necessitating further surgery. some cases prevent the progression to fracture, Success is measured by pain relief and the collapse of the head, and joint replacement. This avoidance of further surgery. Even a partial reduc- would be an ideal outcome in a young individual tion from the natural history of AVN leading to whose cause of AVN has been eliminated. joint replacement makes core decompression an A guide wire is placed through the lateral fem- attractive option in selected younger patients with oral cortex and advanced into the defect under stage 1 or 2 disease.

Fig. 34.1 ( a ) A 40-year-old female with steroid-induced stage 2 avascular necrosis, treated with core decompression. The drill track is seen in (b ) 34 Surgery for Avascular Necrosis of the Femoral Head 363

Fig. 34.2 ( a) A 29-year-old male with idiopathic avascular necrosis. (a ) Prior treatment with free vascularized fi bular autograft and narrowing of the hip joint. (b ) Metal-on-metal hip resurfacing

Osteotomy for realignment of the femoral joint replacement, biologic procedures continue head is intended to move the necrotic defect out to have their place in the early stages of AVN. of the weight-bearing area. Rotational osteotomy through the intertrochanteric region was popular- ized in Japan [ 6 ] , yet the complexity of the proce- Joint Replacement dure and Western surgeons’ inability to replicate the Japanese results has hampered the adoption Partial or total hip replacement has been the of this osteotomy. mainstay of surgical treatment for advanced AVN Varus or valgus osteotomy, combined with of the femoral head. In most cases of stages 3 and fl exion or extension, may remove the defect from 4 AVN, and in cases of failed biologic proce- the weight-bearing area [7, 8 ] . However, progres- dures, prosthetic arthroplasty is the procedure of sion is frequent, and the bone deformity associ- choice. Unfortunately, since many patients with ated with the osteotomy makes future joint AVN are young and active, results of joint replacement more diffi cult. Femoral osteotomies replacement parallel those done for osteoarthritis take several months to heal, with prolonged phys- in young patients or are even worse. At present, ical therapy and use of crutches. Complications there is no ideal solution for young patients need- include infection, thrombophlebitis, and non- ing joint replacement, but signi fi cant progress union of the osteotomy. has been made in prosthesis design, fi xation, and The overall success rate of biologic proce- bearing options. dures is modest, particularly in larger lesions and Partial hip replacement, where only the femo- later stages of AVN. In the older or low-demand ral head is replaced, involves a stemmed unipolar individual, extensive efforts to try to preserve the or bipolar device articulating against the native joint should be tempered by the excellent results acetabulum. Over time, the cartilage of the acetab- offered by joint replacement. However, in the ulum may degrade and pain will result, necessitat- younger patient who is not an ideal candidate for ing conversion to a total hip replacement after 364 P. J. Brook s several years. For this reason, many surgeons pre- must be differentiated from infection. Loosening fer to proceed directly to a total hip replacement. tends to cause activity-related pain, especially at Cementless stems, with the potential for long- start-up, while infection is often painful at rest. term biological fi xation, have revolutionized the Sedimentation rate, C-reactive protein, and aspira- outcomes for younger patients and have replaced tion of the hip joint with cell count, differential, cemented fi xation as the “gold standard.” What and culture are useful studies. Revision surgery remains are concerns about the longevity of the may be quite complex and involve extensive graft- bearing materials. ing and specialized revision components. Polyethylene has a long history as an acetabu- Attempts to improve implant longevity by lar bearing material for hip replacement, with limiting wear have led to alternative bearings either a metal or a ceramic head. Advances in such as ceramic on ceramic and metal on metal. manufacturing processes, notably radiation- These “hard-on-hard” bearings release far fewer induced cross-linking [ 9 ] , have the promise of wear particles and are typically used in younger better wear properties. Cross-linking, though, patients such as those with AVN (Fig. 34.3 ). As while improving wear resistance, has adverse noted previously, however, there is no ideal solu- effects on material strength. Some liner breakage tion. Ceramic-on-ceramic bearings are brittle, so has been seen, especially at the periphery of the only a narrow range of implant sizes are avail- polyethylene liner, where it locks into the metal able. Chipping, cracking, and breakage of the acetabular shell. ceramic components may occur, and residual Polyethylene wear particles are biologically ceramic debris may cause rapid wear of a replace- active, and a cascade of infl ammatory mediators is ment bearing. Squeaking of ceramic-on-ceramic mobilized in conjunction with a macrophage hip replacements is reported in up to 14% of response. The result may be signifi cant osteolysis cases and may be intolerably loud [10 ] . of the femur and pelvis, with ultimate loosening Metal-on-metal total hip replacement is and the potential for fractures occurring even years another example of a hard bearing. Many sizing later. Loosening may become quite painful and options are available since these are essentially

Fig. 34.3 ( a ) A 55-year-old male with alcohol-induced stage 4 avascular necrosis. There is severe head collapse. Ceramic-on-ceramic cementless total hip replacement is shown in (b ) 34 Surgery for Avascular Necrosis of the Femoral Head 365 unbreakable. Very large head diameters avoid is necessary. Either procedure provides excellent dislocation, which is a common complaint fol- pain relief. lowing hip replacement. However, poor implant Outcomes from hip replacement and hip resur- design or poor surgical implantation may cause facing done for AVN are worse than those done excessive metal debris, which has been associ- for osteoarthritis. Many factors may account for ated with local tissue necrosis, infl ammation, and this difference, including the young age and solid or cystic “pseudotumors” [11 ] . increased activity level of many AVN patients, Complications of total hip replacement include and, in the case of hip resurfacing, the poor qual- infection, thrombophlebitis, dislocation, leg length ity of supporting bone. inequality, femoral fracture, component loosening, wear, osteolysis, and heterotopic ossi fi cation. Hip resurfacing [12 ] has seen a resurgence since Treatment Algorithm it was reintroduced as a metal-on-metal bearing (Fig. 34.2b). Indicated especially in younger For asymptomatic patients, observation is indi- patients, hip resurfacing removes very little bone cated, and surgical treatment should be avoided. from the proximal femur, a few millimeters as Symptomatic patients with stages 1 and 2 AVN opposed to several inches with hip replacement. A should be considered for core decompression thin metal cap covers the femoral head and articu- with or without adjunctive grafting, especially if lates with a metal acetabular component. As well the precipitating etiology such as steroids or as being bone-conserving, hip resurfacing offers alcohol has been eliminated. Osteotomy is now several other advantages. The normal diameter rarely recommended due to the lengthy healing femoral head almost completely eliminates the risk process and the diffi culties it may present for of dislocation. Loading of the proximal femur is later hip replacement. normal, so stress shielding with gradual bone loss In stages 3 and 4 AVN, with femoral head col- from the upper femur is avoided. Importantly for lapse and no acetabular involvement, partial or younger patients, revision on the femoral side is total hip replacement may be recommended. very easy, amounting to a simple total hip. This Where there is acetabular involvement due to avoids the long stems and bone grafting typical of secondary degenerative changes, total hip replace- revision of a total hip replacement. ment or hip resurfacing is indicated. Complications of hip resurfacing include fem- oral neck fracture in 1Ð3% of patients within the fi rst year, after which it is rare. For this reason, References crutches are used for several weeks, followed by a period of up to one year of restricted activity 1. Mankin HJ. Nontraumatic necrosis of bone (osteone- while the femoral neck remodels and strengthens. crosis). N Eng J Med. 1992;326:1473Ð9. As with metal-on-metal total hip replacement, 2. Ficat RP, Arlet J, Hungerford DS (eds). Necrosis of poor implant design or poor surgical technique the femoral head. In: Ischemia and necrosis of bone. Baltimore, MD: Williams and Wilkins; 1980. p. can lead to excessive metal debris, osteolysis, 53Ð74. and pseudotumors. 3. Hungerford DS. Core decompression for the treat- Hip resurfacing is only possible in cases of ment of avascular necrosis of the femoral head. Semin AVN which involve less than one-third to one- Arthroplasty. 1991;2:182Ð8. 4. Steinberg ME, Brighton CT, Corces A, et al. half of the femoral head. Healthy bone is needed Osteonecrosis of the femoral head: Results of core to support the resurfacing implant. Continuing decompression and grafting with or without electrical steroid use is a contraindication, as further bone stimulation. Clin Orthop. 1989;249:199Ð208. collapse will jeopardize fi xation. In many cases, 5. Urbaniak JR, Coogan PG, Gunneson EB, Nunley JA. Treatment of osteonecrosis of the femoral head with the necrotic bone is largely removed during free vascularized fi bular grafting: A long-term follow- femoral preparation for resurfacing, but in cases up study of one hundred and three hips. J Bone Joint of extensive AVN, a traditional hip replacement Surg. 1995;77A:681Ð94. 366 P. J. Brook s

6. Sugioka Y, Hotokebuchi T, Tsutsui H. Trans- the 49th Annual Meeting of the Orthopaedic trochanteric anterior rotational osteotomy for idio- Research Society. Rosemont, IL, Orthopaedic pathic and steroid-induced necrosis of the femoral Research Society 2003:1430 head: Indications and long-term results. Clin Orthop. 10. Jarrett CA, Ranawat AS, Bruzzone M, Blum YC, 1992;277:111Ð20. Rodriguez JA, Ranawat CS. The squeaking hip: a phe- 7. Mont MA, Fairbank AC, Krackow KA, Hungerford nomenon of ceramic-on-ceramic total hip arthroplasty. DS. Corrective osteotomy for osteonecrosis of the J Bone Joint Surg. 2009;91(6):1344Ð9. femoral head. J Bone Joint Surg. 1996;78A:1032Ð8. 11. Pandit H, Glyn-Jones S, McLardy-Smith P, et al. 8. Shannon BD, Trousdale RT. Femoral osteotomies for Pseudotumours associated with metal-on-metal hip avascular necrosis of the femoral head. Clin Orthop. resurfacings. J Bone Joint Surg. 2008;90B(7): 847Ð51. 2004;418:34Ð40. 12. Khan M, Kuiper J-H, Edwards D, Robinson E, 9. Digas G, Karrholm J. RSA evaluation of wear of Richardson JB. Birmingham hip arthroplasty: fi ve conventional versus cross-linked polyethylene to eight years of prospective multicentre results. acetabular components in vivo. In: Proceedings of J Arthroplasty. 2009;24(7):1044Ð50. Laparoscopic Splenectomy 3 5 R. Matthew Walsh

to 6.6% [ 1 ] . Owing to this success in children, Introduction nonoperative management has expanded to the treatment of splenic injury in the adult, where the Both the operative approach and indications for spleen is injured in roughly 50% of all injuries to splenectomy have changed markedly over the abdominal organs [2 ] . Not surprisingly, the more last two decades. It is an operation that re fl ects severely damaged the spleen, the higher the evolving management strategies and the intro- chance of failed nonoperative management. duction of minimally invasive surgery. The guid- Failure of nonoperative management will occur in ing principle in splenectomy is that the choice of up to 38% of the highest grade of injury, espe- operative technique, and in large measure the cially in association of blunt head trauma [ 3 ] . operative outcomes, is determined by the opera- Currently, traumatic injury is the indication for tive indication. It is important to frame the splenectomy in 16% of adults which has a reduc- discussion in this context since the indication for tion of 36% over 10 years [ 4 ] . splenectomy should heighten the concern for a The most typical indication for splenectomy variety of potential short- and long-term postop- in adults is coincident with another organ resec- erative morbidities. tion. The organs requiring resection that result in Blunt traumatic splenic injury had been the incidental splenectomy are the stomach, pan- most common indication of splenectomy for many creas, colon, adrenal, or kidney. This typically years. The advent of nonoperative management of occurs for malignant neoplasms in the primary splenic trauma has resulted in a marked reduction organ. Nonmalignant iatrogenic injury to the in splenectomy for that indication. Nonoperative spleen occurs most often during colectomy where treatment of splenic injury was initially employed a splenic laceration occurs from traction on the over 50 years ago in the pediatric population in lien colic ligament. Overall, splenectomy is most the hope of avoiding post-splenectomy sepsis. commonly performed for nonsplenic disease, Over the last half century, nonoperative manage- accounting for half of all splenectomies [ 5 ] . ment of splenic trauma has increased from 42% These two common indications for splenectomy, to 97% with improvement in splenic salvage to trauma, and incidental splenectomy are nearly nearly 99% and decrease in mortality from 19% always performed by the open procedure.

R. M. Walsh , M.D., F.A.C.S. () Department of General Surgery , Cleveland Clinic Foundation , 9500 Euclid Avenue – A100 , Cleveland , OH 44195 , USA e-mail: [email protected]

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 367 DOI 10.1007/978-1-4614-2203-7_35, © Springer Science+Business Media, LLC 2013 368 R.M. Walsh

A rheumatologic indication specifi c for Indications for Laparoscopic splenectomy is Felty’s syndrome. Felty described Splenectomy the association of arthritis with neutropenia and splenomegaly in 1924 [13 ] . Felty’s syndrome is Laparoscopic splenectomy (LS) is only per- now recognized to occur in less than 1% of formed in the elective circumstance and therefore patients with rheumatoid arthritis, typically in done for hematologic indications. Both benign patients with longstanding disease with severe and malignant hematologic diseases are amena- joint destruction. There is an increased frequency ble to the laparoscopic approach and account for of bacterial infections in some patients with a third of all patients requiring removal of the Felty’s syndrome; neutropenia is believed to be spleen. Laparoscopic splenectomy has rapidly the main cause of increased infection rate [ 14 ] . replaced the traditional open splenectomy in the The cause of neutropenia lies in both decreased elective setting [6 ] . granulopoiesis and increased peripheral destruc- Benign hematologic diseases predominate as tion of granulocytes. While spontaneous remis- the indication for LS, with idiopathic thrombocy- sions can occur, recurrent infections may lead to topenic purpura (ITP) being the single most com- increased mortality. The fi rst choice of treatment mon indication. It is a heterogeneous disease with in Felty’s syndrome with granulocytopenia and variable pathogenesis, severity, spontaneous increased rate of infection should be low-dose course, and response to treatment. Chronic ITP methotrexate [15 ] . Splenectomy is reserved for occurs in the adult and is insidious in onset and treatment-resistant patients and can result in an spontaneous remission is rare. Hemorrhage immediate improvement of neutropenia in 80%, represents the life-threatening risk of the disease, but the rate of infection decreases to a lesser with a relative mortality risk of 1.3 relative to the degree [16 ] . Roughly, 30% of patients have large general population [ 7 ] , and complications from granular lymphocyte expansion, and in these high-dose corticosteroids in refractory ITP repre- patients, splenectomy is contraindicated. sent another major indication for surgery. Despite Laparoscopic splenectomy is also indicated being a relatively common disease, there are no for patients with malignant hematologic disease, standardized indications or treatment regimen. both lymphoproliferative and myeloproliferative Commonly accepted indications for treatment are disease [17 ] . The indications for these patients patients with a platelet count of less than involve a combination of diagnostic and thera- 10 × 109 /L and those with a serious to moderate peutic reasons, particularly symptomatic spleno- bleeding tendency and a platelet count less than megaly and cytopenias. This topic is covered in 20 × 10 9 /L [ 8 ] . The standard initial therapy is cor- depth elsewhere [ 18 ] , but it is important to recog- ticosteroids, but the optimal dose and duration of nize that the majority of these patients present therapy is unknown, and some patients may be with splenomegaly which usually requires an over treated by aiming for complete remission altered operative approach and affects outcomes. [9 ] . In patients who do not have a sustained response to steroids, the most effective single therapy is splenectomy. Response to splenectomy Operative Preparation and Technique can be partially predicted by combining data on age, sex, and preoperative platelet count [10 ] . Some familiarity with the operation is essential in Recent pooled data based on 1,200 splenectomies understanding early postoperative morbidity. The for ITP indicate an immediate nonresponse rate most important preoperative preparation is the of 8.2% and an approximate failure rate of 28% administration of vaccines for encapsulated bacteria, at 5 years [ 11 ] . Other benign indications for LS a minimum of 2 weeks prior to surgery to ensure include hereditary spherocytosis, thalassemia, an optimal antibody response [19 ] . Vaccination for idiopathic autoimmune hemolytic anemia, sickle the encapsulated bacteria pneumococcus, hemo- cell disease, and splenic artery aneurysm [12 ] . philus in fl uenza B, and meningococcal C is advised. 35 Laparoscopic Splenectomy 369

The currently available polyvalent pneumococcal the surgeons left hand through a device that main- vaccine (PPV23 ) contains capsular polysaccharides tains pneumoperitoneum while the hand is intra- from the 23 serotypes responsible for 90% of the abdominal and retracting the spleen. This serotypes that cause invasive pneumococcal infec- technique allows better access to the hilum and tions. Re-immunization is recommended every 5 particularly assists with bagging the specimen. years. Both hemophilus in fl uenza B and meningo- coccal C conjugate vaccines are immunogenic and are recommended, but re-immunization is not Early Postoperative Morbidity required. Preoperative antibiotics, typically a fi rst- and Outcomes generation cephalosporin, are administered imme- diately prior to operation. Similar timing is Similar to other minimally invasive surgical pro- employed for administering “stress corticosteroids” cedures, compared to open splenectomy, patients in appropriate patients. undergoing LS benefi t from rapid advancement The technique of laparoscopic splenectomy of diet, reduced postoperative pain and analgesic was introduced in 1992, a few years after the requirements, a shorter postoperative stay, and adoption of laparoscopic cholecystectomy. improved cosmetic results. Although no prospec- Laparoscopic cholecystectomy was introduced tive, randomized, controlled trials comparing and largely remains a minimally invasive, but open to laparoscopic splenectomy have been basically unaltered, operative approach compared completed, or are ever likely to be done, to the open technique. Patients with a normal-sized retrospective, case-controlled series consistently spleen, as in ITP, are placed completely right favor the laparoscopic approach [ 21, 22] . The lateral and the table placed in an inverted “V” bene fi ts of LS for benign hematologic disease are shape to extend the distance between the costal well established resulting in shorter hospital stay margin and the anterior iliac crest. This simulta- (3.6 days vs. 7.2 days, p < 0.001) and overall neously allows access to the left upper quadrant fewer complications (15.5% vs. 26.6%, p < 0.0001) and manipulation of the spleen without grasping compared to open splenectomy [21 ] . The bene fi ts (read fracturing) the spleen, instead utilizing in malignant hematologic disease are less certain gravity to maneuver the organ. This altered posi- owing to the frequently associated splenomegaly tioning does change the visualization of the and attendant increased blood loss, overall organ and its relationship to adjacent organs, increased length of stay, and mortality from the namely, the stomach and pancreas. This altered underlying disease [ 18 ] . visualization must be learned and anticipated by There are particular early complications asso- the surgeon. A variety of laparoscopic energy ciated with LS that are important to recognize. devices such as the endoscopic shears are The fi rst relates to the chronic corticosteroid use employed to divide the attachments to the kid- in autoimmune conditions necessitating splenec- ney, stomach, diaphragm, and colon. The hilum tomy, such as ITP and hemolytic anemia. The is transected with a vascular-loaded endoscopic nonstandardized treatment of ITP with steroids stapler with care taken to avoid the pancreatic equally applies to the tapering regimen following tail. The spleen is then placed in an impermeable surgery. extraction bag and mechanically morcellated at Procedure-speci fi c complications begin with the largest trocar site. Although delivered to the patient positioning. Right-sided paresthesia, pain, pathologist in bits, it does not appear to effect and weakness consistent with a brachial plexus or their interpretation. peroneal nerve injury are a consequence of inad- The operation is modi fi ed further in the setting equate padding. Should these nerve injuries occur, of splenomegaly. Patients in whom the cranial- they are readily discernible by patient symptoms caudal length exceeds 22 cm are best approached and physical exam. They are best avoided by as a hand-assisted LS [ 20 ] . This involves placing careful attention to the position of axillary role the patient at 45° instead of 90° and placement of pillows beneath the legs and securing with tape. 370 R.M. Walsh

The importance of proper postponing of the para- that include subcutaneous octreotide, pan- lyzed anesthetized patient cannot be overstated. creatic stenting, and total parenteral nutrition. Should injury occur, some symptoms may persist Fortunately, most resolve and rarely require in one-third of the patients for a year. The most reoperation. Injuries to other organs such as the frequent and dreaded intraoperative complication stomach, diaphragm, and colon have been is bleeding, either from capsular tears or inade- reported, but are distinctly uncommon and thus quately controlled short gastric vessels or splenic unworthy of further discussion [ 23 ] . hilum vessels. This problem should be recognized Acute portosplenic venous thrombosis is an and resolved by the surgeon and is the most fre- increasingly recognized complication of LS. This quent cause of conversion to open laparotomy begins as a thrombus at the divided splenic hilum, [23 ] . Overall, conversion to open splenectomy which propagates along the long splenic vein occurs in 6% of patients, and it is more common remnant and may progress into the portal system. in patients with splenomegaly. The risk for con- The clinical consequence can be disastrous if it version can be altered by patient selection and results in thrombosis of the superior mesenteric can be predicted by body mass index and hemato- vein and complete venous infarction of the small logical malignancy. Inadequate hemostasis may intestine. The onset of ischemia is insidious be a consequence of cytopenias and marrow dys- compared to arterial infarction. Thus, symptoms function that persist in the postoperative period typically begin with vague periumbilical pain and require return to the operating room. Early that progresses over a variable time course to postoperative bleeding is also the most common symptoms of infarction. Infarction is identifi ed cause for reoperation. The need for reoperation is by persistent pain and localized tenderness while typically easy to discern but should be coordi- infarction with perforation demonstrates general- nated with available blood products based on the ized peritonitis. Prospective cohort studies reveal cytopenias. that the incidence of portal venous thrombosis A particularly feared complication is pancre- after splenectomy ranges from 5% to 37%, all atic injury which can occur at the time of hilar occurring within 2 months and the majority transaction. This pancreatic injury may result within 2 weeks of surgery [ 26, 27 ] . The variabil- from the anatomic relationship of the splenic ity in incidence is a re fl ection of how aggressively hilum to the pancreatic tail. The tail of the pan- patients are screened, but fortunately, the inci- creas lies within 1 cm of the splenic hilum in dence of bowel infarction is universally rare. 75% of patients and touches the splenic hilum in These thrombosis complications are compounded 30% of these patients [24 ] . The risk of pancre- by a hypercoaguable state that is exacerbated by atic injury appears to be more likely in the set- splenectomy due to a variety of factors [28 ] . ting of splenomegaly where there may be Underlying conditions which exacerbate this associated hilar lymphadenopathy and more state include splenomegaly and thalassemia, diffi cult to expose hilar vessels [ 25 ] . Should a which makes it reasonable to routinely screen pancreatic injury result in pancreatic duct dis- patients with these conditions at one week post- ruption, the consequence will be a subdiaphrag- operatively with mesenteric venous duplex. matic collection. Since most patients will be in The hematologic response to splenectomy is hospital less than 3 days, this collection will be partly determined by the indication. In patients clinically manifest following discharge, typi- operated for ITP, 60–75% of patients will increase cally with abdominal pain, respiratory symptoms, their platelet count to the normal range. Those or sepsis if it becomes infected. Symptomatic patients that respond to splenectomy will typi- post-splenectomy fl uid collections should cally obtain a normal platelet count by day 7. ideally be percutaneously drained and sampled Patients who have removal of a normal spleen for amylase and bacteria. An amylase-rich will demonstrate both leukocytosis and thrombo- collection may result in a pancreatic fi stula cytosis. In the immediate postoperative period, which can be subjected to a variety of strategies the platelet count rises steeply with a peak value 35 Laparoscopic Splenectomy 371 at 7–12 days and usually subsides over the next infections. To that end, the British Committee for 2–3 months. Leukocytosis occurs immediately Standards in Haematology has published guide- post-splenectomy in normal patients with a mean lines on how asplenic patients should be managed WBC count of 15 × 10 3 /uL which gradually [ 32] . These guidelines include recommendations returns to normal over 14 days. Patients who on vaccinations, prophylactic antibiotics, and demonstrate postoperative sepsis have mean patient education. A high measure of success for WBC counts over 20 × 103 /uL and a platelet count implementation has not been documented on any to WBC ratio less than 20. of these fronts. As many as 20–30% of patients are discharged without vaccinations [29, 33 ] . Preoperative vaccinations remain ideal since 20% Overwhelming Post-splenectomy of asplenic patients have a poor immunological Sepsis (OPSI) response to vaccines, with post-pneumococcal vac- cination antibody levels declining faster than in Splenectomized patients are at a signifi cant those patients with an intact spleen [34 ] . infection risk since the spleen is the largest accu- Additionally, recommended prophylactic antibiot- mulation of lymphoid tissue in the body. OPSI is ics (for minimum of 3 years) were not prescribed a serious fulminant process that carries a high in 50% of patients in the UK [ 33] . Lastly, patients mortality. The true incidence and outcome of are not educated about their asplenic status. From OPSI are diffi cult to determine due to poor 11% to 50% of splenectomized patients remain de fi nitions of the disease, variability of preopera- unaware of their increased risk for serious infec- tive vaccinations, and diverse management of tion or that health precautions should be under- af fl icted individuals. OPSI should be de fi ned as taken [ 35] . Ideally, patients should be given written documented septicemia and/or meningitis that is advice on immunizations and antibiotics and wear usually fulminant but not necessarily fatal [29 ] . a medical bracelet. These are intended to increase The lifetime risk of OPSI is reported to be 1–5% awareness of patients and their doctors, increase with an associated mortality of 40–70% [4, 29, compliance with prophylactic antibiotics, and 30] . Allowing for a more generous “severe infec- improve the speed and appropriateness of treat- tions requiring readmission following splenec- ment for OPSI. tomy,” defi nition conveys a lifelong risk of 7.0 per 100–person-years [5 ] . In the trauma popula- tion, there is no apparent increase in sepsis dur- References ing the immediate management of patients requiring splenectomy versus nonoperative treat- 1. Davies DA, Pearl RH, Ein RH, Langer JC, Wales PW. ment of splenic injury [ 2] . The risk of OPSI is Management of blunt splenic injury in children: evo- lution of the nonoperative approach. J Pediatr Surg. highest within the fi rst 2–3 years post-splenec- 2009;44(5):1005–8. tomy [30 ] . The clinical course of OPSI may rap- 2. Heuer M, Taeger G, Kaiser GM, et al. No further inci- idly progress to coma and death within 24–48 h dence of sepsis after splenectomy for severe trauma: a due to associated shock, acidosis, and dissemi- multi-institutional experience of the trauma registry of the DGU with 1,630 patients. Eur J Med Res. nated intravascular coagulation [ 31 ] . Nearly 90% 2010;15:258–65. of OPSI cases are due to Streptococcus pneumo- 3. Velmahos GC, Zacharias N, Emhoff TA, Feeney JM, niae with treatment geared towards antibiotics, Hurst JM, Crookes BA, Harrington DT, Gregg SC, intravenous immunoglobulin, vasopressors, and Brotman S, Burke PA, Davis KA, Gupta R, Winchell RJ, Desjardins S, Alouidor R, Gross RI, Rosenblatt MS, blood products as necessary [29– 31 ] . Splenectomy Schulz JT, Chang Y. Management of the most severely performed for hematologic disorder has a higher injured spleen: a multicenter study of the Research risk for OPSI, with the highest risk being in older Consortium of New England Centers for Trauma patients operated for hematologic malignancy. (ReCONECT). Arch Surg. 2010;145(5): 456–60. 4. At R, Newman MI, Debelak J, et al. The incidence of A concerted effort has been made to raise patient splenectomy is decreasing: lessons learned from and physician awareness of post-splenectomy trauma experience. Am Surg. 2000;66(5):481–6. 372 R.M. Walsh

5. Kyaw MH, Holmes EM, Toolis F, et al. Evaluation of 21. Er W, Brunt LM. Perioperative outcomes of laparo- severe infection and survival after splenectomy. Am J scopic versus open splenectomy: a meta-analysis with Med. 2006;119(3):276 e1–7. an emphasis on complications. Surgery. 6. Walsh RM, Heniford BT, Brody F, Ponsky J. The 2003;134(4):647–53. ascendance of laparoscopic splenectomy. Am Surg. 22. Brunt LM, Langer JC, Quasebarth MA, Whitman ED. 2001;67(1):48–53. Comparative analysis of laparoscopic versus open 7. Portielje JE, Westendorp RG, Kluin-Nelemans HC, splenectomy. Am J Surg. 1996;172(5):596–9. Brand A. Morbidity and mortality in adults with idio- 23. Vecchio R, Gelardi V, Intagliata E, Barbaros U, pathic thrombocytopenic purpura. Blood. 2001;97(9): Cacciola RR, Cacciola E. How to prevent intraopera- 2549–54. tive risks and complications in laparoscopic splenec- 8. Lechner K. Management of adult immune thrombocy- tomy. G Chir. 2010;31(1–2):55–61. topenia. Rev Clinic Exp Hematol. 2001;5(3): 222–35. 24. Baronofsky ID, Walton W, Noble JF. Occult injury to 9. Chouhan JD, Herrington JD. Treatment options for the pancreas following splenectomy. Surgery. chronic refractory idiopathic thrombocytopenic pur- 1951;29(6):852–7. pura in adults: focus on romiplostim and eltrombopag. 25. Chand B, Brody F, Walsh RM, Ponsky J. Pancreatic Pharmacotherapy. 2010;30(7):666–83. complications following laparoscopic splenectomy. 10. Duperier T, Brody F, Felsher J, Walsh RM, Rosen M, Surg Endosc. 2001;15(11):1273–6. Ponsky J. Predictive factors for successful laparo- 26. Ikeda M, Sekimoto M, Takiguchi S, et al. High inci- scopic splenectomy in patients with immune throm- dence of thrombosis of the portal venous system after bocytopenic purpura. Arch Surg. 2004;139(1):61–6. laparoscopic splenectomy: a prospective study with 11. Mikhael J, Northridge K, Lindquist K, Kessler C, contrast-enhanced CT Scan. Ann Surg. Deuson R, Danese M. Short-term and long-term fail- 2005;241(2):208–16. ure of laparoscopic splenectomy in adult immune 27. Romano F, Caprotti R, Scaini A, et al. Elective laparo- thrombocytopenic purpura patients: a systemic review. scopic splenectomy and thrombosis of the spleno- Am J Hematol. 2009;84(11):743–8. portal axis: a prospective study with ecocolordoppler 12. Sharma D, Shukla VK. Laparoscopic Splenectomy: ultrasound. Surg Laparosc Endosc Percutan Tech. 16 Years since Delaitre with review of current litera- 2006;16(1):4–7. ture. Surg Laparosc Endosc Percutan Tech. 28. Crary SE, Buchanan GR. Vascular complications after 2009;19(3):190–4. splenectomy for hematologic disorders. Blood. 13. Felty AR. Chronic arthritis in the adult associated 2009;114(14):2861–8. with splenomegaly and leucopenia. Bull Johns 29. Waghorn DJ. Overwhelming infection in asplenic Hopkins Hosp. 1924;35:16–20. patients: current best practice preventive measures are 14. Campion G, Maddison PJ, Goulding N, James I, not being followed. J Clin Pathol. 2001;54:214–8. Ahern MJ, Watt I, Sansom D. The Felty syndrome: a 30. Davidson RN, Wall RA. Prevention and management case-matched study of clinical manifestations and of infections in patients without a spleen. Clin outcome, serologic features, and immunogenetic Microbiol Infect. 2001;7:657–60. associations. Medicine. 1990;69(2):69–80. 31. Okabayashi T, Hanazaki K. Overwhelming postsple- 15. Rashba EJ, Rowe JM, Packman CH. Treatment of the nectomy infection syndrome in adults – A clinically neutropenia of Felty syndrome. Blood Rev. preventable disease. World J Gastroenterol. 2008; 1996;10(3):177–84. 14(2):176–9. 16. Balint GP, Balint PV. Felty’s syndrome. Best Pract 32. Davies JM, Barnes R, Milligan D. Update of guide- Res Clin Rheumatol. 2004;18(5):631–45. lines for the prevention and treatment of infection in 17. Walsh RM, Brody F, Brown N. Laparoscopic splenec- patients with an absent or dysfunctional spleen. Clin tomy for lymphoproliferative disease. Surg Endosc. Med. 2002;2(5):440–3. 2004;18(2):272–5. 33. O’Donnell J, McGreal G, Daly P, et al. Management 18. Walsh RM, Heniford BT. Laparoscopic Splenectomy of patients undergoing splenectomy in an Irish teach- for Malignant Diseases. In: Greene EL, Heniford BT, ing hospital: impact of guidelines. Ir J Med Sci. editors. Minimally invasive cancer management. New 2004;173(3):136–40. York, NY: Springer; 2001. p. 241–53. 34. Hazlewood M, Kumararatne DS. The spleen? Who 19. Harji DP, Jaunoo SS, Mistry P, Nesargikar PN. needs it anyway? Clin Exp Immunol. 1992;89(3): Immunoprophylaxis in asplenic patients. Int J Surg. 327–9. 2009;7(5):421–3. 35. White KS, Covington D, Churchill P, Maxwell JG, 20. Kercher K, Matthews B, Walsh R, Sing R, Backus C, Norman KS, Clancy TV. Patient awareness of health Heniford BT. Laparoscopic splenectomy for massive precautions after splenectomy. Am J Inect Control. splenomegaly. Am J Surg. 2002;183(2):192–6. 1991;19(1):36–41. Lung Biopsy 3 6 Sudish C. Murthy

Despite continued advances in histochemical and to antibiotics. Of increasing importance is the use molecular diagnostics, as well as improving nonin- of navigation systems (e.g., electromagnetism) to vasive imaging techniques, lung biopsy still remains guide bronchoscope direction toward small lesions, an important diagnostic intervention for patients thereby greatly improving diagnostic yields and with pulmonary disease. Common indications reducing the number of failed bronchoscopies [ 2 ] . include solitary pulmonary nodule (SPN), focal Bronchoscopy is performed in the outpatient indeterminate in fi ltrate, and diffuse disease, partic- setting with conscious sedation. Preoperative ularly in the setting of a systemic disease of unclear assessment includes a clear indication for the pro- etiology. In each of these instances, malignant, cedure and normal coagulation profi le, though infectious, and in fl ammatory causes populate the thrombocytopenia is not an absolute contraindica- differential diagnostic list and must be separated. tion [ 3] . Neutropenia is not a contraindication for Three different approaches are used for tissue bronchoscopy, however [ 4 ] . Clopidogrel should acquisition, each with clear indications and be stopped, particularly when used in combina- contraindications. Bronchoscopy is often the fi rst tion with aspirin, 5Ð7 days before bronchoscopy invasive intervention employed. For certain dis- as a signifi cantly increased risk of bleeding has seminated diseases (e.g., sarcoidosis), TBBx is been reported [5 ] . Moreover, prior to recommend- surprisingly effective. Bronchoscopy with bron- ing lung biopsy, full appreciation of any underly- choalveolar lavage (BAL) or endoscopic ultrasound ing systemic illness is critical, as interstitial lung and transbronchial needle aspiration (EBUS- disease in a patient with scleroderma might favor TBNA) have diagnostic yields approaching 90% secondary lung involvement from silent re fl ux and for sarcoidosis when used together [ 1 ] . The BAL not necessarily a primary pulmonary process. allows for CD4:CD8 ratio assessment, and EBUS- Other contraindications include known bleeding TBNA can target suspicious lesions and uncover diathesis, pulmonary hypertension, and failed prior nonnecrotizing granulomatous disease and infec- bronchoscopy attempts (usually two). In addition, tious processes. In addition, this combination of TBNA is seldom performed in patients on mechan- bronchoscopic techniques is frequently employed ical ventilatory support. Important complications to confi rm lymphangitic pulmonary cancers and include pneumothorax and hemoptysis, both of assess curious infi ltrates that have failed to respond which occur infrequently, but with signi fi cant impact. Perhaps most importantly, transbronchial S. C. Murthy , M.D., Ph.D. () biopsy is rarely effective in establishing a de fi nitive Center of Major Airway Disease, Department diagnosis of pulmonary vasculitides [ 6 ] . of Thoracic and Cardiovascular Surgery , Cleveland Clinic Surgical lung biopsy is most often reserved Foundation , 9500 Euclid Avenue - J4-1 , Cleveland , OH 44195 , USA for failure of bronchoscopy. This is clearly a e-mail: [email protected] more invasive procedure, but delivers several

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 373 DOI 10.1007/978-1-4614-2203-7_36, © Springer Science+Business Media, LLC 2013 374 S.C. Murthy

orders-of-magnitude more tissue for pathologic assessment, immunohistochemical characteriza- tion, and microbiologic culturing. Unclear focal in fi ltrates demonstrating chronic in fl ammation on TBNA might better demonstrate subtle vascu- litis/capillaritis with more tissue sampled. Architecture of lung is far better appreciated on surgical lung biopsy specimens and tissue-inva- sive processes more easily diagnosed. Moreover, peripheral parenchymal processes are not easily accessible bronchoscopically for fear of pneu- mothorax and frequently can only be interrogated surgically. Surgical lung biopsy is the diagnostic of choice for intensive care unit patients in acute respiratory failure with interstitial lung disease and negative BAL [7 ] . Surgical lung biopsy can be performed using open or video-assisted thoracic surgery (VATs) techniques. The goal of either is the same, pro- curement of lesional tissue. VATs biopsy is gener- ally performed in the more elective setting, before signi fi cant respiratory insuf fi ciency has developed. This approach mandates that patients have enough pulmonary reserve to tolerate single-lung ventila- Fig. 36.1 Diagram depicting approach for a VATS tion without developing hypercarbia/hypoxemia procedure during the operation. For VATs operations, three 10Ð15 mm thoracoports are placed on the thorax

(Fig. 36.1 ), and for patients with diffuse lung disease, 2Ð3 random lung biopsies are taken from different lobes. This allows the pathologist to understand the progression of disease and helps to more accurately de fi ne the disease process. A pre- operative chest CT scan will be useful in planning which side to biopsy in an attempt to increase the yield of the procedure (Fig. 36.2 ). VATs excisional lung biopsies are particularly useful for SPN of indeterminate nature. The typi- cal clinical scenario is an SPN identi fi ed in a patient with a moderate tobacco-use history that proves to be of intermediated avidity on positron emission tomography (PET) scan. The differen- Fig. 36.2 Chest CT demonstrating interstitial lung dis- ease with left-side predominance in a patient with sclero- tial includes non-small cell lung cancer or metas- derma and end-stage esophagus tasis, sarcoidosis, localized fungal infection (histoplasma, blastomycosis, etc.), noninfectious granulomatous disease (e.g., Wegener’s, rheuma- Open lung biopsy refers to a procedure per- toid nodule), tuberculosis, as well as a number of formed through a thoracotomy (usually truncated benign entities [ 8 ] (Fig. 36.3 ). Limited wedge to 8Ð10 cm). This procedure is employed in the resection can be performed for both diagnostic ICU setting, particularly in patients with acute and therapeutic intent for SPN. respiratory distress syndrome (ARDS) [ 7 ] . The 36 Lung Biopsy 375

Fig. 36.3 ( a ) Chest CT of a patient with SPN suspicious for lung cancer. ( b ) VATS resected nodule from (a ) was a Wegener’s nodule critical illness of the patient, and often protracted excessive surface tension at the biopsy site (staple mechanical ventilatory requirement, will not per- line), and some will remain on positive pressure mit single-lung ventilation for VATS and occa- ventilation for several days after their procedure sionally mandates that the procedure be done in because of their respiratory failure, magnifying the ICU itself. For diffuse disease, the tip of the stress on the biopsy site(s). In addition, some lingular can be relatively easily resection through patients will have underlying wound-healing prob- a left anterolateral mini-thoracotomy. Transient lems because of chronic steroid use, neutropenia, intermittent apnea is used to brie fl y collapse the or malnutrition. All of these factors can conspire to ipsilateral lung and allow for safer biopsy. perpetuate air leak. Accordingly, chest tubes are Advanced illness, as well as the postoperative left in place until air leak is undetectable (1 or mechanical ventilator requirement and risk of 2 days for elective biopsies), and patients are dis- ventilator-associated pneumonia, clearly makes charged shortly thereafter. The consequences of a this a risky undertaking. protracted air leak can be formidable and include In the elective setting, preoperative assess- increased hospital stay, delay in therapy, empyema, ment of patients for surgical lung biopsy includes and rarely, reoperation. thorough radiographic imaging that is current Because the differential diagnosis list is so and, depending on age and vitality, often a com- large for patients requiring lung biopsy, treatment plete workup for occult cardiopulmonary disease. for a suspected in fl ammatory/rheumatologic pro- Pulmonary function testing suggesting severe cess may be delayed for a few weeks to allow for restrictive lung disease and rapid desaturation an infectious process, particularly tuberculosis or with exercise might favor open over VATs biopsy other indolent infection, to be ruled out. This because of the anticipated diffi culty of tolerance interval does permit more complete recovery for single-lung ventilation. Extensive pleural dis- prior to institution of high-dose steroids or other ease noted on the chest CT might similarly favor immunosuppressants that might be indicated an open procedure as ipsilateral lung collapse based on the biopsy results, but should circum- might not be technically possible because of stances dictate, appropriate medical therapy can adhesions. be instituted immediately, including glucocorti- The most common complication of surgical coids. Delayed pneumothorax in this setting lung biopsy is protracted air leak from the biopsy (>1 week postdischarge) can occur and mandates site. This occurs because many patients requiring chest X-ray follow up out to 12 weeks. biopsy have interstitial lung disease and relatively All elective patients should be seen in the noncompliant lungs. The standard wedge resection outpatient clinic, with CXR obtained at one week for tissue procurement (whether performed open postoperatively. It is not uncommon to observe a or with VATS) is nonanatomic and can create small residual space on the postoperative CXR, 376 S.C. Murthy and unless this is enlarging on serial examina- 3. Kim YH, Suh GY, Kim MH, et al. Safety and usefulness tions, no intervention is necessary. Otherwise, of bronchoscopy in ventilator-dependent patients with severe thrombocytopenia. Anaesth Intensive Care. healthy patients undergoing VATs for in fl am- 2008;36(3):411Ð7. matory nodule diagnosis should be able to 4. Peikert T, Rana S, Edell ES. Safety, diagnostic yield, resume a normal schedule of activities within and therapeutic implications of fl exible bronchoscopy 2Ð3 weeks. There is an extremely low, but not in patients with febrile neutropenia and pulmonary in fi ltrates. Mayo Clin Proc. 2005;80(11):1414Ð20. insignifi cant, mortality associated with surgical 5. Ernst A, Eberhardt R, Wahidi M, Becker HD, Herth FJ. lung biopsy. This, however, is far more likely Effect of routine clopidogrel use on bleeding complica- attributable to the indication for biopsy than to tions after transbronchial biopsy in humans. Chest. the procedure itself. 2006;129(3):734Ð7. 6. Schnabel A, Holl-Ulrich K, Dalhoff K, Reuter M, Gross WL. Ef fi cacy of transbronchial biopsy in pul- monary vaculitides. Eur Respir J. 1997;10(12): References 2738Ð43. 7. Papazian L, Doddoli C, Chetaille B, et al. A contribu- 1. Costabel U, Bonella F, Ohshimo S, et al. Diagnostic tive result of open-lung biopsy improves survival in modalities in sarcoidosis: BAL, EBUS, and PET. acute respiratory distress syndrome patients. Critical Semin Respir Crit Care Med. 2010;31(4):404Ð8. Epub Care Medicine. 2007;35(3):755Ð62. 2010 Jul 27. 8. Murthy SC, Rice TW. The solitary pulmonary nodule: 2. Yarmus L, Feller-Kopman D. Bronchoscopes of the a primer on differential diagnosis. Semin Thorac twenty- fi rst century. Clin Chest Med. 2010;31(1):19Ð27. Cardiovasc Surg. 2002;14(3):239Ð49. Review. Renal Transplantation 3 7 David A. Goldfarb and Natarajan Sezhian

Introduction (0.4%), HSP is 53 (0.06%), and polyarteritis is 32 (0.04%) [4 ] . Therefore, transplantation for such Systemic autoimmune disease causes kidney diseases is a relatively uncommon occurrence rep- injury that may result in irreversible renal failure, resenting only 4% of the kidney wait list. requiring renal replacement therapy [2 ] . Renal transplantation continues to be the best treatment option for most patients with end-stage renal dis- ease (ESRD). Transplantation offers improved life Recipient Evaluation expectancy and quality of life compared to dialy- sis. The most commonly observed systemic vascu- The evaluation begins with the early nephrology litides referred for a renal transplant evaluation are referral of patients diagnosed with progressive systemic lupus erythematosis (SLE), Wegener’s chronic kidney disease (CKD). Early referral granulomatosis (WG), and Henoch-Schönlein ensures better preparation for dialysis and subse- purpura (HSP). Not all patients who develop renal quent transplantation [1 ] . The transplant evalua- involvement in systemic vasculitis will progress to tion process involves patient education, informed ESRD because of the availability of potent immu- consent, detailed history, and physical examina- nosuppressive therapy. For example, only 10–15% tion along with appropriate laboratory and radio- of patients with SLE develop ESRD, and 20% of graphic studies. patients with anti-neutrophilic cytoplasmic anti- Patients should have favorable general health body–associated vasculitis (AAV) will develop and functional status to be a renal transplantation ESRD. There are 87,387 candidates on the national candidate. Assessment addresses not only the can- renal transplant wait list. The number of wait list didate’s tolerance of surgery but also to address the patients with SLE is 2,526 (2.9%), WG is 321 patient’s short- and long-term survival following transplantation. Major pulmonary, neurologic, vas- D. A. Goldfarb , M.D. cular problems or other comorbidities may pre- Renal Transplantation Program, Glickman Urological clude safe transplantation. In particular, attention and Kidney Institute, Department of Urology , Cleveland should be paid to cardiovascular assessment Clinic Foundation , 9500 Euclid Avenue - Q10-1, because this is a major source of morbidity and Cleveland , OH 44195 , USA e-mail: [email protected] mortality posttransplant. SLE patients are predis- posed to atherosclerotic complications, so screen- N. Sezhian , M.B.B.S., F.R.C.S (Urol) () Glickman Urological and Kidney Institute , ing with stress testing, echocardiography, Duplex Cleveland Clinic Foundation , 9500 Euclid Avenue , ultrasound evaluation of carotid, or peripheral Cleveland , OH 44195 , USA vascular disease may be indicated. Major cardio-

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 377 DOI 10.1007/978-1-4614-2203-7_37, © Springer Science+Business Media, LLC 2013 378 D.A. Goldfarb and N. Sezhian vascular comorbidities need to be optimized pre- related and the interval to development of cancer transplant to ensure good outcomes. Hypertension may be a decade or more. For those patients who and hyperlipidemia should also be optimized. have received large doses of cyclophosphamide, In general, there should be inactivity of clini- screening for urothelial cancer with fl exible cys- cal disease in systemic vasculitis patients at the toscopy, renal imaging, and urine cytology can be time of renal transplantation in order to prevent performed. recurrent disease in the new graft [ 7– 9 ] . Patients with SLE should be free of extra renal manifesta- tions and require only low doses of prednisone Timing of Transplantation (no more than 10 mg) to maintain quiescence, and Potential for Recurrence before transplantation. The determination of dis- ease inactivity should be made by the nephrolo- The timing of transplantation depends on the gist in consultation with a rheumatologist. nature of the disease. Transplantation is often post- Adjunctive use of serum markers such as comple- poned after initiation of dialysis to allow for poten- ment components (C3, C4) and anti-dsDNA have tial renal recovery and permit disease quiescence. been used to assess activity of renal disease. Many will have quiescent disease by the time they Some form of antiphospholipid antibodies reach ESRD, but some may have a rapid course (APLA) is present in 25–75% of SLE patients; and requiring more intensive treatment as they however, most do not experience thrombotic dis- approach ESRD. It is important that the disease be ease. Patients with SLE can be screened for inactive at the time of transplant to prevent early hypercoagulability due to the presence of recurrence in the new graft. In contemporary prac- antiphospholipid antibodies (APLA) especially if tice, the recurrence of the lupus nephritis after there is a history of thrombotic disease such as transplantation is low, about 3–10%. stroke, DVT, or recurrent vascular access throm- Transplantation in anti-neutrophilic cytoplas- bosis. This may impact the need for perioperative mic antibodies (ANCA)–associated vasculitis anticoagulation management. (AAV) should also be deferred until clinical man- Lastly, SLE patients may experience problems ifestations of the disease are quiescent [5, 6 ] . The with immunological assessment owing to the time on dialysis following clinical remission does presence of auto antibodies that interfere with not alter recurrence. While it is ideal to have a cross match results. These may cause a “false- negative ANCA prior to transplant, detectable positive cross match.” Tissue-typing laboratories ANCA does not preclude successful renal trans- can perform an auto–cross match to determine plantation and does not predict risk of recurrence. the presence of such interfering antibodies. The When present, ANCA should be monitored. A presence of autoantibodies does not infl uence the posttransplant recurrence rate of up to 20% by outcome of a transplant. 3 years has been noted in AAV. The recurrence The prior exposure to immunosuppression can vary in its severity and organ involvement. It should be assessed for these patients. The risk is unclear whether any specifi c immunosuppres- of posttransplant opportunistic infection and sive regimen may be more valuable in AAV. lymphoma is increased in patients who were Recurrent disease can be treated with cyclophos- immunosuppressed during the course of their phamide or rituximab. native kidney disease. The absence of infec- tion is a prerequisite for transplantation and should be screened. Assessment for exposures Anesthetic Considerations to hepatitis, cytomegalovirus, and HIV is mandatory. There should be no active chronic Patients, who are on dialysis, need optimization fungal infections. of their volume status and serum electrolyte lev- Patients who have had prior exposure to cyclo- els immediately prior to transplant. Patients phosphamide are at risk for the development of coming to surgery should have a potassium urothelial cancer of the bladder. This is dose <5.5 meq/L. 37 Renal Transplantation 379

In patients with an AV fi stula for dialysis intravenous heparin bridging to warfarin. If renal access, care should be taken to protect it with a function is normalized posttransplant, then low- towel or blanket to prevent pressure injury during molecular heparin like enoxaparin can be used as surgery resulting in fi stula thrombosis. Dialysis a bridge to warfarin and the entire anticoagulation access is important and may be needed to manage process may occur in the outpatient setting. delayed graft function, antibody-mediated rejec- tion, or early disease recurrence in the early post- operative period. Intraoperative attention to Transplantation Procedure favorable volume status is critical for the perfu- sion of the transplanted kidney. The CVP is main- The kidney allograft occupies the retroperitoneal tained at 12–15 mm Hg, and mean arterial space in the iliac fossa [3 ] . The iliac vessels are pressure is maintained above 70 mm Hg to opti- exposed through a lower quadrant Gibson inci- mized renal function at reperfusion. sion extending from the midline to above the Uremic patients have poor platelet function, and anterior-superior iliac spine. The peritoneum is patients can have signi fi cant bleeding during the rolled medially to enter the retroperitoneal space surgery. On rare occasions, DDAVP may be needed. and expose the iliac blood vessels. The renal Frequent monitoring of hemoglobin is essential, artery is usually anastomosed end to side to the and blood transfusion if required can be given. The common or external iliac artery. The internal iliac target hematocrit should be at least 20–25%. artery may also be used for the anastomosis. It is less frequently used due to atherosclerosis. It is maintained in men to preserve erectile function. Thrombotic Risk The renal vein is anastomosed end to side to the recipient external or common iliac vein. In 20% Renal transplantation would be considered moder- of the cases, there may be multiple renal arteries. ate to high risk for DVT. Perioperative use of anti- This may require more than one arterial anasto- embolic stockings is mandatory to reduce the risk mosis to the recipient vessels or back table vessel of DVT. The APLA present in patients with SLE reconstruction. Note that smaller caliber arteries increases the risk of perioperative thromboembo- may be more prone to thrombosis. Delicate and lic events [ 9 ] . Patients with APLA and a history of meticulous tissue handling is critical. A favorable thromboembolic complications need to be geometric fi nal positioning of the kidney and its identifi ed and are candidates for systemic intrave- vasculature are important to prevent vascular nous heparin prophylaxis during surgery at the thrombosis. time of vascular anastomosis. Continued prophy- The ureter is anastomosed to the bladder extra- laxis postoperatively with subcutaneous heparin peritoneally, with or without detrusor tunnel to should be used in such patients. The decision to prevent urine re fl ux. At the discretion of the sur- initiate long-term anticoagulation with intrave- geon, a ureteric stent may be placed in the ureter. nous heparin and warfarin is individualized, tak- This may help reduce complications when faced ing into account the presence of APLA, a history with questionable tissue quality. A drain is usu- of thrombotic events, the unique anatomic circum- ally placed at the completion of the surgery, to stances related to the transplant operation, and the reduce the incidence of postoperative fl uid potential for bleeding complications. Very early collections. introduction (<1 week) of full-dose anticoagula- tion with systemic heparin can result in major hemorrhagic surgical complications. The risks of Bleeding anticoagulation must be weighed against the risks of thrombosis on a case-by-case basis to determine Renal failure patients are at risk for postoperative the optimal timing for the initiation of systemic bleeding due to defective platelet function and anticoagulation. This is usually done with the use of anticoagulation or aspirin. Postoperative 380 D.A. Goldfarb and N. Sezhian bleeding that results in hemodynamic instability living donation. DGF is managed by dialysis may warrants reoperation for decompression and con- last days or weeks. trol of bleeding points.

Postoperative Collections Vascular Complications A perinephric fl uid collection occurs in 5–20% of Thrombosis of the renal artery or the renal vein the patients. In the immediate postoperative can occur early on in the postoperative period and period, the collection is likely to be hematoma. result in a high rate of graft loss. The incidence of Most of the hematomas are small and resolves renal artery thrombosis is low, about 0.5–3%. spontaneously .Occasionally, they can be large, The risk factors include signifi cant atheroscle- and a procedure to control the bleeding may be rotic disease of the donor or the recipient vessels required. Late appearing collections (beyond and preexisting recipient prothrombotic disorders. 2 weeks) are usually a lymphocele. This is a Patients with SLE are uniquely predisposed due collection of lymph fl uid from severed lymphat- to the presence of APLA. Thrombosis is identi fi ed ics during recipient vessel mobilization or from by a sudden and profound drop in urine output. the transplant kidney. Large lymphoceles can Doppler ultrasound (US) can be used to assess cause symptoms secondary to pressure effects the allograft vasculature. Thrombosis is confi rmed resulting in ureteral obstruction, ipsilateral by the absence of fl ow to the kidney. Doppler US peripheral limb edema, and deep vein thrombo- can help differentiate arterial versus venous sis. Large lymphoceles are treated surgically with thrombosis. Surgical exploration with thrombec- laparoscopic or open marsupialization into the tomy and reanastomosis may be required for peritoneal cavity. Percutaneous drainage with arterial thrombosis; however, the graft is lost in placement of a drain or injection of sclerosants or most cases. After 30 min, warm ischemia per- fi brin glue into the cavity is another option. These manent renal damage follows. Thrombosis of carry a higher rate of lymphocele recurrence. the renal vein also occurs in the early postopera- tive period from kinking of the renal vein, hypercoagulable state, persistent hypotension, Urine Leaks acute rejection, or profound ischemia/reperfusion injury. Thrombolytic therapy or thrombectomy Urine leak can occur in 3–8% of the patients. with revision of anastomosis can be attempted; These are usually caused by poor tissue quality of however, there is a high rate of graft loss similar the recipient bladder or the donor ureter. The to arterial thrombosis. transplant ureter receives its blood supply from the renal artery especially lower polar artery when present. Any damage to the blood supply during Delayed Graft Function procurement can result in distal ureteric ischemia. The other risk factor includes poor recipient blad- Delayed graft function (DGF) refers to acute kid- der tissue. The symptoms of a urine leak include ney injury (AKI) in the freshly transplanted increased drain output and also increasing serum allograft. Typically, this is in association with the creatinine. The drain fl uid creatinine is typically need for dialysis in the fi rst week. This is clini- elevated compared to serum. Imaging studies like cally manifest by oligo-anuria and failure to see CT cystogram or renal scan can con fi rm the clini- any improvement in renal function. Technical cal suspicion. Small leaks can be managed con- complications should be ruled out by either servatively with prolonged Foley catheter. Some Doppler US or renal scan. DGF is due to isch- leaks may respond to proximal diversion with emia reperfusion injury. The incidence is 20–30% nephrostomy drainage. Signi fi cant leaks associ- with deceased donor transplantation and 5% with ated with symptoms warrant surgical correction 37 Renal Transplantation 381 with revision of ureteric anastomosis. If the ureter is nonviable, the native ureter can be anastomosed Posttransplant Immunosuppression to the transplant kidney. Immunosuppression is usually administered as a regimen, the combination of several drugs [5 ] . Ureteral Obstruction Most centers in USA use induction immunother- apy with either IL2 receptor antagonist such as The incidence of obstruction is 2–3%. In the early basiliximab or lymphocyte-depleting antibodies period following surgery, the cause is likely to be like antithymocytic globulin or alemtuzumab. extrinsic obstruction caused by fl uid collections These are used to prevent early rejection and per- such as lymphocele which has been discussed. mit delayed introduction of calcineurin inhibitor Late posttransplant (>4 weeks) obstruction is drugs (preventing early nephrotoxicity in a recov- usually due to ureteral stricture. These are caused ering kidney). Maintenance immunosuppression by ischemia with resulting scar or BK virus typically consists of three drugs: a calcineurin infection. A rare case of recurrent granulomatous inhibitor (CNI), an antiproliferative (mycopheno- obstruction at the ureterovesical anastomosis is lic acid derivatives are more commonly used in reported for WG. End urologic dilatation/stent- preference to azathioprine), and steroids. Many ing may be useful for short strictures; however, programs have omitted steroids. Nonetheless, for longer strictures and those refractory to end many patients with rheumatic disease may already urological management, open surgery may be be on steroids, and it may not be advisable to dis- required. continue such treatment. Blood levels of CNIs need to be monitored due the narrow therapeutic window for optimized results. High levels con- Gastrointestinal Complications tribute to nephrotoxicity, and low levels may pre- dispose to the development of rejection. Steroids Ileus and upper gastrointestinal (GI) bleeding are are tapered to 5–10 mg after 3 months. In patients the most common GI complications. Most without signifi cant proteinuria, CNI inhibitors can patients with extraperitoneal placement of the be switched to an mTor inhibitor (sirolimus, kidney transplant may resume oral intake by the everolimus) after a few months when adequate second or third postoperative day. Prophylaxis wound healing has taken place. There is no for GI bleeding with either an H2 blocker or pro- evidence that a specifi c immunosuppressant ton pump inhibitor may be useful. Neither agent regimen is more effective in patients with sys- has shown superior benefi t in renal transplant temic vasculitis. Despite the immunosuppression, recipient for prevention of GI complications. there remains the risk of recurrent disease both Unusual complications include colonic pseudo- renal and extra renal as already discussed. obstruction (Ogilvie’s syndrome). This can develop due to inactivity, preexisting diabetes, dehydration, electrolyte abnormality, and nar- Infection cotic analgesia. Colonic decompression may be needed by a rectal tube or colonoscopy. The risk of infection is signi fi cant in the early Spontaneous viscus perforation following trans- posttransplant months owing to intense immu- plant carries a very high mortality rate. Rectal nosuppression. There is an increased risk of dis- enemas of any kind are avoided early after trans- ease related to viruses such as cytomegalovirus plantation due to concern for colonic perforation. (CMV), human herpes virus (HHV), hepatitis B, If colonic perforation is suspected, prompt surgi- hepatitis C, and Epstein-Barr virus (EBV). cal treatment is needed. Activation of such viruses may in turn increase 382 D.A. Goldfarb and N. Sezhian the risk of infection with opportunistic pathogens recipients receiving kidney from seropositive like Pneumocystis, Aspergillus, Cryptococci, donor have the highest risk. Extranodal involve- and other fungi. Transplant recipient are also ment is more common. The treatment involves predisposed to other pathogens including Listeria rapid reduction of immunotherapy. Treatment monocytogenes, Nocardia, and Toxoplasma. with anti–CD20 monoclonal antibody has The seroprevalence of CMV is from 40% to reported to be effective. Increasing age, elevated 97% based on the population screened. The highest lactic dehydrogenase values, multiorgan involve- risk of transmission of disease is through the organ ment, and constitutional symptoms have been from a seropositive donor to seronegative recipient. associated with poor prognosis. Conventional Antiviral prophylaxis with valganciclovir is given chemotherapy may occasionally be required. for a minimum of 3 months following transplant. Any recipient who is CMV seropositive, or receiv- ing an organ from a CMV seropositive donor, or Renal Transplant Outcomes has received a lymphocyte-depleting agent should receive prophylactic valganciclovir. According to 2009 SRTR (Scienti fi c Registry of Polyoma or BK virus causes a tubulointerstitial Transplant Recipients), unadjusted patient sur- nephritis (BKVN) and ureteral stenosis in renal vival rates at 5 years were 91% for recipients of transplant recipients. The incidence varies from living donor kidneys, 84% for standard criteria 10% to 60% and usually occurs early posttrans- deceased donor kidneys (SCD), and 72% for plant during which reactivation or reinfection can expanded criteria deceased donor (ECD) kidney occur. Diagnosis is by blood or urine DNA PCR transplants. At 5 years, the unadjusted graft sur- assays. The initial treatment consists of reducing vival rate was 81% for living donor, 72% for the immunosuppression permitting reconstitution SCD, and 57% for ECD transplants. of native immunity to clear the virus. Both BKVN In patients with systemic vasculitis, patient and rejection may be accompanied by allograft and graft survivals are similar to national dysfunction. It is important to distinguish between expectations when risk adjusted for comorbid rejection and BKVN since the treatments are vastly conditions. different and confl icting. Drugs such as lefl unomide and cidofovir may be of clinical bene fi t for BKVN. Note that cidofovir is nephrotoxic and is reserved Refere nces as a last option for persistent disease unresponsive to other therapies. 1. Siddqi N, Hariharan S, Danovitch GM. Evaluation and preparations of renal transplant candidates. In: Danovitch GM, editor. Handbook of kidney transplan- tation. 5th ed. Philadelphia, Pa: Lippincott Williams & Posttransplant Lymph Proliferative Wilkins; 2010. Disease 2. O’Callaghan CA. Renal manifestation of systemic autoimmune disease: diagnosis and therapy. Best Pract Res Clin Rheumatol. 2004;18:411–27. The incidence of PTLD varies from 0.8% to 15% 3. Goldfarb D, Flechner S, Modlin C. Renal transplanta- in renal transplant recipients. It is usually associ- tion. In: Novick A, Jones S, editors. Operative urology ated with over immunosuppression. The total at the cleveland clinic. 1st ed. Humana Press Inc; 2006 cumulative exposure to immunosuppression may p. 121–32 Totona, New Jersey. 4. Annonymous. OPTN/SRTR annual report. 2009 be high for patients with autoimmune vasculitis, 5. Geetha D, Seo P. Renal transplantation in the ANCA- so they may be uniquely predisposed. Most cases associated vasculitides. Am J Transplant. 2007;7: are diagnosed in the fi rst year following trans- 2657–62. plantation. Most are non–Hodgkin’s lymphoma 6. Gera M, Grif fi n MD, Specks U, et al. Recurrence of ANCA-associated vasculitis following renal transplan- and the majority are the B-cell type. EBV infection tation in the modern era of immunosuppression. Kidney is associated with many cases, and seronegative Intl. 2007;71:1296–301. 37 Renal Transplantation 383

7. Appel GB, Radhakrishnan J, D’Agati V. Secondary Comprehensive clinical nephrology. 4th ed. Philadelphia: glomerular disease. In: Brenner B, editor. Brenner and Elsevier Saunders; 2010. Rector’s the kidney. 8th ed. Philadelphia: Saunders 9. Appel GB, Jayne D. Chapter 25, Lupus nepehritis. In: Elsevier; 2008. p. 1067–146. Floege J, Johnson RJ, Feehally J, editors. Comprehensive 8. Jenette JC, Falk RJ. Chapter 24, Renal and systemic clinical nephrology. 4th ed. Philadelphia: Elsevier vasculitis. In: Floege J, Johnson RJ, Feehally J, editors. Saunders; 2010. Lung Decortication 3 8 Sudish C. Murthy

Introduction teroids. On rare occasions, however, fi brothorax and entrapped lung can result from pleural The most common indications for lung decortica- in fl ammation [1 ] . Failure of medical therapy is tion are empyema and fi brothorax. Occasionally, an indication for pleurodesis or decortication. hemothorax will require decortication, although more often, only drainage is necessary. Decorti- cation is used to liberate lung parenchyma that Patient Assessment has become entangled in an ongoing benign pleural infl ammatory process. As this process Radiographic studies are critical in ruling out continues, the lung ultimately becomes con- other disease processes that might mimic this stricted and is prevented from fully in fl ating to clinical presentation, specifi cally pleural-based fi ll the thorax (Fig. 38.1). This results in pulmo- malignancy (either primary or metastatic). Chest nary restriction on the affected side and obligate CT scan can demonstrate a split pleural sign, a respiratory insuf fi ciency, often a result of shunt- fi nding highly associated with empyema ing and V/Q mismatch. Surgical therapy is aimed (Fig. 38.2 ). Similarly, a lung or pleural mass at removing this fi bro-in fl ammatory peel (the would favor malignancy and mandate fi ne-needle cortex) that tethers and restricts both visceral and aspiration for diagnosis. Loculated fl uid is often parietal pleurae, thereby liberating the lung to encountered on both plain radiograms and chest in fl ate. CT scans, and gas within the pleural fl uid sug- Patients with “collagen vascular diseases” gests empyema and fi stula or can represent an (CVD) commonly present with pulmonary artifact from a recent diagnostic thoracentesis. pleural disease. This is particularly true for Clinical history is also important in the overall systemic lupus erythematous (SLE), where up assessment. A recent pneumonia now accompa- to 50% of patients will demonstrate pleuritis nied by malaise, night sweats, chills, chest pain, and/or pleural effusions. Effusions are typically and dyspnea on exertion often points one in the exudative and generally respond to nonsteroidal direction of empyema. Similarly, a patient sev- anti-in fl ammatory drugs or low-dose corticos- eral weeks after chest trauma with gradual onset of respiratory insuffi ciency accompanied by loc- S. C. Murthy , M.D., Ph.D. () ulated fl uid on chest radiogram would suggest Center of Major Airway Disease, Department transition of hemothorax to fi brothorax. Finally, a of Thoracic and Cardiovascular Surgery , Cleveland Clinic patient with a documented history of a systemic Foundation, 9500 Euclid Avenue - J4-1 , Cleveland , OH 44195 , USA in fl ammatory disease, such as rheumatoid arthri- e-mail: [email protected] tis (RA), and known rheumatoid lung may

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 385 DOI 10.1007/978-1-4614-2203-7_38, © Springer Science+Business Media, LLC 2013 386 S.C. Murthy

Fig. 38.3 Operative photo depicting fi bropurulent cortex during a video-assisted decortication for early empyema Fig. 38.1 Standard chest radiogram demonstrating locu- lated fl uid and entrapped lung (e.g., interstitial lung disease, diffuse nodules) as well as the medical history [4 ] . Long-standing rheumatoid fl uids may be pseudochylous. Decortication is a major undertaking. For early empyema, where the process is intervened upon in a fi bropurulent phase (relatively early), the procedure can be done with minimally inva- sive, video-assisted techniques (Fig. 38.3 ). However, for chronic empyema or mature fi brothorax, a thoracotomy is required, and the procedure is quite involved. Regardless of tech- nique, the fundamental goals of decortication are to achieve complete drainage of the thorax, fully liberate the lung, and widely open anatomic fi ssures. This ensures that the lung will fully fi ll the thorax and obliterate any dead space that Fig. 38.2 Chest CT scan showing a split pleural sign, might still be a reservoir for infection/phlegmon. consistent with empyema. Note enhancement of pleural envelopes with intravenous contrast Several drainage tubes are placed within the tho- rax to control the space. The drainage tubes are gradually removed as pleural symphysis eventu- develop empyema secondary to rupture of periph- ally occurs between visceral and parietal pleural eral necrobiotic nodule into the pleural space. envelopes. For empyema, tubes may be gradually Empyema is surprisingly common in patients backed out over a 2- to 3-week time course to with severe RA even without nodule necrosis [ 2 ] , reduce the likelihood of leaving undrained and risks are increased for patients receiving anti- infection. TNF-alpha therapy [ 3 ] . Thoracentesis may be Selecting appropriate candidates for decorti- culture negative, or rarely demonstrate acid-fast cation is critical. Importantly, candidates should bacteria, but chest CT scans will demonstrate have a disease process that actually requires pleural fi ndings indistinguishable for other decortication (disseminated malignancy should patients with empyema, but without CVD. Clues be ruled out). Given the magnitude of the opera- to CVD involvement may come from radio- tion, thorough subjective/objective assessment of graphic assessment of the pulmonary parenchyma patient performance status is important. Severely 38 Lung Decortication 387 debilitated patients with empyema might be bet- ter served by open drainage (a much easier pro- Postoperative Course cess to recover from) instead of thoracotomy and decortication. Also, patients with coagulation The early postoperative period typically occurs in abnormalities are clearly at risk for hemorrhage the ICU setting. Patients will invariably have after decortication. Underlying hypogammaglob- arterial monitoring (radial access) placed at the ulinemia can be a risk for recurrent empyema, time of decortication, and those with Raynaud and correction of the underlying immune syndrome should have this access discontinued defi ciency should occur in concert with manage- as soon as possible. Some surgeons prefer to ment of the closed space infection. mechanically ventilate patients on their fi rst post- Patients with entrapped lung infrequently operative night to ensure optimal lung expansion. present in the outpatient clinic, particularly if The use of positive end-expiratory pressure empyema is present. Fibrothorax can be encoun- (PEEP) helps to tamponade bleeding from the tered in this setting, however. Standard preopera- chest wall and to promote lung in fl ation. Typically, tive workup includes provocative heart testing to PEEP is maintained at 8Ð10 cm H2O for the fi rst rule out occult coronary artery disease, and pulmo- 8Ð12 h with tidal volumes set at 6Ð8 cc/kg. nary function testing. Severely restricted spirome- However, in the presence of multiple visceral try suggests advanced parenchymal fi brosis that pleural breaks and obligate parenchymal injuries might be superimposed on the pleural disease, and from a thorough decortication, extensive air leak a low diffusing capacity can suggest coexistent can lead to hypoventilation and intractable venti- pulmonary hypertension [4 ] . Additionally, assess- lator alarming. In this circumstance, this ventila- ment of coagulation pro fi le and thorough chest tor strategy will have to be abandoned and imaging should be performed. separation from positive pressure mechanical To con fi rm trapped lung, a thoracentesis can ventilation sought. be performed. If the postprocedure chest radio- Decortication for empyema can occasionally gram demonstrates a loculated pneumothorax, induce a sepsis-like syndrome, perhaps from entrapment should be expected. Pulmonary transient bacteremia, and consequently, it is com- hypertension is a relative indication for decorti- mon for this cohort of patients to require vaso- cation because of bleeding, and decortication is pressors for their fi rst 24 h postoperatively. Most not usually indicated for suspected tuberculous patients are extubated within the fi rst day and can empyema. be transferred to a step-down unit shortly More frequently, this syndrome presents as an thereafter. inpatient consult. Often, the admission will be Although speci fi c complications such as pro- the culmination of an inciting pneumonia pre- tracted air leak, chest hemorrhage, and failure to senting with parapneumonic effusion and treated achieve full expansion of the lung occur, practical in the outpatient setting. The parapneumonic pro- considerations such as pain control, deep venous cess then either becomes contaminated directly thrombosis (DVT), and patient mobilization rap- through translocation (or hematogenous spread) idly emerge as important confounders of recov- or remains sterile but densely organized. Patients ery. Epidural analgesia is contraindicated in the are subsequently admitted with dyspnea and a presence of an infectious focus, and pain control chest radiogram demonstrating effusion. Rarely, is relegated to intravenous narcotics for empyema patients with empyema can present with fulmi- decortication, a less-than-optimal option. Patients nant respiratory failure and sepsis, particularly not able to be mobilized are at risk for atelectasis for Staphylococcus aureus infection. Chronic and lung collapse. Multiple chest drains can con- immunosuppression and inability to mount an fuse nursing staffs and entangle patients, both of appropriate response can lead to profound which lead to less frequent ambulation. vasoplegia and refractory shock in this setting. Accordingly, DVT prophylaxis is essential. 388 S.C. Murthy

Patients decorticated for sterile conditions will Success of the intervention is measured by have their chest drains removed when output control of infection (when present), improvement decreases below ~200 cc/24 h of serous fl uid, air of radiograms, and most importantly, palliation leak is undetectable, and lung expansion is con- of dyspnea. Previously vigorous patients should sidered complete. This generally occurs by post- return to an active lifestyle by 8Ð12 weeks after operative day 4Ð6. Slow bleeding from lung and their operation, although a post-thoracotomy pain chest wall can complicate the procedure, and if syndrome can occur in a small percentage. blood is allowed to accumulate within the pleural Patients are closely followed for 3Ð6 months and space, incomplete lung expansion and fi brothorax then can be returned to their primary care team. It can recur. Daily chest radiograms should be is uncommon for recurrence of disease (empy- obtained, and if evidence of fl uid reaccumulation ema) in the same thorax after a successful decor- is noted, postural drainage, dissimpaction of tication, even if the etiology was rupture of a chest drains, and rarely, reoperation might be necrobiotic nodule in RA. Following a well-per- indicated. Deep venous thrombosis prophylaxis formed decortication, complete ipsilateral pleural can be instituted on the morning of the fi rst post- symphysis generally occurs. operative day if chest output has transitioned to a more serous drainage. Pneumatic compression stockings are used until patients are fully References ambulatory. Those with infectious conditions may be dis- 1. Kamen DL, Strange C. Pulmonary manifestations of charged home with drains in place to return to the systemic lupus erythematosus. Clin Chest Med. 2010; 31(3):479Ð88. outpatient clinic twice weekly for gradual chest 2. Jones FL, Blodgett Jr RC. Empyema and rheumatoid tube back-out, and home parenteral antibiotics pleuropulmonary disease. Ann Intern Med. 1978;89(1): are usually continued for 4 weeks. Preoperative 139Ð40. medications, including platelet inhibitors, can be 3. Dixon WG, Hyrich KL, Watson KD, Lunt M, et al. Drug-speci fi c risk of tuberculosis in patients with rheu- resumed within a week postoperatively. Chest matoid arthritis treated with anti-TNF therapy: results radiograms will consistently demonstrate pleural from the British Society for Rheumatology Biologics thickening on the affected side, and chest CT Register (BSRBR). Ann Rheum Dis. 2010;69(3): scan should be reserved for a recrudescence of 522Ð8. 4. Antin-Ozerkis D, Evans J, Rubinowitz A, Homer RJ, symptoms, particularly dyspnea on exertion, and et al. Pulmonary manifestations of rheumatoid arthritis. chest pain. Clin Chest Med. 2010;31(3):451Ð78. Lung Transplantation 3 9 Marie M. Budev

Introduction most experience is in patients with scleroderma undergoing lung transplantation [2 ] . Lung transplantation is now considered a thera- CVDs have diverse clinical presentations, and peutic option for patients suffering from end- some may overlap in terms of symptoms and pre- stage lung disease for those who have no further sentation. Pulmonary fi brosis may complicate therapeutic medical or surgical options. Over each of the CVDs, but it is the diverse extrapul- 29,000 lung transplants have been performed monary comorbidities in patients with systemic across the world in the last 4 decades with the CVD that often excluded them from the trans- most common indications for lung transplan- plant candidacy because of concerns about the tation being chronic obstructive pulmonary shortened long-term outcomes [3 ] . This is pri- disease, idiopathic pulmonary fi brosis, cystic marily the reason why a signifi cant number of fi brosis, and idiopathic pulmonary hypertension. lung transplant programs are reluctant to perform Rheumatological diseases, specifi cally collagen lung transplants in patients with CVD. However, vascular disease (CVDs), accounted for only in 1998, the International Society for Heart Lung 0.8% of lung transplants performed in the past Transplantation consensus statement stated that 15 years according to the most recent data from lung transplantation is a legitimate option for the registry of the International Society for Heart patients with CVD or other systemic disorders and Lung Transplantation [1 ] . The fi ve most provided patients had failed an adequate course common CVDs for which there are published of medical therapy and the systemic disease was accounts of lung transplantation for associated quiescent [4 ] . end-stage pulmonary symptoms include systemic Comorbidities that impact pretransplant selec- sclerosis, rheumatoid arthritis, systemic lupus tion and posttransplant survival include most erythematosus (SLE), dermatomyositis/polymy- commonly gastrointestinal dysfunction (esopha- ositis, and mixed connective tissue disease. geal dysmotility, gastroesophageal re fl ux, and Published accounts and experiences with these gastroparesis), limited exercise endurance and individual disease states are mainly con fi ned to ability (joint disability and degeneration, individual case reports or small case series. The infl ammatory myopathies, and musculoskeletal pain), venous thromboembolism, and associated pulmonary vascular disease. History of previous M. M. Budev , D.o., M.P.H., F.C.C.P. () long-term immunosuppression is not a contrain- Lung Transplantation and Heart Lung Transplantation, dication to being considered for transplantation The Respiratory Institute , Cleveland Clinic , 9500 Euclid Avenue , Cleveland , OH 44195 , USA presently. The purpose of this chapter is to review e-mail: [email protected] the most common factors and comorbidities

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 389 DOI 10.1007/978-1-4614-2203-7_39, © Springer Science+Business Media, LLC 2013 390 M.M. Budev

associated with CVDs that impact lung transplant pulmonary arterial hypertension are the two most patient selection and contribute survival after common complications of scleroderma lung dis- transplantation. In the appropriate CVD patient, ease that can lead to severe disability and death. lung transplantation is feasible, and if the candi- Therefore, lung transplantation offers an impor- date is appropriately selected, the short- and tant potentially lifesaving option for the manage- long-term outcomes can be comparable to out- ment of scleroderma complicated by end-stage comes in patients who do not have CVDs, who pulmonary disease. Table 39.1 focuses on sug- have undergone the same procedure. Candidate gested criteria for consideration for lung trans- should be considered on an individual basis and plantation in patients with scleroderma [ 9 ] . should always be taken into account that extra- Contraindications to lung transplantation in sys- pulmonary organ involvement has the potential temic sclerosis include comorbidities that may of negatively impacting long-term prognosis in lead to worse out comments during the posttrans- this unique group of patients. plant period shortening survival. Patients should be excluded for the consideration of transplanta- tion if they have severe progressive systemic Progressive Systemic Sclerosis (PSSC) involvement of scleroderma. Skin breakdown can occur and ulcerations may form at pressure point There are many pulmonary complications due to areas. The presence of signi fi cant skin break- progressive systemic sclerosis (PSSc) that can down, due to the increased risk of infection, is lead to the need for lung transplantation including considered a relative contraindication to lung fi brosing alveolitis (FA), secondary pulmonary transplantation. In addition, tendon retraction and hypertension, recurrent aspiration pneumonia deformities can impact patient mobility and affect especially in patients with esophageal dysfunc- patient’s rehabilitation potential after posttrans- tion and gastroesophageal re fl ux (GER), and plant and impact overall survival. rarely bronchiolitis obliterans (BO). Progressive Often the pretransplant period, CVD patients pulmonary fi brosis or FA may be present as a including those with systemic sclerosis are complication in over 80% of patients with PSSc treated with immunosuppressive therapies and is the most common cause of death along with including steroids, azathioprine, mycophenolate pulmonary hypertension in this select patient pop- mofetil, and the calcineurin inhibitors. ulation [ 5 ] . The clinical course and progression of Pretransplant use of the calcineurin inhibitors FA progression is diffi cult to predict, but a slow can lead to a reduction in creatinine clearance. decline is usually typical. Compared to the idio- Creatinine clearance below 50 mL/min or pathic pulmonary fi brosis patient, the FA patient impaired renal dysfunction has been proposed as usually demonstrates less severe impairment on a contraindication to lung transplantation [ 9 ] . pulmonary function testing (PFTs) and exercise However, a word of caution in employing a strict tolerance [6 ] . The presence of pulmonary hyper- cutoff determinant for the creatinine clearance tension or a decrease in diffusion capacity (DLCO ) since patients with severe pulmonary hyperten- on PFTs below 40% of predicted had been associ- sion and right ventricular dysfunction may have a ated with an increased mortality in patients with low- fl ow cardiac state leading to a depressed FA. Other systemic factors associated with a creatinine clearance without the presence of worse clinical course in patients with FA include pathological renal disease. In some cases, the the presence of peripheral vascular involvement, creatinine clearance can be improved in a low digital pitting or ulcerations, severe Raynaud’s cardiac output state due to right ventricular dys- phenomenon, and a history of smoking [6 ] . function with the use of vasodilator therapy and The timing for referral for lung transplanta- low dose diuretics while patients are awaiting tion has always been and remains a moving target transplantation [ 10 ] . Renal crisis, a well-known not only in this population but for most patients complication of systemic sclerosis, is rare during with CVD [ 7, 8] . Interstitial lung disease and the postoperative transplant but can occur [2 ] . 39 Lung Transplantation 391

Table 39.1 Proposed selection criteria for lung trans- evaluation for preexisting esophageal issues plantation candidacy in patients with scleroderma including refl ux should be undertaken with a pH Presence of severe pulmonary fi brosis with forced vital probe, manometry, and gastric emptying study in capacity (FVC) and DLCO < 40% every patient with CVD undergoing transplant Presence of pulmonary hypertension with mean evaluation [8 ] . The presence of refl ux in patients pulmonary artery pressures (MPAP) >25 mmHg after transplantation is a risk factor for develop- Presence of a creatinine clearance > 50 ml/min and no evidence of parenchymal renal disease *caution relative ing severe aspiration pneumonia that can impact contraindication in patients with a low cardiac output early lung transplant function and is a strong risk due to right ventricular failure factor based on recent evidence for developing Absence of severe esophageal dysmotility with chronic rejection of the transplanted lung [13 ] . documented aspiration and re fl ux on pH probe and manometry and/or barium swallow Chronic rejection or bronchiolitis obliterans Absence of severe cutaneous thickening and skin syndrome (BOS) remains the Achilles heel of involvement with ulcerations long-term survival in lung transplantation and is Absence of cardiac involvement, arrhythmias, or the most signifi cant contributor toward the reduc- conduction abnormalities tion of health-related quality of life after trans- Absence of small bowel involvement (overgrowth or plant. Approximately half of all lung poor absorption) including large bowel involvement transplantation patients will develop chronic with pseudo-obstruction, diverticulitis or perforation rejection within 5 years after transplant. Treatment Adapted from Rosas et al. (2005) options for chronic rejection are limited in terms of ef fi cacy but can include augmentation or Gastrointestinal disorders are frequently found modi fi cation of immunosuppression [ 14, 15 ] . in patients that suffer from collagen vascular dis- Clinicians are now focusing on ways of prevent- eases. Most commonly, gastrointestinal compli- ing chronic rejection from occurring including cations are found in scleroderma patients with an focusing on pre-lung transplant surgical interven- incidence of over 50% of patients having some tions for refl ux including Nissen fundoplication form of either gastroesophageal re fl ux or gastroe- before transplantation or early postoperatively in sophageal dysmotility that may lead to pulmo- effort to reduce acid and nonacid microaspiration nary aspiration [ 8 ] . Numerous studies have in the posttransplant period [ 16 ] . Davis et al. suggested there is an association between gas- demonstrated that in a single-center retrospective troesophageal re fl ux and microaspiration of gas- study of 43 lung transplantation patients who tric contents contributing to the development of underwent fundoplication for abnormal re fl ux certain pulmonary diseases such as asthma. There studies, over half of whom who had chronic are confl icting reports regarding the association rejection or BOS had improved lung function between chronic re fl ux and aspiration contribut- after fundoplication was performed [ 17 ] . ing to the development of pulmonary fi brosis Currently, no consensus exists on the timing for [10 ] . But gastroesophageal re fl ux is common in surgical intervention for re fl ux, and the type of many patients with advanced lung disease, espe- surgical procedure is best for the treatment of cially those with end-stage lung disease who are refl ux in this patient population undergoing trans- referred for lung transplantation. The Toronto plantation. A larger randomized multicentered Lung Transplant Program noted in a series of 78 trial is currently underway in the United States to consecutive patients who were undergoing evalu- answer these unanswered questions. ation for lung transplantation, 10 of whom had Other contributing factors to developing refl ux scleroderma and 16 of whom had “miscellaneous in the posttransplant period include vagal nerve disease states,” that re fl ux was present at a rate of injury either due to mechanical or thermal injury 63% with 72% of patients demonstrating low or during the surgical procedure and can contribute hypotensive lower esophageal sphincter pres- to gastroparesis and esophageal dysmotility [17 ] . sures and 33% of patients had esophageal body In addition, many of the posttransplant medica- dysmotility noted on manometry [ 12 ] . Therefore, tions especially the narcotics and calcineurin 392 M.M. Budev inhibitors can contribute to gastroparesis and nary hypertension, is a common manifestation of increase the risk of aspiration [ 18 ] . Bowel systemic sclerosis, and SLE and can often be the involvement with scleroderma can lead to bacte- primary consideration for referral for lung trans- rial overgrowth and other signifi cant complica- plantation. It is apparent that the disease course tions leading to decrease survival during the and responsiveness to vasodilator therapies for postoperative period including pseudo-obstruc- pulmonary arterial hypertension associated with tion, diverticulitis, and perforation. systemic sclerosis or SLE is very different from As part of the systemic manifestations of that observed in forms of idiopathic pulmonary scleroderma, heart disease due to scleroderma arterial hypertension. Survival in patients with can be classifi ed into primary and secondary SLE who have pulmonary hypertension seems forms. In primary scleroderma cardiac disease, associated with degree of preservation of the right there is direct involvement of the myocardium, ventricular function. In patients who have moder- pericardium, valves, coronary vessels, and the ate-to-severe pulmonary hypertension with a low conduction system due to vascular, fi brotic, and cardiac index and a high mean right atrial pres- in fl ammatory changes of the disease itself. sure, overall survival has been noted to be poor, Secondary cardiac involvement due to sclero- and therefore, transplantation should be consid- derma occurs in response to the pulmonary vas- ered [22 ] . cular response due to hypoxemia from the Another vascular dysfunctional state in development of fi brotic lung disease [19 ] . Since patients with CVD include Raynaud’s phenome- the signs and symptoms of coexisting lung dis- non, a condition characterized by periodic arte- ease are often occult, the prevalence of cardiac rial vasospasm and vasoconstriction in the digits involvement in scleroderma patients is often in response to cold, stress, or temperature changes underestimated [20 ] . Approximately 5Ð10% of and impact postoperative recovery. The use of patients with scleroderma can have atrial and postoperative hypothermia or vasopressors may ventricular arrhythmias that can be a contraindi- result in peripheral ischemic injury to the digits cation to transplantation. Cardiac fi brosis, thought in patients with Raynaud’s with no reports of car- to be responsible for these conduction abnormali- diac vasospasmic activity with cooling during the ties, is present in more than half of scleroderma recovery period. For patients who were on vaso- patients at autopsy [ 21 ] . Very few patients with dilator therapy preoperatively, most therapies are scleroderma have signifi cant left ventricular dys- weaned off intraoperatively and most often, function, and it is usually found in patients with inhaled nitric oxide may be used postoperatively diffuse scleroderma. Right ventricular dysfunc- to improve the pulmonary hemodynamics. In the tion and failure is more common in limited scle- later postoperative period, sildena fi l may be roderma. In the majority of post-lung transplant added or continued for peripheral digit vasodila- patients, the right ventricle is able to remodel tion due to Raynaud’s [ 8] . It is recommended that itself due to the reduction in pulmonary pressures careful attention be paid to using hand warmers and returns to normal function. But if myocardial and low-to-minimal doses of vasopressors be fi brosis involves the left ventricle in addition to used during the postoperative period. dysfunction of the right ventricle, heart lung transplantation should be considered instead of lung transplantation alone due to the nonrevers- Rheumatoid Arthritis ible dysfunction of the left ventricle [8 ] . Vascular abnormalities that are associated The pulmonary complications of rheumatoid with systemic sclerosis include Raynaud’s phe- arthritis which can lead to the need for lung trans- nomenon, digital ulcers, pulmonary renal disease, plantation include FA, OB, bronchiectasis, pul- renal crisis, and pulmonary arterial hypertension. monary arterial hypertension, and complications Pulmonary vascular disease, specifi cally pulmo- or side effects of therapy [ 4 ] . Only about 1Ð4% of 39 Lung Transplantation 393 patients with rheumatoid arthritis will develop strongly urged all patients with joint pain or mus- severe or disabling fi brosing alveolitis [ 4 ] . Lung culoskeletal pain to enroll in pulmonary rehabili- transplantation is reserved for patients with severe tation, aqua therapy, and reduce their narcotic use progressive fi brosis that is refractory to medical to the lowest possible dose with the aid of chronic therapy and has led to resting hypoxemia and/or pain management consultation. pulmonary hypertension. Other systemic manifestations of rheumatoid arthritis as well as joint and musculoskeletal Systemic Lupus Erythematosus (SLE) damage may directly impact pre- and posttrans- plant exercise tolerance, endurance, and survival Pulmonary complications of systemic lupus ery- outcomes. Degenerative arthropathy due to rheu- thematosus (SLE) that may lead to the need for matoid arthritis can lead to chronic pain and limi- lung transplantation include FA, recurrent pulmo- tations on the 6-min walk test (6MWT). The nary embolism, and pulmonary hypertension due 6MWT is usually measured at various time points to circulating anticardiolipin antibodies, oblitera- before transplantation and has a direct relation- tive bronchiolitis, and lung injury from various ship with functional status after transplant. In immunosuppressive drugs such as methotrexate. clinical practice, the 6-min walk is useful in help- Clinically signifi cant pulmonary fi brosis may ing to guide timing for activation or listing for occur in approximately 3Ð13% of patients with transplantation. If a drop or fall occurs in the dis- SLE, but is rarely severe [ 27 ] . Patients with CVD, tance walked during the 6MWT or an increase in especially SLE, seem to have higher rates of throm- the need for supplemental oxygen occurs during botic complications when compared to the general testing compared to previous 6MWT, this might population; of most concern is the presence of the help clarify if the patient is within the transplant antiphospholipid syndrome (APLS) [ 28 ] . window [23, 24] . A decrease in the 6-min walk Very few reports in the literature exist regarding test distance may represent deconditioning and APLS and lung transplantation, but several studies reduced exercise capacity which have been asso- in kidney transplantation has suggested that ciated with increased morbidity after other tho- patients with APLS are at higher risk for develop- racic surgical procedures [ 25 ] . Many lung ing posttransplant pulmonary embolism as well as transplant programs consider ambulating less graft thrombosis and graft loss [ 29] . The need for than 600 ft to be a strong relative or absolute con- chronic anticoagulation before transplant and traindication to transplant [ 26 ] . Therefore, pul- immediately after surgery may be considered at monary rehabilitation is absolutely essential both certain transplant centers to be a contraindication pre- and post-lung transplant to help with endur- to lung transplantation, especially in patients ance and exercise capacity. already considered as high risk. This may result in It is vital that all patients with any limitation in a diffi cult explantation procedure leading to endurance or exercise tolerance enroll in phase II signifi cant bleeding in the perioperative period. pulmonary rehabilitation program in effort to The posttransplant initiation of full-dose anticoag- maximize endurance. Debilitating joint and mus- ulation can lead to the development of a hemotho- cle problems may impact rehabilitation potential rax or excessive bleeding, especially if the patient and the ability to exercise in patients with rheu- has required systemic anticoagulation for cardio- matoid arthritis. If joint pain is debilitating and pulmonary bypass during the operation. Excessive narcotic therapy has been employed, this could bleeding may require surgical re-exploration and/ be a contraindication to transplantation since or multiple blood transfusions. Long-term survival management of postoperative pain can be dif fi cult is usually not impacted by the presence of APLS, and could potentially affect postoperative wean- but can also complicate routine surveillance biop- ing from the ventilator and subsequent ambula- sies that are necessary for monitoring rejection or tion and rehabilitation [ 11 ] . At our center, we infection of the transplanted organ. 394 M.M. Budev

term survival of lung transplant recipients is Polymyositis (PM) and improved, the major causes of morbidity and mor- Dermatomyositis (DM) tality during the posttransplant course are related directly to pulmonary complications and not the Pulmonary complications of PM/DM that can underlying systemic disease state. Primary graft lead to the need for lung transplantation include dysfunction (PGD) or early injury of the trans- respiratory failure due to progressive fi brosis or planted organ, various infections, and bronchiolitis BO. Chronic progressive fi brosis complicates obliterans syndrome account for the majority of polymyositis and dermatomyositis in only about deaths after the fi rst year after lung transplant. 3Ð10% of patients and can be a presenting feature Recipient-related risk factors for the development of the disease [ 4 ] . When immunosuppressive of PGD include elevated pretransplant pulmonary agents are unable to control the active alveolitis artery pressures, diffuse interstitial lung disease, or progressive fi brosis due to polymyositis or and the use of transfusions in the perioperative dermatomyositis, only then lung transplantation period which can be found in recipients trans- should be considered, but in a very carefully planted with CVD. Management of PGD is mainly selected group of patients. In determining trans- supportive and is similar to that of patients that suf- plant eligibility in this disease state, signi fi cant fer with ARDS. All lung transplant patients, irre- caution should be undertaken regarding lung spective of the reason why they were originally transplantation candidacy due to the possible transplanted, are at higher risk for developing pul- presence of severe neuromuscular weakness monary infectious complications both postopera- which may be progressive in nature and impact tively and throughout life. The reason for the both the pre- and posttransplant outcomes and increased risk of infection is that lungs are more the possibility of postoperative aspiration pneu- immunogenic than most other solid organs, and the monia due to weakness of the pharyngeal muscu- recipients generally require higher levels of immu- lature [11 ] . It is extremely important to consider nosuppression both during the postoperative period if diaphragmatic weakness is present at pretrans- and throughout their lifetimes, making them more plant because its presence can contribute vulnerable to infections. The baseline immunosup- signi fi cantly to failure wean from ventilatory pressive regimen for lung transplantation includes support after transplantation. Simply put, in a calcineurin inhibitors, azathioprine or mycopheno- patient with dermatomyositis or polymyositis late mofetil, and chronic steroids at varying doses. that has diaphragmatic dysfunction, lung trans- There currently does not exist a steroid-free proto- plantation will not improved their hypoxemia or col for managing lung transplant patients postop- pulmonary symptoms, and transplant is contrain- eratively and long term. Due to the heightened dicated. In addition, patients with infl ammatory immunosuppression that is used in lung transplan- myopathy, such as PM/DM, have signifi cant tation, side effects are common including early impairment muscle strength and conditioning renal dysfunction in the development of chronic that can contribute to poor pretransplant rehabili- kidney disease and very serious bacterial, myco- tation and posttransplant functioning [11 ] . bacterial viral, and fungal infections [31 ] .

Postoperative Period and Conclusion Antirejection Regimen In evaluating patients with CVD for lung trans- Lung transplant survival outcomes have slowly plantation, a coordinated, multidisciplinary effort been improving over the past two decades with the to avoid posttransplant morbidity and mortality 5-year median posttransplant survival increasing related to extrapulmonary complications associ- from 4.7 years in the latter half of the 1990s to ated with CVD must be undertaken. Overall, lung 5.7 years in the last decade [30 ] . Although long- transplantation does offer improved survival as 39 Lung Transplantation 395 well as quality of life in many patients with end- lung disease candidate for lung transplant. Ann Thorac stage lung disease. But in patients with CVD, care- Surg. 2005;80:1254Ð60. 13. Hadijiliadis D, Duane Davis R, Steele MP, et al. ful evaluation of the signifi cant extrapulmonary Gastroesophageal re fl ux disease in lung transplant complications and comorbidities may limit the recipients. Clin Transplant. 2003;17:363Ð8. availability of this as a therapeutic option. But in 14. Burton CM, Carlsen J, Mortensen J, et al. Long-term appropriate patients with CVD-associated end- survival after lung transplantation depends on devel- opment and severe ID of bronchiolitis obliterans syn- stage lung disease patients who have adequate drome. J Heart Lung Transplant. 2007;26:681Ð6. muscle strength, exercise tolerance, little-to-no 15. Kugler C, Fischer S, Gottlieb J, et al. Health related acid or nonacid re fl ux, and without any evidence of quality of life in 280 lung transplant recipients. diaphragmatic dysfunction or neuromuscular dis- J Heart Lung Transplant. 2007;26:2262Ð8. 16. Davis Jr RD, Lau CL, Eubanks S, et al. Improved lung ease, lung transplantation may be a viable option. allograft function after fundoplication in patients with gastroesophageal refl ux disease undergoing lung transplantation. J Thorac Cardiovasc Surg. 2003; 125:533Ð42. References 17. Akindipe OA, Faul JL, Vierra MA, et al. The surgical management of severe gastroparesis and heart back/ 1. Christie JD, et al. J Heart Lung Transplant. 2010;10: lung transplant recipients. Chest. 2000; 117:907Ð10. 1105Ð14. 18. Folch E, Shakoor H, Gomez J, et al. Gastric bezoar 2. Saggar R, Khanna D, Furst D, et al. Systemic sclerosis after lung transplantation in non-cystic fi brosis and bilateral lung transplantation; a single center patients a review of the literature. J Heart Lung experience. Eur Respir J. 2010;36:893Ð900. Transplant. 2007;26:739Ð41. 3. The American Society for Transplant Physicians 19. Boueiz A, Mathai SC, Hummers LK, et al. Cardiac (ASTP)\American Thoracic Society (ATS)\European complications of systemic sclerosis; recent prog- Respiratory Society (ERS)\International Society for ress in diagnosis. Curr Opin Rheumatol. 2010;22: Heart Lung Transplantation (ISHLT). International 696Ð703. guidelines for the selection of lung transplant candi- 20. Ioannidis JB, Vlachoyiannopoulos PG, Haidich AB, date. Am J Respir Crit Care Med. 1998;158:335Ð9. et al. or telemetry in systemic sclerosis; and interna- 4. Lynch III JP, Orens J, Kazerooni EA. Collagen tional meta-analysis of individual patient data. Am J vascular diseases. In: Sperber M, editor. Diffuse lung Med. 2005;118:2Ð10. disease: a comprehensive clinical- radiological over- 21. Follansbee WB, Miller TR, Curtiss EL, et al. A con- view. London: Springer; 1999. p. 325Ð55. trolled clinicopathological study of myocardial 5. Wells AU, Hansell DM, Rubens MB, et al. Functional fi brosis and systemic sclerosis (scleroderma). impairment in lone cryptogenic fi brosing alveolitis J Rheumatol. 1990;17:656Ð62. and a fi brosing alveolitis associated with systemic 22. Ramirez A, Varga J. Pulmonary arterial hypertension sclerosis; a comparison. Am J Respir Crit Care Med. and systemic sclerosis; clinical manifestations, 1997;155:1657Ð64. pathophysiology, evaluation, and management. Treat 6. Groen H, Wichers G, Borg T, et al. Pulmonary diffus- Respir Med. 2004;3:339Ð52. ing capacity disturbances are related to nailfold cap- 23. Lederer DJ, Arcasoy SM, Wilt JS, et al. Six minute illary changes in patients with Raynaud’s phenomenon walk distance predicts waiting list survival in idio- with and without an underlying connective tissue dis- pathic pulmonary fi brosis. Am J Respir Crit Care ease. Am J Med. 1990;89:34Ð41. Med. 2006;174:659Ð64. 7. Minai OA, Budev MM. Referral for lung transplant: a 24. Tuppin MP, Paratz JD, Chang AT, et al. Predictive moving target. Chest. 2005;127:1006Ð16. utility of the 6 minute walk distance on survival in 8. Shitrit D, Amital A, Peled N, et al. Lung transplanta- patients awaiting lung transplantation. J Heart Lung tion in patients with scleroderma: case series, review Transplant. 2008;27:729Ð34. of the literature, and criteria for transplantation. Clin 25. Benzo R, Kelley GA, Recchi L, et al. Complications Transplant. 2009;23:178Ð83. of lung resection and exercise capacity: a meta-analy- 9. Rosas V, Conte JV, Yang S. Lung transplantation and sis. Respir Med. 2007;101:1790Ð7. systemic sclerosis. Ann Transplant. 2000;5:38. 26. Levine SM. A survey of clinical practice of lung 10. Tarver JH, Roseas I, Diette GB, et al. Chronic ambula- transplantation in North America. Chest. 2004;125: tory dopamine infusion therapy for refractory right 1224Ð38. heart failure due to pulmonary hypertension area. Am 27. Orens JB, Martinez FJ, Lynch III JP. Pleuropulmonary J Resp Crit Care Med. 2000;161:A56. manifestations of systemic lupus erythematosus. 11. Lee JC, Ahya VN. Lung transplantation in autoim- Rheum Dis Clin North Am. 1994;20:159Ð93. mune diseases. Clin Chest Med. 2010;10:589Ð603. 28. Burgos PI, Alarcon GS. Thrombosis and systemic 12. D’Ovidio F, Singer LG, Hadijiliadis D, et al. lupus erythematosus: risk and protection. Expert Rev Prevalence of gastroesophageal re fl ux and end-stage Cardiovasc Ther. 2009;7:1541Ð9. 396 M.M. Budev

29. Wagenknect DR, Becker DG, LeFlor WM, et al. Transplantation: twenty-sixth of fi cial adult lung and Antiphospholipid antibodies are a risk factor for early heart-lung transplantation report -2009. J Heart Lung renal allograft failure. Transplantation. 1999;68: Transplant. 2009;28:1031Ð49. 241Ð6. 31. Ahmad S, Sholobin OA, Nathan SD. Pulmonary com- 30. Christie JD, Edwards LB, Aurora P, et al. The registry plications of lung transplantation. Chest. 2011;139: of the International Society of Heart and Lung 402Ð11. Comanagement Models for the Patient with Joint Disease 4 0

Preethi Patel and Christopher M. Whinney

“When a team outgrows individual performance and learns team con fi dence, excellence becomes a reality” – Joe Paterno

does not always happen. If the urgency of the Introduction consult is not clearly communicated, the consul- tant may or may not see the patient in a timely Patients with rheumatologic diagnoses typically manner. If the consultant makes recommendations have complex medical histories due to the under- only and does not write orders (as is often the lying pathophysiology that is associated with these case in academic medical centers), then delays disorders. Therefore, when these patients present often can occur between making and executing to the hospital for surgery, comanagement by a the recommendations of the consultants by the medical specialist, either an internist or a rheuma- primary team. Subsequently, the follow-up care tologist, may help optimize patient outcomes and by the consultant might be inconsistent, and improve quality of care and patient experience. additional time might be lost in communicating Comanagement is defi ned as the state of the exact recommendations by the consultant at shared equal responsibility and accountability discharge. It has been shown that the quality of for the hospitalized patient across clinical care received by patients who had multiple con- subspecialities. For example, in the case of an sultations is no better than those who did not orthopedic surgical patient, the surgeon takes have such consultations, and the cost of care and care of the procedure and procedure-related care length of stays are higher [ 1] . Comanagement on (mobility, weight bearing, wound care), while the other hand may be seen as a patient care the internist manages the medical problems. referral. The comanager takes ownership of the Historically, in many centers, the surgeon and patient’s medical issues and follows the patient internist have collaborated with each other within daily along with the primary team. He or she the framework of consultation. There are known rounds, writes notes, orders appropriate diagnos- inherent inef fi ciencies in this system. When a tic and therapeutic interventions, and is actively consultation is formally requested, it must be involved in discharge planning and setting up communicated effectively and seamlessly, which follow-up care.

P. Patel , M.D. Department of Hospital Medicine , Cleveland Clinic The Benefi ts of the Comanagement Foundation , 9500 Euclid Avenue, M2 Annex , Cleveland , Model OH 44121 , USA C.M. Whinney , M.D., F.A.C.P., F.H.M. () The comanagement model in which both surgical Department of Hospital Medicine, Cleveland Clinic and medical specialists collaborate in patient care Foundation , 9500 Euclid Avenue , Cleveland , OH 44121 , USA has been studied in several other countries. Early e-mail: [email protected] literature on the comanagement model originated

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 397 DOI 10.1007/978-1-4614-2203-7_40, © Springer Science+Business Media, LLC 2013 398 P. Patel and C.M. Whinney from the 1970s and 1980s from the United in 1996 to 41.7% in 2006, while rates for cardio- Kingdom, mostly involving geriatric patients thoracic surgery fell. Again, this is not surprising with hip fractures. Models of care included nurse- since many of the studies that showed the bene fi t based liaison services, multidisciplinary liaison of comanagement were in the higher-risk older services, and daily geriatric rounding. Analyses orthopedic patient population. of the effi cacy of these models have noted vari- The American Academy of Orthopedic able results. A Cochrane meta-analysis of 12 ran- Surgeons hosted a national consensus conference domized controlled trials demonstrated that on improving care of patients with hip fractures in multidisciplinary care is no better than usual care 2001 [6 ] . They identifi ed a pressing need for evi- in reducing hospital mortality and readmission dence-based multidisciplinary care and better rates in geriatric patients with hip fractures, but coordination of care between different providers was found to be moderately bene fi cial in reduc- and care settings in order to improve quality of ing postoperative medical complications, and care delivered to hip fracture patients. Despite an enhancing mobility and rates of return to home. aging patient population and increasing comor- However, there was considerable variation in the bidities, administrative pressures toward lower defi nitions of multidisciplinary care compared to length of hospital stay and fewer readmissions cre- usual care. The authors concluded that there was ate a signifi cant challenge for optimizing patient a tendency toward better outcomes in the multi- outcomes. This creates a substantial opportu- disciplinary care models [1 ] . nity for generalist physicians to step in as coman- In the United States, with the advent of the agers of complex medical patients rather than as hospitalist movement, a new breed of specialized consultants [ 7 ] . physicians have evolved to care for hospitalized One of the fi rst randomized control trials of medical patients and to provide perioperative medical comanagement of surgical patients care. In a survey conducted nationwide in 1999, looked specifi cally at reducing rates of delirium about 44% of hospitalists reported to be serving in elderly patients admitted with hip fractures [ 8 ] . as primary physician of record for the hospital- One hundred twenty-six patients were random- ized surgical patient [ 2 ] ; a recent survey reported ized to usual care versus proactive geriatrics con- that 91% of the hospitalists have cared for a sur- sultation with implementation of protocol-based gical patient in one capacity or another [3 ] . Since recommendations. There was a 77% adherence the number of hospitalists has increased from rate to the consultant’s recommendation. The rate 6,000 in 2004 to 20,000 currently, such an of acute delirium in the intervention group was increase in perioperative care participation is not 32% (20/62) versus 50% (32/64) (P = 0.04) in the surprising [4 ] . Using a 5% national Medicare usual care group. Acute delirium rates were also sample, Sharma et al. [5 ] conducted a study of lower in the intervention group than the usual trends in comanagement of surgical patients from care group (12% vs. 29%, P = 0.02). However, 1996 to 2006. They looked at 15 procedures using length of stay and disposition destinations the diagnosis-related group coding (DRG) at dis- remained the same in both groups. charge and defi ned comanagement if claims were A retrospective cohort study performed in the submitted by a medicine physician for at least University of Rochester looked at two models of 70% of the inpatient days. There were 2 distinct care that were followed in their hospitals [ 9 ] . The trends that emerged from this study. The percent- Geriatric Fracture Center (GFC) was established age of patients that were comanaged from 1996 there in 2004 and was modeled after similar cen- to 2000 remained relatively stable; however, from ters in the United Kingdom and other countries. 2001 to 2006, it increased from 33.6% to 40.8%. It is staffed by a geriatrician and orthopedic sur- That increase was generally fueled by hospital- geon at all times. This model of care was com- ists. Also, comanagement rates increased by the pared with the Usual Care (UC) model where type of surgery, for example, comanagement hospitalists are consulted as needed. Although rates in orthopedic surgery increased from 28.6% the GFC patients had higher comorbidity scores 40 Comanagement Models for the Patient with Joint Disease 399 and more likely to have dementia, they went to provided focused medical postoperative care and surgery earlier than the UC patients, were more saw these patients daily. There were 232 patients likely to be discharged earlier (LOS 4.6 vs. in the HOT model and 237 patients in the stan- 8.3 days), and had fewer complications (30.6% dard practice group. There were no signi fi cant vs. 46.3%). These results were more pronounced differences in the length of stay; however, when in patients over 85 years of age. The improve- adjusted for delays due to disposition issues, the ments with GFC care were attributed to standard- HOT patients were ready for discharge earlier. ized protocols and to 24-h availability of the The minor complication rates were also lower in geriatric staff. Limitations of this study include the HOT group, but there was no signifi cant dif- that it was an unblinded retrospective cohort ference among the intermediate and the major study subject to chart documentation inaccura- complication rates. Moreover, this study was the cies and potential for bias. Another study, per- only one that surveyed surgeons and nurses formed at the Mayo Clinic, examined the effects regarding their preferences and experience with of the Hospitalist model on hip fracture patients the hospitalist model and it was largely favor- [10 ] . This was also a retrospective cohort study able. Both groups endorsed the point that high- which compared outcomes before and after the quality postoperative medical care was much hospitalist comanagement program was initiated. more coordinated and prompt in this multidisci- The primary outcomes of interest were length of plinary approach. stay, 30-day readmission rates, time to surgery, Despite existing data about the bene fi ts of and time from surgery to discharge. Their results comanagement, evidence is lacking regarding were also comparable to the GFC study. The long-term outcomes of comanagement services. mean overall length of stay was 2.2 days shorter Information on mortality, medical complica- in the hospitalist group, patients went to surgery tions, and readmissions for complications is still earlier (25 vs. 38 h; P < .001), and the time from largely unknown. There has been criticism from surgery to discharge was also shorter (7 vs. several quarters that since the primary care phy- 9 days; P = 0.04). There was no difference in the sician (PCP) is less involved in the care of the 30-day readmission rates and inpatient mortality hospitalized patient, there might be discrepan- or surgical complications between the groups. cies in understanding of the care plan when the The above studies echoed the results of the previ- patient is discharged home and returned to the ous studies that comanaged orthopedic patients auspices of the PCP. This risk can be mitigated had shorter lengths of stay and went to surgery by clearly de fi ning speci fi c communication earlier. However, due to study design limitations, mechanisms between the discharging physician the results of these studies must be interpreted and the PCP so that the patient does not “fall with caution. through the cracks.” The use of electronic medi- A randomized control trial done at Rochester cal records and HIPAA-secured communications Methodist Hospital enrolled elevated risk patients can facilitate and expedite this communication that were undergoing elective primary and revi- stream. Additionally, primary care physicians sion total knee or hip arthroplasties [ 11] . These are less frequently serving as hospital consul- patients were randomly assigned to either the tants; they are relying more on the hospitalist to standard orthopedic practice or the Hospitalist- serve this role. Orthopedic Team (HOT) model. Both teams used the standard postoperative clinical path- ways developed by the orthopedic surgeons. In Establishing a Comanagement the standard practice, the orthopedic surgeon Program was identifi ed as the primary physician; manage- ment of postoperative complications and deci- Traditionally, in academic settings, surgical resi- sions about consultations were at the discretion dents served as the liaison for staff surgeons in of the team. In the HOT model, the hospitalists providing the lion’s share of preoperative and 400 P. Patel and C.M. Whinney postoperative management of surgical patients. Table 40.1 Checklist for starting a comanagement They managed complications and consulted service medical specialists at their discretion. With Identify program champions ACGME work hour rules, the time the surgical Identify program stakeholders residents can spend outside the operating room Hold consensus meeting has been compromised, decreasing their ability to Determine stakeholder goals respond to fl oor calls. Staff surgeons, with their Develop service agreement increasing demands for operative and offi ce pro- De fi ne key program metrics ductivity and quality, fi nd it increasingly diffi cult Address fi nancial concerns Select patients appropriate for comanagement to attend to ward needs. In such a scenario, the Establish staf fi ng model and communication plan choice of the hospitalist or a hospital-based sub- Develop program support materials specialist to take on additional responsibilities is Pilot program natural; since their practices are hospital based, Adapted from [12 ] they can respond promptly to these calls and are not constrained by the demands of a busy outpa- tient schedule. In an academic teaching institution, the educa- going to follow to measure improvement? tional bene fi ts of having residents and fellows How do we know that the program is participate in a comanagement program are obvi- effective? These are questions that should ous; however, the addition of more staff members be answered and goals that should be set to the surgical team may create confl ict among based on the stakeholders’ priorities. providers regarding roles and responsibilities Some potential goals of the program could which may be counterproductive to comanage- be reducing length of stay, reducing mor- ment efforts, unless these roles are clearly delin- tality, and increasing patient, provider, eated in advance. and nursing satisfaction. Other relevant Numerous academic centers in the country goals might be clinical metrics such as have successfully initiated comanagement pro- improving VTE prophylaxis rates and grams; the structure and function of these pro- decreasing hospital-acquired infection, grams vary signifi cantly. The Society of Hospital sepsis, and readmission rates. Medicine Comanagement Advisory Task Force (b) De fi ne roles and responsibilities: How are has identifi ed key components of successful patients selected for a comanagement programs and released a white paper detailing program? Is the hospitalist going to be suggested steps for implementing and running involved preoperatively? Does the hospi- a successful comanagement program [12 ] . talist write orders? Who does the nurse Table 40.1 outlines a practical checklist for start- call for any urgent issues? Who plans dis- ing a comanagement service. charges? How does communication Steps to establishing a comanagement between the specialists work? program: (c) Identify potential obstacles that might arise 1. Initial meeting: An initial meeting should be and have a con fl ict resolution system in held by relevant stakeholders including ortho- place. Anticipate fi nancial, legal, and service pedic surgeons, hospitalists, ancillary care associate risks and establish appropriate services such as case management, pharma- hospitalist workloads. In academic centers, cists, therapists, nursing staff leaders, and hos- identify how the education of residents and pital administration representatives to discuss students will be affected by this program. the following measures: 2. Before implementation: The task force recom- (a) Goals of the program: What are we trying mends that several key components should be to achieve? How do we de fi ne improve- in place before a pilot program goes into ment and what are the metrics that we are effect. 40 Comanagement Models for the Patient with Joint Disease 401

(a) Service agreement: Based on the discus- give highest quality of care to the patient with his sions and conclusions of the stakeholder or her consent only and any fi nancial should not meetings, create a service agreement out- be tolerated. lining the duties and responsibilities of each of the stakeholders. All the questions noted previously should be answered suc- Conclusion cinctly and documented clearly so that there is little confusion once the program The delivery of safe, effective, and ef fi cient health is initiated. care is a team pursuit, and multidisciplinary care (b) Metrics/measures: As noted above, select in the form of comanagement has been shown to key metrics to measure and follow that are improve satisfaction for everyone involved – sur- relevant to your program’s stakeholders geons, comanagers, nurses, and patients. As more and to your institution. providers inevitably will participate in surgical (c) Financial aspects: Determine how the hos- comanagement, more research will be needed to pitalist will submit his or her billing (pri- identify processes of care and relevant outcomes mary provider or as consultant), and to ensure that this emerging practice pattern pro- determine if the hospital will provide vides not only satisfaction but safe, timely, fi nancial support to the program. ef fi cient, and effective care [15 ] . (d) Staf fi ng: Determine staf fi ng needs based on prior patient volumes: How many hos- pitalists are needed? Are midlevel provid- References ers needed? Will current nursing staff suf fi ce, or are additional beds needed to 1. Auerbach AD, Rasic MA, Sehgal N, et al. Opportunity accommodate the program? missed: medical consultation, resource use and qual- (e) Education: Educate staff members, resi- ity of care of patients undergoing major surgery. Arch Intern Med. 2007;167(21):2338–44. dents, medical students, and nursing and 2. Cameron ID, Handoll HH, Finnegan TP, et al. ancillary providers about the comanage- Co-ordinated multidisciplinary approaches for inpa- ment process and clarify how each of their tient rehabilitation of older patients with proximal roles and practices will be affected, and femoral fractures. Cochrane Database Syst Rev. 2001;3:CD000106. highlight the benefi ts of this collaboration 3. Lindenauer PK, Pantilal SZ, Katz PP, Wachter RM. in patient care. Hospitalists and the practice of inpatient medicine: 3. Piloting the program: Initiating a pilot pro- results of survey of the National Association of Inpatient gram in the fl ow of practice will give a chance Physicians. Ann Intern Med. 1999;130: 343–9. 4. Vasilevskis E, Knebel J, Wachter R, Auerback A. The to address practical issues that might arise rise of the hospitalists in California. Oakland: once the program is implemented. Feedback is California Heathcare Foundation; 2007. important in improving the program and 5. Huddleston JM, Long KL, Naessens JM, et al. should be sought actively and appropriate Medical and surgical comanagement after elective hip and knee athroplasty. Ann Intern Med. adjustments should be made to address these 2004;141:28–38. issues. If the program is not satisfactory to the 6. Sharma G, Kuo YF, Freeman J, et al. Comanagement people involved and is thought not to meet its of hospitalized surgical patients by medicine physi- goals, it should be revised and implemented cians in the United States. Arch Intern Med. 2010;170(4): 363–8. again if necessary. 7. Dorn B, Bowen J, Downes E, et al. National consen- It is important to recognize that there are ethical sus conference on improving the continuum of care implications to any surgical comanagement team, for patients with hip fracture. Washington, DC: and the AMA and the ACS have both published American Academy of Orthopedic Surgeons; 2001. 8. Whinney CM, Michota M. Surgical comanagement: a papers that clearly outline these principles [13, 14 ] . natural evolution of hospitalist practice. J Hosp Med. These programs should only be implemented to 2008;3:394–7. 402 P. Patel and C.M. Whinney

9. Marcantonio ER, Flacker JM, Wright RJ, Resnick Available online at http://www.hospitalmedicine.org/ NM. Reducing delirium after hip fracture: a random- Content/NavigationMenu/Publications/WhitePapers/ ized control trial. J Am Geriatr Soc. 2001; White_Papers.htm# . 49(5):516–22. 13. American Medical Association. Opinion 8.043. 10. Friedman SM, Mendelson DA, Bingham KW, Kates Ethical Implications of Surgical Comanagement. SL. Impact of a comanaged geriatric fracture center Available online at http://www.ama-assn.org/ama/ on short-term hip fractures outcomes. Arch Intern pub/physician-resources/medical-ethics/code- Med. 2009;169(18):1712–7. medical-ethics/opinion8043.page . 11. Phy MP, Vanness DJ, Melton LJ, et al. Effects of hos- 14. American College of Surgeons. ACS statement of pitalist model on elderly patients with hip fracture. principles underlying perioperative responsibility. Arch Intern Med. 2005;165:796–801. Bull Am Coll Surg. 1996;81(9):39. 12. The Society of Hospital Medicine’s Co-Management 15. Institute of Medicine. Crossing the Quality Chasm: A Advisory Panel. A White Paper on A Guide to New health System for the Twenty-First Century. Hospitalist/Orthopedic Surgery Co-Management. Washington, DC, National Academy Press, 2001. Index

A Antibiotic therapy Abatacept , 81 laminectomy , 300–301 ABT. See Autologous blood transfusion (ABT) prosthetic joint infection Activated partial thromboplastin time (aPTT) , 5, 6 antibiotic choices , 265 Acute kidney injury (AKI) antibiotic therapy type and duration , 265–266 avoidance , 170 chronic oral antibiotic suppression , 267 etiology , 166–169 pseudogout , 273 orthopedic surgeries , 170 total hip arthroplasty , 330–331 perioperative outcomes , 169–170 Anticoagulation predictors of , 169 aPL positive patient risk factor , 166 arterial and/or venous thrombosis , 97–98 Acute pain. See Pain management bridging anticoagulation , 96–97 Airway management , 2–3 clinically signi fi cant aPL patient , 97 Alkaline phosphatase , 236 high-thrombosis-risk patients , 95–96 American Academy of Orthopedic Surgeons , 398 monitoring , 98–99 Anakinra , 82 neuraxial anesthesia , 96 Anemia , 42, 187–188 pregnancy morbidity , 98 Anesthesia cardiac surgery fat embolism syndrome (see Fat embolism syndrome ACS/PCI in APS patient , 118 (FES)) joint replacement anticoagulant bridging recommendations , anesthetic selection , 6–7 111–112 methyl methacrylate , 8–9 antiplatelet recommendations , 112 recovery issues , 10, 11 cardiopulmonary bypass , 116–117 regional vs. general anesthesia , 11–13 dosing for ACS and PCI , 115–116 revision total hip arthroplasty , 9–10 management , 114 total hip replacement , 7–8 monitoring , 116–118 total knee replacement , 11 parenteral anticoagulants , 112–113 regional anesthesia perioperative management , 123 coagulopathy , 5–6 recommendations for , 119–120 infection , 4 surgery/interventional procedures , 116 neurological disease , 4–5 venous thromboembolism , 52–54 patient selection , 3–4 Antiphospholipid antibodies (aPL) positive patient rheumatoid arthritis , 3 anticoagulation airway management , 2–3 arterial and/or venous thrombosis , 97–98 preanesthetic preparation , 1–2 bridging anticoagulation , 96–97 Aneurysms , 222–223 clinically signi fi cant aPL patient , 97 Ankylosing spondylitis high-thrombosis-risk patients , 95–96 laminectomy , 301 monitoring , 98–99 total hip replacement , 254 neuraxial anesthesia , 96 total joint arthroplasty pregnancy morbidity , 98 heterotopic ossi fi cation , 250 aspirin , 102 in fl ammation , 245 assessment

B.F. Mandell (ed.), Perioperative Management of Patients with Rheumatic Disease, 403 DOI 10.1007/978-1-4614-2203-7, © Springer Science+Business Media, LLC 2013 404 Index

Antiphospholipid antibodies (aPL) Arthroscopy positive patient (cont.) biopsy , 354 aPL pro fi le , 93–94 complication , 356 bleeding risk , 94–95 contraindication , 354 patient-surgical team communication , 95 indication , 353–354 perioperative anticoagulation planning , 95 in fl ammatory arthritis , 353 thrombosis risk , 94 lavage , 354 bleeding and thrombosis management , 101–102 post-op care , 356 dental surgery , 99 synovectomy , 355 emergency surgery , 99 technique hydroxychloroquine , 102–103 clinical setup , 355 inferior vena cava fi lters , 100 synovectomy , 355–357 neurosurgery/spine surgery , 99–100 Aspiration pneumonia , 203 nonaspirin anti-platelet/anticoagulant agents , 103 Aspirin (ASA) , 71, 74, 102, 228, 239, 281, 282 perioperative considerations , 92–93 Atheroma , 59 postoperative microthrombosis , 101 Atlantoaxial instability (AAIS) , 2 prevalence , 91 Atrial septostomy , 147 renal transplantation , 100–101 Autologous blood transfusion (ABT) statin , 103 vs. allogeneic blood transfusion , 41 test , 91 PABD (see Preoperative autologous blood donation thrombosis (see Thrombosis) (PABD)) Antiphospholipid syndrome (APS) preparation surgery , 41 cardiac surgery Avascular necrosis (AVN) , 188 anticoagulation (see Anticoagulation) biologic procedure anti fi brinolytic agents , 118–119 core decompression , 362–363 antiphospholipid triangle , 109 osteotomy , 363 antiplatelet agents , 119–120 clinical manifestation , 361 coronary artery bypass rethrombosis , 110–111 joint replacement incidence , 110–111 cementless stems , 364 interventional procedures , 121–123 ceramic-on-ceramic hip replacement , 364 interventional procedures complications and hip resurfacing , 365 outcomes , 121–122 metal-on-metal hip replacement , 364–365 intracardiac thrombi , 110 partial/total hip replacement , 363–364 intraoperative management , 114–115 polyethylene , 364 myocardial infarction , 110 staging , 361–362 myocardial microthrombosis , 110 treatment algorithm , 365 on-pump vs. off-pump CABG , 113 AVN. See Avascular necrosis (AVN) preoperative management and approach , 111 Azathioprine , 78 protamine , 119 restenosis , 111 surgical complications and outcomes , 120–121 B thrombosis , 109–110 Bacteremia , 89 valvuloplasty/mechanical/bioprosthetic valve Bacteriuria , 256 replacement , 113–114 B-blocker therapy , 64–65 immune thrombocytopenic purpura (see Immune Beta-blockade , 281 thrombocytopenic purpura (ITP)) Bilateral laminectomy , 297, 298 noncardiac surgeries (see Antiphospholipid Blood transfusion. See Autologous blood transfusion antibodies (aPL) positive patient) Bone mineral density (BMD) testing , 234, 235 revised Sapporo classi fi cation criteria , 92 Bony ingrowth acetabular cup , 329 Antiplatelet agents Bridging anticoagulation , 96–97 periprocedural , 112 Bronchiolitis obliterans syndrome (BOS) , 391 postoperative , 119–120 Bronchoscopy , 373 postprocedural , 120 Antirejection drugs , 394 Antiresorptive agents , 237 C Antithrombotic therapy , 228 Calcium pyrophosphate-associated arthritis. Anti-tumor necrosis factor a drugs , 79–81 See Pseudogout Aortic regurgitation , 222 Cardiac Risk Index , 61–62 Apixaban , 52 Cardiac surgery and pulmonary hypertension , 140, 143 Arixtra® , 112 Cardiomyopathy , 203 Index 405

Cardiopulmonary bypass (CPB) , 116–117 preoperative workup , 290 Cardiovascular risk transoral decompression , 290 atherosclerosis subaxial subluxation atheroma , 59 basilar invagination , 290, 291 connective tissue disease , 59–60 cervical laminectomy , 291 coronary calci fi cation , 59 posterior instrumented fusion , 291 spondyloarthropathies , 59 preoperative workup , 290–292 systemic lupus erythematosus , 58–59 Chronic kidney disease (CKD) coronary artery disease , 57–58 acid-base homeostasis , 172 in fl ammation , 57–58 acute kidney injury (see Acute kidney injury (AKI)) preoperative risk assessment anemia , 172 ACC/AHA recommendations for noninvasive bone-mineral disorders , 172 ischemia , 63 cardiovascular risk , 172 B-blocker therapy , 64–65 de fi nition , 165 Cardiac Risk Index , 61–62 hemodialysis (see Hemodialysis) coronary artery stents , 63 hypertension (see Hypertension) morbidity and mortality , 61 morbidity and mortality , 166 percutaneous coronary intervention , 64 perioperative management , 166 statin therapy , 65–66 peritoneal dialysis , 179 treatment goals , 61 potassium homeostasis , 170–171 rheumatoid arthritis , 66–67 prevalence , 165–166 Carpal tunnel syndrome (CTS) sodium homeostasis , 171 anesthesia considerations , 320 staging of , 166 carpal tunnel release , 319 volume homeostasis , 171 disease-associated perioperative issues , 320 Clindamycin , 88 pathogenesis , 319 Clopidogrel , 282 postoperative management and rehabilitation , 321 Clostridium dif fi cile disease , 257 surgical indications Collagen vascular disease (CVDs) , 389 . See also Lung electrodiagnostic studies , 320 transplantation physical examination , 319 Comanagement radiographic evaluation , 319 academic settings , 399–400 sensory and motor function , 319 checklist , 400 surgical site infection , 320–321 de fi nition , 397 Celecoxib , 73–74 ethical implication , 401 Cemented polyethylene cup , 328 geriatric patients with hip fractures Ceramic-on-ceramic total hip replacement , 364 delirium , 398 Cervical instability , 2–3 diagnosis-related group codes , 398 Cervical spine disease hospitalist model , 399 asymptomatic , 212 hospitalist-orthopedic team model , 399 intubation risk , 213 multidisciplinary care model , 397–398 snif fi ng position, AAS , 213 usual care model , 398–399 symptomatic , 212 before implementation , 400–401 X-rays , 213 initial meeting , 400 Cervical spine stabilization outcomes , 399 ankylosing spondylitis pilot program , 401 HLA-B27 genetic predisposition , 292, 294 primary care physician , 399 posterior cervicothoracic fusion , 294 Compression stockings , 50, 51 atlantoaxial instability Congestive heart failure , 222 anterior atlantoaxial subluxation , 286, 287 Connective tissue disease anterior atlantodental interval , 286 arthroplasty (see also Total joint arthroplasty) C1–2 segmental fi xation , 289, 292 ankylosing spondylitis , 245 neck pain , 287 avascular necrosis , 245 occipito-cervical articulation , 285 femoral head , 245 surgical stabilization , 287–288 HAQ score , 245 transarticular screw fi xation , 288–289 hip resurfacing , 245 basilar impression , 294–295 in fl ammatory arthritis , 244–245 neurological de fi cits , 290 systemic lupus erythematosus , 245 occipital condylar C1 joint destruction , 289–290 pulmonary hypertension , 137–138 occipitocervical fusion , 290 Core decompression , 362–363 posterior occipitocervical fusion , 295 Coronary artery disease , 57–58 406 Index

Coronary calci fi cation , 59 renal transplantation (see Renal transplantation) Coronary heart disease (CHD) , 228–229 sodium homeostasis , 171–172 Corticosteroid. See Glucocorticoids Epidural catheter complications , 30–32 hip fracture , 27, 28 D shoulder surgery , 27 Dabigatran , 53–54 spine surgery , 28 D-dimer test , 217 total joint replacement , 28–30 Decortication of lung. See Lung decortication Evans’ syndrome , 156 Deep vein thrombosis (DVT) , 30 Extracorporeal membrane oxygenation (ECMO) , 147 arthroscopic synovectomy , 356 dabigatran , 53–54 elective spine surgery , 51 F etiology Facetectomy , 299 hypercoagulability , 46 Fat embolism syndrome (FES) , 247 intimal injury , 46 arthroplasty , 16 stasis , 45 central nervous system signs , 14 hip fracture , 239 CNS injury , 14–16 joint replacement surgery , 50 cotton-wool , 14, 15 knee arthroscopy , 51 cutaneous manifestations , 14 postoperative infection and fever , 257–258 DIC , 15 prophylaxis , 47, 49 hemodynamic consequences , 14 risk factor assessment , 46–48 high-risk surgical procedure , 16–17 rivaroxaban , 52–53 indication , 15 total hip arthroplasty , 335 laboratory tests/diagnosis , 15 total knee arthroplasty , 348–349 mechanical theory , 14 Delayed graft function (DGF) , 380 microscopic fat embolism , 13–14 Deoxypyridinoline , 237 occurrence , 13–14 Dermatomyositis , 394 pulmonary artery catheterization , 16 Digital spasm , 194 pulmonary consequences , 14–15 Direct thrombin inhibitor (DTI) , 111 steroid therapy , 16 Disease-modifying antirheumatic drugs tissue oxygenation , 17 (DMARDs) , 324 total joint replacement , 16 biologic disease-modifying antirheumatic drugs transesophageal echocardiography , 14 abatacept , 81 type II pneumocyte , 14 anakinra , 82 Felty’s syndrome , 156, 157, 159, 160, 368 anti-tumor necrosis factor a medications , 79–81 Femoral stems , 329 herbal supplements , 82–83 FES. See Fat embolism syndrome (FES) rituximab , 81–82 Fever , 250 tocilizumab , 82 Fibrosing alveolitis (FA) , 390 nonbiologic disease-modifying antirheumatic drugs Fibrothorax , 385–387 azathioprine , 78 Fluconazole , 256 hydroxychloroquine , 78 Focal indeterminate in fi ltrate , 373–374 le fl unomide , 77–78 Foraminotomy , 299 methotrexate , 76–77 Fragmin® , 112 mycophenolate mofetil , 78–79 Funguria , 256 sulfasalazine , 78 perioperative infection and wound healing , 76 Disseminated intravascular coagulation (DIC) , 15 G Dual energy X-ray absorptiometry (DXA) , 235–236 General anesthesia D V T . See Deep vein thrombosis (DVT) methyl methacrylate , 8 neurological disease , 5 recovery issues , 10, 11 E vs. regional anesthesia Eltrombopag , 132 coagulation , 12–13 Empyema , 385–387 DVT prophylaxis , 12 Endovascular stent , 230 EBL , 12 End-stage renal disease (ESRD) infection , 13 kidney transplant , 179 mental status , 13 potassium homeostasis , 171 nerve injury , 13 Index 407

thromboembolism , 11–12 joint replacement , 206 urinary retention , 13 malignancy-associated myositis , 207 total hip replacement , 7, 8 muscle biopsy , 206 total knee replacement , 11 postoperative considerations , 205 Geriatric Fracture Center (GFC) , 398–399 preoperative considerations Glucocorticoids aspiration pneumonia , 203 adrenal insuf fi ciency , 74–75 cardiomyopathy , 203 aldosterone , 75 interstitial lung disease , 202 cortisol , 74 medication , 204 in fl ammatory arthritis , 75–76 oropharyngeal dysmotility , 203–204 perioperative stress dosing , 75 pneumomediastinum , 203 prednisone , 75 pneumothorax , 203 Granulocyte colony-stimulating factor (GCSF) , 158–159 respiratory muscle weakness , 202–203 Growth factor therapy for neutropenia , 158–159, 161 Idiopathic thrombocytopenic purpura (ITP) , 368 Immune thrombocytopenic purpura (ITP) anti-D antibodies , 132 H classi fi cation , 129 Health Assessment Questionnaire (HAQ) , 245 diagnosis , 130 Hemarthrosis , 356 general perioperative management Hematoma , 246–247, 336 IVIG , 131 Hemodialysis platelet transfusion , 130 access management , 178 steroids , 131 anesthetics , 177 surgery , 130–131 anticoagulation , 177 occurrence , 129 narcotics removal , 176–177 pathophysiology , 129–130 perioperative issues , 177 recommendations for management time for surgery , 178 elective surgery , 133–134 uremia , 178–179 emergent surgery , 133 volume management , 178 urgent surgery , 133 Henoch-Schönlein purpura (HSP) , 377 rituximab , 132 Heparin for venous thromboembolism , 47, 50–52 splenectomy , 132 Herbal supplements , 82–83 thrombopoietic agents , 132–133 Heterotopic ossi fi cation , 249–250, 337 Immunosuppressants , 227–228 Hip fracture. See Osteoporotic hip fractures Indomethacin , 74 Hip resurfacing , 365 In fl ammation , 57–58 Hydroxychloroquine , 78, 102–103 Intermittent pneumatic compression (IPC) device , 239 Hydroxyproline measurement , 237 Interstitial lung disease , 202 Hyperkalemia , 170–171 Intra-aortic balloon pump , 147 Hypertension , 222 Intravenous immunoglobulin (IVIG) , 131 chronic hypertension , 173 Intubation , 3, 7 diagnosis , 172 medications , 173–174 renal disease K hemodialysis ( see Hemodialysis) hepatic Kidney transplantation , 179 . See also clearance of drugs , 174 Renal transplantation medication dosing , 174 Knee arthroplasty. See Total knee arthroplasty (TKA) narcotic analgesics , 176 Knee replacement. See Arthroscopy; Total knee NSAIDs , 176 arthroplasty (TKA) pharmacokinetic changes , 174 renal clearance of drugs , 174–175 rheumatology-speci fi c medications , 175–176 L surgical outcomes , 172 Laminectomy , 302 ankylosing spondylitis , 301 back pain , 298 I bilateral , 297, 298 Idiopathic in fl ammatory myopathy (IIM) complications calcinosis , 205–206 incidental durotomy , 300 intraoperative considerations neurological injury , 300 anesthesia/neuromuscular blockade , 204–205 postlaminectomy instability , 301 malignant hyperthermia , 205 prophylactic antibiotics , 300–301 408 Index

Laminectomy (cont.) polymyositis , 394 facet joints degeneration , 298 postoperative care , 394 postoperative care progressive systemic sclerosis analgesics , 299 bowel involvement , 392 anticoagulants , 299–300 chronic rejection/bronchiolitis obliterans incentive spirometry , 300 syndrome , 391 physical therapy , 300 fi brosing alveolitis , 390 postoperative infection , 301 gastrointestinal disorders , 391 rheumatoid arthritis , 301 narcotics and calcineurin inhibitor , 391–392 spinal stenosis , 297 primary and secondary cardiac Laminotomy , 298, 299, 302 disease , 392 Laparoscopic splenectomy (LS) pulmonary hypertension , 390 blunt traumatic splenic injury , 367 Raynaud’s phenomenon , 392 complication vagal nerve injury , 391 hematologic response , 370–371 vascular abnormalities , 392 pancreatic injury , 370 rheumatoid arthritis , 392–393 procedure-speci fi c , 369–370 systemic lupus erythematosus , 393 steroid treatment , 369 venous thrombosis , 370 indication , 368 M operative preparation and technique , 368–369 Malignancy-associated myositis , 207 OPSI , 371 Medication-induced fevers , 257 Laryngeal mask airway (LMA) , 214 Metacarpophalangeal arthroplasty Latrogenic infection , 87–89 anesthesia considerations , 324 Le fl unomide , 77–78 complications , 324–325 Leukopenia , 188 . See also Neutropenia contraindications , 324 Local anesthesia disease-associated perioperative issues , 324 allergy , 31 indications , 323–324 central block , 26 postoperative management and hip fracture , 27 rehabilitation , 325 knee surgery , 30 Metal-on-metal total hip replacement , 364–365 neurological injury , 33 Methotrexate , 76–77 peripheral nerve block , 25–26 cricoarytenoid arthritis , 214 seizure activity , 32 rheumatoid arthritis , 218 shoulder surgery , 26–27 Methyl methacrylate (MMA) , 8–9 spine surgery , 28 Mycophenolate mofetil (MMF) , 78–79 total joint replacement , 29 Myocardial infarction (MI) Lovenox ® , 112 diagnosis Low-dose unfractionated heparin (LDUH) , 239, 240 cardiac troponin , 277–278 Low molecular weight heparin (LMWH) , 239, 240 CK-MB , 278 Lung biopsy echocardiography , 278–279 bronchoscopy , 373 medical therapy contraindication , 373 aspirin , 282 indications , 373 beta-blockade , 281 post-operative care , 375–376 clopidogrel , 282 surgical lung biopsy NSAIDS , 282–283 complication , 375 statin therapy , 281–282 thoracotomy , 374–375 steroids , 282 VAT , 374, 375 in orthopedic patients , 280 Lung decortication postoperative , 63 indication , 385 preoperative risk assessment , 61, 62 patient assessment , 385–387 rheumatologic disorders , 280–281 postoperative care , 387–388 SLE , 58–59 Lung transplantation statin therapy , 65 antirejection drugs , 394 stent thrombosis , 63 comorbidities , 389–390 type 1 , 279 contraindication , 389 type 2 dermatomyositis , 394 ischemia , 279–280 end stage lung disease , 389 mechanisms , 280 indication , 389 troponin , 279 Index 409

N hip fracture , 27–28 Neuropraxias , 247–248 knee surgery , 30 Neurovascular injury , 336 preemptive analgesia , 26 Neutropenia shoulder surgery , 26–27 de fi nition , 155 spine surgery , 28 growth factor therapy , 158–159, 161 total hip replacement , 28–30 infectious risks , 156 mechanism of acute pain , 23–24 mechanisms causing , 156–157 pain physiology , 24 medications , 159–160 postoperative analgesia occurrence , 155–156 central blocks , 26 prophylactic antibiotics , 159 NSAID , 24–25 splenectomy , 160 parenteral opioids , 25 surgical consideration , 155 peripheral nerve blocks , 25–26 treatment goals , 157–158 regional anesthesia complication Non-steroidal anti-in fl ammatory drugs (NSAIDs) , 24–25 allergy , 31 aspirin , 74 anticoagulant drugs , 30–31 clinical manifestation , 71–72 infection , 31–32 COX-1 inhibitor , 72–73 neurological injury , 33 COX-2 inhibitor , 73–74 seizure activity , 32 half-lives , 73 vascular injury , 33 heterotopic ossi fi cation , 74 Periprosthetic fracture , 249, 337 mechanism of action , 72 Platelet transfusion , 130 myocardial infarction , 282–283 Pleural surgery. See Lung decortication rheumatoid arthritis , 212 Pneumomediastinum , 203 Pneumonia , 257 Pneumothorax , 203 O Polymerase chain reaction (PCR) assays , Oral infection , 88–89 264–265 Oropharyngeal dysmotility , 203–204 Polymyositis , 394 Osteocalcin , 236 Postlaminectomy instability , 301 Osteonecrosis. See Avascular necrosis (AVN) Postoperative infection , 71 Osteoporotic hip fractures fever alendronate , 237 bloodstream infections , 255–256 anabolic therapy , 238 Clostridium dif fi cile disease , 257 annual costs , 233 deep venous thrombosis , 257–258 antiresorptive therapy , 237–238 medication-induced fevers , 257 bone turnover assay pneumonia , 257 bone formation , 236 urinary tract infections , 256–257 bone resorption , 236–237 wound infection , 255 limitations , 237 immunosuppressive medications cemented vs. noncemented hip arthroplasty , 238–239 corticosteroids , 253 delayed surgery methotrexate , 254 low-energy fall and fracture , 233–234 TNF-a blockade , 254 medical comorbidities , 234 rheumatologic disorder mortality , 233, 234 colonization in , 254–255 operative repair delay , 233 knee arthroplasty , 254 prefracture comorbidities , 233 total hip replacement , 254 patient risk assassment Posttransplant lymph proliferative disease BMD testing , 234, 235 (PTLD) , 382 dual energy X-ray absorptiometry , 235–236 Pregnancy and pulmonary hypertension , 143–144 WHO fracture risk assessment model , 234, 236 Preoperative autologous blood donation (PABD) perioperative anticoagulation , 239–240 contraindications , 42 Overwhelming post-splenectomy sepsis (OPSI) , 371 cost , 43 erythropoietin , 43 hematocrit , 42 P indications , 42 PABD. See Preoperative autologous blood donation patient selection , 42 (PABD) process , 41–42 Pain management risk , 42–43 analgesia for orthopedic surgery Procollagen type I propeptide , 236 410 Index

Progressive systemic sclerosis (PSSC) Pulmonary function test (PFT) , 202 bowel involvement , 392 Pulmonary hypertension (PH) chronic rejection/bronchiolitis obliterans cardiac surgery , 140, 143 syndrome , 391 classi fi cation , 137 fi brosing alveolitis , 390 clinical manifestation , 137 gastrointestinal disorders , 391 connective tissue diseases , 137–138 narcotics and calcineurin inhibitor , 391–392 de fi nition , 137 primary and secondary cardiac disease , 392 intraoperative management , 145–146 pulmonary hypertension , 390 lung transplant , 390 Raynaud’s phenomenon , 392 management vagal nerve injury , 391 acute decompensated PH , 146 vascular abnormalities , 392 mechanical support , 147 Prophylactic antibiotics vasodilators , 146–147 endocarditis , 88 vasopressors , 146 oral infection , 88–89 noncardiac surgery , 140–142 prosthetic joint infection , 87 pathophysiological considerations , 139–140 recommendation for intraoperative doses , 88 postoperative care , 147 surgical site infection , 87–88 pregnancy , 143–144 TNF blockers , 87 preoperative management , 144–145 urological infection , 89 surgerical consideration , 138–139 Prosthetic joint infection (PJI) Pulmonary vascular resistance (PVR) , 139, 140, 146 diagnosis Pyridinoline , 237 blood tests , 262 histopathology and microbiology , 263 infection probability , 263 R intraoperative tissue culture , 263–264 Raynaud phenomenon , 193–194 molecular assays , 264–265 Raynaud’s phenomenon , 392 plain radiographs , 263 Regional nerve block , 4–5, 7, 11, 25–26 preoperative phase , 261 Renal failure synovial fl uid analysis , 262–263 rheumatology-speci fi c medications , 175–176 virulent pathogens , 262 SLE , 189 management Renal transplantation , 100–101 antibiotic choices , 265 anesthetic consideration , 378–379 antibiotic therapy type and duration , 265–266 bleeding , 379–380 chronic oral antibiotic suppression , 267 clinical manifestation , 377 debridement and retention , 265 DGF , 380 future aspects , 267 gastrointestinal complications , 381 infection timing , 265 infection , 381–382 reimplantation surgery , 266–267 outcomes , 382 microbiology , 261, 262 patient evaluation , 377–378 prophylactic antibiotics , 87–89 postoperative collections , 380 risk factors , 262 posttransplant immunosuppression , 381 Protamine , 119 procedure , 379 Protrusio acetabuli , 333 PTLD , 382 Pseudogout recurrence risk , 378 acute attack thrombotic risk , 379 anti-IL-1 antibody canakinumab , 274 timing of transplantation , 378 colchicine , 274 ureteral obstruction , 381 corticosteroids , 274 urine leaks , 380–381 hypouricemic therapy , 274–275 vascular complications , 380 intra-articular steroid , 274 Respiratory muscle weakness , 202–203 NSAID therapy , 273–274 Reverse shoulder arthroplasty , 316 diagnosis Rheumatoid arthritis (RA) antibiotic therapy , 273 cardiovascular disease risk arthrocentesis , 273 clinical history , 210 hyperuricemia , 272 disease duration , 210 US examination , 272 preoperative ECGs , 211 prevention , 275 stress test , 211 Pulmonary embolism (PE) , 239 cervical spine disease Pulmonary Embolism Prevention (PEP) trial , 239 asymptomatic , 212 Index 411

intubation risk , 213 humeral component migration , 316 snif fi ng position, AAS , 213 intraoperative fracture , 316 symptomatic , 212 neurovascular complications , 316 X-rays , 213 patient selection , 314–316 corticosteroids , 211 radiographic workup , 313–314 cricoarytenoid arthritis , 213–214 rehabilitation program , 316–317 diabetes , 211 Silicone-induced lymphadenopathy , 325 operative day considerations Sjogren’s syndrome , 155–156, 159 ankle and foot , 216 Society of Hospital Medicine Comanagement Advisory cervical spine , 215 Task Force , 400–401 elbow , 216 Solitary pulmonary nodule (SPN) , 373–375 hip and knee , 215 Splenectomy , 132 intraoperative monitoring , 215 indication for , 367 patient positioning , 215 laparoscopy (see Laparoscopic surgical site-speci fi c considerations , 215 splenectomy) neutropenia , 160 osteoarthritis , 212 Split pleural sign , 385, 386 postoperative considerations Spondyloarthropathies (SpA) , 59 analgesic management , 216–217 Staphylococcus aureus , 262 DMARD therapy , 217 Statin therapy , 65–66, 103, 281–282 immunosuppressive medications , 217–218 Steroids , 131, 282 tocilizumab , 217 Sulfasalazine , 78 VTE prophylaxis , 217 Surgical site infection (SSI) , 87–88 postoperative rehabilitation planning , 212 Synovectomy , 355–357 preoperative lab testing , 09–210 Systemic lupus erythematosus (SLE) , 245 pulmonary disease , 211 antimalarial drugs , 184 recombinant erythropoietin , 211–212 atherosclerosis , 58–59 temporomandibular joint arthritis , 213 azathioprine , 185 Right ventricular (RV) failure and pulmonary biologic therapies hypertension , 138 belimumab , 186 intraoperative evaluation , 145 rituximab , 185 management , 146–147 cardiovascular manifestations , 186–187 noncardiac surgery , 140 cyclophosphamide , 185 pathophysiology , 139–140 cytotoxic therapy , 185 postoperative care , 147 ESRD (see Renal transplantation) exocrine preoperative evaluation , 144 glands , 189 volatile anesthetic agent , 146 glucocorticoids , 184 Rituximab , 81–82, 132, 160 hematologic abnormalities , 187–188 Rivaroxaban , 52–53 immune system , 189 Romiplostim (AMG351) , 132 immunosuppressive therapy , 185 Rotational osteotomy , 363 lung transplantation , 392 musculoskeletal manifestation , 188–189 mycophenolate mofetil , 185 S neutropenia , 155, 157 Scleroderma NSAIDs , 184 calcinosis , 195 renal involvement , 189 cardiovascular manifestation , 196 surgical outcomes , 183 gastrointestinal motility , 196–197 vascular manifestation , 189–190 gastroparesis , 197 GI bleeding , 197 hematology , 198 T interstitial lung disease , 195 Takayasu’s arteritis (TA) musculoskeletal manifestation , 198 antithrombotic therapy , 228 pulmonary arterial hypertension , 195–196 cardiac assessment , 228–229 renal crisis , 197 cerebral revascularization , 229 skin manifestation , 195 disease activity assessment , 226 wound healing , 195 algorithm , 227 Septic arthritis , 87, 89 CT angiography , 224 Shoulder arthroplasty 18FDG-PET , 225 anesthesia considerations , 315 isolated vessel wall anomalies , 225 hematologic complications , 316 MRI/MR angiography , 224–225 412 Index

Takayasu’s arteritis (TA) (cont.) uncemented constrained liner insert , 328 ultrasonography , 224 fi xation vascular involvement , 225 cement , 328–329 disease extension , 227 cementless , 328 endovascular procedures , 230 late postoperative patient , 337–338 in fl ammatory components , 221 patient preoperative assessment medications , 227–228 allergies , 332 pulmonary artery involvement , 221 anesthesia considerations , 331 revascularization interventions antibiotic prophylaxis , 330–331 aneurysms , 222–223 blood loss , 330 aortic regurgitation , 222 bony deformity , 333 congestive heart failure , 222 contraindications , 330 hypertension , 222 deformity and contractures , 332 stenosed vessels , 222 hip pain , 331 symptoms and clinical features , 221 indications , 330 Team management approaches. See Comanagement infections sources , 331–332 Temporomandibular joint (TMJ) arthritis , 213 medical considerations , 330 Thoracentesis , 387 osteoporosis , 332–333 Thoracotomy , 374–375 protrusio acetabuli , 333 Thrombocytopenia , 187 . See also Immune rheumatoid arthritis , 332 thrombocytopenic purpura (ITP) skin manifestations , 331 Thromboembolism postoperative treatment and considerations apixaban , 52 deep vein thrombosis , 335 clinical consideration , 54 pain control , 335 dabigatran , 53–54 physical therapy , 334–335 elective spine surgery , 51 preoperative pain , 334 etiology , 45–46 rehabilitation facility , 333–334 joint replacement surgery , 50–51 sutures and staples , 334 knee arthroscopy , 51–52 venous thromboembolism , 335 prophylaxis , 47, 49–50 weight bearing status , 334 risk factor assessment , 46–48 Total joint arthroplasty rivaroxaban , 52–53 connective tissue disease Thrombosis ankylosing spondylitis , 245 aPL-positive patients , 91–92 avascular necrosis , 245 arterial and/or venous , 92–93 femoral head , 245 bridging anticoagulation , 97–98 Health Assessment Questionnaire score , 245 management , 101–102 hip resurfacing , 245 microthrombosis , 101 in fl ammatory arthritis , 244–245 occurrence , 92 systemic lupus erythematosus , 245 pregnancy morbidity , 98 epidemiologic observations , 243–244 prophylaxis , 92–93 postoperative complications risk , 94, 96 dislocation , 247 cardiac surgery , 109–110 (see also Antiphospholipid fat embolism syndrome , 247 syndrome (APS)) fever , 250 TKA. See Total knee arthroplasty (TKA) hematoma , 246–247 Tocilizumab , 82 heterotopic ossi fi cation , 249–250 Total hip arthroplasty (THA) neuropraxias , 247–248 articulating surfaces , 330 periprosthetic fracture , 249 complications vascular compromise , 248 dislocation , 336–337 venous thromboembolism , 246 hematoma , 336 Total knee arthroplasty (TKA) heterotopic ossi fi cation , 337 basic total knee arthroplasty , 341, 342 neurovascular injury , 336 bone cement , 342, 343 periprosthetic fracture , 337 complications surgical site and prosthetic infection , 336 heterotopic ossi fi cation , 350 venous thromboembolism , 336 infection , 349 components , 327 neurovascular injury , 349 bony ingrowth acetabular cup , 329 patellofemoral complications , 349 cemented polyethylene cup , 328 periprosthetic fractures , 350 femoral stem variety , 329 VTE and DVT , 348–349 Index 413

follow-up , 350 Uncemented constrained liner insert , 328 hinge total knee arthroplasty , 341, 343 late postoperative care , 350 postoperative treatment and consideration V continuous passive motion machine , 347 Vancomycin , 88 pain control , 347 Varus/valgus osteotomy , 363 physical therapy , 347 Vasodilator therapy VTE and DVT , 348 inhaled nitric oxide , 146 weight-bearing ability , 347 intravenous vasodilator , 147 preoperative assessment pulmonary vasodilator , 146–147 anesthesia considerations , 346–347 Venoarterial extracorporeal membrane bilateral total knee arthoplasty , 344–345 oxygenation , 147 blood loss , 345–346 Venous thromboembolism (VTE) , 246, 335, 336 bone quality , 346 Vertebroplasty contraindication , 343 contraindications , 306 indications , 342–343 fl uoroscopy imaging , 306, 307 infection , 345 indications , 305–306 medical issues and medications , 344–345 patient position , 306, 307 skin manifestation , 345 patient selection soft tissue characteristics , 346 clinical history , 304 walking aids/walker , 346 physical examination , 304 tibial polyethylene inserts , 341, 342 posteroanterior and lateral radiographs , Tracheostomy , 214 304–306 Tumor necrosis factor (TNF) , 87 Video-assisted decortication , 386 Video-assisted thoracic surgery (VATs) , 374, 375

U Ultrahigh molecular weight polyethylene (UHMWPE) W acetabular insert , 330 Wegener’s granulomatosis (WG) , 377