The Journal of Trauma: Injury, Infection and Critical Care

The Journal of Trauma: Injury,

Infection and Critical Care

November 2007, Volume 63, Issue 5,pp.965-1194

Original Articles 965 The Benefit of Higher Level of Care Transfer of Injured Patients From Nontertiary Hospital Emergency Departments. Craig D. Newgard, MD, MPH; K John McConnell, PhD; Jerris R. Hedges, MD, MS; Richard J. Mullins, MD 972 Pre-injury ASA Physical Status Classification is an Independent Predictor of Mortality After Trauma. Nils O. Skaga, MD; Torsten Eken, MD, PhD; Signe Søvik, MD, PhD; J Mary Jones, PhD; Petter A. Steen, MD, PhD 979 Postmortem Computed Tomography, "CATopsy", Predicts Cause of Death in Trauma Patients. Brian A. Hoey, MD; James Cipolla, MD; Michael D. Grossman, MD; Nathaniel McQuay, MD; Pratik R. Shukla, MD; Stanislaw P. Stawicki, MD; Christy Stehly, BS; William S. Hoff, MD 987 Acute Renal Failure in Critically Ill Surgical Patients: Persistent Lethality Despite New Modes of Renal Replacement Therapy. Soumitra R. Eachempati, MD; John C. L. Wang, MD; Lynn J. Hydo, MBA; Jian Shou, MD; Philip S. Barie, MD, MBA 994 All-Terrain Vehicle Crash Factors and Associated Injuries in Patients Presenting to a Regional Trauma Center. Mark A. Brandenburg, MD, FACEP; Sheryll J. Brown, MPH; Pam Archer, MPH; Edward N. Brandt Jr, MD, PhD 1000 Delta V, Principal Direction of Force, and Restraint Use Contributions to Motor Vehicle Crash Mortality. Gabriel E. Ryb, MD, MPH; Patricia C. Dischinger, PhD; Joseph A. Kufera, MA; Cynthia A. Burch, MPH 1006 Increased Fatalities After Motorcycle Helmet Law Repeal: Is it All Because of Lack of Helmets? Terence O'Keeffe, MBChB, MSPH; Steve R. Dearwater, BA, MPH; Larry M. Gentilello, MD, FACS; Todd M. Cohen, BA; James D. Wilkinson, MD, MPH; Mark M. McKenney, MD, FACS 1010 Brain Lobectomy for Severe Head Injuries is not a Hopeless Procedure. Didem Oncel, MD; Demetrios Demetriades, MD, PhD, FACS; Peter Gruen, MD, FACS; Ali Salim, MD, FACS; Kenji Inaba, MD, FACS; Peter Rhee, MD, FACS; Timothy Browder, MD, FACS; Shot Nomoto, RN; Linda Chan, PhD

1014 Traumatic Carotid Cavernous Fistula Accompanying Basilar Skull Fracture: a Study on the Incidence of Traumatic Carotid Cavernous Fistula in the Patients With Basilar Skull Fracture and the Prognostic Analysis About Traumatic Carotid Cavernous Fistula. Wen Liang, MD; Yang Xiaofeng, MD, PhD; Liu Weiguo, MD; Qiu Wusi, PhD; Shen Gang, PhD; Zheng Xuesheng, MD 1021 Brachial Plexus Injury: Long-Term Functional Outcome is Determined by Associated Scapulothoracic Dissociation. Kevin P. Riess, MD; Thomas H. Cogbill, MD; Nirav Y. Patel, MD; Pamela J. Lambert, RN; Michelle A. Mathiason, MS 1026 Agreement Between Prehospital and Emergency Department Glasgow Coma Scores. Jeffrey D. Kerby, MD, PhD; Paul A. MacLennan, PhD; Jon N. Burton, MD; Gerald McGwin Jr, MS, PhD; Loring W. Rue III, MD 1032 Hemodynamic and Oxygen Transport Patterns After Head Trauma and Brain Death: Implications for Management of the Organ Donor. Howard Belzberg, MD; William C. Shoemaker, MD; Charles C. J. Wo, BS; Timothy P. Nicholls, MD; Alexis B. C. Dang, BS; Vladimir Zelman, MD; J Peter Gruen, MD; Thomas V. Berne, MD; Demetrios Demetriades, MD, PhD 1043 Treatment Strategies for Complex Fractures of the Tibial Plateau With External Circular Fixation and Limited Internal Fixation. Maurizio A. Catagni, MD; Giulia Ottaviani, MD, PhD; Massimiliano Maggioni, MD 1054 Proximal Femoral Nail for the Treatment of Reverse Obliquity Intertrochanteric Fractures Compared With Gamma Nail. Woo-Kie Min, MD; Shin-Yoon Kim, MD; Tae-Kong Kim, MD; Kyu-Bong Lee, MD; Myung- Rae Cho, MD; Yong-Chan Ha, MD; Kyung-Hoi Koo, MD 1061 Plating of Femoral Shaft Fractures: Open Reduction and Internal Fixation Versus Submuscular Fixation. Michael Zlowodzki, MD; Dennis Vogt, MD; Peter A. Cole, MD; Philip J. Kregor, MD 1066 The Epidemiology of Pelvic Ring Fractures: A Population-Based Study. Zsolt Balogh, MD, PhD, FRACS; Kate L. King, RN, MN; Peter Mackay, RN; Debra McDougall, RN; Stuart Mackenzie, BMed, BMedSc; Julie A. Evans, RN; Timothy Lyons, MBChB, MD, FRCS (Ed), FRCPATH, FRCPA, DMJ (Path), DipAvMed; Stephen A. Deane, MB BS, FRACS, FACS, FRCSC 1074 Optimal Plaster Conformation Derived Using a Custom-Made Jig to Obtain Maximum Strength of Protective Plaster of Paris for Hand Surgery. Christoph Theopold, MA, MRCS; James A. Bush, MRCS; Stuart W. Wilson, FRCS, FRCS (Plast.); Ardeshir Bayat, MRCS, PhD 1079 In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures. Bijan S. Kheirabadi, PhD; Angel V. Delgado, PhD; Michael A. Dubick, PhD; Michael R. Scherer, MA; Chriselda G. Fedyk, MS; John B. Holcomb, MD; Anthony E. Pusateri, PhD 1087 Immunocompetence of the Severely Injured Spleen Verified by Differential Interference Contrast Microscopy: the Red Blood Cell Pit Test. Mark Falimirski, MD, FACS; Amjad Syed, MD; David Prybilla, MD 1093 Predicting the Severity of Systemic Inflammatory Response Syndrome (SIRS)-Associated Coagulopathy With Hemostatic Molecular Markers and Vascular Endothelial Injury Markers. Toshiaki Iba, MD; Satoshi Gando, MD; Atsuo Murata, MD; Shigeki Kushimoto, MD; Daizoh Saitoh, MD; Yutaka Eguchi, MD; Yasuhiro Ohtomo, MD; Kohji Okamoto, MD; Kazuhide Koseki, MD; Toshihiko Mayumi, MD; Toshiaki Ikeda, MD; Hiroyasu Ishhikura, MD; Masashi Ueyama, MD; Yuji Ogura, MD; Shigeatsu Endo, MD; Shuji Shimazaki, MD; the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Study Group 1099 The Effects of Gammahydroxybutyrate on Hypermetabolism and Wound Healing in a Rat Model of Large Thermal Injury. Kevin D. Murphy, MD, MCh, MMS, FRCSI; Mary W. Rose, PsyD; David L. Chinkes, PhD; Walter J. Meyer III, MD; David N. Herndon, MD, FACS; Hal K. Hawkins, MD, PhD; Arthur P. Sanford, MD 1108 Packed Red Blood Cell-Associated Arginine Depletion is Mediated by Arginase. Andrew Bernard, MD; Cynthia Meier, MS; Nicholas Lopez, MD; John May, BS; Phillip Chang, MD; Bernard Boulanger, MD; Paul Kearney, MD 1113 Resuscitation From Hemorrhagic Shock Comparing Standard Hemoglobin-Based Oxygen Carrier (HBOC)-201 Versus 7.5% Hypertonic HBOC-201. Fernando A. Rivera-Chavez, MD; Sergio Huerta, MD; Ronnie Brown, BS; Gregory B. York, MD; Joseph P. Minei, MD 1120 Range-of-Motion Restriction and Craniofacial Tissue-Interface Pressure From Four Cervical Collars. Ann N. Tescher, RN, PhD, CNS; Aaron B. Rindflesch, PT, PhD; James W. Youdas, PT; Therese M. Jacobson, RN, CNS; Lisa L. Downer, RN, CNS; Anne G. Miers, RN, CNS; Jeffrey R. Basford, MD, PhD; Daniel C. Cullinane, MD; Susanna R. Stevens, MS; V Shane Pankratz, PhD; Paul A. Decker, MS 1127 Use of a Pediatric Cohort to Examine Gender and Sex Hormone Influences on Outcome After Trauma. Herb A. Phelan, MD; Shahid Shafi, MD, MPH; Jennifer Parks, MPH; R Todd Maxson, MD; Naveed Ahmad, MD, MPH; Joseph T. Murphy, MD; Joseph P. Minei, MD 1132 Can Increased Incidence of Deep Vein Thrombosis (DVT) be Used as a Marker of Quality of Care in the Absence of Standardized Screening? The Potential Effect of Surveillance Bias on Reported DVT Rates after Trauma. Elliott R. Haut, MD; Kathy Noll, MSN; David T. Efron, MD; Sean M. Berenholz, MD; Adil Haider, MD, MPH; Edward E. Cornwell III, MD; Peter J. Pronovost, MD, PhD 1138 Ethnic Disparities Exist in Trauma Care. Shahid Shafi, MD, MPH; Carlos Marquez de la Plata, PhD; Ramon Diaz-Arrastia, MD, PhD; Aaron Bransky, MD; Heidi Frankel, MD; Alan C. Elliott, MAS, MBA; Jennifer Parks, MPH; Larry M. Gentilello, MD

1143 Development of a Hospital-Based Trauma Registry in Haiti: An Approach for Improving Injury Surveillance in Developing and Resource-Poor Settings. Caleb R. Schultz, MD; Henri R. Ford, MD, FACS; Laura D. Cassidy, PhD; Barbara L. Shultz, RN; Christian Blanc, MD; Leslie W. King-Schultz, MPH; Henry B. Perry, MD, PhD, MPH, FACS Case Report 1155 Improved Cerebral Oxygenation After High-Dose Inhaled Aerosolized Prostacyclin Therapy for Acute Lung Injury: A Case Report. Michael F. Stiefel, MD, PhD; Kareem A. Zaghloul, MD, PhD; Stephanie Bloom, MSN; Vicente H. Gracias, MD; Peter D. LeRoux, MD 1159 Surgical Stabilization of a Rib Fracture using an Angle Stable Plate. Roel Beelen, MD; Jan Rumbaut, MD; Raphaël De Geest, MD 1161 Colorectal and Vaginal Injuries in Personal Watercraft Passengers. Sashil Singh Kapur, BA; Lonnie Warren Frei, MD, FACS, FCCM 1165 Laparoscopy and the Management of Blunt Bladder Trauma. Jonathan L. Wright, MD; James R. Porter, MD

1167 Perforated Meckel's Diverticulum in a Child After Blunt Abdominal Trauma. Kennith H. Sartorelli, MD; Christopher Healey, MD; Anthony Deross, MD 1169 Extensor Pollicis Longus Rupture After Fixation of Radius and Ulna Fracture With Titanium Elastic Nail (TEN) in a Child: A Case Report. Tomar Kravel; Neer Sher-Lurie, PhD; Abraham Ganel, PhD 1171 Damage Caused by a Kirschner Wire. Tammo S. de Vries Reilingh, MD; Michel F. P. van der Jagt, MD; William A. H. van der Stappen, MD; Wout B. Barendregt, MD, PhD E105 Intrapelvic Penetration of the Dynamic Hip Screw During Removal: Lesson Learnt-Always Use a Coupling Screw. Rahij Anwar, MS, MSc, MRCS; Venkat Boorgula, MRCS; James E. Nicholl, FRCSOrth E107 Hybrid Procedures Combining Open and Endovascular Surgical Techniques for the Management of Subclavian Artery Injuries. Christos D. Karkos, FRCSEd, PhD; Richard Mair, MB, ChB; George Markose, FRCR; Guy Fishwick, FRCR; Nicholas J. M. London, MD, FRCS; A Ross Naylor, MD, FRCS E111 Low-Molecular-Weight Heparin for Prevention of Thrombosis: Inverted Role. Zoe H. Dailiana, MD; Konstantinos N. Malizos, MD; Sokratis Varitimidis, MD; Michael Hantes, MD; George Basdekis, MD; Nikolaos Rigopoulos, MD E116 Peri-Operative Considerations During Biliary Exploration and Reconstruction: Report of Delayed Biliary Obstruction by a Bullet. William Elliott Stansfield, MDCM; Kenneth A. Andreoni, MD Review Article 1173 Esophageal Perforations: New Perspectives and Treatment Paradigms. James T. Wu, MD; Kenneth L. Mattox, MD; Matthew J. Wall Jr, MD Brief Report 1185 A Simplified Technique of Using Bipedicled Fasciocutaneous Flaps in Closure of Soft Tissue Defects of the Anterior Leg in Patients With Fasciotomy Wounds. Deemesh Oudit, MRCSEd; Omar Tillo, MS, MRCS; Gavin McCoubrey, MBBS; Louise Crawford, MRCSEd; Ali Juma, FRCS 1187 Carboxyhemoglobin Monitored by Bedside Continuous CO- Oximetry. Troilus Plante, MD; Darcy Harris, MD; Julie Savitt; Fatemeh Akhlaghi, PharmD, PhD; James Monti, MD; Gregory D. Jay, MD, PhD Erratum

1190 Erratum.

Departments

1191 Medicinal Leech Therapy. Nicholas Namias, MD, FACS

Departments

1192 Lung Torsion Associated With Complete Bronchial Transection After Blunt Chest Trauma. Ming-Shian Lu, MD; Yao-Kuang Huang, MD; Chiung-Lun Kao, MD; Hui-Ping Liu, MD, FACS Departments

1193 Letters to the Editor. James E. Silberzweig, MD

1193 Letters to the Editor. Riyad Karmy-Jones, MD

1193 Letters to the Editor. Madhuri Anupindi; Michael Sugrue, MB, BCh, BAO, MD, FRCSI, FRACS

Departments

1194 Meetings/Courses. The Journal of TRAUMA௡ Injury, Infection, and Critical Care

The Benefit of Higher Level of Care Transfer of Injured Patients From Nontertiary Hospital Emergency Departments Craig D. Newgard, MD, MPH, K. John McConnell, PhD, Jerris R. Hedges, MD, MS, and Richard J. Mullins, MD

Background: Although injured per- transfer from the ED to one of six Level I which was strongest among patients trans- sons presenting to nontertiary hospitals or II trauma centers. Propensity scores ferred to Level I hospitals (OR 0.62, 95% are routinely transferred for further care, were used to adjust for the known non- CI 0.40–0.95). There was no measurable it is unknown whether there is an outcome random selection of patients for higher benefit for patients transferred to Level II benefit associated with this practice. We level of care transfer. The outcome mea- hospitals (OR 0.82, 95% CI 0.47–1.43). sought to assess whether the transfer of sure was inhospital mortality. Conclusions: After adjusting for in- injured patients from nontertiary hospital Results: There were 10,176 trauma jury severity and the nonrandom selection emergency departments (EDs) is associ- patients who presented to nontertiary of patients for transfer, trauma patients ated with improved survival. hospital EDs and were included in the transferred from nontertiary EDs to ma- Methods: This was a retrospective analysis, of which 3,785 (37%) were trans- jor trauma centers had lower inhospital cohort analysis of all consecutive injured ferred to a tertiary hospital from the ED. mortality than patients remaining in non- children and adults meeting state trauma Transfer patients had higher unadjusted trauma hospitals. Recognition and early criteria, presenting to 1 of 42 nontertiary mortality (odds ratio [OR] 2.83, 95% con- transfer of at-risk rural trauma patients hospital EDs (primarily rural) and requir- fidence interval [CI] 2.06–3.89). After may improve survival in a regionalized .adjusting for the propensity to be trans- trauma system ؍ ing either admission or transfer (n 10,176) from January 1998 through ferred, transfer from the ED to a tertiary Key Words: Trauma, Transfer, Ru- December 2003. Higher level of care hospital was associated with a reduction in ral, Mortality. transfer was defined as interhospital mortality (OR 0.67, 95% CI 0.48–0.94), J Trauma. 2007;63:965–971.

he interhospital transfer of trauma patients is sanctioned in outcomes at the tertiary trauma centers, although there is sparse regional trauma systems as a process that provides optimal literature to support these assumptions. Ttertiary trauma care to all seriously injured persons, regard- Although previous studies have demonstrated the sur- less of the geographic region and proximity to a major trauma vival benefit associated with trauma systems1–9 and trauma center. Interhospital transfers are resource intensive, particularly centers,10 the health outcome benefit among certain sub- in rural regions where patients may require transport over hun- groups treated within trauma systems (e.g. interhospital trans- dreds of miles, and transport may delay emergency treatments. fer patients) is unclear. Transfer patients are often critically Advocates of interhospital transfer assume that the risks associ- ill, with higher mortality rates and longer hospital stays com- ated with transfer are overcome by superior care and better pared with patients transported directly from the scene to a trauma center,8,11–13 yet it is not practical to transport all trauma patients directly from the scene of injury to tertiary Submitted for publication July 1, 2006. care centers in all settings. Particularly in rural regions, per- Accepted for publication October 16, 2006. Copyright © 2007 by Lippincott Williams & Wilkins sons seriously injured in remote areas are often evaluated first From the Department of Emergency Medicine (C.D.N., K.J.M., in local, nontertiary care facilities where physicians make a J.R.H.), Center for Policy and Research in Emergency Medicine; and De- critical decision of whether to admit the patient or transfer to partment of Surgery (R.J.M.), Trauma or Critical Care Section, Oregon a higher level of care hospital. Health and Science University, Portland, Oregon. In this study, our objective was to assess the potential Presented in abstract form at the 2006 Society for Academic Emer- gency Medicine Annual meeting in San Francisco, CA (May 2006). survival benefit of higher level of care interhospital trans- Supported by the 2004–2005 Emergency Medicine Foundation Career fer from the emergency department (ED) (vs. admission, Development Grant. with or without subsequent transfer) of injured persons Address for reprints: Craig D. Newgard, MD, MPH, Department of initially presenting to rural hospitals. Rather than restrict- Emergency Medicine, Center for Policy and Research in Emergency Medicine, Oregon Health and Science University, 3181 SW Sam Jackson ing the sample to seriously injured patients or patients with Park Road, mail code CR-114, Portland, OR 97239-3098; email: specific injuries, we sought to assess a large, heteroge- [email protected]. neous sample of trauma patients (both children and adults) DOI: 10.1097/TA.0b013e31803c5665 that would allow more generalizability of the study results.

Volume 63 • Number 5 965 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

nontertiary facilities (limited surgical and intensive care ca- Table 1 Inclusion Criteria for Entry Into the Oregon pacity) and are primarily located in rural areas. We restricted State Trauma System the analysis to patients presenting initially to nontertiary care Prehospital physiologic criteria centers because these hospitals have limited resources, serve Systolic blood pressure Ͻ90 mm Hg more geographically isolated regions of the state, and are Ͻ Ͼ Respiratory rate 10, 29, or need for airway management expected to transfer injured patients requiring more resources Glasgow Coma Scale score Յ12 Anatomic criteria than can be provided locally. Flail chest Trauma patients who died in the ED (n ϭ 351), were Two or more long bone (humerus or femur) fractures discharged home from the ED (n ϭ 3,475), left against Penetrating injury to the head, neck, torso, or groin medical advice (n ϭ 70), or who had missing information for Amputation proximal to the wrist or ankle ED disposition (n ϭ 54) were excluded from the analysis. Suspected spinal cord injury with paralysis Mechanism of injury Extrication time Ͼ20 min Intervention Death of occupant in same vehicle Transfer was defined as interhospital transfer from the Ejection from vehicle ED of a nontertiary care hospital (i.e., Level III or IV hospi- Discretionary criteria tals) to one of six tertiary care hospitals (i.e., a Level I or II High energy mechanism (fall Ͼ20 feet, pedestrian vs. auto, motorcycle, or ATV or bicycle crash, rollover, passenger space hospitals), coded as a dichotomous variable. Patients trans- intrusion) ferred between nontertiary care hospitals and patients initially Comorbid conditions (age Ͻ5orϾ55 yr, anticoagulation, medical admitted to a rural hospital and later transferred to a tertiary illness, pregnancy, intoxication) care center were kept in the comparison group to isolate the effect of early transfer to a higher-level center.

PATIENTS AND METHODS Variables Study Design and Setting Twenty-two clinical, demographic, and hospital-based This was a retrospective cohort study using consecutive variables that were available in the database and poten- injured persons presenting to 42 nontertiary, primarily rural tially associated with interhospital transfer were included hospitals from January 1, 1998 through December 31, 2003. in the propensity analysis. Clinical factors included initial Patients were identified prospectively in the field or ED using ED Glasgow Coma Scale score, shock (initial ED systolic standardized criteria (Table 1), and captured in the Oregon blood pressure Ͻ90 mm Hg), Injury Severity Score, seri- State Trauma Registry, as mandated by state law for all ous head injury (Abbreviated Injury Scale score for head hospitals participating in our trauma system. Patients meeting injury Ն3), intoxication, mechanism of injury, ED proce- such criteria have a wristband applied in the field with a dures (blood transfusion, thoracostomy tube placement, unique identifier, which is used to track patients transferred cardiopulmonary resuscitation), prehospital or ED intuba- throughout the state. tion, comorbid conditions, and need for major nonortho- Data for the state registry were collected by structured pedic surgical procedure14,15 undertaken within 3 days of review of patient care records by trained trauma data abstrac- initial ED arrival (to account for delays in diagnoses, tors at each hospital participating in the state trauma system. surgical procedures that were initiated after transfer, dif- The data are submitted at regular intervals to the state trauma ferences in early surgical decision-making, and because program manager who coordinates central processing of the Ͼ90% of all such operative interventions were performed data under the Emergency Medical Services and Trauma within the first 3 days). Systems section of the Department of Human Services for Patient demographics included age, gender, race (black, Oregon. Data submission is a legislated mandatory require- Hispanic, white, other), primary insurance type (nonspon- ment for all hospitals participating in the state trauma system sored, Medicare, Medicaid, other [automotive, worker’s com- and there are standard procedures in place to ensure reliable pensation, ward of the State], private), day of presentation and consistent chart abstraction. The Institutional Review (weekday vs. weekend), and time of presentation. Hospital Board at Oregon Health and Science University approved this characteristics included driving distance to nearest Level I study. and Level II hospitals, trauma level16 (III vs. IV), designation as a Critical Access Hospital,17 and hospital type17 (A, B, or Selection of Participants diagnosis-related group). Detailed explanations of hospital The study cohort consisted of all injured persons (chil- characteristics are listed in Table 2. dren and adults) meeting state trauma criteria, presenting to The following covariates were included as continuous an ED at 1 of 42 nontertiary care hospitals (i.e., Level III or variables: Injury Severity Score, comorbid conditions,18 and IV hospitals) (Table 2) during the 6-year period, and requir- distance to nearest Level I and II hospitals. All other covari- ing either hospital admission or interhospital transfer. In our ates were considered as categorical variables. The primary system, Level III and Level IV hospitals are considered outcome was in-hospital mortality.

966 November 2007 Benefit of Higher Level of Care Transfer

Table 2 Definitions for Hospital Characteristics in Oregon14,15

Characteristic Definition Level I trauma center Level I trauma centers provide the highest level of definitive care to the severely injured adult or pediatric patient with complex, multisystem trauma. An emergency physician, general surgeon, anesthesiologist, subspecialists (including neurosurgery), nursing, and ancillary personnel are in-house and able to initiate resuscitation and immediate surgery upon arrival of the patient to the emergency department. A Level I trauma facility is the regional resource center in the system, has the capability to provide total patient care for every aspect of injury, and is responsible for resident training, research, regional quality improvement, community education, outreach, and injury prevention Level II trauma center Level II trauma facilities provide definitive trauma care and subspecialty care for severely injured adult and pediatric patients with complex trauma. Emergency physicians, nurses, and ancillary personnel are in- house and immediately available to initiate resuscitative measures. A board-certified general surgeon, anesthesiologist, and subspecialists (including neurosurgery) are on-call and available to the patient within 30 min. Level II centers serve as regional resource centers for definitive care, quality assurance, community education, outreach, and injury prevention Level III trauma center Level III trauma facilities provide initial evaluation and stabilization, including non-neurosurgical operative intervention, of the severely injured adult or pediatric patient. A Level III trauma center will provide comprehensive inpatient services to those patients who can be maintained in a stable or improving condition. Critically injured patients who require specialty care are transferred to a higher-level trauma center. Level III trauma centers provide community education, outreach, and injury prevention, and are generally located in smaller, rural communities Level IV trauma center Level IV trauma centers provide resuscitation and stabilization of the severely injured adult or pediatric patient before transfer to a higher-level trauma system hospital. Resuscitation and stabilization may include non-neurosurgical operative intervention, though this is uncommon. Nurses who are specifically trained in trauma care are immediately available to initiate live-saving maneuvers, and physicians are promptly available to provide patient resuscitation (and may be present upon patient arrival to the emergency department). Ancillary staff is also in-house or promptly available. Level IV trauma facilities provide community education, outreach, and injury prevention resources, and are generally located in remote areas Critical access hospital Յ25 beds, rural, Ն15 miles from closest hospital, annual average hospital length of stay Ͻ96 h, 24-h emergency services, and participation in a rural health network; Medicare reimbursement—101% Hospital type Type A Յ50 beds, rural, and Ͼ30 miles from closest hospital; Medicaid reimbursement—100% Type B Յ50 beds, rural, and Յ30 miles from closest hospital; Medicaid reimbursement—100% DRG Ͼ50 beds; standard Medicare reimbursement based on diagnosis-related groups (DRGs)

Statistical Analysis ancing score may further reduce the inherent bias in se- We used a combination of deterministic and probabilistic lecting patients for a given “treatment” and make direct linkage (LinkSolv v.5.0, Strategic Matching, Morrisonville, comparisons more meaningful.25,27 In an observational NY) to match interhospital transfer records to records from analysis, deriving the propensity score allows an investi- the initial ED presentation.19,20 We have previously validated gator to recreate the mechanism for treatment group as- the accuracy of probabilistic linkage using similar datasets.21 signment and to integrate this mechanism into the analysis, To avoid the potential bias associated with complete case thus minimizing differences between groups and poten- analysis, we used multiple imputation to impute missing data tially improving comparability.27 This process has been for patients included in the sample.22,23 considered a means of quasi-randomization of treatment To adjust for the nonrandom selection of injured patients groups to minimize bias and to better estimate the true for interhospital transfer (i.e., sicker patients with higher risk effect of treatment.26 of adverse outcomes are often transferred) and the variability To generate the propensity for higher level of care trans- of hospital transfer patterns,24 we used propensity score ad- fer (i.e., transfer from the ED to a Level I or II hospital), we justment based on covariates in the dataset potentially asso- used a multivariable logistic regression model. All potential ciated with transfer and mortality. The propensity score is a interaction terms were tested in the model generating the conditional probability (between 0 and 1) of a subject being propensity score, with interactions having p Ͻ 0.05 level of exposed to a certain treatment or intervention (in this case, significance retained for the final nonparsimonious model. higher level of care transfer) based on an observed group of Separate propensity scores were also calculated for propensity to covariates.25–27 Confounding covariates are collapsed into transfer to a Level I hospital and propensity to transfer to a Level one “score” or propensity (probability) to have received one II hospital for subanalyses. The Hosmer-Lemeshow goodness of treatment (e.g. interhospital transfer) over the other.27 When fit was used to assess goodness of fit for all models. patients in one treatment group (e.g. transfer patients) differ To test the ability of the propensity score to create systematically from the other treatment group, such a bal- comparability between the two groups (i.e., transfer vs. non-

Volume 63 • Number 5 967 The Journal of TRAUMA௡ Injury, Infection, and Critical Care transfer), we regressed each covariate on transfer status while This survival benefit was most pronounced among patients adjusting for the propensity score. We also checked the dis- transferred to Level I hospitals, which is consistent with an tribution of the propensity scores between the two groups to earlier study that compared outcomes among patients with ensure adequate overlap throughout the full range of the head injuries presenting to rural hospitals and transferred score. The propensity score for higher level of care transfer from the ED to Level I versus Level II centers.29 We were was then included as a covariate in a multivariable logistic unable to demonstrate a survival benefit of higher level of regression model assessing the association between ED trans- care transfer to Level II hospitals. fer and mortality. As an alternative method for handling the Although the interhospital transfer of trauma patients has propensity score, we repeated the above analyses using a become firmly integrated into most trauma systems and is propensity-matched analysis, based on a greedy matching assumed to result in improved outcomes, this is the first study algorithm.28 All models were adjusted for clustering by in- to demonstrate a survival benefit associated with the transfer cluding fixed effect terms for hospital of initial presentation24 process. In addition, this effect was measurable in a broad, and year. heterogeneous, population-based sample of injured children Database management was performed using SAS (SAS and adults, representative of actual trauma transfer processes. 8.1, SAS Institute, Cary, NC). SAS-callable IVEware (Sur- Because higher level of care transfer is unlikely to be ever vey Methodology Program, Survey Research Center, Institute studied in a randomized fashion and because transfer patients for Social Research, University of Michigan, MI) was used generally constitute a selected group at high risk for adverse for multiple imputation and all multivariable analyses. outcomes (i.e. selection bias), demonstrating an outcome benefit is particularly difficult. We used a propensity score to RESULTS reduce the selection bias inherent in determining which pa- There were 10,176 trauma patients that initially pre- tients are transferred from the ED and to allow comparability sented to 42 nontertiary hospitals and required either admis- between the groups. sion or interhospital transfer. Three thousand seven hundred Although demonstrating an outcome benefit associated eighty-five patients (37%) were transferred from the ED to a with the interhospital transfer process is important in validat- Level I or II hospital, and an additional 298 patients were ing the use of interhospital transfers in a trauma system, transferred to a tertiary hospital after admission. No persons several specific points deserve mention. First, we defined were excluded for missing interhospital transfer information. “transfer” as interhospital transfer from the ED of the initial Patient demographics, by transfer status, are listed in Table 3. nontertiary care hospital. We cannot assume that the demon- Mortality rates for injured patients admitted to nontertiary strated survival benefit necessarily applies to injured patients care hospitals, transferred from the ED to a Level I hospital, first admitted to nontertiary care hospitals and later trans- and transferred from the ED to a Level II hospital were 4%, ferred. Second, these findings should not be construed to 8%, and 10%, respectively. mean that all injured patients would benefit from transfer. Patients selected for transfer to tertiary care facilities These results do not delineate which patients should be trans- were at high risk for mortality (unadjusted odds ratio [OR] for ferred or which patients are most likely to benefit from in-hospital mortality 2.83, 95% confidence interval [CI] transfer, though previous studies have suggested that the 2.06–3.89). However, the propensity-adjusted analysis sug- mortality reduction associated with trauma system implemen- gested that early transfer to a tertiary care center (Level I or tation and trauma center care is most apparent among seri- II hospitals) was associated with lower mortality (OR for ously injured patients and those with certain index in-hospital mortality 0.67, 95% CI 0.48–0.94, p ϭ 0.009). injuries.2,3,8–11,13 In addition, although these results suggest a The survival benefit was strong among patients transferred to survival benefit with ED transfer, this benefit was only dem- Level I hospitals (OR 0.62, 95% CI 0.40–0.95, p ϭ 0.01), but onstrated after accounting for the probability of being trans- was not demonstrable for patients transferred to Level II ferred using a propensity score. If a survival benefit is to be hospitals (OR 0.82, 95% CI 0.47–1.43, p ϭ 0.42) (Fig. 1). realized on a broader scale, more standardized, objective, and Matching on propensity score substantially reduced the sam- practical transfer guidelines will likely need to be imple- ple size available for analysis (n ϭ 3,630), but demonstrated mented across nontertiary care hospitals to reduce the qualitatively similar results for patients transferred from the variability in hospital transfer patterns.24 Such variability ED to a Level I or II center (OR 0.67, 95% CI 0.45–1.00, p ϭ in deciding which patients to transfer could have negative 0.02). All models were well fit, as assessed by the Hosmer- effects on the health outcomes of injured patients present- Lemeshow goodness of fit test. ing to nontertiary care centers and may offer insight as to why there has not been a measurable mortality reduction DISCUSSION from trauma system implementation in rural areas,30,31 In this study, we demonstrate that although transfer pa- despite increased transfer rates and redistribution of hos- tients are a high-risk population, there appears to be a sur- pitalized injured patients with implementation of a trauma vival benefit associated with the transfer of such patients system.8,9,32 These findings underscore the importance of from nontertiary (primarily rural) EDs to tertiary care centers. early identification of high-risk injured patients and stan-

968 November 2007 Benefit of Higher Level of Care Transfer

Table 3 Characteristics of Patients Transferred From Nontertiary Hospital Emergency Departments to a Level I Hospital, to a Level II Hospital, and Admitted to Nontertiary Hospitals

Transferred From Transferred From Admitted to Rural the ED to a Level I the ED to a Level II Hospital (n ϭ 6,391) Hospital (n ϭ 2,651) Hospital (n ϭ 1,134) Clinical characteristics and procedures ISS (mean) 15.2 16.1 10.0 Head AIS score Ն3 742 (28) 398 (35) 745 (12) ED blood transfusion 178 (7) 96 (8) 223 (3) ED chest tube placement 189 (7) 84 (7) 389 (6) ED CPR 28 (1) 15 (1) 40 (Ͻ1) ED initial GCS (mean) 13.3 12.6 14.0 ED initial systolic blood pressure Ͻ90 (mm Hg) 120 (5) 66 (6) 194 (3) EMS or ED intubation 509 (19) 248 (22) 431 (7) Major nonorthopedic surgery within 3 d 1,280 (48) 600 (53) 838 (13) Ն1 Comorbid condition 712 (27) 327 (29) 1,050 (16) Alcohol intoxication 445 (17) 159 (14) 1,183 (19) Mechanism Motor vehicle crash 1,079 (41) 547 (48) 3,229 (51) GSW or stabbing injury 135 (5) 75 (7) 532 (8) Fall 567 (21) 165 (15) 1,004 (16) Other mechanism 870 (33) 347 (31) 1,626 (25) Demographics Mean age (yr) 37.0 38.2 39.7 Female 806 (30) 343 (30) 2,141 (34) Primary insurance type Private 877 (33) 339 (30) 1,627 (25) Nonsponsored 375 (14) 161 (14) 681 (11) Medicaid 207 (8) 71 (6) 399 (6) Medicare 230 (9) 100 (9) 587 (9) Other 962 (36) 463 (41) 3,097 (48) Race White 2,328 (88) 1,008 (89) 5,584 (87) Black 14 (Ͻ1) 3 (Ͻ1) 33 (Ͻ1) Hispanic 228 (9) 63 (6) 591 (9) Other 81 (3) 60 (5) 183 (3) Time of day of ED presentation 8 AM–4 PM 1,019 (38) 465 (41) 2,412 (38) 4 PM–8 PM 786 (30) 314 (28) 1,717 (27) 8 PM–8 AM 846 (32) 355 (31) 2,262 (35) Weekend 947 (36) 444 (39) 2,177 (34) Characteristics of initial hospital of presentation Level IV hospital 874 (33) 489 (43) 904 (14) Hospital type DRG 793 (30) 241 (21) 4,123 (65) Type A 455 (17) 467 (41) 718 (11) Type B 1,403 (53) 426 (38) 1,550 (24) Critical access hospital 219 (8) 125 (11) 140 (2) Mean distance to nearest Level I hospital (miles) 100.8 216.6 128.4 Mean distance to nearest Level II hospital (miles) 73.3 89.7 73.1 Outcome Mortality 204 (8) 115 (10) 257 (4) Values in parenthesis indicate percentage values. GCS, Glasgow Coma Scale; ISS, Injury Severity Score; CPR, cardiopulmonary resuscitation; DRG, diagnosis-related group; ED, emergency department; AIS, Abbreviated Injury Scale; EMS, emergency medical service; GSW, gunshot wound. dardized ED trauma transfer programs in nontertiary hos- prominent differences include presence of surgical specialists pitals when direct transport from the scene to a major (e.g. neurosurgeons and trauma surgeons), intensive care ca- trauma center is not possible. pacity and expertise, experienced staff, residency programs, Although many differences exist between tertiary and and immediate availability of ancillary services and operating nontertiary care hospitals, it is unclear which of these differ- rooms. There are also differences between Level I and Level ences has the largest survival impact. Some of the more II centers that may explain, in part, these findings. Level I

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10 of measurable effect may have been secondary to the presence of a smaller effect size that this study was un- derpowered to detect (i.e., inadequate number of patients transferred to Level II centers), the lack of a Level II effect on survival, or presence of unmeasured confounders re- 1 garding transfer to a Level II center that could not be accounted for in the analysis. There are still many unanswered questions, including which patients derive the most benefit from transfer, criteria

lowerr mortality higher that could be used to identify such patients early in the 0.1 clinical course, which patients should be transferred to a Unadjusted - Transfer to Level 1 or 2 Adjusted - Transfer to Level 1 or 2 Level I center, which to a Level II center, and which may Adjusted - Transfer to Level 1 Adjusted - Transfer to Level 2 receive quality care at a nontertiary care hospital. Answers to these questions may allow the survival benefits suggested Fig. 1. Propensity-adjusted odds ratios for inhospital mortality among here to be actualized in practice without over-utilizing trauma injured patients transferred from nontertiary hospital emergency de- resources. partments to tertiary trauma centers (Level I and II hospitals). CONCLUSIONS hospitals have a neurosurgeon immediately available 24 Among injured persons initially presenting to nonter- hours a day (vs. within 30 minutes), additional specialty care tiary hospital EDs, there appears to be a survival benefit services, adherence to evidence-based clinical practices, ed- for patients transferred to tertiary trauma centers when ucational and training programs, and although less tangible, compared with patients remaining in nontrauma hospitals. there are philosophical differences between such centers re- This benefit was driven primarily by patients transferred to garding management decisions and invasive monitoring (e.g. Level I centers. Recognition and early transfer of at-risk placement of intracranial pressure monitors). rural trauma patients may improve survival in a regional- There are limitations in this study. The selection bias ized trauma system. inherent in the process of selecting patients for transfer is strong, and difficult to fully eliminate. We used propensity REFERENCES score methods to address this bias, but the propensity score 1. Mullins RJ, Veum-Stone J, Helfand M, et al. Outcome of relies on available, observed variables associated with the hospitalized injured patients after institution of a trauma system in intervention of interest (i.e. higher level of care transfer). an urban area. JAMA. 1994;271:1919–1924. Unmeasured factors that may have affected the decision to 2. Mullins RJ, Mann NC, Hedges JR, et al. Preferential benefit of implementation of a statewide trauma system in one of two adjacent transfer but were not available in the database could not be states. J Trauma. 1998;44:609–617. included in the derivation of the propensity score, and it is 3. Hulka F, Mullins RJ, Mann NC, et al. Influence of a statewide possible that the inclusion of such factors may alter these trauma system on pediatric hospitalization and outcome. J Trauma. results. Nonetheless, it is unlikely that the transfer process 1997;42:514–519. will ever be subject to a prospective, randomized, controlled 4. Mullins RJ, Mann NC. Population-based research assessing the effectiveness of trauma systems. J Trauma. 1999;47:S59–S66. trial, so observational methodology (such as the use of pro- 5. Mann NC, Mullins RJ, Mackenzie EJ, et al. Systematic review of pensity scores) is required when attempting to draw causal published evidence regarding trauma system effectiveness. J Trauma. inferences. We were also unable to assess for additional 1999;47:S25–S33. factors such as futility of care, patient preference, weather, 6. Nathens AB, Jurkovich GJ, Cummings P, et al. The effect of and transport limitations that may have prevented direct organized systems of trauma care on motor vehicle crash mortality. JAMA. 2000;283:1990–1994. transfer from the ED. 7. Nathens AB, Jurkovich GJ, Rivara FP, et al. The effectiveness of We included trauma patients presenting to 42 nontertiary state trauma systems in reducing injury-related mortality: a national care hospitals (located primarily in rural areas), which may evaluation. J Trauma. 2000;48:25–31. limit the generalizability of these findings for urban trauma 8. Sampalis JS, Denis R, Lavoie A, et al. Trauma care regionalization: systems and in regions without an organized trauma system. a process-outcome evaluation. J Trauma. 1999;46:565–581. 9. Mullins RJ, Veum-Stone J, Hedges JR, et al. Influence of a In addition, we were unable to assess additional important statewide trauma system on location of hospitalization and outcome health outcome measures (e.g. complication rates and func- of injured patients. J Trauma. 1996;40:536–545. tional status at discharge) because of inadequate information 10. Sampalis JS, Denis R, Frechette P, et al. Direct transport to tertiary in the database. Assessing only inhospital mortality may not trauma centers versus transfer from lower level facilities: impact on provide a full picture of health outcomes affected by the mortality and morbidity among patients with major trauma. J Trauma. 1997;43:288–296. transfer process. 11. Johnson DL, Krishnamurthy S. Send severely head-injured Finally, we were unable to demonstrate a benefit of children to a pediatric trauma center. Pediatr Neurosurg. 1996; higher level of care transfer to Level II hospitals. This lack 25:309–314.

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12. Young JS, Bassam D, Cephas GA, et al. Interhospital versus direct 24. Newgard CD, McConnell KJ, Hedges JR. Variability of trauma scene transfer of major trauma patients in a rural trauma system. Am transfer practices among non-tertiary care hospital emergency Surg. 1998;64:88–91. departments. Acad Emerg Med. 2006;13:746–754. 13. MacKenzie EJ, Rivara FP, Jurkovich GJ, et al. A national evaluation 25. Rosenbaum PR, Rubin DB. The central role of the propensity of the effect of trauma-center care on mortality. N Engl J Med. score in observational studies for causal effects. Biometrika. 2006;354:366–378. 1983;70:41–55. 14. Henry MC, Hollander JE, Alicandro JM, et al. Incremental benefit of 26. D’Agostino RB. Tutorial in biostatistics—propensity score individual American College of Surgeons trauma triage criteria. methods for bias reduction in the comparison of a treatment to a Acad Emerg Med. 1996;3:992–1000. non-randomized control group. Stat Med. 1998;17:2265–2281. 15. Baxt WG, Upenieks V. The lack of full correlation between the 27. Newgard CD, Hedges JR, Arthur M, et al. The Propensity Score: a injury severity score and the resource needs of injured patients. Ann method to estimate treatment effect in observational research. Acad Emerg Med. 1990;19:1396–1400. Emerg Med. 2004;11:953–961. 16. Oregon Department of Human Services, Health Services Office of 28. Parsons LS. Reducing bias in a propensity score matched-pair sample Public Health Systems, Emergency Medical Services and Trauma using greedy matching techniques. In: Proceedings of the Twenty-Sixth Systems. Oregon Trauma System Triennial Report 1999–2001, Annual SAS Users Group International Conference. Cary, NC: SAS Portland, Oregon: Oregon Department of Human Services; Institute Inc; 2001. Available at: http://www2.sas.com/proceedings/ November 2003. sugi26/p214-26.pdf. 17. Office for Health Policy and Research. Oregon’s acute care hospitals— 29. McConnell J, Newgard CD, Mullins RJ, Arthur M, Hedges JR. capacity, utilization and financial trends 1995–2003. December 2004. Mortality benefit of transfer to Level I vs. Level II trauma centers 18. Elixhauser A, Steiner C, Harris RD, et al. Comorbidity measures for use with administrative data. Med Care. 1998;36:8–27. for head-injured patients: analysis using instrumental variables. 19. Clark DE. Practical introduction to record linkage for injury Health Serv Res. 2005;40:435–457. research. Inj Prev. 2004;10:186–191. 30. Mann NC, Mullins RJ, Hedges JR, Rowland D, Arthur M, Zechnich 20. Jaro MA. Probabilistic linkage of large public health data files. Stat AD. Mortality among seriously injured patients treated in remote Med. 1995;14:491–498. rural trauma centers before and after implementation of a statewide 21. Newgard CD. Validation of probabilistic linkage for matching de- trauma system. Med Care. 2001;39:643–653. identified prehospital records to a state trauma registry. Acad Emerg 31. Mullins RJ, Hedges JR, Rowland D, et al. Survival of seriously Med. 2006;13:69–75. injured patients first treated in rural hospitals. J Trauma. 2002; 22. Little RJA, Rubin DB. Statistical Analysis With Missing Data. New 52:1019–1029. York, NY: John Wiley and Sons; 1987. 32. Mann NC, Hedges JR, Mullins RJ, Helfand M, Worrall W, 23. Newgard CD. The validity of using multiple imputation for missing Zechnich AD. Rural hospital transfer patterns before and after out-of-hospital data in a state trauma registry. Acad Emerg Med. implementation of a statewide trauma system. Acad Emerg Med. 2006;13:314–324. 1997;4:764–771.

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Pre-injury ASA Physical Status Classification is an Independent Predictor of Mortality After Trauma Nils O. Skaga, MD, Torsten Eken, MD, PhD, Signe Søvik, MD, PhD, J. Mary Jones, PhD, and Petter A. Steen, MD, PhD

Background: The ability of an organ- linear logistic regression analysis, control- justed for ISS, RTS, and age. There were ism to withstand trauma is determined by ling for Revised Trauma Score (RTS), In- no interaction effects between pre-injury the injury per se and inherent properties of jury Severity Score (ISS), and age. ASA-PS and the other variables. the organism at the time of injury. We an- Results: Mortality increased with in- Conclusions: Pre-injury ASA-PS alyzed whether pre-injury morbidity scored creasing pre-injury ASA-PS, age, and ISS, score was an independent predictor of mor- on a four-level ordinal scale according to the and with decreasing RTS. Unadjusted tality after trauma, also after adjusting for American Society of Anesthesiologists Phys- mortality rates were 5.7% in ASA-PS 1, the major variables in the traditional TRISS ical Status (ASA-PS) classification system 12.3% in ASA-PS 2, and 26.4% in ASA-PS (Trauma and Injury Severity Score) for- predicts mortality after trauma. 3-4. This increasing mortality trend across mula. Including pre-injury ASA-PS score Materials: From a total of 3,773 pro- pre-injury ASA-PS group was evident in might improve the predictive power of a spectively collected patients (years 2000– nearly all categories of ISS, RTS, and age. survival prediction model without compli- 2004), 3,728 patients were included. Main Odds ratio for death was 1.76 (95% CI, cating it. outcome measure was mortality 30 days 1.14–2.72) for pre-injury ASA-PS 2, and Key Words: Trauma, Prognosis, Co- after injury. The effect of pre-injury 2.25 (95% CI, 1.36–3.71) for ASA-PS 3-4 morbidity, Validation, ASA-PS score, Lin- ASA-PS on mortality was assessed using compared with for ASA-PS 1 and ad- ear logistic regression, Outcome. J Trauma. 2007;63:972–978.

utcome after trauma depends not only on the challenge chotomous variable5,8,9 or as an ordinal categorical variable of the injury per se, but also on the organism’s condi- calculated from the number of preexisting medical conditions Otion at the time of challenge. Previous trauma model work in each trauma victim.1,3,6,7 However, to our knowledge, has mostly focused on the challenge—mechanism of injury, previously published models have not succeeded in quanti- anatomic lesions, and immediate physiologic derangement— fying comorbidity on an ordinal scale of severity expressing and not on the condition of the victim before the traumatic both the number and severity of existing disease processes. event, apart from age. Since the implementation of a hospital-based trauma Several authors1–4 have recognized the importance of registry at Ulleval University Hospital in year 2000, we have physical status before trauma, and it has been suggested that scored pre-injury physical status of all trauma victims accord- comorbidity should be included in a new survival prediction ing to the American Society of Anesthesiologists Physical model. Status (ASA-PS) Classification system (Table 1).10 Physio- Association between preexisting disease and trauma out- logic derangement resulting from the present injury is not come has been reported in studies from North America,3,5–8 reflected in our pre-injury score, solely comorbidity existing Australia,9 and the United Kingdom,1 despite differences in before the incident. The ASA-PS classification system pro- trauma populations, case mix, trauma care systems, and study vides a global index whose components are multivariate, not methods. Preexisting disease has been categorized as a di- specifically defined. It is applicable under any circumstance and stratifies patients into one of five categories of global Submitted for publication June 26, 2006. medical illness. A sixth category is reserved for a donor Accepted for publication February 12, 2007. before organ harvesting. Classification is independent of the Copyright © 2007 by Lippincott Williams & Wilkins planned operative or anesthetic procedure and the qualifica- From the Department of Anesthesiology, Ulleval University Hospital (N.O.S., S.S., P.A.S.), Oslo, Norway; the Department of Anesthesiology, tions of the surgeons and anesthesiologists. Aker University Hospital (T.E.), Oslo, Norway; and the Mathematics De- The original ASA-PS classification was devised by Sak- 11 partment, Keele University (J.M.J.), Staffordshire, UK. lad et al. in 1941 on behalf of the American Society of Supported by Ulleval University Hospital’s Scientific Advisory Anesthetists, a forerunner of the American Society of Anes- Council (N.O.S.), the Norwegian Air Ambulance (N.O.S., P.A.S.), East- thesiologists. The aim was to design a system for “tabulation ern Norway Regional Health Authority (T.E., P.A.S.), and Laerdal and Jahre 11 Foundations (P.A.S.). of statistical data in anesthesia”, to enhance communication Address for reprints: Nils O. Skaga, MD, Department of Anesthe- and benchmarking on a uniform platform of understanding. siology, Ulleval University Hospital, 0407 Oslo, Norway; email: noskaga@ The classification system quickly gained worldwide ac- online.no. ceptance, and it is currently used by anesthesia providers in DOI: 10.1097/TA.0b013e31804a571c almost every preoperative assessment of a patient’s physical

972 November 2007 Pre-injury ASA Physical Status Classification

Injury Coding Table 1 ASA Physical Status Classification System ISS was calculated according to convention based on the P1 A normal healthy patient Abbreviated Injury Scale 1990 update 98 (AIS 98)23 for P2 A patient with mild systemic disease anatomic injury. P3 A patient with severe systemic disease P4 A patient with severe systemic disease that is a Patients in general anesthesia or intubated on arrival constant threat to life were assigned Glasgow Coma Scale (GCS) score and respi- P5 A moribund patient who is not expected to ratory rate categorization based on pre-intubation values, i.e., survive without the operation reported from the emergency department (ED) of the deliv- P6 A declared brain-dead patient whose organs are ering hospital or by the anesthesiologist at the site of injury in being removed for donor purposes cases of transportation by physician manned air or ground From http://www.asahq.org/clinical/physicalstatus.htm. ambulance. This strategy has been described previously.9,24 In cases of missing Revised Trauma Score (RTS) variables health. ASA-PS rating has been shown to correlate well with (GCS score, systolic blood pressure, respiratory rate), normal overall postoperative morbidity12 and surgical mortality.13–18 values were assigned if the patient was awake or somnolent, The system used today10 is in all essential elements identical hemodynamically stable, and eupneic, respectively. This 5,24 to the original classification,11 although some minor changes strategy has previously been advocated. If no information 24 have been implemented during the past years.19–21 was obtainable, the normal value was assigned as default. The aim of the present study was to analyze whether This highly conservative approach was chosen to reduce the pre-injury ASA-PS score is an independent predictor of mor- number of exclusions because of missing RTS. tality after trauma. Application of the ASA-PS Classification System MATERIALS AND METHODS Physiologic derangement resulting from injury will con- Population tribute to a trauma patient’s ASA-PS score in routine anesthesia practice. In our study, the classification system was Ulleval University Hospital is the major trauma hospital solely used to categorize illness before injury. Assignment of for 540,000 citizens and the trauma referral center for 2.5 pre-injury ASA-PS score was based on all accessible infor- million people. Annually, approximately1,000 patients, in- mation, i.e., all parts of the patient record including previous cluding nearly 100 children younger than 15 years, are en- hospital records, prehospital data, X-ray study reports, and tered in the hospital-based trauma registry. Approximately autopsy reports. In cases where no information on pre-injury 40% have serious injury, i.e., Injury Severity Score22 (ISS) health was obtainable, the patient was excluded from the Ͼ15. Ninety percent are exposed to blunt and 10% to study. penetrating injury. The defining information from the American Society of The study inclusion period was August 1, 2000 to De- Anesthesiologists on the ASA-PS Classification System is cember 31, 2004. Inclusion criteria were as follows: (1) All very limited (Table 1).10 The original publication by Saklad patients with ISS Ն10 were included, whether they were et al.,11 presented both guidelines and clinical examples, later admitted to Ulleval directly or via a local hospital within 24 textbooks and publications have presented other clinical hours after injury. (2) All patients admitted with trauma team examples.25–28 In this study, we employed the international activation or penetrating injuries toward the torso or proximal ASA-PS edition presented by the American Society of An- to elbow or knee were included, irrespective of ISS. This esthesiologists (ASA),10 supported by clinical guidelines enabled inclusion of patients with the combination of severe from the edition from the Norwegian Society of Anaesthesiol- physiologic derangement and a minor anatomic injury. Pa- ogy (Table 2). The latter adheres to the international edition, tients classified as dead on arrival were also included. with the exception of the specific Norwegian recommenda- Trauma team activation criteria were obvious severe injury, tion to assign ASA-PS score 2 for patients Ͼ80 years or Ͻ3 circulatory or respiratory instability, reduced level of con- months. We did not follow this part of the Norwegian guide- sciousness, high-energy trauma, or other situations with a lines because of the recommendation by Owens et al.,29 high index of concern. Patients with an isolated fracture of a arguing that a raised ASA-PS score should not be assigned single extremity were excluded unless the trauma team was according to age per se. Pregnant victims of trauma and activated. smokers (Ͼ5 cigarettes/d) were assigned ASA-PS 2.26 Survival was defined as being alive 30 days after injury, and was determined by hospital records and information from the Norwegian Population Registry. For some repatriated Statistical Analysis foreign citizens, information on 30-day survival was unob- No patients were ASA-PS grade 5 or 6 pre-injury, and tainable; they were coded as survivors if discharged alive to only six patients were ASA-PS grade 4 pre-injury (1 survivor, their home country within 30 days after injury (41 of the 73 5 nonsurvivors). Hence, in the analysis, the ASA-PS grade 4 foreign citizens in this study). group was combined with the ASA-PS grade 3 group.

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Distributions of ISS, RTS, and age were skewed and Table 2 ASA Physical Status Classification System, hence are summarized using the median and the 25th and Norwegian Edition 75th percentiles. Mean values are also presented to enable ASA-PS 1 A healthy patient comparison with previous literature. ISS, RTS, and age dis- Guidelines: No organic, physiologic, biochemical, or tributions were compared across the three ASA groups using psychiatric disturbance. Any disorder is the Kruskal-Wallis test and the Jonckheere-Terpstra test for localized, without systemic effects. Smoking Ͻ5 cigarettes/d. Age Ͻ80 yr.* trend. The effects of ISS, RTS, age, and pre-injury ASA-PS 2 Example: Healthy 50-yr-old nonsmoker, admitted on mortality were assessed using ␹ tests. This was followed for varicose vein operation. by a linear logistic regression analysis,30 with death within 30 ASA-PS 2 Moderate organic disease or disturbance days of injury as outcome variable. Risk factors were pre- not impairing normal function. injury ASA-PS, handled as a three-level categorical variable Guidelines: Present pathology might imply specific measures or anesthesia related (1, 2, 3–4), and ISS, RTS and age, handled as numerical precautions. The disturbance(s) might variables. Interaction effects between variables were incor- be caused by the condition to be porated into the model fitting procedure. The resultant effect surgically treated or by another of ASA-PS on mortality is presented using adjusted odds Ͼ pathologic process. Age 80 yr* or ratios with 95% confidence intervals (CI). Analyses were infants Ͻ3 months of age.* Smoking Ͼ5 cigarettes/d. undertaken using Statistical Package for the Social Sciences, Examples: Mild organic heart disease. release 11.0 (SPSS, Inc., Chicago, IL). Uncomplicated diabetes mellitus (type 1 The Regional Committee for Medical Research Ethics or 2). Benign hypertension without approved the study. complications. Healthy 20-yr-old patient with trismus. ASA-PS 3 Severe organic disease or disturbance that limits activity. RESULTS Examples: Diabetes mellitus with organ Of 3,852 patients entered in the trauma database during complications. Disabling heart disease. the study period, 124 were excluded; 79 with injury unsuit- Moderate to severe respiratory disease. able for AIS scoring (drowning, hypothermia, or asphyxia, Angina pectoris. Myocardial infarction Ͼ6 months ago. registered because of trauma team activation), two because of ASA-PS 4 Life-threatening organic disease. unknown survival status 30 days after injury, and 43 lacking Guidelines: The disease is not necessarily related to information of pre-injury ASA-PS score (median age, 39 the condition to be surgically treated, [mean, 47.7]; median ISS, 24 [mean, 24.4]; median RTS, 5.4 neither is it necessarily improved by the [mean, 4.5]; blunt 33, penetrating 10, survivors 17, nonsur- surgical intervention per se. Examples: Malignant hypertension. Myocardial vivors 26, of whom 16 died in the ED). Of the resulting 3,728 infarction Ͻ6 months ago. Severe liver, patients in the study population, 709 (19%) were in general kidney, respiratory, or endocrine anesthesia and intubated on arrival. dysfunction. Manifest cardiac failure. Descriptive data of the study population are presented in Unstable angina pectoris. Subarachnoid Table 3. Mean ISS was 15.3, i.e., severe injury according to hemorrhage—patient awake or Ͼ 31–33 somnolent. the convention of defining severe injury as ISS 15. ASA-PS 5 Moribund patient, not expected to survive Median ISS was 10 (5–22), median RTS 7.84 (7.11–7.84), 24 h with or without surgery. and median age 33 (22–51). Age and ISS increased and RTS Examples: Patient in circulatory shock because of decreased with increasing pre-injury ASA-PS group (p Ͻ ruptured aortic aneurysm. Deeply 0.001). comatose patient with intracranial hemorrhage. Overall mortality was 8.5%. Mortality increased with ASA-PS 6 A declared brain-dead patient whose increasing pre-injury ASA-PS group, age, and ISS, and with organs are being removed for donor decreasing RTS (p Ͻ 0.001). The unadjusted mortality rates purposes. by ASA-PS group were 5.7% (ASA-PS 1), 12.3% (ASA-PS Table 2 is a translation of the Norwegian edition (Ref. 28), published 2), and 26.4% (ASA-PS 3-4) (Fig. 1). This increasing trend in with permission from the Norwegian Society of Anaesthesiology. mortality across pre-injury ASA-PS group was evident for In the present study, we have categorized pre-injury ASA-PS, most categories of ISS, RTS, and age (Figs. 2–4). i.e., any derangement resulting from the injury is not considered, only comorbidity existing before the incident. Linear logistic regression analysis showed that pre-injury * The Norwegian recommendation to assign ASA-PS 2 for ASA-PS remained as a significant predictor of mortality (p ϭ patients Ͼ80 yr or infants Ͻ3 months of age is not in agreement 0.004) after adjusting for the effects of ISS, RTS, and age. with the original publication by Saklad, 1941,11 or by Owens, Adjusted odds ratio for death was 1.76 (95% CI, 1.14–2.72) 29 1978. We have followed the international understanding in the for pre-injury ASA-PS 2 and 2.25 (95% CI, 1.36–3.71) for current study. ASA-PS 3-4, compared with ASA-PS 1. There were no interaction effects between ASA-PS and the other variables.

974 November 2007 Pre-injury ASA Physical Status Classification

Table 3 Summary Data for Study Population, Overall and by ASA-PS Group

All Patients ASA-PS 1 ASA-PS 2 ASA-PS 3–4 Total population 3,728 2,791 634 303 Gender Male 2,676 2,051 440 186 Female 1,052 740 194 117 Injury type Blunt 3,385 2,524 572 289 Penetrating 343 267 62 14 Age Median* 33 (22–51) 29 (20–41) 47 (34–63) 73 (60–80) Mean 37.4 31.4 48.6 68.7 ISS Median* 10 (5–22) 10 (5–21) 16 (8–25) 17 (10–26) Mean 15.3 14.5 16.9 19.0 RTS Median* 7.84 (7.11–7.84) 7.84 (7.55–7.84) 7.84 (6.90–7.84) 7.84 (6.08–7.84) Mean 7.20 7.24 7.16 6.91 * Median (25th–75th percentile).

DISCUSSION The present study showed that patient pre-injury morbidity categorized by ASA-PS classification score was an independent predictor of mortality after injury. Mortality rate increased with increasing level of pre-injury ASA-PS in almost all strata of ISS, RTS, and age (Figs. 2–4), and pre-injury ASA-PS remained as a significant predictor of mortality after adjusting for the effects of ISS, RTS, and age. A strength of our study is that it included mortality after discharge and 30 days follow-up in virtually all patients. Previous mortality studies have largely been confined to status at discharge or end of acute care. This Fig. 1. Unadjusted mortality rate in 3,728 trauma patients across represents a problem if patients are transferred to a second pre-injury ASA-PS groups. ASA-PS group 3 and 4 were combined acute care hospital. In a recent study, Clark et al.34 re- because there were only six patients in the latter group. No patient ported substantial posthospital injury mortality within 30 was assigned pre-injury ASA-PS 5 or 6. days of injury, especially in the older population. In our study, almost 40% of the patients (mean ISS, 19.9) were transferred to other acute care hospitals, from where survival data were obtained. A limitation of our study is that it is based on data from a single trauma center. Further, we could not estimate mortality risks from trauma victims with pre-injury ASA-PS score of 4 or 5, as it would take an extremely large study population to obtain statistically sufficient numbers of such patients. Underreporting of comorbidity resulting in study bias has been considered likely in previous studies,3,7 because more comprehensive information is usually obtained from survivors than nonsurvivors. In case of fatality, follow-up collection of data from family members may be awkward or difficult, or impossible because of lack of information. This also applies to our study: the 43 patients in whom scoring of pre-injury ASA-PS was impossible had a mor- Fig. 2. Unadjusted mortality rate in 3,728 trauma patients across tality rate of 60.5%. Nine of these 43 patients were dead on ASA-PS groups, stratified by Injury Severity Score. arrival, a further seven died in the ED.

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populations, trauma care systems, and study methods. How- ever, an overall quantification of the effect of comorbidity on trauma outcome has been difficult to achieve because of major methodological differences concerning grading of disease. The ASA-PS classification system, already widely in use, may be the means for categorizing pre-injury disease called upon by several authors. Improving the quality of trauma survival prediction models is demanding. Traditional TRISS methodology35 has been shown to be insufficient for comparison of results between different trauma systems.24,36 Inclusion of a parameter expressing pre-injury disease in a trauma survival prediction model might improve its predictive power. The present study was meant as a feasibility trial. Although it included nearly 4,000 trauma victims, the development of a reliable, predictive model requires a larger, multicenter patient material analyzed with separate design and validation Fig. 3. Unadjusted mortality rate in 3,728 trauma patients across data subsets. The finding that pre-injury ASA-PS score seems ASA-PS groups, stratified by Revised Trauma Score. to be an independent predictor of mortality, adjusted for the main variables used in the TRISS model, indicates that such a large study is warranted.

Categorization of Comorbidity With the ASA-PS System ASA-PS classification system is recognized worldwide, routinely used for most surgical patients, straightforward, multivariate, and fulfills the criterion of quantifying the whole load of preexisting medical conditions. Thus, it is well suited for comparison of comorbidity between trauma populations. Though ASA-PS rating correlates well with postoperative morbidity12 and surgical mortality.13–18 interrater inconsistencies in the assignment of ASA-PS scores have been Fig. 4. Unadjusted mortality rate in 3,728 trauma patients across reported in several studies.26,29,37,38 However, the design in ASA-PS groups, stratified by age. the latter studies has been far from optimal, with cases being hypothetical, no statistical determination of an appropriate Importance of Categorizing Comorbidity in Trauma number of raters and cases, and use of inappropriate methods Populations of analysis.39 Inconsistencies in ASA-PS coding have been To improve trauma care, institutions need to evaluate and demonstrated for specific entities, like myocardial infarction compare their results with others’. In the process of such and angina pectoris, pregnancy, smoking, and physiologic benchmarking, it is important to ensure that outcome differ- derangement before emergency surgery. Keats13 concluded ences are caused by differences in trauma system organiza- that the ASA-PS classification system per se is well designed, tion and quality of care and not to differences in population but that a new agreed-upon convention with precise guide- characteristics including case mix. A valid classification of lines and clinical examples is necessary to decrease coding pre-injury disease enables better risk stratification and thus variability. The ASA-PS classification guidelines imple- more valid comparison between the prediction and study mented in Norway (Table 2) address these problems and databases. probably contribute to reduced rating inconsistencies. In the Previous studies have reported significant but varying present study, inconsistencies were greatly reduced as only incidence of preexisting disease in the trauma population: two experienced raters coded the patients’ pre-injury ASA-PS 4.8% to 19% in North America, more prevalent with advanc- score. The advantage of such a study design has been under- ing age, and 38.8% in the United Kingdom.1 We report a 25% lined previously.15 incidence of ASA-PS grades Ͼ1, representing the load of comorbidity in our population. Alternative Categorization of Pre-Injury Disease Association between preexisting disease and trauma out- Assignment of pre-injury ASA-PS score in the present come has been reported1,3,5–9 despite differences in trauma study was based on all accessible information, i.e., all parts of

976 November 2007 Pre-injury ASA Physical Status Classification the patient record. Previous studies have recorded preexisting model. ASA-PS is a simple and robust classification system medical conditions based on secondary diagnosis codes in in routine use worldwide. Including pre-injury ASA-PS score hospital discharge notes, according to different editions of the in a survival prediction model might improve its predictive World Health Organization’s International Classification of power. This classification of comorbidity in trauma patients Diseases (ICD-9,40 ICD-1041). However, using the ICD sys- might also be beneficial for correct prehospital triage and tem raises several general problems. First, different editions interhospital transfer decisions. (ICD-9 and ICD-10) are used in different parts of the world, with or without national clinical modifications. Second, drug ACKNOWLEDGMENTS abuse, chronic alcohol consumption, smoking, and physio- We thank trauma registrar Morten Hestnes for his endeavor in mainte- logic changes caused by pregnancy, host factors associated nance and development of the Trauma Registry at Ulleval University Hospital. with unfavorable trauma outcome,42–44 are in many countries usually not formally coded according to ICD. These factors REFERENCES 11,26,45 are all included in an ASA-PS classification. Third, 1. Wardle TD. Co-morbid factors in trauma patients. Br Med Bull. unlike the ASA-PS score, the ICD system often does not 1999;55:744–756. allow categorization of medical condition on a scale of in- 2. Jones JM, Maryosh J, Johnstone S, Templeton J. A multivariate creasing physiologic severity. Therefore, in studies using the analysis of factors related to the mortality of blunt trauma ICD system, pre-injury disease has been categorized as a admissions to the North Staffordshire Hospital Centre. J Trauma. 5,8,9 1995;38:118–122. dichotomous variable or as an ordinal categorical variable 3. Morris JA Jr, MacKenzie EJ, Edelstein SL. The effect of preexisting calculated from the victim’s number of preexisting medical conditions on mortality in trauma patients. JAMA. 1990;263:1942– conditions, regardless of their severity.1,3,6,7 These studies 1946. demonstrated significant effects of pre-injury medical condi- 4. Dick WF, Baskett PJ. Recommendations for uniform reporting of tions on trauma mortality. However, the effects were modi- data following major trauma—the Utstein style. A report of a working party of the International Trauma Anaesthesia and Critical fied by ISS and age, i.e., the effects were generally larger Care Society (ITACCS). Resuscitation. 1999;42:81–100. among younger patients and those with less severe injuries. A 5. Bergeron E, Rossignol M, Osler T, Clas D, Lavoie A. Improving the high number of diagnoses in a younger patient probably TRISS methodology by restructuring age categories and adding represents more severe illness than the same number of di- comorbidities. J Trauma. 2004;56:760–767. agnoses in an older patient. Use of the ASA-PS score elim- 6. Milzman DP, Boulanger BR, Rodriguez A, Soderstrom CA, Mitchell KA, Magnant CM. Pre-existing disease in trauma patients: a inates many of these issues, as it comprises the physiologic predictor of fate independent of age and Injury Severity Score. impact on the patient, whether it be caused by one or several J Trauma. 1992;32:236–243; discussion 243–234. disease processes. 7. McGwin G Jr, MacLennan PA, Fife JB, Davis GG, Rue LW III. Preexisting conditions and mortality in older trauma patients. Clinical Perspectives J Trauma. 2004;56:1291–1296. 8. Perdue PW, Watts DD, Kaufmann CR, Trask AL. Differences in Triage is the process of assigning a trauma patient to an mortality between elderly and younger adult trauma patients: appropriate medical facility for definitive care. For appropri- geriatric status increases risk of delayed death. J Trauma. 1998; ate triage at the scene of injury or at a lower-level hospital, 45:805–810. pre-injury health status should be included as a formal pa- 9. Brennan PW, Everest ER, Griggs WM, et al. Risk of death among rameter in transfer algorithms, in addition to physiologic cases attending South Australian major trauma services after severe trauma: the first 4 years of operation of a state trauma system. derangement, anatomic injury, and mechanism of injury. J Trauma. 2002;53:333–339. ASA-PS score is a good candidate for scoring of pre-injury 10. ASA Physical Status Classification System. American Society of status in prehospital triage. Anesthesiologists. Available at: http://www.asahq.org/clinical/ Identification of pre-injury medical conditions may be physicalstatus.htm. Accessed January, 19, 2006. important to determine thresholds for specific actions, and to 11. Saklad M. Grading of patients for surgical procedures. 46 Anesthesiology. 1941;2:281–284. design specific clinical strategies and treatment protocols. 12. Cullen DJ, Apolone G, Greenfield S, Guadagnoli E, Cleary P. ASA Examples are correct targeting of resuscitation and level of Physical Status and age predict morbidity after three surgical invasive monitoring. Early invasive monitoring has been doc- procedures. Ann Surg. 1994;220:3–9. umented to improve survival in geriatric trauma patients.47 13. Keats AS. The ASA classification of physical status—a According to published guidelines for the use of pulmonary recapitulation. Anesthesiology. 1978;49:233–236. 48 14. Prause G, Ratzenhofer-Comenda B, Pierer G, Smolle-Juttner F, artery catheters in trauma, such invasive monitoring should Glanzer H, Smolle J. Can ASA grade or Goldman’s cardiac risk be more liberally used in patients with preexisting medical index predict peri-operative mortality? A study of 16,227 patients. conditions. Anaesthesia. 1997;52:203–206. 15. Wolters U, Wolf T, Stutzer H, Schroder T. ASA classification and CONCLUSION perioperative variables as predictors of postoperative outcome. Br J Anaesth. 1996;77:217–222. ASA-PS score of pre-injury medical condition was an 16. Biondo S, Ramos E, Deiros M, et al. Prognostic factors for mortality independent predictor of mortality after trauma, also after in left colonic peritonitis: a new scoring system. J Am Coll Surg. adjusting for the major variables in the traditional TRISS 2000;191:635–642.

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17. Marx GF, Mateo CV, Orkin LR. Computer analysis of postanesthetic 32. Sava J, Alo K, Velmahos GC, Demetriades D. All patients with deaths. Anesthesiology. 1973;39:54–58. truncal gunshot wounds deserve trauma team activation. J Trauma. 18. Prause G, Offner A, Ratzenhofer-Komenda B, Vicenzi M, Smolle J, 2002;52:276–279. Smolle-Juttner F. Comparison of two preoperative indices to predict 33. Haut ER, Chang DC, Efron DT, Cornwell EE III. Injured patients perioperative mortality in non-cardiac thoracic surgery. Eur have lower mortality when treated by “full-time” trauma surgeons J Cardiothorac Surg. 1997;11:670–675. vs. surgeons who cover trauma “part-time”. J Trauma. 2006;61:272– 19. Dripps RD, Lamont A, Eckenhoff JE. The role of anesthesia in 278; discussion 278–279. surgical mortality. JAMA. 1961;178:261–266. 34. Clark DE, Anderson KL, Hahn DR. Evaluating an inclusive trauma 20. Anon. New classification of physical status. Anesthesiology. 1963; system using linked population-based data. J Trauma. 2004;57:501–509. 24:111. 35. Boyd CR, Tolson MA, Copes WS. Evaluating trauma care: the 21. ASA Physical Status Classification. American Society of TRISS method. Trauma Score and the Injury Severity Score. Anesthesiologists: Handbook for Delegates. Vol. 416-3.2. American J Trauma. 1987;27:370–378. Society of Anesthesiologists; 1974:3. 36. Demetriades D, Chan L, Velmanos GV, et al. TRISS methodology: 22. Baker SP, O’Neill B, Haddon W Jr, Long WB. The Injury Severity an inappropriate tool for comparing outcomes between trauma Score: a method for describing patients with multiple injuries and centers. J Am Coll Surg. 2001;193:250–254. evaluating emergency care. J Trauma. 1974;14:187–196. 37. Haynes SR, Lawler PG. An assessment of the consistency of ASA 23. Association for the Advancement of Automotive Medicine. The physical status classification allocation. Anaesthesia. 1995;50:195–199. Abbreviated Injury Scale 1990 revision—Update 98. Des Plains, IL: 38. Ranta S, Hynynen M, Tammisto T. A survey of the ASA physical Association for the Advancement of Automotive Medicine; 1998. status classification: significant variation in allocation among Finnish 24. Skaga NO, Eken T, Steen PA. Assessing quality of care in a anaesthesiologists. Acta Anaesthesiol Scand. 1997;41:629–632. trauma referral center: benchmarking performance by TRISS- 39. Dunn G. Design and Analysis of Reliability Studies: The Statistical based statistics or by analysis of stratified ISS data? J Trauma. Evaluation of Measurement Errors. London: Edward Arnold; 1992. 2006;60:538–547. 40. International Classification of Diseases, 9th revision (ICD-9). 25. Dripps RD, Eckenhoff JE, Vandam LD. Introduction to Anesthesia: Geneva: World Health Organization; 1979. The Principles of Safe Practice. 5th ed. Philadelphia: WB Saunders; 41. International Classification of Diseases, 10th revision (ICD-10). 1977:13–15. Geneva: World Health Organization; 1989. 26. Aronson WL, McAuliffe MS, Miller K. Variability in the American 42. Jurkovich GJ, Rivara FP, Gurney JG, et al. The effect of acute Society of Anesthesiologists Physical Status Classification Scale. alcohol intoxication and chronic alcohol abuse on outcome from AANA J. 2003;71:265–274. trauma. JAMA. 1993;270:51–56. 27. Goodchild JH, Glick M. A different approach to medical risk 43. Castillo RC, Bosse MJ, MacKenzie EJ, Patterson BM. Impact of assessment. Endodontic Topics. 2003;4:1–8. smoking on fracture healing and risk of complications in limb- 28. ASA Physical Status Classification (ASA-klassifikasjonen). threatening open tibia fractures. J Orthop Trauma. 2005;19:151–157. Norwegian Association for Anaesthesia. April 28, 2005. Available 44. Weiss HB, Songer TJ, Fabio A. Fetal deaths related to maternal at: http://www.legeforeningen.no/index.gan?idϭ68383&subidϭ0. injury. JAMA. 2001;286:1863–1868. Accessed January 19, 2006. 45. Bayes J. Asymptomatic smokers: ASA 1 or 2? Anesthesiology. 1982; 29. Owens WD, Felts JA, Spitznagel EL Jr. ASA physical status 56:76. classifications: a study of consistency of ratings. Anesthesiology. 46. Fleisher LA. Risk indices: what is their value to the clinician and 1978;49:239–243. patient? Anesthesiology. 2001;94:191–193. 30. Hosmer DW, Lemeshow S. Applied Logistic Regression. 2nd ed. 47. Scalea TM, Simon HM, Duncan AO, et al. Geriatric blunt multiple New York: John Wiley; 2000. trauma: improved survival with early invasive monitoring. J Trauma. 31. Lossius HM, Langhelle A, Pillgram-Larsen J, et al. Efficiency of 1990;30:129–134; discussion 134–126. activation of the trauma team in a Norwegian trauma referral centre. 48. McCunn M, Dutton RP. End-points of resuscitation: how much is Eur J Surg. 2000;166:760–764. enough? Curr Opin Anaesthesiol. 2000;13:147–153.

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Postmortem Computed Tomography, “CATopsy”, Predicts Cause of Death in Trauma Patients Brian A. Hoey, MD, James Cipolla, MD, Michael D. Grossman, MD, Nathaniel McQuay, MD, Pratik R. Shukla, MD, Stanislaw P. Stawicki, MD, Christy Stehly, BS, and William S. Hoff, MD

Background: The autopsy remains which was a noncontrast whole body scan. Topsy not previously identified on any ra- the gold standard for evaluating trau- The patient then underwent an autopsy. diographic studies or on the autopsy. matic deaths. The number of autopsies These results were compared with those These findings were addressed as part of performed has declined dramatically. generated by the CATopsy. our performance improvement process. This study examines whether postmortem Results: There were 12 patients en- Conclusion: This study suggests computed tomography (“CATopsy”) can rolled in the study; average Injury Sever- that a postmortem imaging test, a CA- be used to determine cause of death in ity Scores was 33.5 ؎ 19.0. In 10 of the 12 Topsy, can be used to determine cause of trauma patients. cases (83%), the CATopsy successfully in- death in trauma patients. Beyond offer- Methods: Patients who presented to dicated cause of death when compared ing a noninvasive alternative to autopsy, the trauma service and subsequently died with the autopsy. Seven of the 12 (58%) it provides similar information to that within the first 24 hours of their hospital- CATopsies demonstrated air in various provided in postmortem examination ization were prospectively enrolled. Any parts of the circulatory system, including and may be used in trauma performance patient who underwent a major invasive the heart in four cases. Five of the 12 improvement activities. procedure within this time frame was ex- (42%) patients had clinically significant Key Words: Autopsy, Performance im- cluded. After pronouncement of death, findings (including the presence of an provement, CATopsy, Trauma, Mortality. each patient had a CATopsy performed, esophageal intubation) noted on the CA- J Trauma. 2007;63:979–986.

comprehensive review of all deaths is a requirement of without precedent as radiography has been used in forensic trauma services.1 The autopsy is the current gold stan- investigation for more than a century.5–7 Common accepted Adard for determining cause of death in these patients.2,3 applications include imaging of human remains to assist in Beyond assuring quality control, forensic autopsy provides identification, routine documentation of fractures, and estab- valuable epidemiologic data, is a superlative educational tool, lishment of injury patterns.5 The recent improvements in and often helps to assure and provide closure to relatives of multislice CT and magnetic resonance imaging (MRI) now the deceased. Unfortunately, the number of autopsies per- allows for two-dimensional and three-dimensional reformat- formed has declined dramatically in recent years.3,4 The rea- ting and virtual reconstruction of the patient. Given these sons for this decline are multifactorial including budgetary improvements, we hypothesized that CATopsy can be used to constraints, lack of time and interest on the part of involved determine cause of death in trauma patients. physicians, and ethical and religious beliefs. Moreover, the dramatic technical radiologic advancements, in computed to- PATIENTS AND METHODS mography (CT) in particular, have proven to be helpful in The study was performed at St. Luke’s Regional Trauma ascertaining diagnoses before the demise of a patient. Center, a Level I trauma center in Bethlehem, PA, and a Given this improvement in technology coupled with the member of the University of Pennsylvania Trauma Network. decline in the number of autopsies, the purpose of this study The Institutional Review Board reviewed and approved the was to determine the utility of postmortem CT (CATopsy), in study. In an effort to identify those patients who died as a predicting cause of death in trauma patients. This idea is not result of their traumatic injuries, the study population was limited to those patients who presented to the trauma service Submitted for publication November 14, 2006. and died within the first 24 hours of their hospitalization. Any Accepted for publication July 16, 2007. patient who underwent a major invasive procedure (i.e., lapa- Copyright © 2007 by Lippincott Williams & Wilkins rotomy and thoracotomy) was also excluded as cause of death is From the St. Luke’s Hospital, a member of the University of Pennsyl- usually obvious once an exploration has been performed. vania Trauma Network, Bethlehem, PA. After pronouncement of death, all study patients were Presented at the 65th Annual Meeting of the American Association for the Surgery of Trauma, September 28–30, 2006, New Orleans, Louisiana. imaged from skull vertex to distal femur with a General Address for reprints: Brian A. Hoey, MD, St. Luke’s Hospital, a Electric (GE) Light Speed 16-slice Multidetector CT Scanner member of the University of Pennsylvania Trauma Network, 801 Ostrum St., (Milwaukee, WI). The head and neck were scanned at 2.5 Bethlehem, PA 18015; email: [email protected]. mm collimation and reconstructed at 1.25 mm with 0.625 mm DOI: 10.1097/TA.0b013e318154011f overlap. The chest, abdomen, pelvis, and lower extremities

Volume 63 • Number 5 979 The Journal of TRAUMA௡ Injury, Infection, and Critical Care were scanned at 5.0 mm collimation and reconstructed at 2.5 both autopsy and CATopsy. With regard to the thorax, nine mm with 1.25 mm overlap. Images were reviewed on GE patients had hemothoracies identified on both the CATopsy Centricity Picture Archiving System with coronal and sagittal and the autopsy. Similarly, one patient had hemopericardium reformatted images reviewed via the Centricity Picture Ar- noted on both the CATopsy and autopsy. Three patients had chiving System integrated GE Advantage Windows Suite aortic transections identified on autopsy. All three of these software. A board-certified radiologist performed image inpatients had mediastinal blood seen on CATopsy. In two of terpretation. A panel of three trauma surgeons reviewed the three patients, the radiologist identified the aortic injury on history of each case as well as the CATopsy images and the CATopsy scans (Fig. 2). With regard to the abdomen, reports to determine probable cause of death. Given the similar findings also were noted at autopsy and CATopsy. At historic precedent of our local forensic pathologists for vic- the autopsy, five patients were noted to have hemoperito- tims of blunt trauma, cause of death was to be defined as one neum; the same was also identified on CATopsy in all five of the following: (1) blunt trauma to the head or neck; (2) cases. Collectively, there were a total of four solid organ blunt trauma to the chest; (3) blunt trauma to the abdomen or injuries noted on the autopsy. The radiologist identified three any combination of the above. of these injuries on the CATopsy. With regard to intravascu- After completion of the CATopsy, each patient then lar abdominal injuries, three patients had mesenteric lacera- underwent a complete autopsy. Board-certified forensic pa- tions noted on autopsy. The radiologist identified a “probable thologists completed of the autopsies. Standard procedure mesenteric injury” based on the presence of mesenteric included thorough external physical examination followed by stranding in two of these patients. An inferior vena cava complete dissection of the cranium, chest, abdomen, and (IVC) injury was identified in one patient on autopsy; this pelvis. Internal organs were opened and examined. Conven- was not seen on the CATopsy, although the radiologist did tional autopsy procedures were modified according to need. note the presence of “stranding along the kidney” adjacent to After completion of the autopsy, the pathologist detailed the this juxtarenal IVC injury. findings and listed probable cause of death. Table 3 is a comprehensive list of injuries that were missed at either autopsy or CATopsy. One patient had an esophageal RESULTS intubation picked up only at CATopsy (Fig. 3). Similarly, two The study population consisted of 12 patients, all victims patients in the study that had cervical spine fractures identified of blunt trauma. The mean patient age was 31 years and the on the CATopsy that were not seen at autopsy (Fig. 4). The average Injury Severity Score (ISS) was 32.3 Ϯ 12.8 based autopsy was unable to demonstrate air in various body cavities on findings at autopsy. The average ISS based on CATopsy or air in the circulatory system. There were two unrecognized findings was 28.9 Ϯ 9.5. To determine the strength of the pneumothoracies; one was a tension pneumothorax (Fig. 5). An relationship between CATopsy ISS and autopsy ISS, a Spear- additional two patients had pneumoperitoneum. The CATopsy man’s rank order correlation (rs) was calculated because of demonstrated intravascular air in 7 of the 12 cases (58%), in- the small sample size (N ϭ 12) and non-normal distribution cluding the heart in four cases (Figs. 6 and 7). ϭ ϭ of both CATopsy ISS and autopsy ISS. The rs 0.58, p With few exceptions, the CATopsy demonstrated the 0.05 (0.047), suggesting a moderate strength of association majority of findings on the autopsy. All fractures identified at between the ISS. Eight patients died as a result of a motor autopsy were seen at CATopsy with the exception of those vehicle crash or motorcycle crash. After pronouncement of outside the parameters of the study (upper extremity and death, each of the patients first underwent CATopsy; the below the knee). As noted above, there were three vascular average time to CATopsy was 5.5 hours. Each of the patients injuries that were not clearly seen (aortic transection, IVC then underwent autopsy; the average time to autopsy was 20 injury, and mesenteric laceration). Moreover, superficial lac- hours. Table 1 provides a comprehensive list of all patients, erations and contusions were also not seen. demographic information, autopsy findings, and proposed With regard to proposed cause of death, the CATopsy cause of death as determined by the forensic pathologist. successfully indicated cause of death in 10 of the 12 cases As can be appreciated in Table 2, with few exceptions, (83%). In those two patients in whom there was disagree- the CATopsy demonstrated nearly all of the injuries identi- ment, with the exception of some focal contusions, the CA- fied on the autopsy. Given the large number of findings or Topsy did demonstrate all of the injuries noted in the autopsy. injuries noted on both studies, this can best be appreciated by focusing on clinically significant specific traumatic injuries in DISCUSSION three primary anatomic regions: head or neck, thorax, and Radiography has been a vital part of forensic medicine abdomen. With regard to the head or neck, there were nine for well over 100 years.5 In fact, the same year (1895) that patients who demonstrated evidence of severe traumatic brain Wilhelm Rontgen discovered this technology, it was being injury on the autopsy. For the purposes of this study, this was used as court evidence to document the presence of a bullet in defined as the presence of one or more of the following: a patient’s leg. As radiographic modalities appeared and basilar skull fracture, cerebral edema, or traumatic head bleed evolved, the use of this technology in forensic science has (Fig. 1). In nine of nine patients, all injuries were identified at increased. Radiography is now used routinely to help identify

980 November 2007 CATopsy Predicts Cause of Death in Trauma Patients

Table 1 Demographics, Injury Severity, and Autopsy Findings with Proposed Cause of Death

Mechanism of Proposed Cause of No. Age ISS Autopsy Findings Injury Death 1 24 Jet ski crash 75 Head or neck: marked hemorrhage in paraspinal neck muscles associated Head or cervical with disruption of atlanto-occipital ligament and disarticulation of spine blunt force C1-occiput; marked epidural and subdural hemorrhage (SDH) along spinal trauma cord; C4-C5 fractures; L SDH and subarachnoid hemorrhage (SAH); multiple lacerations (lacs) on scalp and face. Chest: Multiple rib fractures (fxs); L hemothorax; L lung contusion. Extremities: Open L humeral fracture. 2 18 Motor vehicle 50 Head or neck: multiple scalp lacs; L SDH or SAH; cerebral edema with uncal Head or cervical crash herniation. Chest: Bilateral hemothoraces; bilateral rib fxs; bilateral spine blunt force pulmonary contusions. Abdomen: Spleen or liver lacs; hemoperitoneum; lac trauma of L renal artery with retroperitoneal hemorrhage. 3 4 Crush injury 17 Head or neck: contusions of strap muscles of right neck, anterior thyroid Head or cervical cartilage, right lobe of thyroid gland; diffuse cerebral edema. spine blunt force trauma (asphyxia) 4 16 Motor vehicle 34 Head or neck: multiple face lacs; mandible fx; SDH; SAH; interventricular Blunt force trauma crash hemorrhage. Chest: R first rib fx; diffuse chest wall hemorrhage; bilateral to head hemothoraces. Abdomen: Contusion of terminal ileum and colon; hemoperitoneum. Extremities: Fracture of R femur. 5 18 Motor vehicle 9 Head or neck: occipital scalp contusion; L SAH with small contusion; mild Blunt force trauma crash cerebral edema. Chest: T9-T10 fx with complete transection of spinal cord; to chest massive subpleural hemorrhage; bilateral hemothoraces; sternal fx, anterior mediastinal hemorrhage; focal lacs of pericardial sac; right atrial contusion. 6 44 Motorcycle 26 Head or neck: hard palate fx. Chest: Transected aorta; bilateral Blunt force trauma crash hemothoraces. Abdomen: Multiple mesenteric lacs; lac of splenic flexure of to chest colon; hemoperitoneum; retroperitoneal hemorrhage. 7 40 Fall 14 Head or neck: facial fxs, basilar skull fx, SAH, SDH, multiple cerebral Head or cervical lacerations and contusions. Chest: Bilateral rib fxs; bilateral hemothoracies; spine blunt force sternal fx. trauma 8 23 Motor vehicle 35 Head or neck: L SDH, SAH, frontal lobe contusion; diffuse cerebral edema; Head or cervical crash basilar skull fx. Chest: RLL consolidation; pulmonary edema; laryngeal and spine blunt force epiglottic edema. trauma 9 21 Motorcycle 22 Head or neck: SDH; SAH; cerebellar tonsillar coning. Chest: Bilateral rib fxs; L Blunt force trauma crash clavicle fx; Sternal fx; T12/L1 fxs; bilateral hemothoraces; transected aorta; to chest and right lower lobe contusion; pericardial laceration with hemopericardium. abdomen Abdomen: Hemoperitoneum; sigmoid colon contusion; liver laceration; multiple mesenteric lacerations; pelvic fx. Extremities: Fxs—L humerus, bilateral wrists, L femur, L tibia and fibula. 10 37 Motor vehicle 41 Head or neck: multiple scalp lacerations, basilar skull fx; SDH; SAH; cerebral Head or cervical crash contusions or lacerations; nasal fxs. Chest: R rib fxs; R hemothorax; L rib spine blunt force fxs; R lung contusions or lacs; R diaphragm lac. Abdomen: IVC lac; liver trauma lac; L2/L4 transverse process fxs. 11 50 Motorcycle 75 Chest: transected aorta; L hemothorax; pericardial lac; right atrial lac; superior Blunt force trauma crash vena cava or pulmonary vein lacs; multiple lung lacs; bilateral rib fxs, to chest and sternal fx. Abdomen: Pubic symphysis fx; bilateral sacroiliac fxs; multiple abdomen mesenteric lacs; hemoperitoneum. Extremities: Fxs: L femur, L patella, L tibia. 12 75 Fall 45 Head or neck: diffuse cerebral edema with SAH; multiple skull base fxs. Head or cervical Chest: Bilateral pulmonary contusions. spine blunt force trauma whole corpses or specific body parts; radiographic applica- graphic technological advances, we hypothesized that CA- tions in forensic dentistry are particularly useful for this Topsy, could be used to predict cause of death in a select purpose. Imaging techniques are often used in the investiga- group of trauma patients. Given the decline in the number of tion of gunshot wound victims to help demonstrate the loca- autopsies being performed for the aforementioned reasons, tion, caliber, and direction of fire. Similarly, child abuse our contention was that CATopsy offered an alternative investigations routinely employ the use of this technology. In method of obtaining much valued information. Ultimately, it fact, most recently, postmortem MRI has proven to be useful could be used to assure quality, provide epidemiologic infor- in the evaluation of child abuse victims.8 mation, supplement education of the trauma team, and, in Given the success of the various radiologic imaging some cases, provide a source of closure for victim’s families. modalities in forensic medicine coupled with recent radio- This idea is not without precedent. In 1994, Donchin et al.

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Table 2 Injuries Found on Autopsy and CATopsy Table 3 Missed Injuries or Findings

Autopsy CATopsy Patient Autopsy CATopsy Head or neck 1 Humeral fracture SDH/SAH 9 9 2 Pelvic fracture Splenic laceration Basilar skull fractures 4 4 3 Hemoperitoneum; Contusions of thryroid Cerebral edema 6 6 extensive air within gland, cartilage, Chest vasculature strap muscles Hemothorax 9 9 4 Pneumoperitoneum; L1 Contusions of Rib fractures 7 7 fracture; air within R terminal ileum or Hemopericardium 1 1 atrium and ventricle colon Aortic transection 3 2 5 Extensive pneumotosis; Focal lacerations of Abdomen portal venous air pericardial sac Liver or spleen injuries 4 3 6 Frontal bone fracture; Aortic transection Hemoperitoneum 5 5 air in the right Vascular ventricle; portal IVC 1 0 venous air Mesenteric 3 2 7 Basilar skull fracture, Mesenteric laceration subarachnoid hemorrhage, interventricular blood; C6 fracture 8 Right pneumothorax 9 Air in R ventricle Mesenteric lacerations; humeral fractures 10 C1 and C2 fractures; air Inferior vena cava in jugular vein laceration 11 Left tension pneumothorax; extensive air within vasculature; pneumoperitoneum

Fig. 1. CT scan of the head demonstrating an open skull fracture with pneumocephalus.

Fig. 3. CT scan of the neck demonstrating an esophageal intubation. Fig. 2. CT scan of the upper chest with arrows noting linear dense stranding in the mediastinal fat adjacent to the aortic arch suggesting aortic injury. study evaluated the role of postmortem whole-body MRI as an adjunct to autopsy.9 Our study was the first prospective study designed to were the first to formally compare autopsy with CATopsy.6 determine whether CATopsy could be used to determine They were able to demonstrate that CT increased the yield of cause of death in a group of trauma patients. Twelve patients findings when combined with autopsy. In 2000, Farkash et al. were enrolled during a 3-year time frame. The paucity of published a preliminary study targeting victims of penetrating autopsies that were performed during this time frame limited trauma.7 They concluded that CATopsy scans can potentially the number of patients in the study. The majority of our help assess treatment provided in the field. Another recent patients were enrolled during a 2-year time frame; at that time

982 November 2007 CATopsy Predicts Cause of Death in Trauma Patients

Fig. 6. CT scan of the chest demonstrating a large amount of intracardiac air.

Fig. 4. CT scan of the cervical spine demonstrating a fracture of the first cervical vertebrae that was missed at the autopsy.

Fig. 7. CT scan of the upper abdomen demonstrating a significant amount of portal venous air.

a clinically occult perforation was missed at autopsy. Finally, intravascular air was also noted in 7 of the 12 patients on their CATopsy. This finding has been reported previously in similar studies.6,7 Most likely this finding represents either an air em- Fig. 5. CT scan of the chest demonstrating a left tension bolus and postmortem decay. Given the small number of pa- pneumothorax. tients, it is difficult to draw any conclusions regarding this finding. there were 160 mortalities and only 14 autopsies were per- Similar to the autopsy, the CATopsy also missed several formed. Ultimately, 12 patients underwent a CATopsy fol- injuries. Given that this was a noncontrast study, we antici- lowed by a formal complete autopsy. As noted in the results, pated a low sensitivity for identifying solid organ and vascu- a comparative analysis demonstrated several interesting find- lar injuries. Regarding solid organ injuries, the radiologist ings. First, two patterns emerged with regard to missed injuries on autopsy. There were several patients who had fractures saw three of four. The one that was missed was a very identified on CATopsy that were not appreciated on autopsy. superficial laceration to the spleen in a patient that had a Given the standard technique for performing autopsies, this is recognized liver laceration with large amount of hemoperi- to be expected. Most of the missed fractures were not clini- toneum. The ability to visualize some of these solid organ cally significant. However, two patients had cervical spine injuries is most likely a result of improved CT technology. A fractures that were missed. Beyond the missed fractures, there multidetector CT scanner was used throughout the study, were several patients who had air in various body cavities and which allows for two-dimensional and three-dimensional re- intravascular air that was unappreciated at autopsy. Two construction. With regard to vascular injuries, the radiologist patients had missed pneumothoracies; one was clearly signif- had to rely on other findings (i.e., “mesenteric stranding”) to icant as it was a tension pneumothorax. Pneumothoracies will identify potential vascular injuries. Although he was able to not be appreciated during autopsy as opening up the chest identify some of the injuries noted at autopsy, several were releases the entrapped air. Similarly, there were two patients missed (Table 3). Given the limitations of the technology, this in the study who had pneumoperitoneum noted on the CA- comes as no surprise. Potential solutions to this problem Topsy. Both patients had intestinal contusions noted on au- include even more innovative radiographic modalities such as topsy without evidence of full thickness perforation. Perhaps selective postmortem angiography.10

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The primary hypothesis of this study was to demonstrate An economic comparison between CATopsy and autopsy is that CATopsy scan be used to determine cause of death in a difficult, if not impossible, and beyond the scope of this article. subset of trauma patients. As has been previously noted, in 10 In this subset of patients, who have not undergone multiple of the 12 cases, the panel of trauma surgeons and forensic computerized axial tomography scans or invasive procedures, pathologists agreed. The first case in dispute, patient 10, cause of death is not always readily apparent from an external suffered a closed head injury as well as chest and abdominal examination of the body. If this is the case, and criminal charges injuries as a result of a motor vehicle crash. The pathologist are not pending, a CATopsy should be performed. As is the case deemed the death to be because of a head injury. The trauma with an autopsy performed after a death in the hospital, the surgeons thought the head and chest injuries ultimately hospital (presumably trauma center) should be responsible for caused the death. The patient had greater than 1.5 L of blood the nominal cost of performing and interpreting the study. If drained from the right chest after placement of a chest tube. there are criminal charges pending, and the coroner requests the The other discrepant case involved a crush injury to the neck CATopsy, then this ought to come out of the coroner’s budget. with reported asphyxiation. Subtle bruising within the strap If cause of death cannot be discerned from the CATopsy, then a muscles and thyroid cartilage and gland were not appreciated complete autopsy should be performed. on CATopsy. Interestingly, the CATopsy did demonstrate a One potential weakness of the study is that the mecha- large amount of intravascular air and hemoperitoneum, which nism of injury in all cases was blunt trauma; similar analyses was not detected at autopsy. The pathologist thought the need to be performed on penetrating trauma victims. The death to be the result of asphyxiation related to the reported relatively small number of patients in this study is arguably crush injury to the anterior neck. The panel of trauma sur- its biggest weakness. Again, this was primarily a function of geons thought the injury to be related to both head or neck the limited number of autopsies that were performed. Plans to and abdominal blunt force trauma. recruit additional patients from our other two network trauma These cases illustrate two very important points. First, centers are already underway. Moreover, trauma patients that cause of death, even with all the clinical information and die beyond the 24-hour window and have invasive procedures autopsy findings, remains very subjective. This is a lesson will now be included. Finally, given their expertise, the ad- that most surgeons who attend weekly morbidity and mortal- dition of a forensic pathologist to the physician panel that ity conferences learn very early in their careers. The second reviews the CATopsies is essential. lesson is the value of well-performed autopsy. The subtle In conclusion, the data from this preliminary study sug- findings (thyroid or strap muscle contusions) appreciated on gests that a CATopsy scan provides an alternative to autopsy the second case illustrates the value of performing autopsies. in this select group of trauma patients. As shown, this nonin- Even with the advent of alternative imaging modalities that vasive option offers an immediate, cost-effective answer that not reportedly increase the sensitivity of virtual autopsies, for only demonstrates the majority of the autopsy findings, but also now autopsy remains the gold standard. can be used to effectively determine cause of death. From a performance improvement perspective, CATop- sies have proven to be very useful. Two patients had findings noted only on CATopsy that were of obvious clinical signif- REFERENCES icance. The aforementioned patient with a tension pneumo- 1. Committee on Trauma, American College of Surgeons. Resources thorax had obvious signs of chest wall trauma on arrival. for Optimal Care of the Injured Patient. Chicago, IL: Committee on Trauma, American College of Surgeons; 1999:73. Clearly, he should have had his chest decompressed in the 2. West JG, Trunkey DD, Lim RC. Systems of trauma care. A study of field or on arrival to the trauma bay. Similarly, the other two counties. Arch Surg. 1979;114:455–460. patient with the esophageal intubation was an unrecognized 3. Quality AfHRa. Autopsy as an outcome and performance measure. complication. Interestingly, this was missed by both the air- Summary, evidence report/technology assessment [government way team and by the coroner. In addition to these 12 cases, 3 report]. 2002;58:1–9. 4. Stothert JC Jr, Gbaanador GB, Herndon DN. The role of autopsy in patients were noted to have right mainstem intubations seen death resulting from trauma. J Trauma. 1990;30:1021–1025; only on CATopsy. All three of these patients arrived in full discussion 1025–1026. arrest and only one got a chest roentgenogram. The radiolo- 5. Brogdon BG. Forensic Radiology. Boca Raton, Boston, London, gist and trauma surgeon missed the misplaced tube on the one New York, Washington, DC: CRC Press; 1998. chest roentgenogram that was obtained. In all five of these 6. Donchin Y, Rivkind AI, Bar-Ziv J, et al. Utility of postmortem computed tomography in trauma victims. J Trauma. 1994;37:552–556. cases, this information was shared with the appropriate staff 7. Farkash U, Scope A, Lynn M, et al. Preliminary experience with who assisted in the care of these patients. Information postmortem computed tomography in military penetrating trauma. obtained from CATopsies is routinely included in our im- J Trauma. 2000;48:303–308; discussion 308–309. provement perspective discussions. Similar to an autopsy, 8. Hart BL, Dudley MH, Zumwalt RE. Post-mortem cranial MRI and CATopsy is invaluable from an education standpoint. More- autopsy correlation in suspected child abuse. Am J Forensic Med Pathol. 1996;17:217–224. over, from an efficiency standpoint, it allows for immediate 9. Patriquin L, Kassarjian A, Barish M, et al. Postmortem whole-body review of the case. Obviously, the autopsy results are even- magnetic resonance imaging as an adjunct to autopsy: preliminary tually reviewed in detail to provide closure in these cases. clinical experience. J Magn Reson Imaging. 2001;13:277–287.

984 November 2007 CATopsy Predicts Cause of Death in Trauma Patients

10. Saimanen E, Jarvinen A, Pentitila A. Cerebral cast angiography as specifically identify air in the coronary vessels. I am not an aid to medicolegal autopsies in cases of death after adult cardiac certain if our pathologist looked for this specifically. surgery. Int J Legal Med. 2001;114:163–168. As far as who is going to pay for these studies, that’s a very interesting question; obviously, these patients, because DISCUSSION they’re part of a study and aren’t getting charged. That’s Dr. Martin Schreiber (Portland, Oregon): Dr. Hoey and something that we’ve sort of thrown around as a group. This his colleagues have attempted to address a critical on-going is a non-contrast study. It takes 12 minutes for the hospital to issue facing trauma surgeons. do this study at this point, and about the same amount for our The increasing inability to obtain autopsies has resulted radiologist to interpret the study. We’re not talking about in a corruption of trauma data collection. For example, a scanning a significant number of patients, even at the busiest patient with a subdural hematoma, a pelvic fracture, a Grade trauma centers. So as far as we’re concerned, we think the V liver injury, who happens to also have a laceration on their hospital should pick up that bottom line. head, would be given an ISS of 1 if the patient dies before he With regard to the ISS, we didn’t include that informa- reaches evaluation or treatment. tion in this particular study. We are going to include that In Oregon alone, we have a large spike of patients, who information in another study that we’re going to do with some die with an ISS of zero or one. This group of patients ranges of this same data. The one thing that I can share with you is all the way from patients who have a heart attack and down that using CATopsy results, as you might expect, the ISS was to patients like the one I have just described. significantly higher in this cohort of patients. Again, we’ll Luckily, Dr. Hoey has shown that CATopsy is a reason- have those numbers in another study. able alternative to autopsy, although major vascular injuries When we set this study up, we were primarily interested may be missed due to the absence of a beating heart and IV in dealing with patients in whom we had no idea what the contrast. diagnosis was. And our thought process was that the best I have several questions for the authors. Number one, an cohort to pick was those patients who had really, essentially important shortcoming of this study is a small number of pa- no diagnostic workup – no X-rays, no CT scans, no MRIs, tients involved. Why do the authors limit the study to patients and no operations, and that’s why we chose this cohort. who died within 24-hours, and why did they exclude patients Dr. Howard Champion (Annapolis, Maryland): About who had major procedures? two years ago, as part of an effort to get data on combat The second group of patients, the patients that had major casualties, I proposed that a CT scanner be installed down at procedures, may be especially educational, as perhaps they’re Dover, Delaware facility, where all of the decedents from undergoing a laparotomy, or a thoracotomy and actually died Iraq and Afghanistan arrive. from a spinal cord injury, or a head injury. Since January 2005, every person who comes through I think that group is particularly interesting, especially from a peer review standpoint. Number two, why didn’t the there has had a complete autopsy and a CT scan. We’ve been authors evaluate ISS based on clinical findings, versus ISS in the process of analyzing 1.2 gigs of data and comparing based on autopsy, versus ISS based on CATopsy? them to autopsy on bout 1,599 decedents from Iraq and This would be very revealing and allow an enumeration Afghanistan to date. of the benefit of the use of CATopsy, compared to the clinical The publication which you referred to, which was a small findings of the study. number of gunshot wounds, is the only one that escaped, sort Number three, who will pay for these CATopsies? Will of clamped down on getting these data out for public con- the patient pay? Will the hospital pay? Or will the trauma sumption; thus, I think it’s very important that your paper system pay? does appear here. Who benefits the most from the CATopsy? I would In reviewing these cases, I’ve found that there’s an awful argue the physicians by potentially learning from their mis- lot of free air, which can confuse things. Obviously, it will takes, and also the trauma system for learning about the not pick up bowel injuries, vascular injuries, and I’ve had a epidemiology of their trauma injuries. lot of trouble with liver injuries. Finally, did the pathologist look specifically for air in the I wanted to know if you’ve been using any gray scale coronary vessels or in the cerebral vessels, which is indicative techniques that radiologists use to look at classified lung of an error embolus? injuries, or try to apply them to liver injuries, because we’re This is probably a largely unrecognized source of death grasping at the present time to try and mobilize the technol- in patients who die for unknown reasons. ogy in the digital databases to get more refined diagnosis. Dr. Brian A. Hoey (Bethlehem, Pennsylvania): I’m go- The other thing I just would like to point out, there’s a ing to, I think, go backwards here. It will be easier for me. big difference in the way that trauma surgeons, radiologists With regard to the air in the coronaries or air in the brain, and forensic pathologists view injuries, and it’s good to have there were several patients in the study who were noted to a multi-disciplinary team looking at these, and I would en- have air in their cerebral vessels. Our radiologist did not courage you to continue this work.

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I think it’s a very important adjunct to trauma diagnosis. Dr. Brian Hoey: That’s a great question, and when we Finally, I just want to comment, are you sure you didn’t mean actually started this study – Dave was a resident at our John Hunter? William was the gynecologist. I know they institution. He started this study a number of years ago by worked together for several years, but most of the actual trying to enroll similar types of patients and have them autopsies were done by John, I think. undergo an MRI. This was impractical at best. What we Dr. Brian A. Hoey: You’re right, with regard to your found was, those studies were taking way too long to com- technical question, as I alluded to in our paper, we’re really plete, and we essentially could get the same information from on the front end of the learning curve, and that applies not the CAT scan. So we aborted that study after a couple of only to us interpreting these studies, but also our radiologists. patients, and we went on to our own study. I will tell you, we’ve had one radiologist, who has really As far as the families are concerned, the families love adopted this study at our institution and spent a lot of time this concept. They understand that this is not an invasive test interpreting these. I’ll have to get back to you with regard to and simply want to know why their loved ones died. Now, the techniques he’s using. obviously, we haven’t proven this technology works, so Interestingly enough, regarding the intravascular air, one we’re limited as to what we can tell them. But they’re very other point that I should make is, we had two patients whom interested and have been very supportive. we got to CAT scan in a very short period of time in this particular cohort, in less than an hour. Both of them had the Dr. Steve Shackford (Burlington, Vermont): As you most air noted on the study out of any of the 12 patients. Then know, the reason for post mortem is not only to establish we had another two patients who took the longest to get to cause of death, but also to see if there are associated co- CAT scan, and that was 11 or 12 hours. Neither one of those morbidities, like polyposis coli, which might be either hered- patients had intravascular air. The phenomenon that we’re itary. Why not both, autopsy and CATopsy? Don’t think of seeing is related to either post mortem decay, or air embolus, them as competing, but as complimentary. or a combination of the above. Dr. Brian Hoey: We haven’t looked for those per say. Dr. David W. Scaff (Allentown, Pennsylvania): Were As you saw, this cohort of patients that we’re dealing with any of the families approached and informed of the CATopsy is very young. The average age was in the 30’s, so we results, as they would normally have access to the traditional didn’t see a lot of those co-morbidities. But that’s an autopsy results? excellent point.

986 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Acute Renal Failure in Critically Ill Surgical Patients: Persistent Lethality Despite New Modes of Renal Replacement Therapy Soumitra R. Eachempati, MD, John C. L. Wang, MD, Lynn J. Hydo, MBA, Jian Shou, MD, and Philip S. Barie, MD, MBA

Patients who required RRT .(0.86 ؍ Objective: Despite improved resus- tion score and its individual components, p ؎ citation and sepsis care, acute renal fail- cumulative nonrenal organ dysfunction had a mean APACHE III score of 91 ure (ARF) remains common in critically score, and need for RRT. Patients were 1 point, with 61% mortality (predicted ill surgical patients. New methods of re- stratified January 1994 to January 2001 mortality: 67%), with no difference over nal replacement therapy (RRT) are be- (pre-CRRT) and February 2001 to Decem- time. Independent predictors of mortal- ing used in surgical intensive care units ber 2004 (post-CRRT). The primary end- ity overall and for ARF patients in- (SICUs), including high-flux hemodialy- point was mortality. cluded age and the magnitude of renal, sis (HD) and continuous RRT (CRRT). Results: Among 8,505 SICU pa- cardiovascular, hepatic, and neurologic RRT is being used increasingly early in tients, 530 (6.2%) developed ARF. Three dysfunction. In comparison with CRRT, the course of ARF, but data are scant to hundred and eleven patients were HD was associated with a decreased risk suggest that mortality is improved. Con- treated pre-CRRT and 219 thereafter. of death. sequently, we determined whether out- Female patients comprised 35% of ARF Conclusions: Despite more frequent comes were improved with CRRT in patients. The mean age was 69 years ؎ 2 RRT and the use of CRRT, the mortality SICU patients, and hypothesized that years, and the mean APACHE III score of ARF in critically ill surgical patients CRRT lowers mortality for patients with was 81 ؎ 1 point for ARF patients. HD remains high because of nonrenal organ ARF. was performed in 15.6% of ARF pa- dysfunction. Considering that ARF- Methods: Patients who developed tients before 2001 and 5.5% of ARF pa- related mortality was decreased by in- ARF (acute increase in serum creatinine tients in 2001 and thereafter. CRRT was termittent HD, and that intermittent concentration >2.4 mg/dL) in the SICU performed in 20.1% of ARF patients in RRT is less costly, patients who need from 1993 to 2004 were identified. Data col- 2001 and thereafter. Overall mortality RRT should be treated preferentially lected prospectively included year of admis- for ARF patients was 45% (APACHE with HD. sion, age, gender, Acute Physiology and III normative predicted mortality: 55%) Key Words: Renal, Failure, Critical, Chronic Health Evaluation (APACHE) III with no difference over time (pre- ICU, Surgical, Replacement, Dialysis, He- .modialysis, Hemofiltration ,%45.2 ؍ post-CRRT ,%46.3 ؍ score, cumulative multiple organ dysfunc- CRRT J Trauma. 2007;63:987–993.

ultiple organ dysfunction syndrome (MODS) re- the use of drotrecogin alfa (activated)3 have improved de- mains the leading cause of death in the surgical monstrably the outcomes of patients with MODS. These Mintensive care unit (SICU). Because of improved encouraging results have stimulated intervention in other con- intensive care management, outcomes of critically ill patients ditions where new therapies may improve outcomes. with MODS are improving. Specific interventions such as Acute renal failure (ARF) remains a major cause of low tidal volume ventilation,1 strict glycemic control,2 and morbidity and mortality in surgical patients despite the introduction of renal replacement therapy (RRT) more than 50 Submitted for publication October 12, 2005. years ago. Successful prevention of ARF in critically ill Accepted for publication August 2, 2007. patients remains elusive other than for contrast-induced ne- Copyright © 2007 by Lippincott Williams & Wilkins phropathy and possibly rhabdomyolysis.4 A recent multi- From the Division of Critical Care and Trauma, Department of Surgery center study showed that 5.5% to 6.0% of ICU patients (S.R.E., L.J.H., J.S., P.S.B.); Division of Medical Ethics, Department of Public Health (S.R.E., P.S.B.); Division of Nephrology, Department of develop ARF requiring RRT, with a hospital mortality of 5 Medicine (J.C.L.W.); Weill Medical College of Cornell University; and The 60.3%. New methods of RRT, including high-flux hemodi- Rogosin Institute (J.C.L.W.), New York City, New York. alysis (HD) and continuous RRT (CRRT), have been intro- Presented as a poster at the 64th Annual Meeting of the American duced, but large-scale studies have yet to demonstrate Association for the Surgery of Trauma, September 22–24, 2005, Atlanta, 5,6 Georgia. decreased mortality or cost savings. Address for reprints: Soumitra R. Eachempati, MD, Department of Our institution introduced CRRT to its critical care units Surgery, NewYork-Presbyterian Hospital, 525 E. 68 St., P718A, New York in 2001. As part of a longitudinal prospective study of the City, NY 10021; email: [email protected]. epidemiology and outcomes of MODS in our unit,7 the out- DOI: 10.1097/TA.0b013e3181574930 comes of patients who developed ARF before and after the

Volume 63 • Number 5 987 The Journal of TRAUMA௡ Injury, Infection, and Critical Care availability of CRRT were compared to determine whether analysis of continuous variables was performed using the the epidemiology of RRT was changing, and whether out- Mann-Whitney U test. The Kolmogorov-Smirnov test was comes were improving with the introduction of CRRT. We used to analyze differences in data that were not normally hypothesized that the epidemiology and demographics of distributed (i.e., ULOS and HLOS). Temporal changes in ARF would be similar before and after the introduction of continuous variables were analyzed by repeated-measures CRRT, and that the mortality for patients with ARF would be analysis of variance with Bonferroni correction. Independent lower with CRRT used preferentially. influences on mortality were tested by multivariable logistic regression analysis in the entire cohort of patients to deter- PATIENTS AND METHODS mine the relative influence of ARF on mortality. Two other Consecutive patients who developed ARF (acute in- multivariable regression analyses were performed on the crease in serum creatinine concentration Ն2.4 mg/dL) in the ARF cohort to study ARF in relation to other types of organ SICU at NewYork-Presbyterian Hospital, Weill Cornell dysfunction, and also to study the independent influences on Medical Center from 1993 to 2004 were identified from a mortality with ARF. All models were tested for autocorrela- prospectively collected database. The serum creatinine con- tion between dependent variables. Statistical significance was centration of 2.4 mg/dL corresponds to a MOD score of 2 recognized for ␣ ϭ 0.05. Model discrimination (Hosmer- points by the scoring system of Marshall et al.8 Patients with Lemeshow goodness-of-fit test) was acceptable with a posi- end-stage renal disease or stable chronic renal insufficiency tive ␹2 and p Ͼ 0.05. Model calibration (Nagelkerke R2 test) (CRI) were excluded. Patients who had a baseline serum was acceptable if R2 Ͼ 0.3. Analyses were performed with creatinine concentration of Ն2.4 mg/dL were included if their SPSS software (SPSS v.11, SPSS, Inc., Chicago, IL). renal MOD score increased by at least 1 point during their SICU admission. RESULTS Data collected included year of admission, age, gender, Among 8,505 patients admitted to the SICU during the Acute Physiology and Chronic Health Evaluation (APACHE) study period, 530 (6.2%) developed ARF. Demographic char- III score,9–11 presence of sepsis, the cumulative MOD score acteristics of the entire group and the two temporal cohorts (maximum, 24 points) and the scores for its six individual (groups 1 [4,792 patients] and 2 [3,713 patients]) are pre- components (cardiovascular, neurologic, coagulation, hepatic, sented in Table 1. Female patients represented 40% of total pulmonary, renal; maximum 4 points each), the presence of CRI, patients, but comprised significantly fewer of the patients in and the need for HD or CRRT. The primary endpoint was group 2 (Table 1). Overall, the mean age was 63.3 years Ϯ mortality; hospital length of stay (HLOS) and ICU length of stay 0.2 years, and was significantly less in group 2 (albeit by only (ULOS) were recorded. Mortality rates were compared with the 1.8 years). The mean APACHE III score was 50.9 Ϯ 0.4 APACHE III normative population as described originally.9 For points, and was significantly higher in group 2 patients de- comparison, patients were stratified January 1994 to January spite their lower mean age. 2001 (group 1, pre-CRRT) and February 2001 to December Compared with the overall patient population, the 530 2004 (group 2, post-CRRT). ARF patients were older (mean age 69.2 years vs. 62.8 years, All patients with ARF requiring any RRT were identi- p Ͻ 0.0001), sicker (mean APACHE III score 81.1 vs. 47.7 fied. All RRT orders were written by the nephrology service points, p Ͻ 0.0001), more likely to be female (40.4% vs. in consultation. In February 2001, CRRT was introduced as 34.9%, p Ͻ 0.05), and developed more OD (mean MOD the RRT modality of choice. All CRRT was performed by continuous venovenous hemofiltration, continuous venovenous HD, or continuous venovenous hemodiafiltration. Each CRRT Table 1 Patient Demographics circuit (Prisma, Gambro Healthcare, Lakewood, CO) required a Overall Group 1 Group 2 p new filter generally every 18 hours to 24 hours (up to 72 hours, (N ϭ 8,505) (N ϭ 4,792) (N ϭ 3,713) if possible). All CRRT patients received nursing care with a 1:1 Age 63.3 Ϯ 0.2 64.1 Ϯ 0.3 62.3 Ϯ 0.3 Ͻ0.0001 ICU nurse-to-patient ratio. A floating nurse from the inpatient % Mortality 9.3 9.8 8.8 0.099 Ϯ Ϯ Ϯ Ͻ dialysis unit provided additional nursing care for 3 to 4 hours per APACHE III 50.9 0.4 49.5 0.5 53.0 0.6 0.0001 MOD score 2.4 Ϯ 0.1 2.6 Ϯ 0.1 2.2 Ϯ 0.1 0.376 episode of HD. Anticoagulation was optional for HD, but stan- % Female 40.0 42.7 36.5 0.0001 dard with CRRT absent a contraindication; heparin-sensitive % ARF 6.2 6.5 5.9 0.278 patients received therapeutic argatroban. Anticoagulation was ULOS 5.5 Ϯ 0.1 5.3 Ϯ 0.1 5.7 Ϯ 0.2 0.071 withdrawn for an unexplained two-unit blood transfusion re- HLOS 14.5 Ϯ 0.3 13.9 Ϯ 0.3 15.9 Ϯ 0.5 Ͻ0.0001 quirement or a significant (e.g., hypotension, transfusion re- Group 1 includes patients from January 1994 to January 2001; quirement) new source of bleeding. Patients who received HD group 2 includes patients from February 2001 to December 2004. for ARF after February 2001 were also identified, and the reason p values compare group 1 and group 2 data. MOD score, multiple organ dysfunction score; ARF, acute renal for HD in lieu of CRRT was determined. failure by serum creatinine concentration Ն2.4; CRRT, continuous Univariate analysis of coordinate variables was per- renal replacement therapy; ULOS, ICU length of stay (days); HLOS, formed using ␹2 with the Fisher exact test, and univariate hospital length of stay (days).

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Table 2 Comparison of Patients Who Developed ARF Table 4 Demographics of Patients With Acute Renal and Other ICU Patients (Non-ARF Patients) Failure

ARF Patients Non-ARF Patients Overall Group 1 Group 2 p p (N ϭ 530) (N ϭ 7,975) (N ϭ 530) (N ϭ 311) (N ϭ 219) Age 69.2 Ϯ 0.6 62.8 Ϯ 0.6 Ͻ0.0001 Age 69.2 Ϯ 0.6 69.9 Ϯ 0.8 68.2 Ϯ 1.1 0.182 APACHE III 81.1 Ϯ 1.5 47.7 Ϯ 0.4 Ͻ0.0001 % Mortality 45.8 46.3 45.2 0.860 MOD score 10.9 Ϯ 0.3 1.7 Ϯ 0.1 Ͻ0.0001 APACHE III 81.1 Ϯ 1.4 78.8 Ϯ 1.9 84.4 Ϯ 2.2 0.064 % Female 40.4 34.9 0.013 MOD score 10.9 Ϯ 0.3 11.9 Ϯ 0.3 10.6 Ϯ 0.4 0.376 % Mortality 45.8 7.0 Ͻ0.0001 % HD 11.5 15.6 5.5 0.82 ULOS 15.9 Ϯ 1.0 4.7 Ϯ 0.1 Ͻ0.0001 % CRRT 8.3 N/A 20.1 N/A HLOS 30.7 Ϯ 1.8 13.2 Ϯ 0.3 Ͻ0.0001 % Sepsis 57.7 58.5 56.6 0.721 ULOS 15.9 Ϯ 1.0 16.4 Ϯ 1.2 15.3 Ϯ 1.7 0.605 p values compare ARF patients’ and Non-ARF patients’ data. HLOS 30.7 Ϯ 1.8 35.4 Ϯ 2.3 24.1 Ϯ 2.5 0.002 MOD score, multiple organ dysfunction score; ULOS, ICU length % CRI 26.2 33.1 16.4 Ͻ0.0001 of stay (days); HLOS, hospital length of stay (days). Group 1 includes patients from January 1994 to January 2001; group 2 includes patients from February 2001 to December 2004. Table 3 Characteristics of Patients With Acute Renal p values compare group 1 and group 2 data. Failure Stratified by Peak Serum Creatinine MOD score, multiple organ dysfunction score; ARF, acute renal Ն Concentration According to the Multiple Organ failure by serum creatinine concentration 2.4 mg/dL; CRRT, continuous renal replacement therapy; ULOS, ICU length of stay (days); Dysfunction Score HLOS, hospital length of stay (days); CRI, acute-on-chronic renal Renal Score 2 Renal Score 3 Renal Score 4 insufficiency; N/A, not applicable. Ͼ Serum creatinine 2.4–4.0 4.1–5.7 5.7 difference between renal MOD component scores was too (mg/dL) Number of 243 121 166 small to account for any difference in overall MOD score patients (Table 4). Twelve patients in group 2 received intermittent Number 16 (6.6) 28 (23.1) 60 (36.1)* HD and not CRRT as their primary mode of RRT (Table 5). receiving RRT The overall mortality for both periods was 9.3%, being (%) 45.8% with ARF (APACHE III normative predicted mortal- Mortality (%) 79 (32.5) 54 (44.4) 100 (60.5)* ity, 55%), versus 7.0% absent ARF p Ͻ 0.0001 (Table 4), but Ͻ ␹2 * p 0.01 by multigroup analysis. with no difference over time for patients with ARF. The mean RRT, renal replacement therapy. APACHE III score for patients with ARF who required RRT was 81.1 points with a mortality rate of 61% (APACHE III score 10.9 vs. 1.7 points, p Ͻ 0.0001), particularly nonrenal normative predicted mortality, 67%). Mortality did not differ OD (Table 2). Accordingly, patients with ARF had signifi- over time (pre-CRRT, 61.0%, post-CRRT, 61.9%). Compar- cantly longer ULOS and HLOS. isons of survivors and nonsurvivors for both groups overall Only 51 patients (17 female, 33.3%) developed isolated and for ARF patients are shown in Tables 6 and 7. Overall, ARF, all of whom developed a peak serum creatinine con- nonsurvivors were significantly older, sicker, more likely to centration 2.4 to 4.0 mg/dL (2 points); none required RRT, be female, and developed more OD (all, p Ͻ 0.001). Notably, and all survived. These 51 patients were among 243 patients nonsurvivors were nearly eight times more likely to develop with a peak serum creatinine concentration 2.4 to 4.0 mg/dL ARF, and more than three times more likely to be treated with (Table 3). As the magnitude of ARF increased, the use of CRRT (Table 6). CRRT and the crude rate of mortality also increased. The univariate analysis of factors associated with sur- Demographic characteristics of ARF groups 1 and 2 are vival among patients who developed ARF is shown in Table displayed in Table 4. Three hundred and eleven patients were treated pre-CRRT (group 1) and 219 patients were treated Table 5 Indications for Hemodialysis as Primary Mode post-CRRT (group 2). The incidence of sepsis did not differ of Renal Replacement Therapy in Group 2 Patients between groups. The percentage of patients who received RRT (19.8% of ARF patients overall) was significantly Reason for Intermittent HD No. Patients higher in group 2 (15.6% vs. 25.6%, p Ͻ 0.001), reflecting Ultrafiltration only 4 the use of CRRT for 20.1% of group 2 patients. Group 2 Renal transplant rejection 2 patients trended (p ϭ 0.064) toward higher severity of illness, Repetitive clotting of CRRT machine 2 High access pressure during CRRT 1 perhaps because of a lower incidence of acute-on-chronic Converting to peritoneal dialysis 1 renal failure. The mean MOD score for patients requiring Hyperkalemia 1 RRT differed between groups 1 and 2 (16.2 vs. 14.7 points, Received intermittent HD in previous ICU 1 p Ͻ 0.001), as did the mean renal MOD component score CRRT, continuous renal replacement therapy; HD, hemodialysis; (3.43 vs. 3.30 points, p Ͻ 0.001). Although significant, the ICU, intensive care unit.

Volume 63 • Number 5 989 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

discrimination and calibration of this model are robust, and Table 6 Demographic Comparisons Between Survivors superior to the model for the overall patient population. and Nonsurvivors for the Entire Cohort The second logistic regression performed on the ARF Survivors Nonsurvivors p patient population studied the independent effects of the (N ϭ 7,710) (N ϭ 795) different demographic features on mortality from ARF Age 62.5 Ϯ 0.6 69.2 Ϯ 0.2 Ͻ0.0001 (Table 10). Increasing age was again found to be an inde- APACHE III 44.5 Ϯ 0.3 94.9 Ϯ 1.3 Ͻ0.0001 MOD score 1.4 Ϯ 0.1 12.3 Ϯ 0.2 Ͻ0.0001 pendent predictor of mortality, but this model was domi- % Female 39.4 45.8 0.001 nated by the influence of the overall magnitude of OD. % ARF 3.8 29.6 Ͻ0.0001 Each 1-point increase in the cumulative MOD score in- ULOS 4.6 Ϯ 0.3 21.6 Ϯ 1.1 Ͻ0.0001 creased the risk of death by 47% (odds ratio 1.468, 95% HLOS 13.7 Ϯ 2.7 31.2 Ϯ 2.2 0.824 confidence interval 1.372–1.571). In this model as well, % CRRT 3.5 11.5 0.001 HD reduced significantly the risk of death from ARF, p values compare survivors’ and nonsurvivors’ data. whereas CRRT had no effect. The model validation statis- ARF, acute renal failure; CRRT, continuous renal replacement tics for this model (Table 10) are equally robust to those therapy; MOD score, multiple organ dysfunction score; ULOS, ICU length of stay (days); HLOS, hospital length of stay (days). for the model shown in Table 9.

7. Nonsurvivors of ARF were older and sicker (both, p Ͻ DISCUSSION 0.05) than survivors were, but there was no gender difference. The cause of ARF in the critical care setting is often Nonsurvivors of ARF were more likely to have sepsis (p Ͻ multifactorial. Historically, ARF has been described as pre- 0.0001). Notably, nonsurvivors were nearly twice as likely to renal, intrinsic, or postrenal.6 Hypovolemia leading to renal have been treated with CRRT (p Ͻ 0.05). hypoperfusion is the most common prerenal cause of de- Multivariable regression analysis was performed using creased glomerular filtration, which may be exacerbated by demographic variables significant by univariate analysis as vasoconstriction via prostanoids, cytokines, and activation of independent variables, with mortality as the dependent the renin-angiotensin-aldosterone axis in the setting of sepsis, variable (Tables 8–10). Table 8 examines the relative con- or by vasoconstrictors such as vasopressors and aminoglyco- tribution of ARF to overall mortality compared with other side antibiotics. manifestations of OD. Independent predictors of mortality The renal and postrenal causes of ARF are less common included increasing age, increasing APACHE III score, in the critical care setting. Acute tubular necrosis is the most and cardiovascular, neurologic, hepatic, and renal dysfunc- common intrinsic mechanism of ARF, and is generally tion. Female gender was associated with a decreased risk caused by a toxic or ischemic insult to the kidney. Most of mortality. toxins such as antibiotics, intravascular contrast media,12 and Two logistic regression analyses were performed to de- nonsteroidal anti-inflammatory drugs lead to acute tubular termine independent predictors of mortality among patients necrosis (ATN)-mediated ARF,13 whereas sepsis and cardio- with ARF. The first analysis (Table 9) focused on each type pulmonary bypass may cause both prerenal and intrinsic of OD and the mode of RRT, and confirmed the first regres- ARF.5,14–16 Obstruction distal to the collecting system, such sion analysis in that increasing age and cardiovascular, neu- as nephrolithiasis, prostatic hypertrophy, or operative injury, rologic, hepatic, and renal dysfunction were independent represent the common causes of postrenal ARF. predictors of mortality. Notably, HD was associated with a Mechanical ventilation may influence the development decreased risk of death, whereas CRRT had no effect. The of ARF through several different mechanisms.17 Positive-

Table 7 Univariate Analysis of Factors Associated With Survival Among Patients Who Developed ARF

ARF Survivors ARF Nonsurvivors p (N ϭ 295 patients) (N ϭ 235 patients) Age 68.1 Ϯ 0.8 70.6 Ϯ 0.9 0.048 APACHE III 69.6 Ϯ 1.6 94.7 Ϯ 2.2 Ͻ0.0001 MOD score 7.1 Ϯ 0.3 15.4 Ϯ 0.3 Ͻ0.0001 % Female 35.9 33.7 0.648 % CRI 34.5 16.5 Ͻ0.0001 % Sepsis 46.3 71.2 Ͻ0.0001 ULOS 11.9 Ϯ 1.2 20.6 Ϯ 1.6 Ͻ0.0001 HLOS 30.4 Ϯ 2.7 31.22 Ϯ 2.2 0.824 % CRRT 5.8 11.5 0.026 p values compare ARF survivors’ and ARF nonsurvivors’ data. ARF, acute renal failure; CRI, acute-on-chronic renal failure; CRRT, continuous renal replacement therapy; MOD, multiple organ dysfunction score; ULOS, ICU length of stay (days); HLOS, hospital length of stay (days).

990 November 2007 Acute Renal Failure in Critically Ill Surgical Patients

pressure ventilation affects renal hemodynamics through its Table 8 Logistic Regression Analysis for Mortality of deleterious effects on cardiac output. Strategies such as per- All Patients missive hypercapnia or permissive hypoxemia may compro- B p Odds Ratio 95% CI mise renal blood flow. Also, mechanical ventilation may Age 0.010 0.003 1.010 1.003–1.017 cause a pulmonary inflammatory reaction that leads to sys- APACHE III score 0.036 0.001 1.037 1.033–1.041 temic release of inflammatory mediators. Female gender Ϫ0.252 0.032 0.777 0.618–0.979 Acknowledging these risk factors for ARF and the Pulmonary OD Ϫ0.078 0.133 0.925 0.836–1.024 Renal OD 0.145 0.007 1.156 1.040–1.285 known high rate of mortality despite RRT, investigators have Cardiovascular OD 0.246 0.001 1.279 1.157–1.414 focused on prevention of ARF. Investigators have attempted Hepatic OD 0.459 0.001 1.582 1.355–1.848 to offset the toxicity of intravascular contrast media by the CNS OD 0.482 0.001 1.620 1.480–1.774 use of nonionic media (unsuccessfully), and by pretreatment Hematology OD 0.100 0.166 1.105 0.959–1.273 with N-acetylcysteine (with mixed results).18 Sodium loading 19 Units of increments: Age, 1 year; APACHE III and organ dys- (e.g., 8.4% NaHCO3) may be more effective. Atrial natri- function (OD) scores, 1 point. uretic peptide may enhance renal function and decrease the Hosmer-Lemeshow goodness-of-fit test ␹2 11.2 (p ϭ 0.188) and 2 need for RRT in patients while improving dialysis-free sur- Nagelkerke R 0.569, indicating excellent calibration and discrimina- 20 tion for the model. vival in early, acute renal ischemia. Fenoldopam, a dopa- CNS, central nervous system; CI, confidence interval. mine receptor agonist and renal vasodilator, increases the ratio between renal oxygen supply and demand,21 but data are equivocal regarding its benefit in preventing or reversing Table 9 Odds Ratios for Mortality for All Patients ARF. Interestingly, prophylactic HD may improve morbidity With ARF (Examining the Patterns of Organ and mortality in cardiac surgery patients with preoperative Dysfunction) elevated serum creatinine concentration.22 Diuretics23,24 and B p Odds Ratio 95% CI low-dose dopamine25,26 are probably useless in preventing or Hemodialysis Ϫ0.959 0.014 0.383 0.178–0.825 improving the outcome of ARF. CRRT Ϫ0.084 0.857 0.919 0.369–2.291 In our patients with ARF, HD was superior to CRRT in Age 0.029 0.001 1.030 1.013–1.047 reducing the risk of death. That the method of dialysis im- Renal MOD 0.560 0.001 1.751 1.269–2.417 pacts outcome has been suggested previously. Jaar et al. Cardiovascular MOD 0.432 0.0001 1.540 1.251–1.894 Hepatic MOD 0.700 0.0001 2.013 1.586–2.555 reported that the risk of death in patients with end-stage renal CNS MOD 0.825 0.0001 2.281 1.857–2.802 disease was reduced by HD compared with peritoneal dialysis.27 Schiffl et al. showed that the mortality rate of ARF Units of increments: Age, 1 year; APACHE III and organ dysfunction (OD) scores, 1 point. decreased with daily HD instead of conventional (i.e., thrice 28 Hosmer-Lemeshow goodness-of-fit test ␹2 2.49 (p ϭ 0.962) and weekly) intermittent HD. In that study, daily HD resulted in Nagelkerke R2 0.634, indicating excellent calibration and discrimina- less hypotension, better control of uremia, and more rapid tion for the model, comparable to the model shown in Table 10. resolution of ARF.28 CNS, central nervous system; CRRT, continuous renal replace- In light of the study by Schiffl et al., we hypothesized ment therapy; MOD, multiple organ dysfunction score; CI, confidence interval. that CRRT would provide greater daily clearance than intermittent HD, and reduce the mortality of ARF. However, our study found that CRRT provided no survival benefit; in fact, Table 10 Odds Ratios for Mortality for All Patients it was daily intermittent HD that reduced mortality. At our With ARF (Examining Demographics and the institution, the CRRT dialysate fluid had an average hospital Cumulative Incidence of Organ Dysfunction) cost of $207/d and the CRRT filters cost $160 each, whereas conventional HD costs $140 per session. Because of our B p Odds Ratio 95% CI findings and its higher cost, we no longer prescribe CRRT Hemodialysis Ϫ0.781 0.035 0.458 0.222–0.947 preferentially. Some patients are not candidates for intermit- CRRT 0.012 0.979 1.012 0.425–2.410 tent HD because of labile blood pressure; therefore, hemo- Age 0.024 0.005 1.024 1.007–1.041 MOD 0.384 0.001 1.468 1.372–1.571 dynamically unstable patients now represent the only group Sepsis 0.092 0.728 1.097 0.653–1.842 where the incremental cost of CRRT is justified for the acute APACHE III 0.003 0.488 1.003 0.995–1.011 management of ARF. Units of increments: Age, 1 year; APACHE III and organ dys- Our finding that CRRT provided no benefit compared function (OD) scores, 1 point. with intermittent HD is concordant with other studies. In a Hosmer-Lemeshow goodness-of-fit test ␹2 2.53 (P ϭ 0.960) and small randomized trial of medical ICU patients with ARF, 2 Nagelkerke R 0.614, indicating excellent calibration and discrimina- Augustine et al.,29 found that despite greater control of intra- tion for the model, comparable to the model shown in Table 9. CNS, central nervous system; CRRT, continuous renal replace- vascular volume, CRRT yielded no improvement in survival, ment therapy; MOD, multiple organ dysfunction score; CI, confidence preservation of urine output, or renal recovery compared with interval. intermittent HD. Augustine et al. suggested that the greater

Volume 63 • Number 5 991 The Journal of TRAUMA௡ Injury, Infection, and Critical Care solute removal associated with CRRT may have contributed ber of clinicians were involved in decision-making, CRRT to decreased urine output. Additionally, they echoed the ob- indications were applied consistently. servations of others that the increased mean arterial pressure observed with CRRT may have been because of potentially CONCLUSIONS deleterious vasoconstriction and decreased core temperature, Despite aggressive RRT and the recent use of CRRT, the and not any distinct advantage of the modality.30 mortality of ARF in critically ill surgical patients remains A recent multicenter study by Cho et al.31 showed that high. The most likely reason seems to be the effect of non- CRRT was associated with increased mortality in patients renal OD. Because the risk of mortality is significantly lower with ARF, calling the modality into further question. with conventional HD compared with CRRT, and the latter No single reason can explain definitively why CRRT modality is both more costly and cumbersome, patients who fails to yield a survival benefit comparable to intermittent need RRT should be treated preferentially with HD until data daily HD. Perhaps CRRT may facilitate excessive fluid re- demonstrate a clear benefit of CRRT among patients who can moval, leading to hypoperfusion of other organs. Also, com- undergo HD. plications of the anticoagulation, clotting with frequent filter or tubing changes (each clotted CRRT filter or tubing set ϳ causes loss of 200 mL blood each time), or hemolysis in the REFERENCES CRRT circuit may lead to increased blood transfusions, im- 1. Amato MBP, Barbas CSV, Medeiros DM, et al. 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Acute renal failure. and especially those who have stable hemodynamics.33 Lancet. 2005;365:417–430. Whether newer CRRT machines that permit higher blood 5. Uchino S, Dellum JA, Bellomo R, et al. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. flow rates will prove more beneficial than the technology Acute renal failure in critically ill patients: a multinational, employed herein is currently unknown. Our study revealed multicenter study. JAMA. 2005;294:813–818. that nonrenal ODs, in particular hepatic and cardiovascular 6. Singh N, Ahya SN, Levin ML. Acute renal failure. JAMA. 2003; failure, are more powerful predictors of mortality than ARF 289:747–751. itself. Perhaps, improvement of the management of nonrenal 7. Barie PS, Hydo LJ. Epidemiology of multiple organ dysfunction syndrome in critical surgical illness. Surg Infect. 2000;1:173–186. OD may prove to be more beneficial for ARF patients than 8. Marshall JC, Cook DJ, Christou NV, et al. 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Volume 63 • Number 5 993 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

All-Terrain Vehicle Crash Factors and Associated Injuries in Patients Presenting to a Regional Trauma Center Mark A. Brandenburg, MD, FACEP, Sheryll J. Brown, MPH, Pam Archer, MPH, and Edward N. Brandt, Jr., MD, PhD*

Adults were more likely to (17.5–1.2 ؍ Background: It is widely accepted that related injuries. Among the 190 nonfatally CI all-terrain vehicles (ATVs) can be danger- injured patients, almost half (47%) were be injured in rollover crashes where the ous to operators. Understanding the mech- diagnosed with a head injury. In 63% of ATV was traveling uphill; in all of these anisms of ATV crashes, especially rollovers, crashes the ATV rolled over. The direc- cases the vehicle rolled backwards. can provide important insight to consumers, tion of the rollover was strongly associated Conclusions: These findings suggest legislators, and manufacturers on ATV with the type of riding terrain or slope. that nonrandom, modifiable factors are safety and protection of the users. ATVs traveling on flat or uneven surfaces likely involved. Our data provide unique Methods: From March 1, 2003 to were strongly associated with right-side insight into specific mechanisms of ATV crashes, particularly rollovers, and those %95 ,32.9 ؍ [July 31, 2005, all patients with ATV- rollovers (odds ratio [OR -involving children. Findings may be appli .(221.5–6.6 ؍ [related injuries presenting to a regional confidence interval [CI trauma center were enrolled in an ATV ATVs traveling uphill were strongly asso- cable to changes in ATV design and edu- .cation of users ؍ crash data bank. Data were collected on ciated with backward rollovers (OR ,Children Key Words: All-terrain vehicles .(1,497.0–27.2 ؍ the patients and the circumstances sur- 173.6, 95% CI rounding each crash. had a significantly greater risk compared Crashes, Rollover, Mechanisms, Head Results: A total of 193 persons were with adults of right-side rollovers on flat injuries. %95 ,4.7 ؍ treated during the study period for ATV- and uneven surfaces (OR J Trauma. 2007;63:994–999.

t is widely accepted among experts that children are at cedure (29%).6 Approximately 50% of ATV-injured pa- risk of serious injury when riding all-terrain vehicles tients suffer head injuries9 and in children, approximately I(ATVs).1–6 Although children less than 16 years of age 25% to 35% of ATV-related injuries involve brain injury represent only 14% of all ATV riders, they continue to or spinal cord injury, or both.7,10 account for up to 47% of all ATV-related injuries.7 Soft The present study was conducted to examine and better tissue injuries, extremity fractures, and head injuries are characterize the factors and injuries associated with ATV the most common types of injuries associated with ATV crashes, particularly rollovers. crashes,6 with 38% of children requiring surgery for their injuries in one study,8 and 69% of children requiring either METHODS an orthopedic procedure (40%) or a general surgical pro- From March 1, 2003 to July 31, 2005, all patients presenting to the Trauma Emergency Center (TEC) at St. Francis Submitted for publication March 30, 2007. Hospital in Tulsa, OK, with ATV-related injuries were en- Accepted for publication July 3, 2007. rolled in the ATV surveillance crash data bank. The TEC is Copyright © 2007 by Lippincott Williams & Wilkins a Level II trauma center with 70,000 patient visits annually From the Oklahoma Institute for Disaster and Emergency Medicine (M.A.B.), University of Oklahoma College of Medicine, Tulsa; Trauma that also serves as the regional pediatric trauma center. Staff Emergency Center (M.A.B.), St. Francis Hospital, Tulsa; Injury Prevention emergency physicians and physician assistants collected Service (S.J.B., P.A.), Oklahoma State Department of Health, Oklahoma crash data using a specialized template medical record spe- City; and University of Oklahoma College of Public Health (E.N.B.), Okla- cific for ATV patients. Factors surrounding the crash that homa City, Oklahoma. were collected included the number of passengers, driver or *Dr. Edward N. Brandt, Jr. is now deceased. The content of this report is solely the responsibility of the authors and passenger status, whether the ATV collided with something does not necessarily represent the official view of the Oklahoma State or rolled over, the riding surface, and whether a helmet was Department of Health or the CDC. being used. Other data collected included demographics, date Supported in part by the Oklahoma Institute for Disaster and Emer- and time of injury, emergency department disposition, mode gency Medicine through a grant from the State Department of Health, and of transportation to emergency department, surgical proce- Centers for Disease Control and Prevention (CDC) Grant U17/CCU624802. Address for Reprints: Mark A. Brandenburg, MD, FACEP, Department dures, length of hospitalization, complicating illnesses, and of Emergency Medicine, University of Oklahoma College of Medicine, payer status. In addition, hospitalization data were abstracted Tulsa, 4502 E. 41st St., Suite 2B09, Tulsa, OK 74135; email: mark- from medical records. All data were entered into a computer [email protected]. EpiInfo database (Centers for Disease Control and Prevention DOI: 10.1097/TA.0b013e31814b91fe [CDC], Atlanta, GA).11 The types of injuries were classified

994 November 2007 All-Terrain Vehicle Crash Mechanisms and Injuries into the following categories: facial fractures (including den- the emergency department and two as inpatients). Hospital- tal fractures), closed head injuries (CHIs), traumatic brain ization rates were similar for children Ͻ18 years of age with injuries (TBIs) (including skull fractures), orthopedic injuries nonfatal injuries (52%) and adults (46%). For hospitalized (including fractures and dislocations of the extremities and patients, the median length of stay was 3 days (range 1–38 spine, sprains and strains, and amputations), torso injuries days). Nearly half (49%) of patients were transported to TEC (including internal injuries of the chest and abdomen and rib by private vehicle and slightly more than half (51%) were fractures), spinal cord injuries, and soft tissue injuries (in- transported by emergency medical services (27% ground am- cluding lacerations, abrasions, and contusions). Injury Sever- bulance and 24% by air). Ninety-seven (50%) patients had ity Scores (ISSs)12 for 58 hospitalized patients were obtained private health insurance as the primary payer, 23 (12%) had from the Saint Francis Hospital Trauma Registry. Medicare or Medicaid, 6 (3%) had other government insur- Data analysis was conducted using SAS (SAS Institute, ance, and 67 (35%) did not have any form of health insurance Inc., Cary, NC)13 and EpiInfo (CDC). Analyses included (self-pay). frequency data and summary statistics. Yates-corrected ␹2 and corresponding p values were used to test for differences Injury Types between proportions. Fisher’s exact results were used when Among the 190 nonfatally injured patients, almost half expected cell values were less than 5. Odds ratios (ORs) and (48%) were diagnosed with a head injury, including 65 pa- 95% confidence intervals (CIs) were calculated using EpiInfo 14 tients with TBIs and 26 persons with minor CHIs (Fig. 2). Of (CDC). those patients suffering a TBI, 29 (45%) were children. Of those patients suffering a CHI, 11 (42%) were children. RESULTS Almost all (82%) TBI patients had loss of consciousness. A total of 193 persons (average 6.7 persons per month) Hospitalized patients were significantly more likely to have were treated during the study period for ATV-related in- sustained a TBI than were persons treated and released in the juries in the TEC. Sixty-eight percent of patients were emergency department (OR ϭ 6.6, 95% CI ϭ 3.2–14.0). male and 32% were female. Patients ranged in age from 2 Twenty-one percent of patients sustained torso injuries and years to 71 years of age (median age, 19 years; mode, 14 two patients sustained spinal cord injuries. Torso injuries years). Fifty-one percent of persons treated (99 of 193) were more common among hospitalized patients, but the Ͻ were 20 years of age (Fig. 1), and 44% (85 of 193) were difference was not statistically significant (OR ϭ 2.0, 95% Ͻ children 18 years of age. Forty percent of injuries (78 of CI ϭ 0.9–4.3). Eighteen patients had facial fractures and 193) were among school-age children (ages 5–18 years) nearly half of patients (47%) had orthopedic injuries. and seven children were less than 5 years of age. Nearly For 58 (64%) hospitalized patients who survived, ISS three-fourths (74%) of all the ATV-related injuries during were available. The ISS ranged from 4 to 41 with a median the study period occurred from April to September. A score of 12. Of these, 23 (40%) had minor to moderate similar seasonal pattern for both children and adults was injuries (ISS Ͻ9), 12 (21%) had severe injuries (ISS ϭ observed with a peak in the number of injuries in July and 10–15), and 23 (40%) patients had critical injuries (ISS Ͼ15). August, and another smaller peak in April and May. Among hospitalized children, 18 (42%) had severe or critical Ninety-two (48%) persons with nonfatal injuries were injuries (ISS Ͼ9), 11 (26%) had minor to moderate injuries, admitted to the hospital and 98 (51%) persons were dis- and for 14 (33%) children the severity was not specified. All charged home from the emergency department. Three per- fatally injured patients had brain and torso injuries. The ISS sons (2%) aged 13, 15, and 36 died from their injuries (one in for the two hospitalized persons who died were 38 and 45.

Number 35 Number of Injuries 80 30 Male Female 70 25 60 Torso 20 50 Facial Fx Ortho 40 15 Soft Tissue 30 CHI 10 TBI 20 5 10 0 0 0-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55+ 0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55+ Age Age Fig. 1. Patients with ATV-related injuries by age and gender, Fig. 2. Number and types of ATV-related injuries by age, March 1, March 1, 2003 to July 31, 2005. Source: Saint Francis Hospital 2003 to July 31, 2005 (includes 322 nonfatal ATV-related injuries Trauma Emergency Center; N ϭ 193. among 190 patients).

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Crash Factors Percent of Total 35 Nearly three-fourths (73%) of the patients were the driv- 29 ers of the ATV that crashed including 88% of adults (18 years 30 of age and older) and 54% of children (Ͻ18 years of age). 25 24 ATV drivers ranged in age from 5 years to 71 years with a 20 median age of 22 years and a mode of 14 years. There was 15 only one rider on the ATV in the majority (60%) of crashes, 10 8 8 7 two riders in 35%, three or more riders in 4%, and an 5 5 4 5 3 2 unknown number of riders in 2% of the ATV crashes. Only 1 1 1 1 0 0 0000 20% of the patients injured on ATVs wore helmets and only 0 Backward Forward Left Right 12% of patients treated for TBI wore helmets. Slightly more Direction of Roll children wore helmets (22%) than did adults (19%). Down Up Flat Uneven Jump In 78 (40%) crashes, the ATV collided with another Fig. 3. Direction of ATV roll by slope of riding terrain, March 1, vehicle or object including trees (n ϭ 17), ditches (n ϭ 14), 2003 to July 31, 2005 (includes information on rollovers for 97 barbed wire fences (n ϭ 11), other ATVs (n ϭ 10), automo- persons. The direction of the ATV roll or the riding slope was biles (n ϭ 6), other objects (n ϭ 16), and unknown objects unknown for 24 persons. Includes rollovers with collision, noncol- (n ϭ 4). Collisions were involved in all three of the ATV lision, or collision unknown). deaths. A significantly greater percentage of ATV crashes among children involved collisions compared with that of terrain among children, the patient was the only rider on the adults (51% and 32%, respectively, ␹2 ϭ 5.80, p ϭ 0.016). ATV. Among adults in these types of crashes, the patient was One-fourth of crashes occurred on roads or streets, and 35% the only rider on the ATV in 57% of the crashes. occurred on farms. In all of the backward rollovers among adults, and 75% In 121 crashes (63%), the ATVs rolled over. Adults were of backward rollovers among children the ATV was traveling significantly more likely to have been injured in ATV roll- uphill. Adults were more often than children involved in over crashes (72%) than were children (51%) (␹2 ϭ 8.62, p ϭ ATV rollovers going uphill where the vehicle rolled back- 0.003). Rollover crashes among children were significantly ward (28% and 14%, respectively). When collisions were more likely to involve more than one rider on the ATV (47%) excluded from the analysis, adults had a greater risk than than were rollover crashes among adults (22%) (␹2 ϭ 6.88, ϭ children did of being in backward rollovers traveling uphill, p 0.009). The riding terrain or slope was known in all but ϭ ϭ but the difference was not statistically significant (OR 1.6, 10 of the ATV rollover crashes (n 111). Of these, 45% 95% CI ϭ 0.5–5.7). For 53 (44%) patients in rollovers, the occurred on flat terrain, 31% riding uphill, 15% riding down- ATV landed on them. Among nearly three-fourths (73%) of hill, 8% on uneven terrain, and 1% jumping. In 56% of patients in backward rollovers, 44% in right side, 40% in left rollovers involving children and 45% of rollovers involving side, and 29% in forward rollovers, the ATV landed on them. adults, the ATV was traveling on flat or uneven terrain, as However, patients in rollover crashes were no more likely to opposed to a slope. be hospitalized or have greater ISSs than were patients who In 103 of the rollover crashes, the direction of the were not in rollover crashes. rollover was known. The ATV rolled to the right in 31%, backward in 29%, forward in 20%, and to the left in 19% DISCUSSION of rollover crashes. In 97 of the rollover crashes, both For more than 30 years, ATVs have been popular in the riding slope and direction of the rollover were known (Fig. United States, marketed and sold for off-road travel, recre- 3). ATVs traveling on flat or uneven terrain (combined) ation, competition racing, and used as work tools. During the were strongly associated with right-side rollovers (OR ϭ 1980s, researchers began to report on the dangers of operat- 32.9, 95% CI ϭ 6.6–221.5) and ATVs traveling uphill ing ATVs. In 1988, the US Consumer Product Safety Com- were strongly associated with backward rollovers (OR ϭ mission and the ATV industry agreed to cease manufacturing 173.6, 95% CI ϭ 27.2–1,497.0). three-wheeled ATVs, but not four-wheeled ATVs, through a More than one-third (34%) of ATV rollovers were asso- consent decree negotiated in Federal District Court.16,17 Since ciated with a collision and children had a greater risk of being that time, only four-wheeled ATVs have been manufactured injured in a collision-related ATV rollover (49%) compared and sold to consumers; however, a small number of three- with adults (26%) (OR ϭ 2.6, 95% CI ϭ 1.1–6.1) (Table 1). wheeled ATVs are still in circulation. Studies suggest that in When collision crashes were excluded, children, compared subsequent years, US consumers continued to be at great risk with adults, had a greater risk of having been in rollover of injury while riding ATVs.8,15,18 crashes where the vehicle rolled to the right on flat or uneven In 1998, the consent decree expired and ATV manufac- surfaces (OR ϭ 4.7, 95% CI ϭ 1.2–17.5). In the majority turers subsequently began increasing the speed, power, and (89%) of the right-sided rollover crashes on flat or uneven size of ATVs. The number of ATVs in the US increased from

996 November 2007 All-Terrain Vehicle Crash Mechanisms and Injuries

crash mechanisms than are adults. This type of detailed data Table 1 Mechanisms of ATV Rollover Crashes Among on the circumstances of ATV crashes and the resulting inju- Children and Adults Treated by TEC, March 1, 2003 to ries to riders has not previously been reported. The informa- July 31, 2005 tion provides for a better understanding of how these crashes Mechanism Children Adults Total occur in specific subsets of riders and strategies for injury Total no. rollovers 43 78 121 prevention efforts. With collisions* 21 (49)† 20 (26)† 41 (34)† Children Ͻ18 years of age accounted for nearly half Up 0 2 2 (44%) of all patients. More than half (52%) of the injured Down 5 5 10 Flat 13 9 22 children required hospitalization, 22% suffered severe or crit- Uneven 0 3 3 ical injuries (ISS Ͼ9), and two children died. Nearly half Unknown 3 1 4 (45%) of all TBIs were among children. Children were more Without collisions 22 (52) 54 (69) 76 (63) likely to be injured than were adults in collision-related ATV Up 7 25 32 Down 2 5 7 crashes. In 51% of ATV crashes among children, the vehicle Flat 9 18 27 rolled, and in the majority (56%) of these rollovers among Uneven 2 4 6 children, the ATV was traveling on flat or uneven terrain, as Unknown 1 2 3 opposed to sloping terrain. Collision unknown 0 4 (5) 4 (3) In a previous long-term, retrospective study, 38% of Riding terrain and rollover direction (without ATV-related central nervous system injuries were caused 22 collisions) by rollover crashes. In our study, 63% of crashes were Uphill associated with the ATV rolling over. When collision- Forward 0 1 (2) 1 (1) related rollovers were excluded, children were more likely Backward 6 (27) 20 (37) 26 (34) Right 0 0 0 to be injured in rightward rollovers on flat and uneven Left 1 (5) 3 (6) 4 (5) terrain and most often while riding alone. This finding may Downhill indicate that children operate ATVs more often on flat or Forward 1 (5) 1 (2) 2 (3) uneven terrain than on sloped terrain. It may also be Backward 0 0 0 related to the level of the child’s operating skill in turning Right 0 1 (2) 1 (1) Left 1 (5) 2 (4) 3 (4) or maneuvering the ATV. Flat or uneven Adults were more often injured in rollover crashes where Forward 0 4 (7) 4 (5) the ATV was traveling uphill, in all of these cases the vehicle Backward 0 0 0 rolled backwards. This finding among adult drivers may Right* 9 (41) 7 (13) 16 (21) Left 2 (9) 7 (13) 9 (12) indicate that they are more likely to operate ATVs on more Unknown or all other 2 (9) 8 (15) 10 (13) dangerous terrain and may not understand fully the proclivity Total rollovers (without 22 54 76 of these vehicles to roll backwards when traveling uphill. collisions) Such a high incidence of rollover crashes in both adults and Values within parenthesis indicate percentage values. children suggests that the center of gravity in some ATV * Significantly greater risk among children compared with adults models may be too high. Ͻ (P 0.05). Modifiable factors that could prevent ATV rollovers † Percents may not equal 100 because of rounding. include vehicle speed when traveling uphill, vehicle speed approximately 4 million in 1998 to 6.2 million in 2003.19 when turning, vehicle center of gravity, and change of center Since 2003, production of large engine ATVs has increased of gravity with passengers of specific weight and height. threefold. Large engine ATVs are faster and heavier and Should manufacturers or legislators be called upon to man- some can attain speeds of up to 55 mph and weigh 800 date design changes to these vehicles? Should the basic de- pounds. Although advertising for these vehicles increased sign of these vehicles be modified to lower the center of markedly after 1997, the Consumer Product Safety Commis- gravity? Should roll bars be configured into the design of sion reported significant increases in ATV-related injuries ATVs? These and other questions arise when considering the from 1997 to 2001.19,20 The number of ATV-related injuries high incidence of rollovers in these vehicles. and deaths more than doubled during that 5-year period to TBIs are a leading cause of death and disability in the more than 500 deaths and 110,000 injuries. Children under 16 United States affecting 1.5 million people annually.23–26 In years of age incurred a disproportionate number of injuries Oklahoma, TBI is the leading cause of injury death and and deaths.21 Since 1982, nearly 6,500 persons have been disability among Oklahomans aged 45 years and younger.27 killed in ATV incidents.21 In the United States, approximately 50,000 persons die and an This study provides unique insight into specific mecha- estimated 80,000 to 90,000 persons suffer long-term disabil- nisms of ATV crashes and provides strong evidence that ities caused by TBIs annually.28 Disability after TBI is com- children riding these vehicles are more susceptible to certain mon even among persons with mild TBIs.25

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In this study, 35% (65 nonfatal and 3 fatal) of all ATV physicians and PA’s in the Saint Francis Hospital TEC, Patty Pederson, Susi crash victims suffered TBIs. Only 14% of persons with McCauley, Michael Fusco, and Vicki Burch, St. Francis Medical Center. A nonfatal TBI or CHI and none of the persons with fatal TBI special thanks to Sue Mallonee, RN, MPH, OK State Department of Health, for editorial comments and review, and Nancy Green, Injury Prevention were wearing protective headgear. The Consumer Product Service, OK State Department of Health who assisted with production. Safety Commission estimates helmet use by ATV riders would reduce the risk of death by 42% and the risk of REFERENCES nonfatal head injury by 64%.29 Population-based ATV 1. Accident Prevention Committee, Canadian Pediatric Society. 2-, 3- death rates show that states without any ATV safety leg- and 4-wheel unlicensed off-road vehicles. Can Med Assoc J. 1987; islation have a collective death rate twice that of states 136:119–120. with any safety legislation.30 State legislation requiring the 2. American Academy of Pediatrics Committee on Injury and use of helmets has been shown to be effective.31 Poison Prevention. All-terrain vehicle injury prevention: 2-, 3- This study is subject to specific limitations. Pieces of and 4-wheeled unlicensed motor vehicles. Pediatrics. 1987; 79:306–308. information regarding the circumstances of each crash were 3. Ross RT, Stuart LK, Davis FE. All-terrain vehicle injuries in occasionally unavailable, particularly when a patient suffered children: industry-regulated failure. Am Surg. 1989;65:870–873. severe injuries and was unable to recount the events sur- 4. Shults RA, Wiles SD, Vajani M, Helmkamp JC. All-terrain vehicle- rounding the crash. Information about the mechanisms of the related nonfatal injuries among young riders: United States, 2001– crash was self-reported and may have been subject to self- 2003. Pediatrics. 2005;116:e608–e612. 5. Brown R, Koepplinger M, Mehlman C, et al. All-terrain vehicle and report bias. Certain physical factors could not be objectively bicycle crashes in children: epidemiology and comparison of injury determined such as the speed that the vehicle was traveling, severity. J Pediatr Surg. 2002;37:375–380. its acceleration, and angle of turn. Individual factors such as 6. Cvijanovich N, Cook L, Mann NC, Dean JM. A population-based the driver’s experience and skill in operating the ATV likely assessment of pediatric all-terrain vehicles. Pediatrics. 2001; play a role as well but were beyond the scope of this study. 108:631–635. 7. The U.S. Consumer Product Safety Commission. 2001 Annual Patients in this study represent serious ATV-related injuries Report: All-Terrain (ATV)-Related Deaths and Injuries. Washington, occurring in the eastern region of Oklahoma and may not be DC: United States Consumer Product Safety Commission; 2002. representative of all ATV-related injuries. Saint Francis Hospital 8. Lister DG, Carl J III, Morgan JH III, et al. Pediatric all-terrain TEC is a regional trauma center also serving as the regional vehicle trauma: a five-year statewide experience. J Pediatr Surg. pediatric trauma center; therefore, a selection bias is likely. 1998;33:1081–1083. 9. Acosta JA, Rodriquez P. Morbidity associated with four-wheel all- These data support previous reports that demonstrate the terrain vehicles and comparison with that of motorcycles. J Trauma. high incidence and severity of injuries associated with four- 2003;55:282–284. wheeled ATVs. The incidence of ATV-related injuries and 10. Mangano FT, Menendez JA, Smyth MD, Leonard JR, Narayan P, deaths is expected to steadily increase if the current trend is Park TS. Pediatric neurosurgical injuries associated with all-terrain not reversed. We encourage prevention efforts at all levels vehicle accidents: a 10-year experience at St. Louis Children’s Hospital. J Neurosurg. 2006;105(Suppl):2–5. (local, state, and national) to address this problem. Mandatory 11. EpiInfo [Computer Program]. Version 3.3.2. Atlanta, GA: Centers safety courses, helmet laws, and age restrictions will likely for Disease Control and Prevention; 2005. reduce injuries and deaths secondary to ATV crashes. 12. Association for the Advancement of Automotive Medicine. The A more informative insight into the nature of ATV Abbreviated Injury Scale. Des Plaines, IL: Association for the crashes, especially rollovers, can assist consumers, legisla- Advancement of Automotive Medicine; 1998. 13. SAS [Computer Program]. Version 9.1.3. Cary, NC: SAS Institute; tors, and manufacturers in devising strategies to protect ATV 2000–2004. users. A wealth of existing data are already available to 14. Mehta C, Patel N, Gray R. Computing an exact confidence interval warrant legislation for preventing ATV injuries and deaths. for the common odds ratio in several 2 times 2 contingency tables. However, further research is needed to assist manufacturers J Am Stat Assoc. 1985;78:969–973. in preventing and minimizing ATV-related injuries. Research 15. Lynch JN, Gardner NJ, Worsey J. The continuing problem of all-terrain vehicle injuries in children. J Pediatr Surg. 1998; is needed to examine specific mechanisms of ATV crashes 33:331. and injuries, the risk factors associated with the crashes, and 16. U.S. Consumer Product Safety Commission. All-Terrain Vehicle the effectiveness of safety gear in protecting riders, especially Exposure, Injury, Death and Risk Studies. Bethesda, MD: U.S. children. Rollover proclivity studies similar to those con- Consumer Product Safety Commission; 1988:3. ducted in the automobile industry will be helpful in deter- 17. U.S. District Court for the District of Columbia, 1988, United States of America v. Honda Motor Company, Inc. Washington, DC: U.S. mining the likelihood and cause of ATV rollovers. Although District Court for the District of Columbia; 1992. Civil Action No. multiple factors are likely involved including poor training 87-3525. and improper driving or handling of the vehicle, the role of ATV 18. Helmkamp J. Adolescent all-terrain vehicle deaths in West Virginia, size, speed, and center of gravity should be investigated further. 1990–1998. W V Med J. 2000;96:361–363. 19. Scutchfield SB. All-terrain vehicles: injuries and prevention. Clin Orthop Relat Res. 2003;409:61–71. ACKNOWLEDGMENTS 20. U.S. Consumer Product Safety Commission. Annual Report of ATV We acknowledge the following individuals who provided valuable Deaths and Injuries. Bethesda, MD: U.S. Consumer Product Safety assistance in collecting data for this study or preparing the manuscript: the Commission; 2003.

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21. Ingle R. U.S. Consumer Product Safety Commission. 2004 Annual 26. Centers for Disease Control and Prevention. Traumatic brain injury- Report of ATV Deaths and Injuries. Bethesda, MD: U.S. Consumer related hospital discharges: results from a 14-state surveillance system, Product Safety Commission; 2005. 1997. MMWR CDC Surveill Summ. 2003;52(SS04):1–27. 22. Brandenburg MA, Archer P, Mallonee S. All-terrain vehicle-related 27. Advisory Council on Traumatic Spinal Cord and Traumatic Brain central nervous system injuries in Oklahoma. J Okla State Med Injury. Fourth Annual Summary of Recommendations. Oklahoma Assoc. 2005;98:194–199. State Department of Health; 1996. 23. Thurman DJ, Alverson C, Dunn KA, et al. Traumatic brain injury in 28. Centers for Disease Control and Prevention. Traumatic Brain Injury the United States: a public health perspective. J Head Trauma in the United States: A Report to Congress. Atlanta, GA: National Rehabil. 1999;14:602–615. Center for Injury Prevention and Control; 1999. 24. Guerrero JL, Thurman DJ, Sniezek JE. Emergency department visits 29. Rodgers GB. The effectiveness of helmets in reducing all-terrain associated with traumatic brain injury in the United States, 1995– vehicle injuries and deaths. Accid Anal Prev. 1990;22:47–58. 1996. Brain Inj. 2000;14:181–186. 30. Helmkamp JC. A comparison of state-specific all-terrain vehicle- 25. Centers for Disease Control and Prevention. Report to Congress on related death rates, 1990–1999. Am J Public Health. 2001; Mild Traumatic Brain Injury in the United States: Steps to Prevent a 91:1792–1795. Serious Public Health Problem. Atlanta, GA: US Department of 31. Keenan HT, Bratton SL. All-terrain vehicle legislation for children: a Health and Human Services, CDC, National Center for Injury comparison of the state with and without a helmet law. Pediatrics. Prevention and Control; 2003. 2004;113:e330–e334.

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Delta V, Principal Direction of Force, and Restraint Use Contributions to Motor Vehicle Crash Mortality Gabriel E. Ryb, MD, MPH, Patricia C. Dischinger, PhD, Joseph A. Kufera, MA, and Cynthia A. Burch, MPH

Objective: To measure the combined PDOF; or in vehicles without airbags were (17% vs. 9%). Multiple logistic regression contribution of change in velocity (⌬v), excluded. Mortality was analyzed in rela- findings, after adjusting for age, gender, and principal direction of force (PDOF), and tion to ⌬v (km/h), restraint use, and body mass index, revealed significant ef- restraint use on mortality after vehicular PDOF using ␹2. Multiple logistic regres- fects of lateral PDOF (odds ratio [OR] trauma. sion models were built, including possible 3.06 [2.03–4.61]), unrestrained status (OR Methods: The Crash Injury Re- confounders (body mass index, age, gen- 2.95 [2.01–4.38]), and ⌬v 40–80 km/h search and Engineering Network popula- der) and interactions were explored. An (OR 3.65 [2.44–5.44]). Effect modification .was used for all statistics. was found between PDOF and ⌬v 0.05 ؍ [tion includes patients <8 years old with [alpha one injury with an Abbreviated Injury Results: A total of 1,261 cases were Conclusions: A ⌬v 40 km/h to 80 Scale score >3 or with two injuries with included. Mortality was higher for unre- km/h, lack of restraint use, and lateral an Abbreviated Injury Scale score >2, strained than for restrained patients (17% impact significantly affects mortality. A who were occupants of a vehicle. Patients vs. 9%) and was higher for lateral than for synergistic effect was found between ⌬v 15 years or younger; in rear collisions; frontal impact patients (17% vs. 11%). 40–80 km/h and lateral PDOF. back seat occupants; in crashes with ⌬v Higher mortality rates were also observed Key Words: Crash, ⌬V, Restraint, >80 km/h, unknown ⌬v, or unknown for ⌬v 40–80 km/h than for ⌬v <40 km/h PDOF, mortality, injury, CIREN. J Trauma. 2007;63:1000–1005.

n recent studies, the increase in vehicle speed has been the ⌬v that occurs at the time of the “sudden stop” remains a associated with an increase in injury rates, severity, and critical factor in injury causation. ⌬v has been used as a Imortality1–4 in epidemiologic studies. At the mechanistic measure of crash severity and predictor of occupant injury in level, however, the change in velocity (⌬v) is the determining vehicular crashes.5 The National Automotive Sampling Sys- factor of the quantity of energy that, when transferred to tem/Crashworthiness Data System (NASS/CDS) Manual as- biologic tissues, causes injuries. This concept has been well sumption is that “other factors being equal, the greater the ⌬v articulated in the dictum “it’s not speed that kills but the during a collision, the greater the potential for occupant sudden stop”. injury”.6 Many of the current improvements in vehicular design The objective of this study is to measure the combined are directed at minimizing that energy transfer. Nevertheless, contribution of ⌬v and other vehicular, crash and occupant factors on mortality after vehicular trauma in a modern vehicular fleet. Submitted for publication June 6, 2007. Accepted for publication August 15, 2007. Copyright © 2007 by Lippincott Williams & Wilkins From The Charles McC. Mathias, Jr. National Study Center for Trauma METHODS and EMS (G.E.R., P.C.D., J.A.K., C.A.B.), University of Maryland, Balti- The study population was drawn from the Crash Injury more, Maryland; Program in Trauma (G.E.R.), University of Maryland, Baltimore, Maryland; and the Trauma Division, Prince Georges Hospital Research and Engineering Network (CIREN) database. Medical Center (G.E.R.), Cheverly, Maryland. CIREN is a multicenter research network with a rich Supported by NHTSA under Cooperative Agreement Number source of detailed crash data in combination with highly DTNH22-05-H-01001. detailed injury data on crash-involved occupants who are This work was performed for the Crash Injury Research and Engineer- admitted to a trauma center. This injury information in- ing Network (CIREN) Project at the University of Maryland, National Study Center for Trauma and Emergency Medical Systems in cooperation with the cludes hospital discharge summaries, radiologic images United States Department of Transportation/National Highway Safety Ad- and results narratives, operative reports, autopsy reports, ministration (USDOT/NHTSA). injury photographs, and long-term outcomes. Views expressed are those of the authors and do not represent the views The National Highway Traffic Safety Administration of the NHTSA. coordinates the enrollment of cases in the CIREN system at Presented as a poster at the 20th Annual Meeting of the Eastern Associ- ation for the Surgery of Trauma, January 16–20, 2007, Fort Meyers, Florida. eight trauma centers in the United States. The CIREN data- Address for reprints: Gabriel E. Ryb, MD, National Study Center for base includes patients who sustained at least one injury yield- Trauma and Emergency Medical Systems, 701 West Pratt Street, Fifth Floor, ing an Abbreviated Injury Scale (AIS)7 score Ն3ortwo Baltimore, MD 21201; email: [email protected]. injuries yielding an AIS score Ն2 and were in a late-model DOI: 10.1097/TA.0b013e31815885c8 vehicle (i.e., manufactured within 8 years before the crash).

1000 November 2007 Contributions to Motor Vehicle Crash Mortality

For each enrolled case, the following data are obtained: refers to the use of three-point seatbelts as determined by the medical data on injured occupants, crash scene data, and study team. Curb weight is the total weight of an automobile vehicle damage information. Investigations of crash scenes with standard equipment, oil, lubricants, coolant, and a full and vehicles use the format established by National Highway tank of fuel and not loaded with either passengers or cargo. Traffic Safety Administration’s NASS. Each case is then The interior of the vehicle is inspected to determine the reviewed by a multidisciplinary team consisting of crash points of contact and restraint system use. Contact points are investigators, biomechanical engineers, epidemiologists, re- identified by the presence of scuff patterns, dents on the search nurses, and physicians representing radiology, trauma vehicle interior, and skin or fabric transfers. The interior surgery, emergency medicine, orthopedics, and neurosurgery inspection also includes an assessment of the integrity of the to establish a probable cause and mechanism of injury. Each passenger compartment and measurement of component injury is discussed and sources of injury (contact points) are intrusion. identified and classified by confidence. Injury Data Crash Investigation The multidisciplinary team codes the injury data after Data pertaining to the roadway, traffic controls, road review of hospital reports, radiographs, and, where appropri- surface type, conditions, and road grade at pre- and postim- ate, autopsy reports. Injuries are coded using the 1998 version pact locations are collected. Physical evidence, such as tire of the AIS from the Association for the Advancement of skid marks, is used to determine the heading angle and Automotive Medicine,7 and an overall Injury Severity Score trajectory of the colliding vehicles after impact. A scaled is calculated. Patients are interviewed to supplement crash drawing, showing vehicle motions at preimpact, impact, and and injury data. The institutional review boards of all partic- final rest positions, can be used in the calculations of speed ipating centers approved this study. and the force of impact. Exterior vehicle inspections include Low weight (underweight), normal weight, overweight, detailed measurements of direct and induced damage. Using and obesity were defined using the standard definitions based a contour gauge, a damage crush profile is obtained from the on body mass index (BMI): underweight is Ͻ18.5 kg/m2, impacted plane, and a specific collision deformation classi- normal is 18.5 kg/m2 to 25 kg/m2, overweight is 25 kg/m2 to fication, which incorporates the principal direction of force 30 kg/m2, and obese is Ͼ30 kg/m2.9 (PDOF), is assigned. In some frontal crashes, bumper frame height mismatch results in grill and hood area crush rather Study Population than at the bumper frame. For these cases, a secondary profile The CIREN database was used to identify patients for above the bumper frame is taken and averaged with the this investigation. The database was established in 1996; as of bumper frame profile. These measurements are entered into a October 2005, it contained data on 2,299 patients. For the crash analysis program,8 which estimates the vehicle’s ⌬vat purposes of this study, only patients 16 years and older were impact and the energy absorbed during the crash event. included. Exclusion criteria for this study were as follows: WinSmash NASS-CDS8 uses a computer model that occupants in the back seat, lack of frontal airbags, unknown provides a measure of crash severity in terms of ⌬v. In restraint use, crashes with ⌬v Ͼ80 km/h, unknown ⌬v, vehicle-to-vehicle crashes, the model assumes that the two unknown PDOF, unknown curb weight, unknown patient vehicles approach each other at an impact velocity, reach a weight or height, and being underweight. Rear collisions common velocity, and then separate. ⌬-v is equal to the were also excluded because their small number precluded impact velocity minus the separation velocity. The direction statistical analysis. After applying exclusion criteria, 1,261 of the vector is determined by the investigator as the PDOF. patients were left for analysis. For each vehicle, the components of its ⌬v are expressed along the longitudinal and lateral axes in terms of kilometers Statistical Methods per hour (km/h). For purposes of this analysis, ⌬v is divided Mortality was analyzed in relation to ⌬v, restraint use, into two groups: Յ40 and 40–80 km/h. PDOF (frontal vs. lateral), age, BMI, and gender using ␹2 and For this project, collisions are classified by superimpos- the Student’s t test for dichotomous and continuous variables, ing the face of a compass over the illustration of a vehicle and respectively. An [alpha] level of 0.05 was used to suggest aligning 0 degrees (or 360 degrees) at the front of the vehicle. statistical significance. To further characterize the effect of A “frontal” crash is classified as having a PDOF between 315 ⌬v in different types of crashes, subgroup analysis was per- degrees and 360 degrees or 0 degrees and 45 degrees, “rear” formed by restraint use and PDOF (i.e., restrained frontal, as having a PDOF between 135 degrees and 225 degrees, and restrained lateral, unrestrained frontal, and unrestrained “lateral” as having a PDOF between 226 degrees and 314 lateral). degrees on the left and 46 degrees and 134 degrees on the A multiple logistic regression model was constructed to right. Lateral crashes were further classified as “near” or determine the effect of ⌬v on mortality, before and after “far” depending on the position of the case occupant in adjusting for possible confounders such as BMI, age, gender, relation to the side of the crash. “Restraint use” in this study PDOF, and restraint use. Appropriate interactions with ⌬v

Volume 63 • Number 5 1001 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Table 3 Mortality: Patient Factors (1,261 ؍ Table 1 Patient and Crash Factors (N

Patient factors Mortality (%) P Age, yr (mean) 42 Age (yr) Ͻ0.0001 Male (%) 51 16–30 11 BMI (%) 31–40 7 Normal 40 41–50 7 Overweight 33 51–60 11 Obese 27 61–70 16 Crash factors 71–80 26 ⌬ v (km/h), median (q1–q3) 37, (27–50) Ͼ81 48 Airbag deployment (%) 65 Gender 0.049 Restraint use (%) 59 Male 11 PDOF (%) Female 14 Frontal 70 BMI 0.001 Near lateral 22 Normal 8 Far lateral 8 Overweight 14 Obese 17

؍ Table 2 Injury Severity and Distribution (N 1,261) Table 4 Mortality: Vehicular and Crash Factors

Percent Mortality (%) P Ն AIS body region with score 3 ⌬v (km/h) Ͻ0.001 Head 24 Ͻ40 9 Face 3 40–80 17 Neck 1 PDOF 0.002 Thorax 38 Frontal 11 Abdomen 17 Lateral 17 Spine 9 Airbag deployment 0.006 Upper extremity 10 Yes 9 Lower extremity 46 No 14 ISS (mean) 21 Seatbelt use Ͻ0.001 Yes 9 No 17 were explored and results are displayed in terms of adjusted odds ratios and corresponding 95% confidence intervals. Table 5 Characteristics by Outcome RESULTS Dead Alive P A total of 1,261 patients were available for analysis and (N ϭ 157) (N ϭ 1,104) form the basis for this study. Crash, occupant, and injury ISS (mean) 47.6 16.9 Ͻ0.001* characteristics of the study population are displayed in Tables Age (yr) (mean) 49.8 40.8 Ͻ0.001* 1 and 2. About half of the occupants were men and 60% were ⌬v (km/h) (median) 43 36 Ͻ0.001† classified as being overweight or obese. The mean ⌬v was 40 Curb weight (Kg) 1,380 1,417 0.15* km/h, most crashes were classified as frontal, 59% of occu- * Student’s t test. pants were restrained by seatbelts, and 65% had an airbag † Wilcoxon’s statistic. deploy. As shown in Table 2, the highest prevalence of AIS 3ϩ injuries is found for lower extremity injuries (46%), among unrestrained occupants in lateral crashes for both ⌬v followed by thoracic (38%) and head injuries (24%). Mortal- levels. It was the lowest for restrained occupants in frontal ity increases significantly with increasing age of the occupant crashes for both ⌬v levels. Although lateral PDOF seemed to and with increasing BMI. In addition, women had a higher confer ⌬v 40–80 km/h higher odds of death, restraint status mortality than men did (Table 3). Mortality was also higher within each PDOF did not affect these odds. among those not restrained by a seat belt or without an airbag Table 7 contains the results of the multiple logistic re- deployment (Table 4). As shown in Table 4, those in crashes gression predicting death. Seat belt use, PDOF, age, weight, with ⌬v of 40–80 km/h had a significantly higher mortality, and gender were also included in the model, since they were as did those in lateral crashes. Patients who died had a higher also significantly associated with mortality in the univariate Injury Severity Score, age, and ⌬v (Table 5). analysis. The adjusted model revealed significant odds for Table 6 contains the results of the analysis of mortality dying among high ⌬v crashes (40–80 km/h). Seat belt use, by ⌬v. This was done within each combination of PDOF and PDOF, age, and weight also showed a significant effect on restraint status. It was found that mortality was the highest mortality (Table 7). Significant interactions were found be-

1002 November 2007 Contributions to Motor Vehicle Crash Mortality

Table 6 ⌬v and Mortality: Subgroup Analysis

Mortality (%) Odds of Death* (OR) (CI) ⌬v Ͻ40 km/h ⌬v 40–80 km/h Frontal restrained (N ϭ 477) 5 9 1.99 (0.90–4.63) Frontal unrestrained (N ϭ 404) 11 19 1.99 (1.09–3.67) Lateral restrained (N ϭ 262) 8 25 3.71 (1.66–8.37) Lateral unrestrained (N ϭ 118) 17 47 4.18 (1.55–11.13) * ⌬v 40–80 km/h versus ⌬v Ͻ40 km/h.

⌬v has been included in algorithms attempting to Table 7 Multiple Logistic Regression Predicting Death* predict the need to triage injured occupants to trauma OR 95% Confidence Limits centers (i.e., URGENCY) because of its association with Overweight 1.81 1.14–2.87 injury severity.11,14 Similar effects of high ⌬v have also Obese 2.81 1.75–4.53 been associated with the presence of torso trauma,13,15 the Age (yr) presence of maximum AIS (MAIS) 2ϩ head injury,16 31–40 0.52 0.27–0.98 17 ϩ 41–50 0.65 0.32–1.22 MAIS for the lower extremity, MAIS 2 abdominal 18 51–60 0.95 0.49–1.75 injury, and a poorer clinical course among thoracic 61–70 1.88 0.99–3.48 trauma patients.19 In a study based on NASS/CDS and 71–80 4.50 2.44–8.23 ⌬ Ͼ CIREN data, a positive association of v with the occur- 80 11.07 5.18–23.83 ϩ ⌬v 40–80 km/h 3.65 2.44–5.44 rence of MAIS 3 injuries was found for both frontal and Male 1.11 0.76–1.62 lateral crashes after adjusting for restraint use and other Lateral 3.06 2.03–4.61 occupant and crash characteristics.11 Unrestrained 2.95 2.01–4.38 In concordance with the reviewed literature, we found a * Normal weight, age 16–30, ⌬v Ͻ40 km/h, female gender, fron- positive association between ⌬v and death in car crash occu- tal PDOF, and restrained status used as reference. pants admitted to trauma centers and included in the CIREN data set. A synergistic effect was found between PDOF and ⌬ ⌬ tween ⌬v 40–80 km/h and PDOF. Essentially, the odds for v, as the effect of v on the odds of death is significantly mortality were significantly larger for high ⌬v (40–80 km/h) higher among lateral than frontal crashes. However, no inter- versus a low ⌬v(Ͻ40 km/h) among lateral crashes (Table 8). action was found between ⌬v and restraint use. Also, there It was also found that the odds for mortality were larger for was no effect modification between restraint use and direc- laterals versus frontals among crashes with a high ⌬v. Taken tion of impact. together, the odds ratio is estimated to be 12.86 for a high ⌬v The lack of a significant effect of ⌬v in the subgroup lateral crash relative to a low ⌬v frontal crash. Smaller effects of restrained occupants of frontal crashes, although unex- on mortality were found for ⌬v among frontal crashes and for pected, may be because of an overall decrease in mortality PDOF among low ⌬v crashes (Table 8). secondary to the effect of airbags in frontal crashes at the studied ⌬v. At higher ⌬v, a significant effect in mortality DISCUSSION may have become apparent. Also, the effect of ⌬v in this ⌬v is a known predictor of injury severity in the subgroup may have been more apparent if the outcome adult10,11,5 and pediatric12 populations. In addition, before the measure was injury severity instead of mortality. Never- development of the CIREN network, studies performed at theless, our findings need to be corroborated in a contem- the University of Maryland, Baltimore, revealed an asso- poraneous population based dataset. ciation between PDOF, restraint system use, and higher ⌬v Our findings also show the limitations of the latest im- with the development of medical complications among provements in car design in decreasing mortality in this occupants with nonfatal injuries.13,10 modern vehicular fleet (i.e., frontal airbags were present in all

Table 8 ⌬v—PDOF Interaction

Effect vs. Reference Among Odds Ratio (Death) 95% CI ⌬v 40–80 vs. ⌬v Ͻ40 km/h Frontals 2.39 1.48–3.86 ⌬v 40–80 vs. ⌬v Ͻ40 km/h Laterals 7.35 3.90–13.85 Lateral vs. frontal ⌬v Ͻ40 1.75 1.00–3.07 Lateral vs. frontal ⌬v 40–80 5.39 3.07–9.45 (Lateral and ⌬v 40–80 km/h) vs. (frontal and ⌬v Ͻ40 km/h) 12.86 6.88–24.05

Volume 63 • Number 5 1003 The Journal of TRAUMA௡ Injury, Infection, and Critical Care the vehicles). The higher mortality found for unrestrained Fatality Analysis Reporting System, for which virtually no occupants at all ⌬v and at both studied PDOFs underlines the injury or biomechanical source data are available. need to further develop better passive restraint methods and In summary, among a population of trauma patients more effective educational or behavioral interventions to injured in motor vehicle crashes, high ⌬v, lateral PDOF, and maximize seat belt use. The higher mortality among lateral seat belt nonuse are associated with mortality. In combination crash occupants also reveals a point of weakness of our with other crash and occupant factors, ⌬v could be useful in vehicular fleet (this population, however, does not properly triaging algorithms.11,14,21 Improved car designs before the reflect the introduction of side airbags). Since only 11% of introduction of side airbags seem to have diminished the vehicles were equipped with side airbags and there was only effect of ⌬v on mortality in frontal but not in lateral crashes. 8% side airbag deployments (n ϭ 32) among lateral crashes, Further studies should elucidate the effect of side airbags. lateral airbag effect could not be evaluated in this study. The main limitation of the CIREN dataset is that cases REFERENCES are not selected in a statistically random method, but rather 1. Aarts L, van Schagen I. Driving speed and the risk of road crashes: based on enrollment criteria for occupants presenting to a a review. Accid Anal Prev. 2006;38:215–224. trauma center. Thus, the cases represent a case series rather 2. Elvik R, Christensen P, Amundsen A. Speed and road accidents: than a population based sample, which limits the ability to an evaluation of the Power Model, The Institute of Transport Economics (TOI), Oslo, December 2004. Available at: http:// make inferences to nationwide rates and creating the potential www.toi.no/getfile.php/Publikasjoner/T%D8I%20rapporter/2004/ for selection bias. Nevertheless, the CIREN sample resembles 740-2004/740-2004.pdf. Accessed May 28, 2007. the NASS population subjected to similar selection criteria 3. Singleton M, Qin H, Luan J. Factors associated with higher levels of but has a slightly different AIS score distribution. NASS has injury severity in occupants of motor vehicles that were severely damaged in traffic crashes in Kentucky, 2000–2001. Traffic Inj more injuries representing AIS scores of 2 and fewer injuries Prev. 2004;5:144–150. at AIS scores of 4 and 5; this difference is driven mostly by 4. Bedard M, Guyatt G, Stones MJ, Hirdes JP. The independent lower extremity, abdominal and thoracic injuries. contribution of driver, crash, and vehicle characteristics to driver Another limitation of the study is the accuracy of ⌬vas fatalities. Accid Anal Prev. 2002;34:717–727. calculated in WinSmash. A recent study compared ⌬v values 5. Gabauer DJ, Gabler HC. Comparison of delta-v and occupant impact velocity crash severity metrics using event data recorders. Annu Proc as measured with electronic data recorder with WinSmash Assoc Adv Automot Med. 2006;50:55–69. calculated ⌬v.20 Electronic data recorders store information 6. National Automotive Sampling System (NASS), Crashworthiness about changes of velocity during the course of the event. A Data System, Analytical User’s Manual—2002, (2003 File), National study by Niehoff has shown WinSmash to underestimate ⌬v Center for Statistics and Analysis, National Highway Traffic Safety Administration, U.S. Department of Transportation, Washington, by 23%, on average. However, this value varied from 1% to D.C. 20590. 31%, depending in the type of vehicle and crash studied. Of 7. Abbreviated Injury Scale (AIS) 1990—Update 1998. Des Plaines, interest is that, in frontal crashes, the overestimation was Illinois: Association for the Advancement of Automotive Medicine found to be minimal (1%). The inclusion of categorical stiff- (AAAM). ness coefficients and restitution in the calculation seemed to 8. United States Department of Transportation. WinSmash [computer program]. Version 2007.02.05. increase the accuracy of the measurements. Nevertheless, the 9. National Institutes of Health. Clinical Guidelines on the presence of nonrandom inaccuracy in the measurement of ⌬v Identification, Evaluation, and Treatment of Overweight and Obesity could be an important source of bias in this study, particularly in Adults: The Evidence Report. Washington, DC: National Institutes in the effects within the lateral impact crashes. of Health; 1998. Publication 98-4083. 10. Dischinger PC, Siegel JH, Ho SM, Kufera JA. Effect of change in However, the following CIREN characteristics offer con- velocity on the development of medical complications in patients siderable strengths that offset the above limitations. First, the with multisystem trauma sustained in vehicular crashes. Accid Anal eight CIREN centers function as a coordinated network, with Prev. 1998;30:831–837. uniform methods for case enrollment, crash investigation, 11. Augenstein J, Perdeck E, Stratton J, Digges K, Bahouth G. medical and injury data collection, and analysis of injury Characteristics of crashes that increase the risk of serious injuries. Annu Proc Assoc Adv Automot Med. 2003;47:561–576. sources, and biomechanical causation. Second, CIREN pro- 12. Nance ML, Elliott MR, Arbogast KB, Winston FK, Durbin vides more in-depth injury and medical data than any other DR. Delta V as a predictor of significant injury for children nationwide crash database. This includes confirmation of involved in frontal motor vehicle crashes. Ann Surg. 2006; injuries by the treating physicians and documentation of in- 243:121–125. 13. Siegel JH, Smith JA, Siddiqi SQ. Change in velocity and energy juries by high-quality medical data, including photographs of dissipation on impact in motor vehicle crashes as a function of the external injury, X-ray films (and other radiologic tests), lab- direction of crash: key factors in the production of thoracic aortic oratory data, operating room records, and autopsy reports. injuries, their pattern of associated injuries and patient survival. A Lastly, the case enrollment threshold assures a high cap- Crash Injury Research Engineering Network (CIREN) study. J Trauma. ture rate of persons with severe injuries, thus leading to a 2004;57:760–777; discussion 777–778. 14. Bahouth GT, Digges KH, Bedewi NE, Kuznetsov A, Augenstein JS, greater number of such persons for injury and crash analysis Perdeck E. Development of URGENCY 2.1 for the prediction of than is available in any other nationwide dataset, except the crash injury severity. Top Emerg Med. 2004;26:157–165.

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15. Nirula R, Talmor D, Brasel K. Predicting significant torso trauma. 19. Richter M, Krettek C, Otte D, et al. Correlation between crash severity, J Trauma. 2005;59:132–135. injury severity, and clinical course in car occupants with thoracic 16. Talmor D, Thompson KM, Legedza AT, Nirula R. Predicting severe trauma: a technical and medical study. J Trauma. 2001;51:10–16. head injury after light motor vehicle crashes: implications for 20. Niehoff P, Gabler HC. The accuracy of WinSmash delta-v estimates: automatic crash notification systems. Accid Anal Prev. 2006;38: the influence of vehicle type, stiffness, and impact mode. Annu Proc 767–771. Assoc Adv Automot Med. 2006;50:70–86. 17. Arbabi S, Wahl WL, Hemmila MR, Kohoyda-Inglis C, Taheri 21. Champion HR, Augenstein JS, Blatt AJ, et al. New tools to reduce PA, Wang SC. The cushion effect. J Trauma. 2003;54:1090– deaths and disabilities by improving emergency care: urgency 1093. software, occult injury warnings, and air medical services database. 18. Brasel KJ, Nirula R. What mechanism justifies abdominal evaluation Available at: http://www.cubrc.org/centir/docs/new_tools.pdf. in motor vehicle crashes? J Trauma. 2005;59:1057–1061. Accessed May 30, 2007.

Volume 63 • Number 5 1005 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Increased Fatalities After Motorcycle Helmet Law Repeal: Is it All Because of Lack of Helmets? Terence O’Keeffe, MBChB, MSPH, Steve R. Dearwater, BA, MPH, Larry M. Gentilello, MD, FACS, Todd M. Cohen, BA, James D. Wilkinson, MD, MPH, and Mark M. McKenney, MD, FACS

Background: During the last 10 county for a 3.5-year period before repeal cycles did not change significantly; 11.6 years, the number of motorcycle riders in (prelaw), and a similar period after repeal deaths per 10,000 motorcycles prelaw, and the United States has risen sharply. The (postlaw), using police crash reports and 12.5 deaths postlaw. corresponding increase in fatalities ob- medical examiner records. We compared Conclusions: There was a significant served during this time may be because of the number of fatalities, frequency of hel- rise in motorcycle fatalities after Florida’s the increase in riders, or because the num- met use in fatal crashes, and number of helmet law repeal, which appears to be ber of states that mandate universal hel- registered motorcycles in the two time associated with an increase in the number met use has decreased. We examined the periods. of motorcycle riders. Injury prevention ef- effect of the repeal of Florida’s helmet law Results: There was a decrease in hel- forts focusing on factors other than helmet in July 2000 to test the hypothesis that the met use from 80% to 33%, and an increase use should be developed in light of con- increase in fatalities observed after repeal in motorcycle fatalities after repeal: 72 to tinuing repeal of universal motorcycle hel- resulted from an increase in the number 125. However, repeal was also associated met laws across the nation. of motorcycle riders. with a rise in annual motorcycle registra- Key Words: Injury, Traffic crashes, Methods: We identified all motorcy- tions from 17,270 to 39,043. Fatality rates Motorcycles, Helmets, Health policy. -in Miami-Dade adjusted for numbers of registered motor (197 ؍ cle fatalities (N J Trauma. 2007;63:1006–1009.

uring the last decade, there has been a significant in- helmet laws and an increase in fatal injuries has been reported crease in the number of motorcycle riders in the United by others.3–5 DStates, with registrations increasing from 3.7 million in The increase in fatalities observed after repeal of motor- 1994 to 5.7 million in 2004. During the same time period, the cycle helmet laws is generally attributed to an increased risk number of fatal injuries also increased from 2,300 to over of fatal injury. However, this increase in fatalities may also be 4,000.1 However, the number of states that mandate universal a result of an increase in the number of riders, which in- helmet use has decreased from 47 in 1975 to 21 in the present creases the size of the population at risk. The purpose of this day. In July 2000, the State of Florida repealed its motorcycle study was to determine whether the increase in motorcycle helmet law to allow riders over the age 21 years to ride rider fatalities observed after helmet law repeal is a result of unhelmeted if they possessed $10,000 of personal injury an increased rate of injury, or because repeal is associated insurance. Within 6 months, motorcycle helmet use dropped with an increase in the number of riders at risk. We hypoth- from 83% to 56%,2 with a concomitant increase in the num- esized that the increase in fatal crashes observed after helmet ber of severe head injuries from motorcycle crashes after the law repeal is a result of an increase in the number of motor- law change. A relationship between the repeal of motorcycle cycle riders, rather than an increase in the fatality rate.

MATERIALS AND METHODS Submitted for publication December 19, 2006. The study population consisted of fatally injured motor- Accepted for publication July 20, 2007. cycle riders in Miami-Dade County between January 1, 1997, Copyright © 2007 by Lippincott Williams & Wilkins and December 31, 2003. The study was conducted at the From the Division of Burn, Trauma and Critical Care, Department of Ryder Trauma Center, University of Miami, Miami, Florida. Surgery (T.O.K., L.M.G.), University of Texas Southwestern Medical School, Dallas, Texas; and the Departments of Pediatrics (S.R.D., T.M.C.), The study design was a pre-post analysis comparing two time Public Health (J.D.W.), and Surgery (M.M.M.), University of Miami Miller periods, 42 months before and 42 months after the repeal of School of Medicine, Miami, Florida. the motorcycle helmet law in Florida (July 1, 2000). The Presented as a poster at the 65th Annual Meeting of the American University of Miami Institutional Review Board provided Association for the Surgery of Trauma, September 28–30, 2006, New Or- approval to conduct the study. leans, Louisiana. Address for reprints: Terence O’Keeffe, MBChB, MSPH, Depart- Two separate databases were combined to identify fa- ment of Surgery, University of Texas Southwestern Medical School, 5323 tally injured motorcycle riders in Miami-Dade County, and HarryHinesBoulevard,Dallas,Texas75390-9158;email:terence.okeeffe@ the proportion of helmeted riders involved in fatal crashes utsouthwestern.edu. during the two study periods. The number of fatal crashes DOI: 10.1097/TA.0b013e31815644cd was determined by examination of the medical records of the

1006 November 2007 Motorcycle Fatalities Increase With Registrations

Miami-Dade County Medical Examiner’s office. The helmet use status of fatally injured riders was ascertained using data from the Florida Department of Highway Safety and Motor Vehicle traffic crash reports. These crash reports did not contain personal identifiers. We therefore used probabilistic matching to link persons from the medical examiner database to the crash database using the date and time of the crash, as well as the age and sex of the rider. Next, to determine whether there was an increase in the number of riders over time, the annual number of registered motorcycle riders during the study period was obtained from the Florida State Department of Transportation. The annual fatality rate per 10,000 registered motorcycles pre- and posthelmet repeal legislation was compared. Changes in Fig. 1. Number of motorcycle fatalities in Miami-Dade County population in Miami-Dade County during the study period from 1997 to 2003. were obtained from US census Bureau data. Statistical analysis was performed using statistical software SPSS (Chicago, IL), with significance set as p Ͻ 0.05.

RESULTS A total of 217 fatally injured motorcycle crash victims were identified in the medical examiners database. Fourteen patients were excluded because their injury occurred over- seas, or because they were incorrectly coded as motorcyclists. Six patients had missing crash data in the Florida Department of Highway Safety and Motor Vehicle traffic crash database. The remaining 197 fatally injured riders constituted the study population (184 riders and 13 passengers). This represented 97% of all fatal motorcycle crash victims in Miami-Dade Fig. 2. Percentage changes in helmet use in fatal motorcycle County during the study period. There were 186 men and 11 crashes from 1997 to 2003. women with a mean age of 31 years, and a median age of 28 years (range, 14–63, SD Ϯ10.5). Seventy-two of the deaths occurred before the law change, and 125 occurred afterward. The number of fatal motorcycle crashes increased year to year during the course of the study (Fig. 1). The percentage of riders in fatal crashes who were helmeted decreased by 59%, from 80% in 1997, to 33% in 2003 (Fig. 2). Overall, helmet use in this population decreased from 75% of riders in the prerepeal period to 42% of riders in the postrepeal period. During the same time period, a large increase in the number of registered motorcycles was observed, from 17,047 in 1997, to 39,043 in 2003, with a sharp increase in 2000 after repeal of the motorcycle helmet law (Fig. 3). During the 7-year study period, the population of Miami- Dade County increased from 2,044,600 to 2,349,870, an increase of only 15%. Fatality rates per 10,000 registered motorcycles fluctu- ated year to year but were not significantly different during the course of the study period (Fig. 4). There was no significant difference in fatality rates before and after the helmet law repeal (11.6 versus 12.5 deaths per 10,000 registered Fig. 3. Number of annual motorcycle registrations from 1997 to motorcycles, p ϭ 0.61). 2003.

Volume 63 • Number 5 1007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

age increases in either motorcycle fatalities or registered riders. The finding that repeal of motorcycle helmet laws leads to an increase in motorcycle fatalities because of an increased number of riders has public policy implications. Pennsylvania weakened its motorcycle helmet law in 2003, and California remains a battleground for helmet law proponents and oppo- nents. Increases in motorcycle usage, and therefore motorcycle crashes, lead to increases in the number of crashes, with significant cost implications for trauma centers, taxpayers, and both private and public payers of health care. The $10,000 minimum insurance requirement that was passed in Florida is inadequate in light of the fact that mean costs of Fig. 4. Fatality rates per 10,000 registered motorcycles from 1997 crashes resulting in trauma center admission exceed $30,000 to 2003. to $40,000 per injured rider. This is likely to dramatically underfund the trauma and emergency care of the injured patients resulting from motorcycle crashes.11–13 The legisla- DISCUSSION tion as enacted also left unaddressed the problem of how the This study demonstrates two significant findings. (1) police are meant to identify those riders under the age of 21, Repeal of the motorcycle helmet law was associated with an which is a serious flaw. increase in motorcycle ridership. (2) When adjusted for the Although at some point there is likely to be leveling off increase in motorcycle riders, there was no significant inin the increase in motorcycle registrations as the market crease in the motorcycle fatality rate after the repeal, despite becomes saturated, the data available up to 2004 do not suggest a large increase in the absolute number of motorcycle-related that this point has been reached. In addition, motorcycle- deaths. This is in contrast to at least one previous study,2 and related fatalities have continued to increase while other types a recent analysis conducted by the National Highway Traffic of motor vehicle-related fatalities have remained relatively and Safety Administration.6 However, both of these reports constant. As a result, motorcycle crashes now account for examined shorter time periods before and after helmet law over 10% of all traffic-related deaths. repeal. In addition, the National Highway Traffic and Safety In light of the increasing number of deaths and the Administration data relied on traffic crash reports alone to increasing number of states enacting policies that weaken or analyze fatalities, whereas we combined both medical exam- repeal mandatory helmet laws, injury prevention advocates iner’s office data and crash reports. should investigate other injury prevention approaches that Controversy continues to rage over whether motorcycle might have an impact on fatality rate in addition to focusing helmet laws contribute to lower fatality rates when they on helmet legislation. This is especially important in states mandate use in all riders.7–10 In this study, the increase in such as Florida that appear unlikely to reinstitute a universal fatalities was of a similar order of magnitude to the increase helmet law. These may include lower speed limits, rider in registrations (115% in number of deaths, with a 129% education, graduated licensing, protective or high-visibility increase in the number of registrations). Although motorcycle clothing, stricter enforcement of DUI laws, and better edu- registrations were increasing nationwide during this time pe- cation of other road users to reduce the vulnerability of riod, this increase was higher in Florida compared with that motorcycle riders. These efforts could include outreach ef- of the national average. This excess increase may represent a forts by trauma centers, which disproportionately suffer the rise in the number of motorcycle riders as a direct result of the financial effects of helmet law changes.3,14–16 modification of the helmet law, making riding more attrac- Our study has certain limitations that should be acknowl- tive. However, it is not possible to prove causality of the edged before accepting these results as conclusive. Although relationship between the increase in motorcycle fatalities and all deaths were confirmed with data from the medical exam- increasing numbers of motorcycle registrations, as this rela- iners office, six cases were unable to be matched with cor- tionship is likely to be multifactorial. This study did not seek responding crash data. However, it is unlikely that this biased to address the issue of whether a helmet is protective in the the study results because of the small number of missing actual event of a crash, which has already been extensively cases in any given year. Although we found no increase in studied. fatality rates per 10,000 registered motorcycles, because of The rise in motorcycle fatalities also cannot be explained the limitations of our database, we were not able to evaluate by an increase in the population of the county, unless the nonfatal injuries that may have increased after the helmet law incoming residents were disproportionately likely to be mo- change, in particular severe injuries requiring long-term care. torcycle riders. The population increase during the study This study only looked at mortality, and thus was unable to period was 15%, which is appreciably less than the percent- identify whether repeal of mandatory helmet laws increases

1008 November 2007 Motorcycle Fatalities Increase With Registrations overall injury rates, rates of hospitalization, or discharge to a 4. Ho EL, Haydel MJ. Louisiana motorcycle fatalities linked to long-term care facility. statewide helmet law repeal. J La State Med Soc. 2004;156:151– Also, the number of registered motorcycles may not 152, 154–155, 157. 5. Muller A. Florida’s motorcycle helmet law repeal and fatality rates. equate with usage as measured by vehicle miles traveled Am J Public Health. 2004;94:556–558. (VMTs). We were unable to use VMT data specifically for 6. Vaca F. National Highway Traffic Safety Administration (NHTSA) motorcycles in Miami-Dade County, as they cannot be reli- notes. Evaluation of the repeal of the all-rider motorcycle helmet law ably calculated at the county level. Statewide VMTs revealed in Florida. Ann Emerg Med. 2006;47:203; discussion 204–206. a 56% increase during the study period, with a 112% increase 7. McGwin G Jr, Whatley J, Metzger J, et al. The effect of state in deaths. The state death rate per VMT was not significantly motorcycle licensing laws on motorcycle driver mortality rates. J Trauma. 2004;56:415–419. different pre- and postlaw. VMTs are in themselves an im- 8. Stella J, Cooke C, Sprivulis P. Most head injury related motorcycle perfect measure of motorcycle use, as they do not take into crash deaths are related to poor riding practices. Emerg Med account many other considerations affecting motorcycle (Fremantle). 2002;14:58–61. crashes. The number of registrations may also underestimate 9. Norvell DC, Cummings P. Association of helmet use with death in the number of riders at risk as more than one rider may use motorcycle crashes: a matched-pair cohort study. Am J Epidemiol. the same motorcycle. We did not have access to motor vehi- 2002;156:483–487. cle licensing databases to be able to examine this possibility. 10. Stolzenberg L, D’Alessio SJ. “Born to be wild.” The effect of the repeal of Florida’s mandatory motorcycle helmet-use law on serious Other factors that might have influenced the likelihood of a injury and fatality rates. Eval Rev. 2003;27:131–150. fatal crash, such as size of the motorcycle engine, age of the 11. Hundley JC, Kilgo PD, Miller PR, et al. Non-helmeted rider, type of helmet, weather or road conditions, local traffic motorcyclists: a burden to society? A study using the National congestion, and average vehicle speed were also not exam- Trauma Data Bank. J Trauma. 2004;57:944–949. ined as part of this study. In previous studies, these factors 12. Eastridge BJ, Shafi S, Minei JP, et al. Economic impact of have been identified as playing a role in both the frequency of motorcycle helmets: from impact to discharge. J Trauma. 2006; 60:978–983; discussion 983–984. motorcycle crashes and the likelihood of the crash being 13. Brandt MM, Ahrns KS, Corpron CA, et al. Hospital cost is reduced 17–20 fatal. It would also be useful to examine these factors in by motorcycle helmet use. J Trauma. 2002;53:469–471. other states that have recently repealed their universal helmet 14. Shapiro AJ, Johnson RM, Miller SF, et al. Facial fractures in a level laws to see if the relationship between the number of motor- I trauma centre: the importance of protective devices and alcohol cycle registrations and number of fatalities holds true in other abuse. Injury. 2001;32:353–356. parts of the country. 15. Vaca F, Berns SD. National Highway Traffic Safety Administration. Commentary: motorcycle helmet law repeal–a In conclusion, our study suggests that the increase in mo- tax assessment for the rest of the United States? Ann Emerg torcycle fatalities after repeal of the universal motorcycle helmet Med. 2001;37:230–232. law in Florida is largely a function of a substantial increase in the 16. Vaca F, Berns SD, Harris JS, et al. National Highway Traffic Safety number of registered motorcycles that occurred after the law was Administration. Evaluation of the repeal of motorcycle helmet laws. changed. Injury prevention efforts focusing on factors other than Ann Emerg Med. 2001;37:229–230. helmet use should be developed in light of continuing repeal of 17. Nelson D, Sklar D, Skipper B, et al. Motorcycle fatalities in New Mexico: the association of helmet nonuse with alcohol intoxication. motorcycle helmet laws across the nation. Ann Emerg Med. 1992;21:279–283. 18. Skalkidou A, Petridou E, Papadopoulos FC, et al. Factors affecting REFERENCES motorcycle helmet use in the population of Greater Athens, Greece. 1. National Highway Traffic Safety Administration. Washington D, US Inj Prev. 1999;5:264–267. department of Transportation. Traffic Safety Facts. 1994–2004. 19. Langley J, Mullin B, Jackson R, et al. Motorcycle engine size and 2. Hotz GA, Cohn SM, Popkin C, et al. The impact of a repealed risk of moderate to fatal injury from a motorcycle crash. Accid Anal motorcycle helmet law in Miami-Dade County. J Trauma. 2002; Prev. 2000;32:659–663. 52:469–474. 20. Kraus JF, Riggins RS, Franti CE. Some epidemiologic features 3. Bledsoe GH, Schexnayder SM, Carey MJ, et al. The negative impact of motorcycle collision injuries. I. Introduction, methods and of the repeal of the Arkansas motorcycle helmet law. J Trauma. factors associated with incidence. Am J Epidemiol. 1975;102: 2002;53:1078–1086; discussion 1086–1087. 74–98.

Volume 63 • Number 5 1009 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Brain Lobectomy for Severe Head Injuries is not a Hopeless Procedure Didem Oncel, MD, Demetrios Demetriades, MD, PhD, FACS, Peter Gruen, MD, FACS, Ali Salim, MD, FACS, Kenji Inaba, MD, FACS, Peter Rhee, MD, FACS, Timothy Browder, MD, FACS, Shot Nomoto, RN, and Linda Chan, PhD

Introduction: Posttraumatic tran- intensive care unit and hospital stays, sur- mechanism was identified as the only risk stentorial herniation or intractable intra- vival, and Glasgow Outcome Score. Step- factor for mortality. Overall, 48% of the 133 cranial hypertension are ominous signs, wise logistic regression analysis was used survivors had good functional outcomes, and are associated with very poor out- to identify independent risk factors for and 51.9% had poor functional outcomes comes. Aggressive procedures, such as mortality and functional outcomes. (including 15.0% with persistent vegetative brain lobectomies, may benefit some of Results: During the 13-year study state). Multiple-response logistic regression these patients. The published experience period, there were 183 patients who under- identified blunt trauma, low initial GCS with brain lobectomies is very limited. went brain lobectomy for traumatic score, and frontal lobectomy as independent Patients: Retrospective study of head injuries. Eighty-eight patients (48.1%) un- risk factors for poor outcomes. injury patients with focal brain lesions derwent frontal lobectomy, 67 (36.6%) tem- Conclusion: Selected severe head in- and intractable intracranial hypertension poral lobectomy, and the remaining 28 jury patients with focal brain lesions and or herniation who underwent partial or (15.3%) other or combination lobectomies. intractable intracranial hypertension or anatomic brain lobectomies. The follow- The mean follow-up was 22 days. There herniation may benefit from brain lobec- ing parameters were included in the anal- were 50 deaths (mortality 27.3%). Exclud- tomies. The survival and functional out- ysis: age, gender, mechanism of injury, ing patients with major extracranial inju- comes after this procedure are acceptable. hypotension at admission, initial Glasgow ries, there were 47 deaths (26.9%). Patients Blunt trauma, low initial GCS score, and Coma Scale (GCS) score, Abbreviated In- with blunt trauma had a significantly higher frontal lobectomies are significant risk jury Scale for head, chest, and abdomen, mortality than those with penetrating factors for poor outcomes. -Key Words: Trauma, Brain lobecto .(0.005 ؍ Injury Severity Score, time from admis- trauma had (33.1% vs. 12.0%, p sion to operation, type of brain lobectomy, Among the risk factors studied, blunt injury mies, Outcomes. J Trauma. 2007;63:1010–1013.

ntractable intracranial hypertension or transtentorial her- literature, the experience and publications on brain lobec- niation after head trauma are ominous signs and are tomies are very limited. The purpose of the present study Iassociated with an extremely high mortality and poor was to review the outcomes and identify prognostic out- functional outcomes. In some patients, conventional mo- come factors after decompressive brain lobectomies in dalities, such as evacuation of intracranial hematomas, patients with intractable intracranial hypertension in whom osmotic diuresis, cerebrospinal fluid drainage, hyperven- there are few other options. tilation, and barbiturate-induced coma, fail to control the intracranial hypertension. The survival and functional out- PATIENTS AND METHODS comes in these groups of patients are very poor, with a This is a retrospective review of the trauma registry and 1 These patients may benefit from mortality of up to 86%. patient charts at the Los Angeles County ϩ University of more aggressive procedures such as decompressive crani- Southern California Medical Center, during a period of 13 ectomy or brain lobectomy. Although there is some cov- years (1993 through 2005). The study included patients with erage of the role of decompressive craniectomies in the head injury, who underwent partial or anatomic brain lobectomy for intractable intracranial hypertension or brain stem Submitted for publication March 7, 2007. herniation. All but four patients had severe focal lesions. Accepted for publication July 30, 2007. Patients with no major focal lesions who developed intracta- Copyright © 2007 by Lippincott Williams & Wilkins ble intracranial hypertension underwent decompressive crani- From the Division of Trauma and Surgical Critical Care (D.O., D.D., ectomy. The brain excision included a partial or anatomic A.S., K.I., P.R., T.B., S.N.), and Departments of Neurological Surgery lobectomy, depending on the severity of the focal lesion and (P.G.), and Biostatistics (L.C.), Los Angeles County and University of Southern California Medical Center, Los Angeles, California. edema. Depending on the severity of the brain edema and the Address for reprints: D. Demetriades, MD, PhD, FACS, LAC ϩ USC appearance of the brain at the time of completion of the brain Medical Center, 1200 North State Street, Room 1105, Los Angeles, CA resection, the bone flap was either replaced immediately or 90033; email: [email protected]. implanted in the anterior abdominal wall for subsequent elec- DOI: 10.1097/TA.0b013e318156ee64 tive reimplantation. Patients with minor debridement after

1010 November 2007 Brain Lobectomy for Severe Head Injuries gunshot wounds were not included in the analysis. Seven ated with GOS. ␹2-test was used for categorical variables, and full-time specially trained nurses maintain the trauma regis- Kruskal-Wallis test was used for continuous variables, in- try, and the quality of data is monitored by the Department of cluding ICU days and length of stay. The SAS statistical Health services of the Los Angeles County. The registry software was used for all statistical analysis (The SAS System stores 120 data fields for each patient, including epidemio- for Windows, Version 9.1.3. SAS Institute Inc., Cary, NC). logic data, vital signs, diagnosis, procedures, intensive care unit (ICU) and ventilator days, hospital stay, functional out- RESULTS comes, and survival. An Excel database (Microsoft Corp, During the study period, there were 183 patients who Redmond, WA) that included the following data elements underwent brain lobectomy for traumatic injuries. The most was created for the purpose of the study: age, gender, mech- common mechanisms of injury were gunshot wounds (25%), anism of injury (blunt or penetrating), the presence of shock falls from height (24%), and auto versus pedestrian injuries at admission (systolic blood pressure Ͻ90 mm Hg), initial (20%). The demographic characteristics, clinical presenta- Glasgow Coma Scale (GCS) score, regional Abbreviated tion, and injury severity of the patients are shown in Table 2. Injury Scale (AIS), Injury Severity Score (ISS), time from The most common head injuries were multiple intracra- admission to operation, type of lobectomy, length of ICU nial abnormalities (108), followed by intraparenchymal hem- stay, total hospital stay, Glasgow Outcome Score (GOS) orrhage (28), subdural hematomas (21), brain contusion (17), (Table 1), and mortality. diffuse brain edema (4), epidural hematomas (2), subarach- The Institutional Review Board approved this study, noid hemorrhage (2), and intraventricular hemorrhage (2). which adhered to established guidelines on the treatment of Overall, 88 patients (48.1%) underwent frontal lobectomy, 67 human subjects. (36.6%) temporal lobectomy, and the remaining 28 (15.3%) Statistical Analysis other or combination lobectomies. The mean time from ad- Ϯ For analysis of mortality we used the stepwise logistic mission to operation was 1.2 2.6 days. regression analysis to identify independent risk factors that There were 50 deaths (overall mortality 27.3%) occurring in a mean of 10 days after admission. Excluding the eight were associated with mortality in this group of patients with Ͼ trauma who underwent lobectomy. Before the multivariable patients with major extracranial injuries (AIS 3), the mor- analysis, we conducted univariate analysis to identify risk tality was 26.9% (47 deaths) (Table 3). factors that were associated with mortality. Variables with Patients with blunt trauma had a significantly higher p ϭ p Ͻ 0.2 were included in the multivariate analysis. Fisher’s mortality than penetrating trauma (33.1% vs. 12.0%, exact test or ␹2 test was used for categorical variables, and 0.005). Multivariate analysis, excluding patients with severe extracranial trauma (AIS Ͼ3) and adjusting for age (Ͼ55 and Mann-Whitney rank-sum test was used for continuous vari- Յ ables. For analysis of GOS, a multiple-response variable, we 55), gender, injury mechanism, GCS score at admission (Յ8, Ͼ8), ISS (Ն16, Ͻ16), hypotension at admission, head used the multiple-response logistic regression analysis Յ Ͼ (PROC CATMOD in SAS software; SAS Institute Inc., Cary, AIS ( 3, 3), and type of lobectomy (frontal, temporal), NC) to identify independent risk factors differentiating the identified mechanism of injury as the only significant inde- GOS groups. Before this multivariable analysis we conducted univariate analysis to identify risk factors that were associ- Table 2 Demographic Characteristics of 183 Patients With Brain Lobectomy Table 1 Glasgow Outcome Scale Age (yr), mean Ϯ SD 36.3 Ϯ 18.1 Score Description Male, number (%) 146 (79.9) Blunt trauma, number (%) 133 (72.7) 1 Death Penetrating trauma, number (%) 50 (27.3) 2 Persistent vegetative state—patient exhibits no ISS, mean Ϯ SD 23.7 Ϯ 9.7 obvious cortical function Days from admissions to operation, mean Ϯ SD 1.2 Ϯ 2.6 3 Severe disability—conscious but disabled. Patient depends upon others for daily support because of mental or physical disability or both Table 3 Outcomes in 183 Patients With Brain 4 Moderate disability—disabled but independent. Lobectomies Patient is independent as far as daily life is concerned. The disabilities found include Overall mortality 50/183 (27.3%) degrees of dysphasia, hemiparesis, or Mortality in patients with no major 47/175 (26.9%) ataxia, as well as intellectual and memory extracranial injuries deficits and personality changes Discharge GCS score, mean Ϯ SD 10.6 Ϯ 3.6 5 Good recovery—resumption of normal Discharge GOS, mean Ϯ SD 2.8 Ϯ 1.4 activities even though there may be minor ICU stay (mean days) 10.6 neurologic or psychological deficits Hospital (mean days) 22.0

Volume 63 • Number 5 1011 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Table 4 Mortality by Risk Factor in Trauma Patients Who Underwent Brain Cranial Lobectomy (Excluding Patients With Major Extracranial Injuries)

Relative Risk (95% Risk Factor Subgroup % Mortality (n/N) p Confidence Interval) Age Ͼ55 40 (12/30) 1.66 (0.98–2.80) 0.11 Յ55 24 (35/145) Gender Male 25 (35/141) 0.70 (0.41–1.20) 0.28 Female 35 (12/34) Injury mechanism Blunt 32 (41/128) 2.51 (1.14–5.52) 0.012 Penetrating 13 (6/47) GCS score Յ8 33 (29/88) 1.46 (0.88–2.42) 0.17 Ͼ8 23 (18/80) ISS Ն16 28 (45/158) 2.42 (0.64–9.11) 0.25 Ͻ16 12 (2/17) Hypotension Yes 50 (1/2) 1.86 (0.45–7.59) 0.47 No 27 (45/167) Head AIS Ͼ3 29 (44/154) 1.90 (0.65–5.57) 0.29 Յ3 15 (3/20) Frontal Yes 30 (28/92) 1.36 (0.79–2.34) 0.28 No 22 (15/67) Temporal Yes 27 (19/71) 0.98 (0.59–1.64) 1.00 No 27 (24/88) Stepwise logistic regression identified that injury mechanism was the only significant independent factor for mortality. R-square was 6%. Factors included in the model are age, injury mechanism, and GCS score. pendent factor for mortality (relative risk 2.51, 95% confi- DISCUSSION ϭ dence interval, 1.14–5.52, p 0.012) (Table 4). Standard therapeutic options for patients with posttraumatic The mean ICU and hospital stay in the group of 133 intracranial hypertension include evacuation of intracranial mass survivors were 12.2 and 22.0 days, respectively. lesions, mannitol administration, drainage of cerebrospinal fluid, Overall, 64 survivors (48.1%) had good functional out- hyperventilation, and barbiturate-induced coma. However, some come or moderate disability (GOS 5 or 4) and 69 (51.9%) had patients develop intractable intracranial hypertension not re- poor functional results (GOS 3 or 2) (including 20 patients, sponding to any of these interventions or develop transtentorial 15.0% with persistent vegetative state). Multiple-response herniation. The survival and functional outcomes in these groups logistic regression, which included age (Ͼ55, Յ55), gender, of patients are very poor, unless other more aggressive interven- injury mechanism, GCS score at admission (Յ8, Ͼ8), ISS tions are used. Eisenberg et al.1 reported a mortality rate of 86% (Ն16, Ͻ16), hypotension at admission, head AIS (Ն3, Ͻ3), in patients with intractable intracranial hypertension who failed and type of lobectomy (frontal, temporal), identified blunt to respond to conventional treatment, including pentobarbital. trauma, admission GCS score Յ8, and frontal lobectomy as Different types of decompressive craniectomies have been in use independent risk factors for poor outcome. for many decades, with various degrees of success and Using good recovery as reference, the odds of a patient enthusiasm.2–6 Although earlier studies reported poor results with blunt trauma dying instead of a good recovery was 7.23 after decompressive craniectomies, more recent work reported times of the odds of a patient with penetrating trauma. The encouraging outcomes. Aarabi et al.,5 in a study of 50 patients odds of vegetative state in blunt trauma was 5.86 of the odds who underwent decompressive craniectomy for intractable inin penetrating trauma (Table 5). tracranial hypertension, reported a mortality of 28%, poor func-

Table 5 Adjusted Odds Ratio for Each GOS Group Using Good Recovery as Reference for the Two Significant Risk Factors (Blunt and GCS Score)

Adjusted Odds Ratio (95% CI) Risk Factor Died vs. Good Vegetative vs. Good Severe Disability vs. Moderate vs. Good Recovery Recovery Good Recovery Recovery Blunt vs. penetrating 7.23 (2.16–24.23)* 5.86 (1.29–26.55)† 3.19 (1.07–9.51)† 1.09 (0.38–3.14) GCS score 0.80 (0.69–0.92)* 0.77 (0.65–0.92)* 0.79 (0.69–0.91)* 1.01 (0.87–1.17) Patients with severe extracranial injuries were excluded. *p Ͻ 0.01. †p Ͻ 0.05.

1012 November 2007 Brain Lobectomy for Severe Head Injuries tional outcomes in 32%, and good functional outcomes in 40%. superior results in a group of 13 cases with herniation and severe In a collective review of 10 studies with 323 cases with decom- contusion and swelling of the temporal lobe who underwent pressive craniectomy, Aarabi et al.5 reported an overall mortality lobectomy when compared with a similar group of 16 patients rate of 22.3%, poor functional outcome in 29.4%, and good who underwent craniectomy. In our center, decompressive functional outcome in 48.3%. Polin et al.,6 in a series of 35 craniectomy is usually performed in cases with diffuse brain patients with bifrontal decompressive craniectomy, reported a edema whereas brain lobectomy is reserved for patients with mortality rate of 25% and a favorable outcome in 37%. In a large intraparenchymal focal lesions associated with intractable control group of 92 patients from the Traumatic Coma Data intracranial hypertension or brain stem herniation. Bank, the authors reported a mortality of 30.8% and favorable Our analysis identified blunt trauma as the most important outcome in 15.4%. independent risk factor for death or poor functional outcome. In A more aggressive and marked approach than decom- addition, low initial GCS score and frontal lobectomies were pressive craniectomy is brain lobectomy. The experience also independent risk factors for poor functional outcome. with brain resections is very limited and the few available Brain lobectomies may be underutilized. This procedure publications include only a small number of cases. Nussbaum is not even described as a possible therapeutic option, even in et al.7 reported 10 patients with temporal lobectomy for modern trauma textbooks.10 The main concern after such posttraumatic unilateral swelling and transtentorial hernia- drastic procedures is that any survivor will develop severe tion. The survival was 70% and all seven survivors had permanent disability, including permanent vegetative state. acceptable functional outcomes. Lee et al.,8 in a study from Although this is a legitimate concern, it is obvious from Taiwan, reported 29 patients who sustained uncal herniation previous and also the present study that a significant number secondary to frontotemporal acute subdural hematomas with of survivors have good functional outcomes. Lee et al.8 and severe contusion and swelling of the temporal lobe. One Litofsky et al.9 reported acceptable functional outcomes and group of 16 patients underwent craniectomy, evacuation of no patients in a vegetative state in the survivors group. the hematoma, and debridement of the contused brain. The In conclusion, this study supports that selected trauma mortality in this group was 56%, and the mean GOS was patients with focal brain lesions and herniation or intractable 2.2 Ϯ 0.4 after 24 to 36 months of follow-up. A second group intracranial hypertension may benefit from brain lobecto- of 13 cases underwent craniectomy, evacuation of the hema- mies. The survival and short-term functional outcomes are tomas, and a temporal lobectomy. The mortality in this group acceptable. Blunt trauma, low initial GCS score, and frontal was 8%, and the GOS 4.0 Ϯ 0.4. The authors concluded that lobectomies are independent risk factors for poor outcomes. aggressive lobectomy had better survival and functional outcomes than the less aggressive approach. REFERENCES At our center there has been a tradition of brain lobec- 1. Eisenberg HM, Frankowski RF, Contant CF, Marshall LF, Walker tomies in the appropriate patients with focal lesions and early MD. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988;69:15–23. herniation or intractable intracranial hypertension. Litofsky et 2. Cushing HW. The subtemporal decompressive operation for the 9 al. reported 20 patients with severe blunt head trauma who relief of pressure symptoms due to fracture of the base of the skull. underwent lobectomy for herniation or other significant de- John Hopkins Hosp Bull. 1908;19:48–49. terioration or intractable intracranial hypertension. Overall, 3. Kjellberg RN, Prieto A. Bifrontal decompressive craniotomy 11 patients (55%) had a favorable outcome. The mortality for massive cerebral edema. J Neurosurg. 1971;34:488–493. 4. Britt RH, Hamilton RD. Large decompressive craniectomy in the was 35%, and no patient remained in a persistently vegetative treatment of acute subdural hematomas. Neurosurgery. 1978;2:195–200. state. Younger age, higher initial GCS score, initial pupillary 5. Aarabi B, Hesdorffer DC, Ahn ES, Aresco C, Scalea TM, Eisenberg responsiveness, and the duration of preoperative pentobarbi- HM. Outcome following decompressive craniectomy for malignant tal coma were significant factors correlated with outcome. swelling due to severe head injury. J Neurosurg. 2006;104:460–479. The present study is by far the largest on brain lobecto- 6. Polin RS, Shaffrey ME, Bogorev CA, et al. Decompressive bifrontal craniectomy in the treatment of severe refractory post-traumatic mies for traumatic injuries in the English literature. The cerebral edema. Neurosurgery. 1997;41:84–94. survival and functional outcomes are good, especially when 7. Nussbaum ES, Wolf AL, Sebring L, Mirvis S. Complete temporal considering the abysmal outcomes of patients with herniation lobectomy for surgical resuscitation of patients with transtentorial or intractable intracranial hypertension that fail to respond to herniation secondary to unilateral hemispheric swelling. 1 Neurosurgery. 1991;29:62–66. the usual therapeutic modalities. Overall, our mortality rate 8. Lee EJ, Chio CC, Chen HH. Aggressive temporal lobectomy for was 27.3% and 35% of the study population, or 48.1% of the uncal herniation in traumatic subdural hematomas. J Formos Med survivors had good functional outcome or moderate disabil- Assoc. 1995;94:341–345. ity. The crude outcomes in the present series compare favor- 9. Litofsky NS, Chin LS, Tang G, Baker S, Giannotta SL, Apuzzo ML. ably with those reported after decompressive craniectomy.2–6 The use of lobectomy in the management of severe closed-head trauma. Neurosurgery. 1994;34:628–633. It is difficult to compare outcomes between brain lobectomy 10. Valadka AB. Injury to the cranium. In: Moore EE, Feliciano DV, and decompressive craniotomy because of different study pop- Mattox KL, eds. Trauma. 5th ed. New York: McGraw-Hill. ulations and the paucity of large series. Lee et al.8 reported 2006:385–406.

Volume 63 • Number 5 1013 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Traumatic Carotid Cavernous Fistula Accompanying Basilar Skull Fracture: a Study on the Incidence of Traumatic Carotid Cavernous Fistula in the Patients With Basilar Skull Fracture and the Prognostic Analysis About Traumatic Carotid Cavernous Fistula Wen Liang, MD, Yang Xiaofeng, MD, PhD, Liu Weiguo, MD, Qiu Wusi, PhD, Shen Gang, PhD, and Zheng Xuesheng, MD

Background: Traumatic carotid cav- “no disability” groups, and related clinical between the disability and no disability ernous fistula (TCCF) is a rare vascular factors with potential impact on prognosis groups (p < 0.05). complication of traumatic brain and facial were analyzed. Conclusions: A relatively high inci- injury. The purpose of this study was to Results: In 312 inpatients with basi- dence of TCCF occurred in patients with analyze the incidence of this disorder in lar skull fractures, an overall incidence of middle fossa fractures, especially those different types of basilar skull fracture, 3.8% for TCCF was observed, and the with transverse or oblique fractures. determine whether particular clinical fac- incidence of this disorder with anterior Prompt diagnosis and intervention should tors impacted outcomes, and discuss ways fossa fracture, middle fossa fracture, and be emphasized in the management of pa- of improving prognosis. posterior fossa fracture was 2.4%, 8.3%, tients with TCCF, and noninvasive tech- Method: We performed a retrospec- and 1.7%, respectively. In this retrospec- niques for early detection of TCCF should tive analysis of cases with basilar skull tive analysis, factors such as patients’ age, be considered in cases of middle fossa fracture or angiography-confirmed TCCF gender, number of embolization proce- fractures under certain conditions after in inpatients between 1999 and 2005, as dures performed, and time from injury to brain or facial trauma to ensure positive well as an analysis of the incidence rate of first symptom onset did not significantly outcomes. TCCF in each type of basilar skull frac- affect outcome (p > 0.05). However, the Key Words: Basilar skull fracture, ture. For patients diagnosed with TCCF, time from first symptom onset to endovas- Traumatic carotid cavernous fistula, Inci- cases were divided into “disability” and cular embolization differed significantly dence rate, Prognostic analysis. J Trauma. 2007;63:1014–1020.

n most cases, carotid cavernous fistulas (CCFs) are abnor- have a thorough understanding of this potentially lethal en- mal connections between the internal carotid artery (ICA) tity. Although TCCF occurs rarely after craniofacial trauma, Iand the cavernous sinus; on rare occasions, they may this disorder is thought to occur relatively frequently in pa- appear between the internal carotid or branches of the exter- tients with basilar skull fracture.4 However, to our knowl- nal carotid artery and the venous plexus of the skull.1 Trau- edge, the incidence rate of TCCF in patients with basilar skull matic carotid cavernous fistula (TCCF) is a rare complication fracture has been sparsely reported in the literature. In this of traumatic brain injury and traumatic facial injury that can study, we retrospectively analyzed TCCF cases confirmed by lead to blindness as the disorder progresses and in rare cases angiography and analyzed the incidence rate of TCCF in each can result in paralysis, unconsciousness, and even death.2,3 It type of basilar skull fracture to increase the understanding is important that clinicians operating on the craniofacial re- and awareness of this rare disorder. In addition, although gion, and especially those who manage craniofacial trauma, much has been learned about the anatomy and causes of this disorder and great improvements have been made in treatment since TCCF was first described in 1809, the impact of Submitted for publication July 13, 2006. interrelated factors on outcomes associated with this disorder Accepted for publication January 23, 2007. has only rarely been assessed. Consequently, in this retro- Copyright © 2007 by Lippincott Williams & Wilkins From the Department of Neurosurgery (W.L., Y.X., Z.X.), First Affiliated spective analysis, we also attempted to determine whether Hospital, College of Medicine, Zhejiang University; and the Department of any factors impacted outcomes after TCCF, and we discuss Neurosurgery (L.W., O.W., S.G.), Second Affiliated Hospital, College of Med- methods of improving prognosis. icine, Zhejiang University, Zhejiang Province, PR China. Address for reprints: Yang Xiaofeng, PhD & MD, Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang Uni- PATIENTS AND METHODS versity, No. 79, Qingchun Road, Hangzhou City, Zhejiang Province, 31003, We conducted a retrospective review of inpatients with PR China; email: [email protected] or [email protected]. TCCF confirmed by angiography between 1999 and 2005 DOI: 10.1097/TA.0b013e318154c9fb (Figs. 1 and 2). Patients were treated at the Second Affiliated

1014 November 2007 TCCF Accompanying Basilar Skull Fracture

Fig. 1. The patient was a 43-year-old man. After traumatic brain injury caused by falling, he began to suffer from right exophthalmos, intracranial bruit, chemosis, and limitation of ocular movements. (A) Right internal carotid angiography showed CCF with dramatic right cavernous sinus expansion and dilatation of the left superior ophthalmic vein. Drainage was mainly into the superior ophthalmic vein. ( B) Right internal carotid angiogram (front arteriogram) after embolization with a detachable balloon (arrow). The cavernous sinus did not appear during the arterial phase. Internal carotid flow was preserved. (C): Right internal carotid angiogram (lateral arteriogram) after embolization with detachable balloon (arrow).

Fig. 2. A 28-year-old male patient presented with left bruit, chemosis, progressive proptosis, and vision impairment, as well as orbit pains more than 10 weeks after a traffic crash. (A) Left internal carotid angiography showed CCF, as well as dramatic cavernous sinus expansion and dilatation of the left superior ophthalmic vein. ( B) Left internal carotid angiogram (front arteriogram) after embolization with detachable balloon (arrow). The cavernous sinus did not appear during the arterial phase. The internal carotid flow was preserved. (C) Left internal carotid angiogram (lateral arteriogram) after the embolization with detachable balloon (arrow).

Hospital, Zhejiang University, College of Medicine in China, Table 1 Patients’ Demographics a high-class medical center. The data used in this analysis included patients’ demographics, imaging examinations, No. cases 20 treatments, and outcomes. In total, 18 patients with TCCF Age (yr), mean (range) 40.25 (23–68) were identified by angiography, including 2 patients with 20–39 10 40–59 8 bilateral TCCF (totally 20 TCCF cases were involved in this 60–68 2 study). Patient demographics for this series are shown in Gender (male/female) 12/8 Table 1. Side (left/right) 8/12 Inpatient cases with basilar skull fracture after craniofacial trauma were also reviewed to analyze the relationship For patients with TCCF who were treated with transvas- between basilar skull fracture and TCCF. The incidence rate cular embolization, outcomes were assessed according to of TCCF in each type of basilar skull fracture, including whether TCCF-induced disabilities persisted postsurgery (ex- anterior fossa fracture, middle fossa fracture, and posterior cluding any disabilities caused by primary or other secondary fossa fracture, was analyzed. craniocerebral or nervous injuries). Depending on outcomes,

Volume 63 • Number 5 1015 The Journal of TRAUMA௡ Injury, Infection, and Critical Care cases were divided into “disability” and “no disability” successfully treated with transarterial embolization). Another groups. Clinical factors potentially impacting outcomes were patient with bilateral TCCF was also treated with transarterial analyzed, including the patients’ age, sex, number of embo- embolization; however, only one fistula was successfully lization procedures, time from injury to first symptom onset, occluded with balloons, and ipsilateral ICA blood flow was and time from first symptom onset to endovascular emboli- not preserved. Follow-up was performed 3 to 6 months after zation. The data were analyzed using SPSS 13.0 for Windows embolization in all patients. Common disabilities caused by (SPSS Inc., Chicago, IL). Differences between disability and TCCF included blindness or near-blindness, and neurologic no disability groups were calculated using the independent deficits caused by cerebral ischemia. Of the 16 TCCF cases samples t test. p values less than 0.05 were considered sta- for which embolization was performed, 5 cases remained tistically significant. disabled after embolization, with symptoms including blindness and extremity monoplegia. Depending on outcomes, RESULTS cases were divided into disability and no disability groups for Between 1999 and 2005, 315 inpatients suffering from further analysis. Detailed information is shown in Table 3. As traumatic brain or facial injury were found to have basilar for the remaining three patients who did not undergo endo- skull fractures. Among cases with confirmed TCCF, 12 pa- vascular embolization, one patient died because of severe tients had basilar skull fractures. Of these 12 patients, 4 brain trauma before embolization could be performed, and patients had anterior fossa fractures, whereas 11 had middle the other two refused to accept further treatment after the fossa fractures, and 1 suffered from severe brain trauma with angiogram. all three types of basilar skull fracture. The incidence rate of The data concerning the effects of embolization on the TCCF in each type of basilar skull fracture was analyzed, and 16 TCCF cases were examined with respect to the impact on outcomes are shown in Table 2. Of the 11 patients with TCCF disability. These results are shown in Table 4. In this retro- and middle fossa fractures, computed tomography with three- spective analysis, factors such as patients’ age, gender, num- dimensional reconstruction of the skull base was performed ber of embolization procedures, and the time from injury to in 6 patients, who were all found to have transverse or first symptom onset did not significantly affect outcomes oblique middle fossa fractures. (p Ͼ 0.05). However, the time from first symptom onset to TCCF was confirmed by angiography in all patients. endovascular embolization was significantly different be- Before angiography, computed tomography angiography tween disability and no disability cases (p Ͻ 0.05). It must be (CTA) was performed on three patients, and magnetic reso- noted that a type II error was possible because of the small nance angiography (MRA) was performed on four patients. number of cases. CTA or MRA showed imaging abnormalities in all cases, such as expansion of the cavernous sinus and the ophthalmic veins. According to the classification scheme developed by DISCUSSION Barrow et al., CCF can be divided into four types: type A, TCCF is a relatively rare entity after traumatic brain and direct high-flow shunts between the ICA and the cavernous facial injury, with an incidence ranging from 0.17% to sinus; type B, dural shunts between meningeal branches of 1.01%.6,7 TCCF often accompanies basilar skull fracture, and the ICA and the cavernous sinus; type C, dural shunts be- within our series, TCCF accompanied basilar skull fracture in tween meningeal branches of the external carotid artery and 12 patients (67%), an occurrence lower than what was pre- the cavernous sinus; and type D, dural shunts between men- viously reported.8 ingeal branches of both the internal and external carotid With disease progression, TCCF can lead to disability, arteries and the cavernous sinus.5 Endovascular transarterial such as blindness and hemiparesis. In addition, in some cases embolization was attempted in 15 patients with 16 fistulas, the disorder can progress rapidly and result in emergency including a patient with bilateral TCCF (both of which were situations, leading to permanent impairments in neural function and even death within a short time.9 TCCF presents most commonly as a direct connection between the ICA and cav- Table 2 The Incidence Rate of TCCF in Basilar ernous sinus, forming a high-flow fistula.10 In these cases, the Fracture probability that the fistula heals spontaneously by thrombosis TCCF Accompanying Incidence No. Cases is very low. As such, prompt diagnosis and intervention with BSF Rate (%) this disorder is recommended.11,12 In our study, the time from BSF 312 12 3.8 (12/312) first symptom onset to endovascular embolization signifi- Anterior fossa 168 4 2.4 (4/168) cantly impacted patients’ prognoses. Although a type II error fracture Middle fossa 132 11 8.3 (11/132) was possible because of the small number of cases, these fracture results emphasize the importance of early detection and in- Posterior fossa 58 1 1.7 (1/58) tervention with this disorder. As for the pathophysiology of fracture TCCF, the longer the carotid-cavernous sinus fistula remains BSF, basilar skull fracture. patent, greater are the chances of irreversible changes, as well

1016 November 2007 TCCF Accompanying Basilar Skull Fracture

Table 3 Angiography, Operation, and Outcomes of 16 Cases Treated With Endovascular Transarterial Embolization

Signs and Symptoms Before Sex Age T* T† Treatment Outcomes Embolization The disability group F 55 30 252 Proptosis, bruit, chemosis, and right Type A; TAEDB, ICA flow preserved Signs and symptoms were relieved upper-extremity monoplegia (right except for right upper-extremity side) monoplegia M 33 0 120 Proptosis, vision impairment (almost Type A; TAEDB, ICA flow preserved Signs and symptoms were relieved blind on the left eye), and facial except for vision impairment and palsy (right side) facial palsy F 43 10 86 Proptosis, bruit, chemosis, vision Type A; TAEDB, ICA flow preserved Signs and symptoms were relieved impairment (only left light except for vision impairment perception), and headache (right side) M 23 0 86 Proptosis, bruit, chemosis, vision Type A; It was the second trial of Signs and symptoms were relieved impairment, limitation of ocular the endovascular embolization. except for vision impairment. A movements (right side) TAEDB, the balloon occluded the corneal ulceration after left ICA embolization resulted in great vision impairment F 51 15 160 Proptosis, bruit, vision impairment Type A; TAEDB, ICA flow preserved Signs and symptoms were relieved (only with light perception), and except for vision impairment conscious disturbance (left side) The no disability group M 27 0 55 Proptosis, bruit, chemosis, vision Type A; TAEDB, ICA flow preserved SAT impairment, and limitation of ocular movements (right side) M 41 15 65 Proptosis, bruit, chemosis, and Type A; TAEDB, ICA flow preserved SAT vision impairment (left side) M 43 0 36 Proptosis, bruit, chemosis, and Type A; TAEDB, ICA flow preserved SAT limitation of ocular movements (Fig. 1) (right side) F 43 10 26 Proptosis and bruit (right side) Type A; It was the second trial of SAT the endovascular embolization. TAEDB, ICA flow preserved M 37 60 65 Proptosis, bruit, and chemosis (right Type A; TAEDB, ICA flow preserved SAT side) F (R) 68 0 50 Proptosis, bruit, chemosis, and Type A; Bilateral TCCF. Right TCCF SAT limitation of ocular movements was treated with TAEDB, and (right side) ipsilateral ICA flows preserved F (L) 68 20 30 Proptosis, bruit, chemosis, limitation Type A; Bilateral TCCF. Left TCCF SAT of ocular movements, and facial was treated with TAEDB, and palsy (left side) ipsilateral ICA flows preserved M 36 0 65 Bilateral TCCF confirmed by The left CCF was type A and SAT for the left fistula, and the right angiography. Proptosis, bruit, performed with TAEDB with the symptoms were not apparent at chemosis, limitation of ocular left ICA flow obstructed. The right the time of follow-up‡ movements, and headache (only fistula was too small to be on left side) embolized with balloons F 28 76 19 Bruit and vision impairment (right Type A; TAEDB, ICA flow preserved SAT side) M 28 76 20 Proptosis, bruit, chemosis, vision Type A; TAEDB, ICA flow preserved SAT impairment, and orbit pains (left (Fig. 2) side) F 50 30 25 Proptosis, chemosis, and limitation Type A; TAEDB, ICA flow preserved SAT of ocular movements (right side) * The time (days) from injury to first symptom onset. “0” indicates that the time was less than 1 day. † The time (days) from first symptom onset to operation. It should be noted that this time may be long in some patients. Many patients do not go to the hospital until the symptoms or signs are evident because of the economic considerations (medical insurance is not prevalent yet in this area). In addition, follow up in patients is sometimes difficult because of poor patient compliance, whereas some patients were not admitted to our hospital initially and the treatment may be delayed during the transference of the patients. Accordingly, the diagnosis was delayed in some patients. However, after patients were admitted to our hospital, angiography and endovascular embolization for TCCF were performed as soon as possible after the diagnosis was made according to the clinical presentations. ‡ This is a patient with bilateral TCCF; however, signs and symptoms were only presented on the left side. During the follow-up, signs and symptoms of the left fistula undergoing embolization were relieved without disability or recurrence, and clinical presentations of the right fistula without any endovascular embolization were not apparent. TAEDB, transarterial embolization with detachable balloon; ICA, internal carotid artery; SAT, satisfactory. (This means that after embolization, during the time within the follow-up ranging from 3 to 6 months, the signs and symptoms were relieved without manifest disability or recurrence.)

Volume 63 • Number 5 1017 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Table 4 The Impact of Different Factors on TCCF Outcomes

N Age (yr) M/F Number T* (d) T† (d) Disability 5 41 2/3 1.2 11 140.8 No disability 11 42.6 6/5 1.1 26.1 41.5 p Ͼ0.05 Ͼ0.05 Ͼ0.05 Ͼ0.05 Ͻ0.05 * T (days): The average of the time from injury to first symptom onset. † T (days): The average of the time from first symptom onset to operation. N, the number of embolization procedures. as appearance of urgent conditions. This in turn would hinder the large circular aperture of the carotid canal, which trans- complete recovery and prolong disability.1 mits ICA into the cranium (it is continuous with the carotid The diagnosis of TCCF is generally not complicated, canal, a passage through the petrous part of the temporal bone with clinical manifestations usually being the best indicators that transmits ICA). Middle fossa fractures, especially those for detecting such fistulas. The most frequent signs and related to the petrous part of temporal bone, are liable to be symptoms include exophthalmos, bruit, chemosis, vision im- accompanied by injuries to the carotid canal (canal lacerum) pairment, and limitation of ocular movements.8,13 The final and the superior segment of foramen lacerum (lacerum- diagnosis of TCCF still relies on four-vessel digital subtrac- carotid junction), which are indicators of potential ICA tion cerebral angiography. However, complicated conditions injuries.15,16 As such, it must be noted that craniofacial after brain and facial trauma increase the difficulty of detect- trauma resulting in middle fossa fractures has a latent risk of ing TCCF, and may lead to delays in diagnosis, especially for causing lacerations on the ICA wall, potentially leading to the comatose intubated patients.14 In addition, delays in the oc- formation of a TCCF, as well as other carotid injuries. This currence of clinical symptoms that range from a few hours to analysis also showed a relatively high incidence of TCCF in several weeks also increase the difficulty of promptly diag- patients with middle fossa fracture. In addition, of the 11 nosing TCCF. patients with TCCF who had middle fossa fractures, 6 pa- Although it is thought that TCCF often accompanies tients were found with transverse or oblique middle fossa basilar skull fractures, the frequency of TCCF in basilar skull fractures. This further suggests a high-potential occurrence of fracture is rarely assessed. In this series, an overall incidence TCCF in patients with transverse or oblique middle fossa of 3.8% for TCCF was observed in 312 inpatients with basilar fracture. skull fracture, and the incidences with anterior fossa fracture, Although clinical signs and symptoms are the best way to middle fossa fracture, and posterior fossa fracture were 2.4%, detect this disorder, diagnosis of TCCF may be difficult in 8.3%, and 1.7%, respectively. In this study, patients diag- certain patients with head trauma, such as those in comas or with nosed with middle fossa fracture had a relatively high inci- atypical clinical presentations. The most frequent signs and dence of TCCF compared with other types of basilar skull symptoms of TCCF reported include proptosis, chemosis, and fracture. Anatomically, the cavernous sinuses are paired bruit, as stated above. However, a number of patients suffer from structures within the sphenoid bone in the anterior portion of this disorder without these symptoms or signs. It has been the middle cranial fossa. After bifurcating from the common reported that 13% to 36% of patients with CCF did not show carotid artery in the anterior cervical triangle, the ICA enters proptosis, whereas 6% to 64% were without chemosis and 25% the skull via carotid canal and then traverses foramen to 81% were without bruit.1,8,17 Considering the effects of early lacerum, which is medial to the foramen ovale (the ICA diagnosis and treatment on prognosis, surgeons who manage enters the skull via the foramen lacerum and the carotid patients with brain or facial trauma should be aware that TCCF canal). It continues through the petrosal canal and enters the may have a relatively high incidence rate in those cases with cavernous sinus on the medial aspect of the sinus. Within the middle fossa fracture, especially with increased difficulties in cavernous sinus, the ICA is bound by strong dural filaments diagnosis stemming from patient unconsciousness or other com- and attachments, especially at its entrance and exit by inferior plications. And we think that an examination to detect TCCF for and superior ascending segments. In the cavernous sinus, the prompt diagnosis or avoidance of missed diagnosis should be ICA sends off branches such as the inferior cavernous sinus considered in three populations with middle fossa fractures after artery. The ICA eventually leaves the cavernous sinus below traumatic brain and facial injury to achieve better outcomes. (1) the anterior clinoid process on the lesser wing of the sphenoid The first population consists of patients with neurologic deficits bone.13 Both the foramen lacerum and carotid canal are such as monoparesis or hemiparesis that are incompatible with important anatomic landmarks of the middle fossa. The fo- computed tomography findings. These symptoms may suggest ramen lacerum is located between the apex of the petrous part pathophysiologic changes resulting from blood steal from the of the temporal bone, the body of the sphenoid bone, and the ICA because of the TCCF producing an abnormal connection basilar part of the occipital bones. And on the interior surface between the ICA and cavernous sinus. In general, the symptoms of the temporal bone, behind the rough surface of the apex, is of blood flow steal are not apparent, as most fistulas are not large

1018 November 2007 TCCF Accompanying Basilar Skull Fracture enough, and collateral flow can partially compensate for blood and a prognostic analysis of TCCF was also performed. In steal. When the fistula is large with poor collateral flow (usually this study, TCCF had a relatively high incidence among resulting from underdevelopment of the Circle of Willis) neu- the patients with middle skull fractures, especially cases rologic deficits may occur.18 Patients with head trauma often with transverse or oblique middle fossa fractures. Notably, show symptoms of neurologic deficits stemming from brain the time from first symptom onset to endovascular embo- injury. However, if patients with middle fossa fractures show lization may impact the prognosis of patients with TCCF. impairments in neurologic function without compatible com- Early recognition by neurosurgeons and prompt endovas- puted tomography findings, an examination for early detection cular embolization could reduce morbidity and mortality of TCCF should be considered, given the relatively high inci- associated with TCCF. Considering the relatively high dence of this disorder with middle fossa fractures, and the high incidence of this disorder with middle fossa fractures, the risks associated with TCCF. Moreover, a total blood steal with high risks associated with TCCF and the importance of an poor compensatory collateral flow is always an indication for early intervention in this disorder, we recommend an ex- emergent embolization. (2) The second population consists of amination for prompt diagnosis of TCCF in patients with patients with histories of cardiovascular disease or latent cardio- middle fossa fracture under certain conditions. vascular danger factors. In this population, vascular complications of traumatic brain injury are liable to result in catastrophic ACKNOWLEDGMENTS outcomes.2,19 (3) The third population consists of comatose We thank Dr. Jiang Dingyao, and Dr. Wu Jianjun (Department of patients or patients with speech disturbances, greatly increasing Radiology, the Second Affiliated Hospital, Zhejiang University, College of the difficulty of detecting TCCF. Speech disturbance is one of Medicine) for their support. the most frequent symptoms observed after craniofacial injuries, especially severe brain injuries. Patients with speech distur- REFERENCES bances obviously have difficulties describing symptoms. If clear 1. Louis B, Franz EG, George JA. Vascular complications. In: Louis B, Franz EG, eds. Head Injury. 1st ed. Boston: Brown and Company; signs are not apparent, delays in diagnosis may occur. For the 1980:313–320. conditions mentioned above, noninvasive techniques such as 2. Iida K, Uozumi T, Arita K, et al. Steal phenomenon in a traumatic MRA, CTA, and transcranial duplex sonography, which are carotid-cavernous fistula. J Trauma. 1995;39:1015–1017. also effective in the detection of TCCF, may be more accept- 3. d’Angelo VA, Monte V, Scialfa G, et al. Intracerebral venous able for the patients, because of the safeness and convenience hemorrhage in “high-risk” carotid-cavernous fistula. Surg Neurol. 20–22 1988;30:387–390. compared with angiogram. 4. Samii M, Tatagiba M. Skull base trauma: diagnosis and The goals of TCCF treatment include preserving vision management. Neurol Res. 2002;24:147–156. with the resolution of associated symptoms, while avoiding 5. Barrow DL, Spector RH, Braun IF, et al. Classification and cerebral ischemic complications. Historically, surgery was treatment of spontaneous carotid-cavernous sinus fistulas. the primary treatment option, but had a high operative risk J Neurosurg. 1985;62:248–256. 6. Takenoshita Y, Hasuo K, Matsushima T, et al. Carotid-cavernous and produced great trauma, and also had relatively high sinus fistula accompanying facial trauma. Report of a case with a recurrence rates. Serbinenko was the first to use a catheter review of the literature. J Craniomaxillofac Surg. 1990;18:41–45. with a detachable balloon transarterially to successfully oblit- 7. Zachariades N, Papavassiliou D. Traumatic carotid-cavernous sinus erate a direct CCF while maintaining carotid artery patency.23 fistula. J Craniomaxillofac Surg. 1988;16:385–388. At present, transvascular detachable balloon embolization has 8. Fabian TS, Woody JD, Ciraulo DL, et al. Posttraumatic carotid cavernous fistula: frequency analysis of signs, symptoms, and become a standard treatment for TCCF, with relatively low disability outcomes after angiographic embolization. J Trauma. 24,25 mortality and morbidity. Several other techniques for 1999;47:275–281. treatment of TCCF have been successful in recent years, such 9. Wu Dejun, Wu Zhongxue, Sun Tao, et al. Urgent treatment of the as the transvenous approach and the double-balloon emboli- traumatic carotid cavernous fistula. Chin J Neurosurg. 2005,21: zation technique.26 In this series, 16 cases were treated with 200–202 (Chinese). 10. Barnwell SL, O’Neill OR. Endovascular therapy of carotid transarterial detachable balloon embolization, and the ICA cavernous fistulas. Neurosurg Clin N Am. 1994;5:485–495. flow was preserved in 14 cases. Eleven cases showed no 11. Albuquerque FC, Heinz GW, McDougall CG. Reversal of blindness disability after transarterial embolization, including a patient after transvenous embolization of a carotid-cavernous fistula: case with bilateral TCCF for whom embolization was performed report. Neurosurgery. 2003;52:233–236; discussion 236–237. on both fistulas. 12. Yang D, He Q, Zou Y, et al. Diagnosis and treatment of traumatic carotid cavernous fistula. Chin J Traumatol. 2002;5:112–114. 13. Fattahi TT, Brandt MT, Jenkins WS, et al. Traumatic carotid- cavernous fistula: pathophysiology and treatment. J Craniofac Surg. CONCLUSIONS 2003;14:240–246. TCCF is a rare but potentially lethal entity after brain 14. Kamel HA, Choudhari KA, Gillespie JS. Bilateral traumatic and facial injury. Here, we reviewed cases of TCCF con- caroticocavernous fistulae: total resolution following unilateral occlusion. Neuroradiology. 2000;42:462–465. firmed by angiography, as well as those with basilar skull 15. Wysocki J. Cadaveric dissections based on observations of injuries fractures, in inpatients in a regional medical center. We to the temporal bone structures following head trauma. Skull Base. analyzed the incidence of TCCF in basilar skull fracture, 2005;15:99–106.

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16. Resnick DK, Subach BR, Marion DW. The significance of carotid 26. Miller NR, Monsein LH, Debrun GM, et al. Treatment of carotid- canal involvement in basilar cranial fracture. Neurosurgery. 1997; cavernous sinus fistulas using a superior ophthalmic vein approach. 40:1177–1181. J Neurosurg. 1995;83:838–842. 17. Kirsch M, Henkes H, Liebig T, et al. Endovascular management of dural carotid-cavernous sinus fistulas in 141 patients. EDITORIAL COMMENT Neuroradiology. 2006,48:486–490. The authors analyze the incidence of traumatic carotid 18. Wang HX, Bai RL, Huang CG, Lu YC, Zhang GJ. Hemiparesis in cavernous fistula in different types of basilar skull fracture to carotid cavernous fistulas (CCFs): a case report and review of the literature. Chin J Traumatol. 2004;7:317–320. determine whether particular clinical factors impact outcome. 19. Hantson P, Espeel B, Guerit JM, et al. Bilateral carotid-cavernous This study is a retrospective review of patients with basilar fistula following head trauma: possible worsening of brain injury skull fracture or angiographically confirmed traumatic carotid following balloon catheter occlusion? Clin Neurol Neurosurg. 2006; cavernous fistula in patients seen between 1999 and 2005 at 108:576–579. the Institute of Brain Medicine, the Second Affiliated Hos- 20. Yang ZJ, Li HW, Wu LG, et al. Prognostic analysis and pital, Zhejiang University, College of Medicine. The authors complications of traumatic carotid cavernous fistulas after treatment with detachable balloon and/or coil embolization. Chin J Traumatol. observed a 3.8% incidence of traumatic carotid cavernous 2004;7:286–288. fistula in 312 patients with basilar skull fractures. The highest 21. Chen YW, Jeng JS, Liu HM, et al. Carotid and transcranial color- incidence was found in patients with middle fossa fractures. coded duplex sonography in different types of carotid-cavernous In attempting to identify prognostic factors for this injury, the fistula. Stroke. 2000;31:701–706. authors note that early detection and treatment is associated 22. Rucker JC, Biousse V, Newman NJ. Magnetic resonance angiography source images in carotid cavernous fistulas. Br J with an improved outcome. Ophthalmol. 2004;88:311. In this article, the authors provide a thoughtful review of 23. Serbinenko FA. Balloon catheterization and occlusion of major a relatively rare vascular complication of traumatic brain cerebral vessels. J Neurosurg. 1974;41:125–145. injury and rightly note that their conclusion regarding early 24. Lewis AI, Tomsick TA, Tew JM Jr, et al. Long-term results in detection and treatment is limited by the small number of direct carotid-cavernous fistulas after treatment with detachable patients treated for traumatic carotid cavernous fistula. balloons. J Neurosurg. 1996;84:400–404. 25. Wu Z, Wang C, Yang X, et al. Endovascular embolization of Jack Jallo, MD traumatic carotid cavernous fistulas. Chin Med J (Engl). 1999; Temple University School of Medicine 112:433–437. Philadelphia, Pennsylvania

1020 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Brachial Plexus Injury: Long-Term Functional Outcome is Determined by Associated Scapulothoracic Dissociation Kevin P. Riess, MD, Thomas H. Cogbill, MD, Nirav Y. Patel, MD, Pamela J. Lambert, RN, and Michelle A. Mathiason, MS

Background: Trauma to the brachial term outcome was determined by use of months), all 12 ISOL patients reported plexus may result in devastating neuro- an 18-question telephone survey. that they could carry 5 pounds of weight logic dysfunction associated with muscu- Results: Mean injury severity score with the affected extremity, versus only 4 ؍ loskeletal and vascular injuries. for the ISOL group was 8, versus 22 for (57%) SD patients reported the same (p -Mean length of 0.036). Mean muscle strength at the shoul .(0.002 ؍ Methods: Twenty-nine patients with the SD group (p unilateral brachial plexus injury caused hospital stay for the ISOL group was 1.9 der was rated 4.1 in ISOL patients, versus .(0.009 ؍ by blunt trauma treated at a single insti- days, versus 19.8 days in the SD group 2.3 in SD patients (p At 9-month follow-up, 11 Conclusion: Most patients with .(0.002 ؍ tution were identified and divided into two (p subgroups: those with isolated brachial ISOL patients (61%) had complete neuro- ISOL experienced excellent long-term functional outcome. However, those with ؍ and logic recovery, versus no SD patients (p ;(%62 ,18 ؍ plexus injury (ISOL) (n those with associated scapulothoracic dis- 0.001). Nineteen patients (68%) completed associated SD had significant short- and .Hospital telephone surveys, including 12 (67%) long-term disability .(%38 ,11 ؍ sociation (SD) (n and outpatient records for each patient ISOL patients and 7 (64%) SD patients. Key Words: Brachial plexus injury, .Scapulothoracic dissociation 60 ؍ were retrospectively reviewed, and long- When contacted by phone (median J Trauma. 2007;63:1021–1025.

raumatic brachial plexus disruption results in a spectrum PATIENTS AND METHODS of neurologic injuries. Brachial plexus injuries (BPIs) All patients diagnosed with BPI (International Classifi- Tmost often occur in young men involved in motor vehi- cation of Disease-9 code 953.4) at Gundersen Lutheran Med- 1 cle and motorcycle crashes. BPIs may be associated with ical Center in La Crosse, WI, between January 1, 1993, and muscular, skeletal, and vascular injuries of the upper extrem- December 31, 2003, were identified. Gundersen Lutheran ity. Within the last 21 years, there has been increasing knowl- Medical Center is an American College of Surgeons (ACS)- edge of the combination of injuries resulting from a violent verified Level II regional trauma center for southwestern lateral distraction or rotational displacement of the shoulder Wisconsin, southeastern Minnesota, and northern Iowa. Hos- girdle. In 1984, Oreck et al. first termed this injury pattern as pital charts and outpatient clinic records of BPI patients were scapulothoracic dissociation (SD).2 Since the publication by retrospectively reviewed and patients meeting inclusion cri- Oreck et al., 110 cases of closed scapulothoracic injuries have teria were enrolled in the study. Inclusion criteria were blunt- been reported in the literature.2–24 The outcomes of patients injury mechanisms with documented orthopedic, neurologic, with isolated BPI and SD have been considered poor, even and vascular examinations. Injuries resulting from obstetric with surgical treatment. Few studies have examined long- complications were excluded. The following data were col- term functional outcomes of SD, and no studies have com- lected for each patient: demographics, mechanism of injury, pared the functional outcomes of SD versus those of isolated BPI. We hypothesized that patients with SD have substan- neurologic and vascular findings, injury severity score (ISS), tially worse long-term outcome than do those with injuries length of hospital stay, radiology studies, electromyography limited to the brachial plexus. (EMG), surgical procedures, length of time to last clinic follow-up, morbidity, and mortality. The institutional review board approved the study before its initiation. Submitted for publication January 19, 2006. Patients were subdivided into two groups for compari- Accepted for publication June 8, 2006. son. Medical records were reviewed to categorize types of Copyright © 2007 by Lippincott Williams & Wilkins From the Departments of Surgery (K.P.R., T.H.C., N.Y.P.); and Med- injuries. Patients with isolated BPI were classified as the ical Research (P.J.L., M.A.M.), Gundersen Lutheran Medical Foundation, La ISOL group and patients with BPI associated with SD were Crosse, Wisconsin. categorized as the SD group. The definition of SD was Supported by R. James Trane Surgical Research and Data Center of the consistent with guidelines developed at our institution.21 Cri- Gundersen Lutheran Medical Foundation, La Crosse, Wisconsin. Address for reprints: Thomas H. Cogbill, MD, Gundersen Lutheran teria required musculoskeletal injury to the shoulder girdle, Medical Center, 1900 South Avenue, La Crosse, WI 54601; email: with or without concomitant vascular injuries, in the setting [email protected]. of a violent lateral distraction or rotational displacement of DOI: 10.1097/01.ta.0000233764.54922.55 the extremity.

Volume 63 • Number 5 1021 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

veloped by the authors to assess the patients’ perceptions of their overall health, impact of their injuries upon work and activities of daily living, and functional improvement or recovery from BPI or SD. Lifestyle questions were designed to assess change in work related to injury, effect upon exercise, and change in hand dominance. Function of the injured arm was assessed with questions about strength and range of motion at each joint level compared with the uninjured extremity. These answers were compared with similar questions asked about lifting strength and range of motion at time of discharge. Patients were asked to quantify their strength using two different scales. These included ability to lift a weight equal to a 5-pound bag of flour, a 12-ounce soup can, or inability to lift any objects. The other scale used was a numeric scale scored 0 to 5, with 0 meaning no strength and 5 meaning strength equal to the uninjured contralateral limb. Range of motion was assessed with descriptive Fig. 1. Scapulothoracic displacement is indicated by greater than 1 choices including no limitation, slightly limited, moder- cm difference in distance between the scapular tip and spinous ately limited, severely limited, unable to move joint, or processes on side of injury compared with contralateral side. Note amputated. Sensation was assessed with a scale of 0 to 5, presence of a right clavicle fracture (dotted arrow). with 0 denoting no sensation and 5 denoting sensation equal to the contralateral limb. For ISOL and SD, diagnosis of neurologic injury re- Statistical analysis was conducted with SAS (Cary, NC). quired documentation of an abnormal neurologic examination Statistical tests included ␹2 and Fisher’s exact test for cate- or abnormal EMG. To diagnose SD, musculoskeletal injury gorical variables. Wilcoxon rank sum test and t tests were documentation was required. Anteroposterior radiographs of used for comparisons of continuous variables. The nonpara- the chest showing clavicle fracture, sternoclavicular or acro- metric tests (Fisher’s exact test and Wilcoxon rank sum test) mioclavicular separation, or lateral scapular displacement were used when the assumptions for the parametric tests were were used to assist in the diagnosis of SD. Scapular displace- violated. Level of confidence was defined as p Ͻ 0.05. ment was recognized on a nonrotated anteroposterior radiograph, by comparing distances between the scapula and the spinous processes of the vertebrae on the side of injury to the RESULTS contralateral side (Fig. 1). Scapular displacement was defined The median age of the 20 male and 9 female patients was as a difference of greater than 1 cm on the side of injury 38 years (range, 10–68 years) (Table 1). There was no compared with the uninjured side as described by Lange and significant difference in gender or age between the ISOL and Noel.22 Other radiology studies used to assist in the diagnosis SD groups (p ϭ 1.000 and p ϭ 0.476, respectively). The of musculoskeletal injury included scapular views and comput- mechanisms of injury included motor vehicle crashes (8), erized tomography. Diagnosis of vascular injuries required falls (5), motorcycle crashes (4), agricultural injuries (3), either angiographic or operative identification of disrupted ATV crashes (2), and miscellaneous (7). subclavian or axillary arteries or veins. Eighteen patients (62%) with injuries limited to the bra- Early follow-up results were determined by review of chial plexus were placed into the ISOL group. All patients hospital and outpatient clinic records. Records pertaining to were diagnosed with BPI on neurologic physical examination muscle strength, range of motion, neurologic function, and (Table 1). Nine patients underwent EMG studies. All studies physicians’ impressions were used to assess improvement in confirmed BPI. Eleven patients (38%) had injuries consistent arm function compared with that upon hospital admission. with SD. All SD patients had abnormal neurologic examina- Complete recovery implied no residual neurologic deficits, tions, with eight patients having abnormal EMGs to confirm partial recovery implied incomplete return of neurologic def- the physical examination findings. All 11 had musculoskel- icits, and no recovery implied persistent neurologic deficits etal injuries resulting from rotational or lateral displacement with no improvement or amputation of the extremity. of the shoulder girdle consistent with SD. Skeletal injuries Long-term outcome was determined by use of an 18- included scapula fractures (8), clavicle fractures (6), scapular question telephone survey. An attempt was made to contact displacement (4), and acromioclavicular separation (3). Eight every patient. Both the ISOL and SD groups were given the patients underwent angiography for abnormal physical exam- same survey instrument. The multiple choice survey, which ination findings suggestive of vascular injury. Angiography included elements of the Short Form 36-Item Health Survey revealed disruption of either the subclavian or axillary vessels (SF-36) and the Subjective Shoulder Rating Scale, was de- in four patients. Two patients had normal angiograms, and

1022 November 2007 Brachial Plexus Injury

Table 1 Demographics and Examination Results for Table 3 Nine-Month Clinical Outcome for Isolated Patients With Isolated Brachial Plexus Injuries (ISOL) Brachial Plexus Injuries (ISOL) and Scapulothoracic and Scapulothoracic Dissociation (SD) Dissociation (SD) Patients

ISOL SD p ISOL (n ϭ 18) SD (n ϭ 11) No. patients 18 11 Deaths 0 1 Median age 36 40 0.476 Complete recovery of neurologic 11 0 Male 12 8 1.000 and arm function* Injury severity score (ISS) 8 22 0.002 Abnormal neurologic exam* 7 10 Abnormal extremity neurologic exam 18 11 Amputees 0 1 Electromyography (EMG) 9 8 * Comparison using Fisher exact test, p ϭ 0.002. Abnormal EMG 9 8 Abnormal extremity vascular exam 0 8 Angiograms 0 8 Table 4 Telephone Survey Results* From Isolated Abnormal angiograms NA 6 Disruption of axillary or NA 4 Brachial Plexus Injuries (ISOL) and Scapulothoracic subclavian vessels Dissociation (SD) Patients Other vascular injury NA 2 ISOL SD p NA, not applicable. No. completed surveys 12 7 Injured dominant hand 10 4 0.305 Table 2 Hospital Course for Isolated Brachial Plexus Changed dominant hand (R to L 4 1 0.603 orLtoR) (ISOL) and Scapulothoracic Dissociation (SD) Patients Changed work due to arm injury 4 2† 1.000 ISOL (n ϭ 18) SD (n ϭ 11) p Shoulder strength rating (1–5) 4.1 2.3 0.009 Elbow strength rating (1–5) 4.2 3.6 0.462 Mean length of stay 1.9 19.8 0.002 Hand strength rating (1–5) 4 2.7 0.204 (LOS) Ability to carry 5 pounds 12 4 0.036 No. patients requiring 05 ϭ operation * Median time of survey 60 months. † Amputations 0 1 One patient on disability. Deaths 0 0 Early Follow-Up At 9 months, outpatient follow-up visits for all patients two had occlusion of distal vessels without limb-threatening revealed that 11 ISOL patients (61%) had complete neuro- ischemia. logic recovery and arm function. Complete recovery did not occur in any SD patient (p ϭ 0.001) (Table 3). All other ISOL or SD patients had either partial or no recovery. One Hospitalization patient with SD died from metastatic cancer 6 months after Mean ISS in the ISOL group was 8 versus 22 for the SD injury; he had experienced no improvement of his flaccid p ϭ group ( 0.002). Mean length of hospital stay was 1.9 days limb. in the ISOL group versus 19.8 days in the SD group (p ϭ 0.002) (Table 2). No patients with isolated BPI required any Long-Term Outcome surgery for the affected extremity. Five SD patients under- Telephone surveys were completed at a median of 60 went surgery during the initial hospitalization. Two SD pa- months postinjury by 19 patients (68%), including 12 ISOL tients required orthopedic procedures for repair of clavicle patients and 7 SD patients (Table 4). Fifty-seven percent of fractures, and another patient had acromioclavicular joint the SD patients reported injuring their dominant hand, com- reconstruction. Fractures and separations in all other SD pared with 83% of the ISOL patients (p ϭ 0.305). There was patients were treated nonoperatively. Two patients with SD no significant difference in need to change hand dominance underwent surgery to control hemorrhage from subclavian after injury. Four ISOL and two SD patients reported a need and axillary arteries. Two SD patients did not require surgery to change work because of injury of the arm (p ϭ 1.000). for axillary artery occlusion because there was no limb- Two patients from the SD group were found to have under- threatening ischemia. No patients with SD underwent surgery gone nerve grafting at an outside institution with minimal for treatment of the brachial plexus injury. One patient who improvement in elbow flexion. At the time of telephone underwent subclavian artery repair later required above- contact, all 12 ISOL patients could carry 5 pounds of weight elbow amputation. The amputation was performed for third- with the affected extremity whereas only 4 (57%) of the degree burns of the forearm in the presence of a partial BPI patients with SD could do so (p ϭ 0.036). Mean muscle causing disuse of the distal arm. There were no hospital strength at the shoulder was rated 4.1 in ISOL patients versus deaths in either group. 2.3 in SD patients (p ϭ 0.009). Mean handgrip strength was

Volume 63 • Number 5 1023 The Journal of TRAUMA௡ Injury, Infection, and Critical Care rated 4.0 in ISOL patients versus 2.7 in SD patients (p ϭ scored significantly better on the SF-36 and the Subjective 0.204). Sensation was decreased in 5 of 12 ISOL patients and Shoulder Rating Scale. We elected not to use the entire SF-36 two of six SD patients, excluding the patient with an ampu- scale in favor of a shorter questionnaire designed for tele- tation. All ISOL patients returned to work, with four requir- phone response, which focused on comprehensive evaluation ing a change in their employment because of their injury. of shoulder, elbow, wrist, and hand function and included Five SD patients returned to work; one patient required em- only the most pertinent questions about quality of life in ployment change because of his injury; and another received general. disability. In our series, SD patients were found to have higher ISS than patients with isolated BPI. This may be related to the DISCUSSION magnitude of force necessary to cause both BPI and the BPIs affect a predominantly young and active popula- associated musculoskeletal injury with or without vascular tion. The injuries are most often caused by motorcycle and disruption. The SD patients were also found to have longer motor vehicle crashes. The brachial plexus is the most com- hospital stays. At 9-month follow-up, no SD patient had a plex structure in the peripheral nervous system. It is vulner- complete neurologic recovery. In addition to significantly able to trauma because of its superficial location between two worse short-term outcomes compared with the ISOL patients, highly mobile structures, the neck and shoulder. The brachial the SD patients were found to have worse long-term outcome. plexus is considered the least forgiving structure at the shoul- SD patients reported decreased lifting strength and subjective der with any stretch-type injury. Prognosis of BPI is depen- strength at the shoulder. All these patients perceived weak- dent upon location of injury, levels of involvement, and ness encompassing the extremity. completeness of injury.25 BPI can be categorized as supra- The role of delayed neurolysis or nerve grafting for BPI clavicular or infraclavicular in location. The majority of or SD patients with poor neurologic recovery has been de- injuries are supraclavicular (70%–75%) and carry the worst scribed by Zelle et al. and Sampson et al.20,23 We report a prognosis.26 Injuries isolated to the upper brachial plexus similar experience, as two patients who underwent nerve trunk compared with those to the lower trunk are thought to grafting gained only minimal elbow flexion. These patients have a better prognosis. Additionally, partial brachial plexus had nerve grafting performed at approximately 1 year from disruption is considered to have a much better prognosis than their date of injury. The optimal timing of surgery is debated complete disruption. Signs of recovery from BPI should man- in the literature. Patients with complete brachial plexus dis- ifest themselves by 6 to 12 months.25 Because of the small ruption who have no improvement in function are thought to number of patients and EMG being performed on only 59% be served best by surgery between 3 months and 8 months of all patients, a correlation between type of BPI and outcome after injury.25,26 Amputation rates for patients with SD range could not be made in our series. from 21% to 24%.20,21 Our amputation rate of 9% is likely to Our analysis revealed that 61% of ISOL patients had be lower because of an aggressive approach to timely vascu- complete recovery at the 9-month clinical follow-up. The lar repairs and late orthopedic reconstruction. Early amputa- remaining ISOL patients had some functional recovery. At tion is indicated in patients who have complete brachial the time of telephone survey, all patients were able to carry a plexus disruption found during exploration of vascular and 5-pound object. However, 67% of ISOL patients still per- orthopedic injuries. The rationale for amputation in this set- ceived that the injured extremity felt weaker than the con- ting is based on the conclusion that this subset of patients will tralateral limb. Although four patients required a change in benefit functionally from a contemporary above elbow pros- occupation because of their injury, all ISOL patients returned thesis instead of an insensate, flail limb. to employment. Less than 10% of SD patients develop severe vascular In a review of the SD literature by Damschen and asso- complications of the affected extremity.20 Active hemorrhage ciates at our institution, nerve injuries were described in 96% prompted surgical intervention in half of our patients with of SD patients, with 81% of these injuries being reported as arterial disruption. Two patients did not require surgery for complete brachial plexus disruptions.21 These injuries re- occlusive vascular injuries from intimal or medial disruption. sulted in a flail extremity in 52% of patients or a major Extensive collateral vessels around the shoulder allowed ad- amputation in 21% of patients. Limited functional improve- equate distal perfusion despite occlusion of the subclavian or ment occurred in only 17% of SD patients. Prognostic factors axillary arteries. Support for nonoperative treatment has been were not examined in this review. In a similar series, Samp- described by Sampson and associates with no episodes of son et al. found that the SD patients who regained some limb-threatening ischemia in 15 SD patients with occlusive neurologic function were those with partial BPI.23 They revascular injuries.23 Vascular intervention should be limited to ported partial recovery in only 6% of patients. Moreover, in cases with limb-threatening ischemia or active hemorrhage. a study of 25 patients with SD, Zelle et al. found that all Several limitations of our study result from retrospective patients with complete brachial plexus avulsions had a flail analysis. Prospective data collection could assure more uni- extremity at a mean of 12.6 years after injury.20 In their form acquisition of test results at predetermined intervals. For outcome study of SD patients, patients with partial BPI instance, routine EMG testing for each of these BPIs could

1024 November 2007 Brachial Plexus Injury allow them to be stratified as complete or incomplete and 8. Costa MC, Robbs JV. Nonpenetrating subclavian artery trauma. upper or lower in location. This would clearly help answer J Vasc Surg. 1988;8:71–75. the question of respective recovery in these subgroups. A 9. Kelbel JM, Jardon OM, Huurman, WW. Scapulothoracic dissociation: a case report. Clin Orthop Relat Res. 1986;209:210–214. prospective, longitudinal study with preset interval examina- 10. Oni OO, Hoskinson J, McPherson S. Closed traumatic tions and testing could more accurately document the rate of scapulothoracic dissociation. Injury. 1992;23:138–139. healing and recovery from these injuries. However, these 11. Tuzuner S, Yanat AN, Urguden M, et al. Scapulothoracic injuries are not frequent and patient accrual would require an dissociation: a case report. Isr J Med Sci. 1996;32:70–74. extended study period at any single institution. In our retro- 12. Faris I, Jury P, Malycha P. Blunt injury to the subclavian artery. spective study, patient follow-up and participation in the Aust NZ J Surg. 1984;54:249–251. 13. Morris CS, Lloyd T. Case report 642: traumatic scapulothoracic telephone survey at a mean of 5 years after injury were dissociation in a child. Skeletal Radiol. 1990;19:607–608. excellent. Therefore, we feel that our data accurately reflect 14. Nagi ON, Dhillon MS. Traumatic scapulothoracic dissociation. A the expected long-term outcomes after isolated BPI and SD. case report. Arch Orthop Trauma Surg. 1992;111:348–349. 15. Witz M, Korzets Z, Lehmann J. Traumatic scapulothoracic CONCLUSION dissociation. J Cardiovasc Surg. 2000;41:927–929. We have shown that in patients with BPI, the presence of 16. Goldstein LJ, Watson JM. Traumatic scapulothoracic dissociation: a associated SD is a prognostic sign for poor neurologic recov- case report and literature review. J Trauma. 2000;48:533–535. 17. Masmejean EH, Asfazadourian H, Alnot JY. Brachial plexus ery. Long-term functional outcome is excellent in most pa- injuries in scapulothoracic dissociation. J Hand Surg (Br). 2000; tients with isolated BPI. However, patients with SD report 25:336–340. significant long-term disability. 18. Clements RH, Reisser JR. Scapulothoracic dissociation: a devastating injury. J Trauma. 1996;40:146–149. REFERENCES 19. Ebraheim NA, An HS, Jackson WT, et al. Scapulothoracic dissociation. J Bone Joint Surg Am. 1988;70:428–432. 1. Midha R. Epidemiology of brachial plexus injuries in a multi-trauma 20. Zelle BA, Pape HC, Gerich TG, et al. Functional outcome following population. Neurosurgery. 1997;40:1182–1188; discussion 1188–1189. scapulothoracic dissociation. J Bone Joint Surg Am. 2004;86:2–8. 2. Oreck SL, Burgess A, Levine AM. Traumatic lateral displacement of 21. Damschen DD, Cogbill TH, Siegel MJ. Scapulothoracic dissociation the scapula: a radiographic sign of neurovascular disruption. J Bone caused by blunt trauma. J Trauma. 1997;42:537–540. Joint Surg Am. 1984;66:758–763. 22. Lange RH, Noel SH. Traumatic lateral scapular displacement: an 3. Rubenstein JD, Ebraheim NA, Kellam JF. Traumatic scapulothoracic dissociation. Radiology. 1985;157:297–298. expanded spectrum of associated neurovascular injury. J Orthop 4. Johansen K, Sangeorzan B, Copass MK. Traumatic scapulothoracic Trauma. 1993;7:361–366. dissociation: case report. J Trauma. 1991;31:147–149. 23. Sampson LN, Britton JC, Eldrup-Jorgensen J, et al. The 5. Ebraheim NA, Pearlstein SR, Savolaine ER, et al. Scapulothoracic neurovascular outcome of scapulothoracic dissociation. J Vasc Surg. dissociation (closed avulsion of the scapula, subclavian artery, and 1993;17:1083–1088; discussion 1088–1089. brachial plexus): a new classification, and a review of the literature 24. Tsai DW, Swiontkowski MF, Kottra CL. A case of sternoclavicular and treatment options. J Orthop Trauma. 1987;1:18–23. dislocation with scapulothoracic dissociation. Am J Roentgenol. 6. Katsamouris AN, Kafetzakis A, Kostas T, et al. The initial 1996;167:332. management of scapulothoracic dissociation: a challenging task for 25. Rorabeck CH, Harris WR. Factors affecting the prognosis of brachial the vascular surgeon. Eur J Endovasc Surg. 2002;24:547–549. plexus injuries. J Bone Joint Surg Br. 1981;63:404–407. 7. Tomaszek DE. Combined subclavian artery and brachial plexus injuries 26. Brophy RH, Wolfe SW. Planning brachial plexus surgery: treatment from blunt upper-extremity trauma. J Trauma. 1984;24:161–163. options and priorities. Hand Clin. 2005;21:47–54.

Volume 63 • Number 5 1025 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Agreement Between Prehospital and Emergency Department Glasgow Coma Scores

Jeffrey D. Kerby, MD, PhD, Paul A. MacLennan, PhD, Jon N. Burton, MD, Gerald McGwin, Jr., MS, PhD, and Loring W. Rue III, MD

Background: The Glasgow Coma injury. Weighted ␬-coefficients and their in the patient population with moderate to Scale (GCS) score is widely accepted as the 95% confidence intervals were used to ex- severe head injury. Individual component cornerstone in the assessment of neurologic amine the agreement between Ph-GCS score agreement was moderate for all cate- function after trauma and is being used to and ED-GCS patient classifications. gories, with agreement worsening for pa- select patients for enrollment in prehospital Results: Percent agreement was high tients with longer transport times. Although (Ph) intervention trials. This study was per- for the mild category (97.9%) but dimin- this suggests improvement in the patient’s formed to assess the degree of agreement ished for moderate (9.3%) and severe condition during transport, inter-rater between Ph-GCS and emergency depart- (63.3%) groups. Overall, the ␬-coefficient was variability between Ph and ED personnel ment (ED)-GCS scores in our trauma sys- 0.53 (95% confidence interval 0.48–0.58), in- cannot be excluded. The utility of Ph-GCS tem patients. dicating moderate agreement. By GCS com- in Ph interventional trials for determining Methods: From January 1, 2000, ponent, ␬-coefficients were similar, ranging the presence of significant head injury will through November 30, 2003, 3,669 Emer- from 0.52 for the verbal component to 0.48 need to be further evaluated. gency Medical System records were linked for the eye and motor components. ␬-values Key Words: Traumatic brain injury, to our institution’s trauma registry. Pa- decreased even further for those with longer Glasgow Coma Score, Prehospital GCS tients were classified according to their (i.e. >20 minutes) transport times. assessment, Emergency department GCS Ph-GCS and ED-GCS scores: 13 to 15, Conclusion: In this study, differences assessment. mild; 9 to 12, moderate; and 3 to 8, severe between Ph-GCS and ED-GCS were seen J Trauma. 2007;63:1026–1031.

riginally developed by Jennett and Teasdale as a best score of 15 and low score of 3. The total GCS score means of assessing neurologic function after head is sometimes categorized to denote the severity of brain Oinjury, the Glasgow Coma Scale (GCS) has become injury; a score of 13 to 15 indicates a mild injury, 9 to 12 a the cornerstone in the assessment of neurologic function moderate injury, and 3 to 8 a severe injury.3 In addition to among trauma patients.1,2 The GCS score is the sum of its use in trauma system triage and mortality prediction, three independent measures: eye opening (GCSE, 1–4); the GCS is also being used as an inclusion criterion for verbal response (GCSV, 1–5); and motor response (GCSM, enrollment in prehospital (Ph) intervention trials in head 1–6). These three components are combined for an overall injury.4 However, because these patients are assessed aggressively and soon after injury, appreciable differences in Submitted for publication April 5, 2007. scoring practice between trauma centers and medical per- Accepted for publication August 8, 2007. sonnel have been reported,3,5,6 which may lead to inappro- Copyright © 2007 by Lippincott Williams & Wilkins priate patient enrollment. The impact of enrolling patients From the Section of Trauma, Burns, and Surgical Critical Care (J.D.K., who are subsequently found not to have a true intracranial P.A.M., G.M., L.W.R.), Division of General Surgery, Department of Surgery, School of Medicine, University of Alabama at Birmingham, Birmingham, Al- injury based on Ph-GCS score is currently unknown. abama; Center for Injury Sciences at the University of Alabama at Birmingham Whereas these trials are making adjustments in power (J.D.K., P.A.M., J.B., G.M., L.W.R.), Birmingham, Alabama; and Department calculations to correct for these events, the variability of Epidemiology and International Health (G.M.), School of Public Health, across the numerous emergency medical systems involved University of Alabama at Birmingham, Birmingham, Alabama. in multicenter trials has not been quantified with any This report represents the position of the authors and not necessarily that 4 of the Brain Trauma Foundation or the US Department of Transportation. degree of accuracy. Supported by the U.S. Department of Transportation, National High- A significant correlation between Ph-GCS and emer- way Traffic Safety Administration Grant 22-98-G-05131 through the Brain gency department (ED)-GCS scores has been reported;5,6 Trauma Foundation, New York City, NY, to the Center for Injury Sciences however, concerns still exist regarding the accuracy and at the University of Alabama at Birmingham. validity of the Ph-GCS. The objective of the current study Presented as a poster at the 65th Annual Meeting of the American Associ- ation of the Surgery for Trauma, September 28–30, 2006, New Orleans, Louisiana. was to determine the degree of agreement between Ph- Address for reprints: Paul MacLennan, PhD, 120 Kracke Building, GCS and ED-GCS scores in our trauma system. We also 1922 7th Avenue South, University of Alabama at Birmingham, Birming- evaluated the correlation of individual component scores ham, AL 35294-0016; email: [email protected]. of the GCS to determine whether one component was more DOI: 10.1097/TA.0b013e318157d9e8 consistent from the Ph environment to the ED.

1026 November 2007 Prehospital and Emergency Department GCS Scores

MATERIALS AND METHODS positive for alcohol if their blood alcohol concentration was The Alabama Department of Public Health licenses greater than or equal to 80 mg/dL. In addition, they were ambulance drivers, emergency medical technician (EMT)- characterized as positive for illicit drug use if positive for basics, EMT-intermediates, and EMT-paramedics and their amphetamines, barbiturates, benzodiazepines, cocaine or opi- credentialing is updated every 2 years. All accredited EMTs ates on admission urine drug test. are authorized to perform patient assessment, including taking and recording vital signs as well as obtaining an Statistical Analysis appropriate history when possible. It is the responsibility Comparisons of demographic and injury information 2 of emergency medical service (EMS) providers to ensure were made between Ph-GCS severity groups. We used ␹ - that an accurate and complete patient care report (PCR) is tests for categorical variables and Student’s t test for contin- prepared when a patient is assessed and medical care uous variables (e.g., age, ISS). rendered, transported, pronounced dead at the scene, trans- The ␬-coefficient is a statistic calculated to assess ferred to another licensed service, or transferred from one observer agreement for data that can be organized into a medical service to another.7 contingency table. When there is perfect agreement the ␬-coefficient is equal to 1.0, but when agreement is because of chance only, ␬ ϭ 0.0. ␬-values of less than 0.4 Study Population have low agreement; values greater than or equal 0.4 and PCRs from our regional EMS system were linked to less than 0.8 have moderate agreement; and values of 0.8 our institution’s trauma registry for the period January 1, 10 or more have excellent agreement. For ordinal data like 2000, through June 30, 2003 (the last date that PCR data the GCS score and its three subcomponents, it is appro- were consistently available). The PCR data provided pa- priate to use weighted ␬-coefficients to quantify the level tients’ Ph-GCS information whereas the trauma registry of agreement.10 Weighted ␬-coefficients were used to ex- 8 Several variables com- provided ED-GCS information. amine the agreement for mild, moderate, and severe head mon to both data files were used for the linkage; these injury classifications as determined by Ph-GCS score and included a unique patient identifier, age Ϯ5 years, gender, by ED-GCS score. In addition, agreement between indi- and date and ED arrival time Ϯ15 minutes. Recent re- vidual GCS components (motor, verbal, and eye) overall search has shown that using multiple common variables to and subgrouped by transport time (Ͻ20 minutes and Ն20 link PCR data to state trauma registry data results in a minutes) was examined. relatively high proportion of successful record linkage.9 Our regional EMS system serves six counties with a RESULTS combined population of approximately 1.1 million in the During the study period, 6,448 eligible patients were metropolitan area. The system coordinates with EMS provid- admitted to our trauma center and 3,669 (56.9%) patient ers and EMTs to direct patients to the trauma center or facility medical records were linked to EMS PCR records. Of these, that is best able to respond to their needs. Our hospital is the 3,052 (83.2%) had GCS scores recorded in both the Ph and only Level I trauma center in the state verified by the Amer- ED settings. By Ph-GCS severity category, the majority were ican College of Surgeons. Those patients eligible for study classified as mild head injury (n ϭ 2,618, 85.8%), followed inclusion were 19 years of age and older who had sustained by moderate (n ϭ 257, 8.4%) and severe (n ϭ 177, 5.8%). a blunt or penetrating injury type, were transported to and Demographic and injury characteristics by Ph head in- admitted to our trauma center. To avoid the effect of inter- jury severity category are presented in Table 1. The groups ventions instituted at other institutions on GCS, patients did not differ significantly by age, gender, or race. As ex- transferred from other hospitals after initial stabilization were pected, ISS increased significantly with decreasing GCS not included in the analysis. score. Similarly, pupillary appearance and response differed significantly across GCS groups. Statistically significant dif- Variable Definitions ferences between Ph-GCS severity groups were seen in the Study patients were categorized according to their Ph- field intubation, ED intubation, mortality, injury type, mech- GCS scores. Patients with GCS scores between 13 and 15 anism of injury, EMS transport time to hospital, and use of were classified as having mild head injury, those between 9 alcohol or illicit drugs. and 12 as moderate head injury, and those between 3 and 8 as When comparing categorical percent agreement between severe head injury. Additionally, patients were similarly Ph-GCS and ED-GCS severity categories, the data show that grouped based on their ED-GCS scores recorded when first greatest percent agreement is seen for the mild GCS category assessed in ED. Demographic information included age, gen- (97.9%); with the lowest percent agreement for the moderate der, and race. Injury variables included injury severity score GCS category (9.3%) (Table 2). Of patients with severe head (ISS), pupillary responses and field intubation as recorded by injury in the Ph setting, 63.3% were assessed similarly in the EMS personnel, mortality, injury type (blunt and penetrat- ED. Interestingly, 26.5% of Ph-GCS patients with severe head ing), and mechanism of injury. Patients were considered injury were later categorized as mild head injury in the ED,

Volume 63 • Number 5 1027 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Table 1 Study Subjects’ Demographic and Prehospital GCS Severity Category

Mild Moderate Severe Total Characteristics (GCS Score 13–15; (GCS Score 9–12; (GCS Score 3–8; p (n ϭ 3,052) n ϭ 2,618) n ϭ 257) n ϭ 177) Demographic Age (yr), mean (SD) 38.8 (15.6) 40.1 (16.5) 38.4 (16.5) 38.9 (15.7) 0.4037 Gender (%) Male 68.1 70.3 73.4 68.6 0.2678 Race (%) White 57.3 52.9 50.8 56.9 0.1518 Black 38.2 40.9 45.8 38.5 Other 4.5 6.2 3.4 4.6 Injury ISS score, mean (SD) 9.5 (8.0) 12.1 (9.8) 24.0 (18.6) 10.6 (9.1) Ͻ0.0001 Pupillary appearance (%) Constricted 2.2 8.6 29.4 4.4 Ͻ0.0001 Dilated 1.3 5.8 9.0 2.1 Normal 89.3 70.4 41.2 84.9 Pupillary response (%) Nonreactive 0.6 3.1 14.7 1.6 Ͻ0.0001 Reactive problem 2.8 14.4 18.1 4.6 Field intubation (%) 0.1 1.6 26.0 1.7 Ͻ0.0001 ED intubation (%) 5.5 26.5 66.7 10.8 Ͻ0.0001 Mortality 1.1 3.5 26.5 2.7 Ͻ0.0001 Type of injury 0.0067 Blunt 80.2 88.3 81.4 81.0 Penetrating 19.8 11.7 18.6 19.0 Mechanism of injury (%) 0.0005 Motor vehicle crash 55.9 60.7 46.9 55.8 Gunshot wound or stabbing 18.5 9.7 18.6 17.8 Fall 8.6 8.6 14.1 8.9 Motorcycle crash 5.0 3.5 3.9 4.8 Struck pedestrian 1.4 2.3 0.6 1.4 Other 10.6 15.2 15.8 11.3 Transport time, mean minutes (SD) 17.9 (14.1) 17.5 (15.2) 13.8 (11.9) 17.7 (14.1) 0.0010 ED blood alcohol Ͼ80 mg/dL (%) 20.3 41.3 35.6 22.9 Ͻ0.0001 Positive for illicit drugs (%) 11.3 11.9 13.1 11.4 0.8400

Table 2 Prehospital GCS Injury Severity Groups, Percent Agreement in Corresponding ED GCS Severity Group

Prehospital GCS Severity Group Emergency Department GCS Severity Group Mild Moderate Severe (GCS Score 13–15; n ϭ 2,618) (GCS Score 9–12; n ϭ 257) (GCS Score 3–8; nϭ177) Mild 97.9 (2,564) 83.7 (215) 26.5 (47) Moderate 0.9 (24) 9.3 (24) 10.2 (18) Severe 1.2 (30) 7.0 (18) 63.3 (112) Weighted ␬ ϭ 0.53 (95% confidence interval 0.48–0.58) suggesting a vast improvement in the patient’s neurologic status was little agreement for the motor component’s flexion from the Ph care environment. The weighted ␬-coefficient for (GCSM 3) to pain (4.8%); however, there were only 21 agreement was 0.53 (95% confidence interval 0.48–0.58). patients with this score in the Ph setting. For those subjects Table 3 presents cross tabulations for percent agree- with severe head injury whose ED-GCS score improved ment for component scores of Ph-GCS compared with (n ϭ 65), mean component scores increased by 3.1 (SD ϭ component scores assessed in the ED. The greatest percent 1.9) for motor, 2.6 (SD ϭ 1.5) for verbal, and 1.9 (SD ϭ agreement between the Ph and ED is seen for the highest 1.0) for eye. Weighted ␬-coefficients, indicating agree- component scores (range, 95.8%–97.4%), with the lowest ment between Ph-GCS and ED GCS component scores, component scores having moderate agreement (range, showed greatest agreement for the verbal (k ϭ 0.52). 46.7%–63.3%). On the other hand, percent agreement for Table 4 displays agreement between Ph-GCS and ED- moderate scores is low to nonexistent. For example, there GCS head injury severity category and GCS component

1028 November 2007 Prehospital and Emergency Department GCS Scores

Table 3 Percent Agreement Among Prehospital and Emergency Department GCS Component Scores

654321 Prehospital Eye Component (1–4) Emergency Department Eye 2,448 344 93 128 Component (n) 4 97.1 85.8 52.7 22.7 3 1.3 8.4 17.2 5.5 2 0.6 2.0 14.0 8.6 1 1.0 3.8 16.1 63.3 Weighted [kappa] ϭ 0.48 (95% confidence interval 0.43–0.52) Prehospital Verbal Component (1–5) Emergency Department 2,197 534 69 51 162 Verbal Component (n) 5 95.8 74.5 49.3 29.4 23.5 4 2.9 20.8 30.4 25.5 7.4 3 0.2 1.7 7.2 3.9 3.1 2 0.1 1.3 7.2 25.5 6.2 1 1.0 1.7 5.8 15.7 59.9 Weighted [kappa] ϭ 0.52 (95% confidence interval 0.48–0.56) Prehospital Motor Component (1–6) Emergency Department 2,559 208 115 21 3 107 Motor Component (n) 6 97.4 83.6 59.1 42.9 66.7 29.9 5 1.1 8.6 12.2 9.5 0.0 5.6 4 0.6 3.8 13.0 9.5 0.0 8.4 3 0.1 0.5 4.3 4.8 0.0 5.6 2 0.0 0.0 2.6 4.8 33.3 3.7 1 0.8 3.4 8.7 28.6 0.0 46.7 Weighted [kappa] ϭ 0.48 (95% confidence interval 0.43–0.53)

of consciousness (LOC) remains the same.1 Originally in- Table 4 ␬-Statistics and 95% Confidence Intervals for tended for clinical use at least six hours after neurologic Agreement Between Prehospital and Emergency injury, the GCS now plays an important role influencing the Department GCS Injury Severity Groups and correct triage of patients with head injury.3 Previous studies Component Scores had found significant correlations and agreements between Transport Time Ph and ED GCS scores.5,6,11 Arbabi et al. reported an 82% Ͻ20 min Ͼ20 min correlation between Ph and ED GCS severity categories and ϭ ϭ (n 1,997) (n 1,016) concluded that there was no statistical difference between the GCS injury severity group 0.56 (0.50–0.61) 0.42 (0.32–0.52) two.5 The current study’s results indicate that only the mild Eye component 0.52 (0.46–0.57) 0.37 (0.29–0.46) head injury severity category had a high degree of correla- Verbal component 0.55 (0.51–0.60) 0.43 (0.35–0.50) Motor component 0.52 (0.46–0.57) 0.35 (0.25–0.46) tion. As more studies are conducted in the Ph setting for patients with head injury, the ability of the Ph-GCS to accurately predict true occurrence of intracranial injury will need scores based on transport time (Ͻ20 minutes and Ն20 min- to be quantified so that appropriate adjustments in trial design utes). Faster transport times (Ͻ20 minutes) resulted in sig- or other surrogate markers for head injury used in enrollment nificantly greater agreement between Ph-GCS and ED-GCS protocols. severity groups and component scores compared with slower Menegazzi et al. reported that an intermediate depression transport times (Ն20 minutes). of LOC yielded the greatest amount of variability in GCS scoring between paramedics and ED physicians.11 Their DISCUSSION study supported significant agreement among paramedic and The use of the GCS has changed significantly since it emergency physician scoring, but highlighted GCS’s short- was first devised; however, its premise of providing a simple comings when the patient’s LOC is moderate. Rowley and method to quantify and communicate information about level Fielding noted higher error rates in reporting intermediate

Volume 63 • Number 5 1029 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

LOC.12 Results of the current study suggest that intermediate for Ph and ED GCS scores based on transport time were percent agreements between Ph and ED are low for all com- examined. The data showed that with longer transport times, ponents of GCS and that most of the subjects scored higher in there was less agreement in overall severity category and the ED. The moderate head injury severity category had the individual component scores, suggesting improvements in the lowest percent agreement (9.3%) with the majority of patients patients’ condition as a contributing factor for the differences in the moderate head injury category by Ph-GCS score (Table 4). However, other published studies do not lend support (83.7%) improving to the mild head injury severity category for this conclusion. Bazarian et al. noted that there was not a when assessed in the ED. In addition, of those patients ini- significant difference in EMS and ED blood pressure or respi- tially found to have a severe head injury by Ph-GCS criteria, ratory rate.6 Arbabi et al. found that 31% of 7,823 patients had 10.2% improved to the moderate head injury category by improved systolic blood pressure from the Ph to the ED. Yet, ED-GCS with another 26.5% improving to the mild head they only found 3% with improved GCS categories.5 injury category. Our data shows that 18.7% of the severe Ph-GCS pa- It is interesting to note that this study did not find tients had systolic blood pressures below 90 in the field increased correlation with motor component scores versus versus 7.7% and 3.4% in the moderate and mild Ph-GCS eye or verbal component scores between the Ph and ED categories. Of these, 79% showed improvement upon arrival setting. Weighted ␬-coefficients were greatest for the verbal to the ED. For hemodynamically unstable patients by their component scores and similar for the eye and motor compo- Ph-GCS severity group: 42.9% of severe Ph-GCS, 88.9% of nents. Some research indicates that the motor component moderate Ph-GCS, and 89.2% of mild Ph-GCS showed im- carries most of the predictive power of the GCS, is just as provement upon arrival to the ED. For the mild/moderate effective predictor of mortality, and because of its simplicity Ph-GCS groups, we found that Ph-hemodynamic instability should replace the total GCS as a measure of consciousness in did not play a role in the likelihood of increased or decreased a Ph setting.13–15 It is possible that intubation or severe facial ED-GCS. However, compared with the mild/moderate Ph- swelling may have produced a higher degree of agreement GCS groups, hemodynamically unstable patients in the between the Ph and ED setting than expected, thereby dimin- severe Ph-GCS group were less likely to have increased ishing the differences seen. However, in the current study we ED-GCS (32.1% vs. 59.8%) but were just as likely to have did not account for Ph-intubation status but found that 50% of decreased ED-GCS (14.3% vs. 13.1%). In addition, a signif- intubated patients had identical Ph- and ED-GCS scores com- icantly greater proportion of patients with increased systolic pared with 70% for nonintubated patients and in both groups blood pressure from the time of measurement at the injury 25% of patients had increased ED-GCS scores. Higher agree- scene to the time of measurement at the ED was observed for ment between the Ph and ED at the lowest component scores those with a transport time greater than 20 minutes compared for eye (63.3%) and verbal (59.9%) versus motor (46.7%) with patients with a transport time less than 20 minutes provide some evidence to support this explanation (Table 3). (63.9% vs. 58.2%, p ϭ 0.0004). This further suggests but Regardless, reliance on the motor only component of the GCS does not prove that patient improvement is the primary reason does not result in higher degrees of correlation between the Ph for the differences. Regardless of the reason(s) behind the environment and the ED based on the results of our study. discrepancy in Ph and ED-GCS scores, the impact that this The exact reasons for the differences between Ph and could have on Ph trial design and implementation cannot be ED GCS determinations are difficult to ascertain from this overlooked. study. Poor training and procedures for proper calculation A detailed evaluation of the ability of Ph-GCS to accu- of the GCS by either Ph or ED personnel could account for rately predict traumatic brain injury will need to be performed these differences. In addition, difficult Ph conditions could as a secondary analysis after the conclusion of the primary make accurate calculation of the GCS score difficult. Other interventional trials to accurately assess the impact this will investigators have noted discrepancies in measuring GCS have on trial outcomes. In addition, discrepancies across score and difficulties that arise in making accurate assess- various EMS agencies in multicenter trials will need to be ments. Marion and Carlier observed the differences in how evaluated to provide further insight into the exact reasons and when various hospital personnel assess a patient’s behind these differences. LOC.16 Bouzarth suggested that facial fractures and peri- orbital swelling would affect measurement of the eye and CONCLUSION verbal components of the scale.17 Generally, the eye and This study suggests moderate agreement for GCS and for verbal components are believed to be difficult to measure GCS components between the Ph and ED, especially for in a Ph setting and that summation of all three reduces the patients that fall into intermediate or moderate GCS severity ability to track patient status.13 Another possibility is that groups. Our study results imply that simplification of the with institution of Ph interventions, patient physiologic GCS by relying solely on the motor component may not be status improves leading to an increased LOC and improve- helpful when extended to the Ph setting. The ability of the ment of the patient’s GCS score. To further elucidate the GCS to predict traumatic brain injury in the Ph setting will impact of changing patient condition, weighted ␬-agreements require further study. Additional measures in the Ph setting

1030 November 2007 Prehospital and Emergency Department GCS Scores may be needed for accurate identification of the patient with 9. Newgard CD. Validation of probabilistic linkage to match de- traumatic brain injury. identified ambulance records to a state trauma registry. Acad Emerg Med. 2006;13:69–75. 10. Stokes ME, Davis CS, Koch GG. Categorical Data Analysis Using REFERENCES the SAS System. Cary, NC: SAS Institute Inc.; 1995:99. 1. Teasdale G, Jennett B. Assessment of coma and impaired 11. Menegazzi JJ, Davis EA, Sucov AN, Paris PM. Reliability of the consciousness. A practical scale. Lancet. 1974;2:81–84. Glasgow Coma Scale when used by emergency physicians and 2. Jennet B, Teasdale G. Aspects of coma after severe head injury. paramedics. J Trauma. 1993;34:46–48. Lancet. 1977;1:878–881. 12. Rowley G, Fielding K. Reliability and accuracy of the Glasgow 3. Sternbach GL. The Glasgow coma scale. J Emerg Med. 2000;19:67–71. Coma Scale with experienced and inexperienced users. Lancet. 1991; 4. Resuscitation outcomes consortium, mission statement. Available at: 337:535–538. https://roc.uwctc.org/tiki/tiki-index.php. Accessed March 2008. 13. Ross SE, Leipold C, Terregino C, O’Malley KF. Efficacy of the 5. Arbabi S, Jurkovich GJ, Wahl WL, et al. A comparison of motor component of the Glasgow Coma Scale in trauma triage. prehospital and hospital data in trauma patients. J Trauma. 2004; J Trauma. 1998;45:42–44. 56:1029–1032. 14. Healey C, Osler TM, Rogers FB, et al. Improving the Glasgow 6. Bazarian JJ, Eirich MA, Salhanick SD. The relationship between Coma Scale score: motor score alone is a better predictor. J Trauma. prehospital and emergency department Glasgow coma scale scores. 2003;54:671–678. Brain Injury. 2003;17:553–560. 15. Meredith W, Rutledge R, Hansen AR, et al. Field triage of trauma 7. Alabama State Board of Health, Alabama Department of Public patients based upon the ability to follow commands: a study in Health, Administrative Code, Chapter 420-2-1 Emergency Medical 29,573 injured patients. J Trauma. 1995;38:129–135. Services. Available at: http://www.alabamaadministrativecode.state. 16. Marion DW, Carlier PM. Problems with initial Glasgow Coma Scale al.us/docs/hlth/2hlth1.htm. Accessed March 2006. assessment caused by prehospital treatment of patients with head 8. Regional System Trauma Plan. Available at: http://www.bremss.org/ injuries: results of a national survey. J Trauma. 1994;36:89–95. mdac.htm. Accessed March, 2006. 17. Bouzarth WF. Coma scale. J Neurosurg. 1978;49:477–478.

Volume 63 • Number 5 1031 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Hemodynamic and Oxygen Transport Patterns After Head Trauma and Brain Death: Implications for Management of the Organ Donor Howard Belzberg, MD, William C. Shoemaker, MD, Charles C. J. Wo, BS, Timothy P. Nicholls, MD, Alexis B. C. Dang, BS, Vladimir Zelman, MD, J. Peter Gruen, MD, Thomas V. Berne, MD, and Demetrios Demetriades, MD, PhD

Objectives: The aims of the present dex (CI), mean arterial pressure, heart tempts to maintain hemodynamic stability study were to describe the temporal he- rate, arterial saturation by pulse oximetry for organ donation, the effects of various modynamic and oxygen transport pat- (SapO2), and transcutaneous oxygen and therapies on the hemodynamic patterns terns of patients with head injuries as well carbon dioxide (PtcO2/FIO2 and PtcCO2) were preliminarily described. as the patterns of those who became brain patterns. The latter were used as markers Conclusions: The hyperdynamic dead to better understand the role of un- of tissue perfusion or oxygenation. state with exaggerated peripheral tissue derlying central regulatory hemodynamic Results: Patients with head injuries perfusion or oxygenation in brain-dead mechanisms and ultimately to improve who subsequently became brain dead ini- patients associated with loss of central va- rates of organ donation. tially had low CI with poor tissue perfu- soconstrictive mechanisms of the stress re- Methods: We studied 388 consecu- sion beginning shortly after emergency sponse resulted in unopposed peripheral tive noninvasively monitored patients with department admission. This was followed metabolic vasodilatation producing high severe head trauma; 79 of these became by a prolonged period characterized by CI and tissue perfusion. brain dead. Monitoring was started high CI (4.43 ؎ 1.3 L ⅐ min؊1 ⅐ m؊2) and Key Words: Cardiac output, Tissue shortly after admission to the emergency enhanced tissue oxygenation (PtcO2/FIO2 perfusion, Noninvasive hemodynamic mon- -department and was designed to describe 238 ؎ 186). In the late or end stage of itoring, Pulse oximetry, Temporal hemody the sequence of cardiac, pulmonary, and brain death, hemodynamic deterioration namic patterns in head injury, Therapeutic tissue perfusion functions by cardiac in- and collapse led rapidly to arrest. In at- responses in brain death. J Trauma. 2007;63:1032–1042.

he diagnosis of brain death and the ethical issues in head injury leading to brain death presents a unique oppor- organ donation have been extensively covered in the tunity to evaluate the circulatory physiology of brain death, Tliterature, but we were unable to find descriptions of particularly the effects of absent central vasoconstrictive hemodynamic and oxygen transport patterns in brain-dead mechanisms on the systemic circulation. patients. Because hemodynamic evaluations are useful for Previous studies of patients with head injuries have therapeutic decisions involving circulatory problems of crit- shown elevated CI, HR, and MAP.1–8 In a preliminary study, ically illness, they may also be appropriate for brain-dead we documented patterns of hypertension, tachycardia, inpatients whose circulation must be maintained for organ do- creased CI, and reduced tissue perfusion in severe head in- nation. Moreover, previous head injury series were small, juries, determined by the Glasgow Coma Scale (GCS),9 as consisting of less than 12 patients, and were focused primar- well as in nonsurviving patients with head injuries.10 The ily on mean arterial blood pressure (MAP), heart rate (HR), reduced peripheral tissue perfusion was manifested by low and isolated measurements of cardiac index (CI) along with PtcO2 values and PtcO2/FIO2 ratios compared with normative occasional blood gases. The present report of a large series of standards (normal: PtcO2 on room air 40–50 mm Hg, PtcO2/ FIO2 180–220). These tissue perfusion values were greater in the survivors than in the nonsurvivors, and greater in patients Submitted for publication February 9, 2006. with high GCS compared with those with low GCS, but Accepted for publication June 23, 2006. Copyright © 2007 by Lippincott Williams & Wilkins similar in isolated head injury compared with head injury 10 From the Departments of Surgery (H.B., W.C.S., C.C.J.W., T.V.B., D.D.), with somatic injury. Neurosurgery (J.P.G.), and Anesthesia (V.Z.), Los Angeles County ϩ University High intracranial pressure associated with edema from of Southern California Medical Center; and University of Southern Califor- closed head trauma of varying severity may interfere with nia School of Medicine (H.B., W.C.S., T.P.N., A.B.C.D., V.Z., J.P.G., cerebral perfusion and lead to ischemia, hypoxia, and hyper- T.V.B., D.D.), Los Angeles, California. Address for reprints: William C. Shoemaker, MD, Room 9610, carbia of the brain parenchyma. Hypercarbia activates central LACϩUSC Medical Center, 1200 N State Street, Los Angeles, CA 90033; nervous system pH and CO2-bicarbonate sensors that stimu- email: [email protected]. late the sympathetic nervous system as evidenced by in- DOI: 10.1097/01.ta.0000235995.86162.d2 creases in blood pressure (Cushing response), cardiac output,

1032 November 2007 Circulatory Patterns After Brain Death

11 and VO2 but with limited tachycardia. This response differs neck and one pair on each side of the lower chest at the level from the sympathetic response to hypercarbia produced by of the ziphi-sternal junction. Three electrocardiogram leads 21–23 high-inspired CO2 concentrations because HRs are not af- were placed across the precordium and shoulders. A fected by impaired blood flow from high intracranial pressure 100-kHz, 4-mA alternating current was passed through the or low cerebral perfusion pressure.12,13 patient’s thorax by the outer pairs of electrodes and the inner The physiologic response to head trauma consisted of pairs of electrodes measured the voltage difference. Baseline increased cardiac output and MAP when fluid resuscitation impedance (Zo) was calculated from the voltage changes was adequate. However, elevations of blood pressure with- sensed by the inner pairs of electrodes.23 out increased HR may occur in patients with cerebral CI, HR, pulse oximetry, transcutaneous O2 and CO2 hypoperfusion.11 Reduced peripheral tissue perfusion has tensions, and the fractional inspired oxygen concentration been documented by low transcutaneous oxygen tension (FIO2) were measured continuously and recorded at frequent (PtcO2) and increased carbon dioxide with exaggerated sym- intervals with the other hemodynamic measurements by an pathoadrenal vasoconstriction.14–20 interfaced personal computer.21–27 Flow-related variables Because previous hemodynamic studies on head injury were indexed to body surface area. consisted of small series of patients, the present study describes the time course of hemodynamic patterns in 388 Invasive Hemodynamic Monitoring severe head injuries. The sequential patterns of CI, MAP, HR, After the patients arrived in the operating room or the hemoglobin saturation by pulse oximetry (SapO2), PtcO2/FIO2, intensive care unit, pulmonary artery (PA) thermodilution and PtcCO2 were monitored shortly after emergency depart- (Swan-Ganz) catheter was placed in 97 patients on clinical ment (ED) admission. The sequential hemodynamic patterns indication to confirm the noninvasive cardiac output in brain-dead patients were evaluated separately, because monitoring.24,27 Arterial blood gas samples were taken at the their patterns were different. Finally, preliminary data on the time of the thermodilution measurements and immediately therapeutic effects of fluids were observed. analyzed to calculate oxygen delivery (DO2).

PATIENTS AND METHODS Blood Pressure Clinical Series Arterial blood pressures were measured with an automatic noninvasive system (Dinamap, Critikon, Tampa, FL) The temporal patterns of cardiac, respiratory, and tissue and recorded at frequent intervals simultaneously with other perfusion functions were noninvasively monitored shortly monitored values. after admission in 388 monitored patients with head injuries; 79 of these became brain-dead. Of the 309 patients who were Pulse Oximetry not brain-dead, 238 survived, whereas 71 died during their A standard pulse oximeter (Nellcor, Pleasanton, CA) current hospital course of sepsis, renal, or cardiorespiratory was used to measure continuously arterial blood oxygen failures. Continuous noninvasive hemodynamic monitoring saturation (SapO ). The sensor was placed on a finger in was started shortly after admission to the ED. Table 1 2 the routine fashion.27 Measurement were observed contin- details the clinical data of the survivors and nonsurvivors uously and recorded at frequent intervals simultaneously of head injury and compares these data with the data of with other monitored values. Appreciable or sudden those who became brain dead. All 79 of our brain-dead changes in these values were confirmed by arterial hemo- patients met the clinical criteria for brain death, i.e., evi- globin oxygen saturation obtained with the standard in dence of loss of brain stem and cerebral function before, or vitro blood gas analyses. during, the monitored period. Some of these brain-dead patients arrested shortly after they were pronounced brain- Transcutaneous O and CO Monitoring dead, but most were maintained for a limited period in a 2 2 PtcO was continuously monitored (Respironics Inc, relatively stable hemodynamic state by transfusions, flu- 2 Youngwood, PA). This system uses a Clark polarographic ids, and supportive therapy for organ donation. The pro- oxygen electrode routinely used in the standard in vitro tocol for monitoring was approved by the Institution blood gas analysis.17–20,27–30 Gel electrolyte was applied to Review Board. the sensor and the sensor was fixed by an adhesive ring to alcohol-prepped skin on the anterior chest wall or shoulder Monitoring Systems depending on area of injury and planned surgical proce- Noninvasive Cardiac Output Monitoring dures. Twenty minutes was allowed for equilibration after A thoracic bioelectric impedance device (IQ 101 System, application as recommended by the manufacturer before Noninvasive Medical Technologies, LLC, Las Vegas, NV) monitoring is begun. At 44°C the lipopolysaccharide layer was applied as soon as possible after admission to the ED. of the stratum corneum changes from a sol to a gel state, Four pairs of disposable prewired hydrogel electrodes were facilitating gas diffusion from the subepidermal tissue to positioned on the skin, one pair on each side at the base of the the sensor.28,29 This heating also inhibits local vasoconstric-

Volume 63 • Number 5 1033 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Table 1 Clinical Characteristics of Patients With Head Injuries Who are With and Without Brain Death

Head Injury Without Brain Death Brain Dead (N ϭ 79) Survivors (N ϭ 238) Nonsurvivors (N ϭ 71) Age (yr), mean Ϯ SD 49 Ϯ 21 40 Ϯ 20* 35 Ϯ 17 Males/females, n (%) 187 (78)/51 (22) 46 (65)/25 (35) 59 (75)/20 (25) Blunt trauma, n (%) 197 (83) 56 (79) 41 (52)† Falls, n (%) 22 (9) 8 (11) 7 (9) Gunshot wounds, n (%) 15 (6) 5 (7) 29 (36) Stab wounds, n (%) 4 (2) 2 (3) 2 (3) Isolate head injuries, n (%) 68 (29) 9 (13) 60 (76)† Associate somatic injuries, n (%) 170 (71) 62 (87) 19 (24) Glasgow Coma Scale, mean Ϯ SD, median (range) 9.2 Ϯ 4.4, 9 (3–15) 6.5 Ϯ 4.3*, 4 (3–14) 4.1 Ϯ 2.8†, 3 (3–15) Injury Severity Score, mean Ϯ SD, median (range) 22.8 Ϯ 13.1, 22 (1–75) 35.6 Ϯ 13.9*, 34 (8–75) 31 Ϯ 15.4, 26 (1–75)† * p Ͻ 0.01, unpaired Student’s t test comparing survivors vs. nonsurvivors. † p Ͻ 0.01 using ␹2 test. ‡ p Ͻ 0.01 unpaired Student’s t test comparing nonsurvivors vs. brain-dead patients.

Table 2 Hemodynamic Values of 309 Patients With Head Injuries Who Did Not Become Brain Dead

Normal Survivors (N ϭ 238), Nonsurvivors (N ϭ 71), Variable Values Mean Ϯ SD Mean Ϯ SD CI (L ⅐ minϪ1 ⅐ mϪ2) 3.1 Ϯ 0.17 3.92 Ϯ 1.35 3.62 Ϯ 1.24* MAP (mm Hg) 84 Ϯ 486Ϯ 16 81 Ϯ 24† HR (beat/min) 72 Ϯ 3 103 Ϯ 21 108 Ϯ 24† Ϯ Ϯ Ϯ SapO2 (%) 98 1983977 Ϯ Ϯ Ϯ † PtcCO2 (mm Hg) 43 34416 49 21 Ϯ Ϯ Ϯ † PtcO2/FIO2 200 14 215 136 132 106 * p Ͻ 0.05 for survivors vs. nonsurvivors of head injury. † p Ͻ 0.01 for survivors vs. nonsurvivors of head injury.

CI, cardiac index; MAP, mean arterial pressure; HR, heart rate; SapO2, arterial hemoglobin saturation by pulse oximetry; PtcCO2, transcutaneous carbon dioxide tension; PtcO2/FIO2, transcutaneous oxygen tension indexed to FIO2.

Table 3 Mean Values ؎ SD for Monitored Variables: Baseline at the Time of Diagnosis of Brain Death, During Brain Death, and at the Terminal Hemodynamic Stage

Baseline Brain Death During Brain Death Terminal Stage Variable (N ϭ 21)* 1.3 Ϯ 1.7 h† (N ϭ 87) 4.9 Ϯ 2.4 h (N ϭ 9) 1.3 Ϯ 1.6 h CI (L ⅐ minϪ1 ⅐ mϪ2) 3.19 Ϯ 1.26 4.43 Ϯ 1.33 1.76 Ϯ 1.10 HR (beats/min) 119 Ϯ 29 113 Ϯ 23 126 Ϯ 28 MAP (mm Hg) 71 Ϯ 23 89 Ϯ 22 61 Ϯ 16 Ϯ Ϯ Ϯ SapO2 (%) 98 39938621 Ϯ Ϯ Ϯ PtcCO2, (mm Hg) 54 24 40 15 59 33 Ϯ Ϯ Ϯ PtcO2/FIO2 103 86 238 186 70 53 ⅐ Ϫ1 ⅐ Ϫ2 Ϯ Ϯ Ϯ DO2, (mL min m ) 399 152 738 185 283 108 * Number of patients in each group. † Mean Ϯ SD hours of continuous monitoring. tion at the site of measurement. To avoid electrode-induced was monitored with the standard Stowe-Severinghaus first-degree skin burns; the sensor was recalibrated and electrode.31,32 replaced at an adjacent area of skin in the same general area every 4 hours. The PtcO2 values were monitored Experimental Design and Protocol continuously, indexed to FIO2, expressed as PtcO2/FIO2, and Continuous noninvasive hemodynamic monitoring recorded by an interfaced personal computer. Previous was begun, when possible, shortly after ED admission. CI, O studies demonstrated the ability of Ptc 2 to measure tissue MAP, HR, SapO2, PtcO2, and PtcCO2 were monitored con- 17–20 oxygen tension. PtcO2 values were found to parallel tinuously. GCS was obtained at the time of admission for the mixed venous oxygen tension under controlled experi- each patient by the ED and trauma surgery team assess- 17 mental conditions. Transcutaneous carbon dioxide (PtcCO2) ments. The CI was also measured by thermodilution at

1034 November 2007 Circulatory Patterns After Brain Death

4 CI 3

2 140 120 100 HR 80 60 120 100 80 MAP 60 40 100

2 95

SapO 90

85 300 2 200 /FIO 2 100 PtcO 0 1 246 8 12 16 20 24 36 48 TIME (hours) Survivors Nonsurvivors

Fig. 1. Hemodynamic patterns for CI, HR, MAP, SapO2, PtcCO2, and PtcO2/FIO2 of head injury survivors (solid line) and nonsurvivors (dashed line) during the first 48 hours after ED admission. The survivors generally have higher CI, SapO2, and PtcO2/FIO2 than do the nonsurvivors. intervals and recorded; arterial blood gas values were RESULTS obtained at the time of the CI measurements and used to Patients With Head Injuries calculate DO2. CI by thermodilution was occasionally used to Table 2 summarizes the hemodynamic and oxygen trans- confirm the noninvasive measurements. Previous studies docu- port values of 238 survivors and 71 nonsurvivors of head injury, mented satisfactory correlation between thermodilution and bio- compared with values of normal, healthy, resting volunteer 24–27 impedance CI values. subjects.27 Not included in Table 2 are data of patients during Data from each of the 79 brain-dead patients were times of brain death. The survivors’ hemodynamic patterns had analyzed to describe and evaluate the hemodynamic pat- significantly higher CI, MAP, SapO2, and PtcO2/FIO2 values than terns. The patterns of brain-dead patients were compared did the nonsurvivors. The nonsurvivors had relatively normal SAO2 with normal values27 and those of the 309 noninvasively with low PtcO2/FIO2 and high PtcCO2 values, which were consis- monitored head injuries who were not brain-dead (Tables tent with the concept of increased arteriolar-venous shunting. 2 and 3, and Figs. 1 and 2). PA catheters were placed in 21 nonsurviving and 44 surviving patients with head injuries. In 185 paired thermodilution Statistical Analysis and bioimpedance measurements the correlation coefficient, r ϭ Mean values and SD were calculated for each variable 0.94, r2 ϭ 0.89. at comparable times after ED admission. Evaluation of data sets obtained under comparable temporal conditions was evaluated using the two-tailed Student’s t test and the Brain-Dead Patients Mann-Whitney U test. We used GraphPad Prism software Table 3 lists hemodynamic and oxygen transport values (GraphPad Software, Inc., San Diego, CA) for these cal- (mean Ϯ SD) of the 79 brain-dead patients for three periods: (1) culations. Differences were considered significant at prob- the baseline period at, or just before, the time of brain death ability values Ͻ0.05. diagnosis, (2) the main period of brain death after its diagnosis,

Volume 63 • Number 5 1035 The Journal of TRAUMA௡ Injury, Infection, and Critical Care 2 SapO 2 PtcCO 2 /FIO 2 PtcO

Ϯ Fig. 2. Mean SEM values for CI, HR, MAP, SapO2, PtcCO2, and PtcO2/FIO2 at the baseline time of brain death diagnosis, during brain death, and in the terminal hemodynamic collapse. The thin horizontal line represents the upper limit of the normal range. Initially, the CI, MAP, and PtcO2/FIO2 values were low, whereas HR was higher than normal. During brain death, CI and PtcO2/FIO2 values increased markedly. The terminal state began with a general decline of monitored parameters, except HR and PtcCO2, leading to sudden hemodynamic collapse. and (3) the terminal hemodynamic end stage just before circu- brain death. Initially, there was hypotension that usually re- latory collapse and arrest. The patterns are more clearly evident sponded to fluid and supportive therapy and there were episodic in the flow and tissue perfusion parameters, than in blood pres- elevations of CI and PtcO2/FIO2 values (Table 4). PA catheters sure and HR. The significant findings during the major time of were placed in 32 brain-dead patients and in 91 paired thermodi- brain death were increased CI, PtcO2/FIO2, and DO2 values. The lution and bioimpedance measurements, the correlation coeffi- ϭ 2 ϭ low PtcO2/FIO2 and high PtcCO2 values became normal during cient, r 0.93, r 0.87.

1036 November 2007 Circulatory Patterns After Brain Death

Table 4 Episodes of High and Low Values and Percent of Time These Abnormalities Lasted in Brain-Dead Patients

Low Percent High Percent Cardiac index (L ⅐ minϪ1 ⅐ mϪ2) 2.07 Ϯ 0.34 7 5.64 Ϯ 1.17 42 Heart rate (beats/min) 58 Ϯ 8 1 173 Ϯ 12 31 Mean arterial pressure (mm Hg) 37 Ϯ 4 2 135 Ϯ 15 6 Ϯ Ϯ PtcO2/FIO2 (mm Hg) 66 37 30 352 192 47 Ϯ PtcCO2 (mm Hg) — — 74 14 15 Oxygen delivery (mL ⅐ minϪ1 ⅐ mϪ2) 324 Ϯ 76 7 951 Ϯ 215 40

Fig. 3. Illustrative example of a 25-year-old man who sustained a gunshot wound of his head and chest; the GCS score was 4, and the

ISS 26. The CI, HR, MAP, and PtcO2/FIO2 values are shown for the periods before and after the diagnosis of brain death, indicated by the first vertical fine line. His hemodynamic values began to deteriorate, indicated by the second vertical line, and led to hemodynamic collapse with cardiopulmonary arrest immediately after the last values were taken.

Hemodynamic Patterns of Brain-Dead Patients PtcO2/FIO2, and PtcCO2 values than did non–brain-dead survivors Compared With Survivors and Non–Brain-Dead with head injuries and nonsurvivors (Tables 2 and 3). There

Nonsurvivors of Head Injury were transient reductions in SapO2 in only nine of the brain-dead There were higher CI and PtcO2/FIO2 values in the brain- patients. Two, who were in the initial stage, responded to in- dead patients compared with the surviving patients with head creased FIO2, and seven who were in the terminal stage, failed injuries. In general, the brain-dead patients had higher CI, HR, to respond and continued on their downhill course.

Volume 63 • Number 5 1037 The Journal of TRAUMA௡ Injury, Infection, and Critical Care 2 SapO 2 PtcCO 2 /FIO 2 PtcO

Fig. 4. Case example of a 31-year-old man who sustained a gunshot to his forehead with subdural hematoma, GCS score of 3, and ISS of

16. He was pronounced brain-dead. The CI (upper section), HR, MAP, SapO2, PtcCO2, and PtcO2/FIO2 (lowest section) values show episodes ⅐ Ϫ1 ⅐ Ϫ2 ⅐ Ϫ1 ⅐ Ϫ2 of very high CI varying from 6 L min m to8L min m and very high PtcO2/FIO2 ratios varying from 400 to 900 (normal 185–225). The thin horizontal lines represent the upper limit of the normal range.

Temporal Patterns of Hemodynamic and Oxygen death. Table 4 shows the increased values found during these Transport Data in Brain-Dead Patients episodes and the percentage of time during monitored periods The patients with head injuries, who subsequently be- that these episodes occurred. Figure 3 illustrates the data of a came brain dead, started from a baseline hemodynamic pat- patient with head injuries before the diagnosis of brain death, tern of low CI, MAP, and PtcO2/FIO2 (Table 2, Figs. 3 and 4). during the period of brain death with increased hemodynamic After brain death became clinically established, the CI, HR, values, and during the terminal stage of circulatory deterio-

PtcCO2, and PtcO2/FIO2 were higher than normal and remained ration and arrest. Figure 4 shows the data of a patient in a high until the final period of hemodynamic collapse and prolonged period of brain death with CI values varying be- ⅐ Ϫ1 ⅐ Ϫ2 ⅐ Ϫ1 ⅐ Ϫ2 arrest. tween 5 L min m and9L min m and PtcO2/ The high CI with increased tissue oxygenation, measured FIO2 values between 400 mm Hg and 900 mm Hg. by PtcO2/FIO2, was the principal distinguishing pattern in brain death. This striking but unanticipated finding was ob- Terminal Hemodynamic Deterioration Leading to served in each brain-dead patient. Cardiopulmonary Arrest Inspection of the data of individual patients also revealed The terminal stage of brain death was characterized by multiple and sometimes prolonged episodes of increased CI, rapidly decreasing CI, MAP, SapO2, and PtcO2/FIO2 leading to HR, MAP, and PtcO2/FIO2 values during the period of brain cardiopulmonary arrest. The PtcO2/FIO2 values were the first

1038 November 2007 Circulatory Patterns After Brain Death

6.00 5.00 4.00

CI 3.00 2.00 1.00 0.00 170 160 150 140

HR 130 120 110 100 200

150

100 MAP 50

0 100 80

2 60 40 SapO 20 0 80

60 2 40

PtcCO 20

0 250

2 200 150 /FIO 2 100

PtcO 50 Somatic Death 0 -7 -6 -5 -4 -3 -2 -1 0 TIME (hour) Fig. 5. Illustrative example of a 47-year-old woman who sustained head injury with intracerebral hemorrhage from motor vehicle crash; the

GCS score was 3. She was declared brain-dead just before monitoring began. Data represent CI (upper section), HR, MAP, SapO2, and

PtcO2/FIO2 (lowest section) values, and show high PtcO2/FIO2 values in the brain death period, and the final hemodynamic collapse with arrest at the end of the monitoring period. to decrease; then the other hemodynamic parameters fell of 1,000 mL crystalloids (lactated Ringer’s solution or sa- during the patients’ circulatory collapse and arrest (Fig. 5). line), 500 mL colloids (fresh frozen plasma, 5% albumin, or 6% hydroxyethyl starch), or 1 unit of packed red cells. The Effects of Therapy in Brain-Dead Patients therapeutic objective was to maintain circulatory stability by The effects of fluid therapies were observed in many of fluids rather than vasopressors. these patients when the agent could be given one at a time Dopamine given to six normovolemic patients led to with measurements obtained in a baseline period before the mild hemodynamic improvement (Table 5). However, Figure agent was administered and at the end of the infusion. He- 6 shows the dramatic effect of a 5 ␮g ⅐ kgϪ1 ⅐ minϪ1 dose of modynamic values were maintained close to their normal dopamine on tissue oxygenation in a hypovolemic patient. range by fluids and supportive therapy to maintain circulatory The PtcO2/FIO2 fell from over 400 mm Hg to less than 50 mm stability for organ donation. Table 5 summarizes the effects Hg, MAP fell from 60 mm Hg to 33 mm Hg, and CI de-

Volume 63 • Number 5 1039 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

of central vasoconstrictive mechanisms, produce peripheral Table 5 Effects of Therapy vasodilatation that increases CI and tissue oxygenation. Baseline After Catecholamine effects immediately after trauma include Crystalloids, 1,000 mL (N ϭ 59) increased blood pressure, HR, cardiac contractility, minute CI (L ⅐ minϪ1 ⅐ mϪ1) 3.86 Ϯ 1.28 4.33 Ϯ 1.38* ventilation, and peripheral vasomotor tone. These adaptive † HR (beat/min) 125 Ϯ 26 122 Ϯ 25 effects are usually beneficial, but exaggerated uneven vaso- MAP (mm Hg) 80 Ϯ 24 81 Ϯ 23 Ϯ Ϯ constriction leads to unevenly distributed microcirculatory SapO2 (%) 99 3994 Ϯ Ϯ flow with localized areas of hypoperfusion, hypovolemia, and PtcCO2 (mm Hg) 41 18 40 15 Ϯ Ϯ † 12,27,28 PtcO2/FIO2 (mm Hg) 189 153 203 168 tissue hypoxia. Colloids, 500 mL (N ϭ 48) The brain-dead patients’ unique pattern of high cardiac Ϫ1 Ϫ1 CI (L ⅐ min ⅐ m ) 4.81 Ϯ 1.95 5.27 Ϯ 2.09* output and tissue oxygenation may represent a state in which HR (beat/min) 120 Ϯ 24 125 Ϯ 22 MAP (mm Hg) 77 Ϯ 21 85 Ϯ 24* neurally mediated inhibitory hemodynamic influences are lost Ϯ Ϯ and other non-neurally mediated mechanisms such as unop- SapO2 (%) 99 1993 Ϯ Ϯ PtcCO2 (mm Hg) 47 22 42 18 posed peripheral vasodilation, the renin-angiotensin-aldosterone Ϯ Ϯ PtcO2/FIO2 (mm Hg) 222 186 233 189 axis, or the effects of therapy may predominate. Possible expla- Packed red cells, 1 unit (N ϭ 23) nations for the brain-dead patient’s responses include (1) loss of CI (L ⅐ minϪ1 ⅐ mϪ1) 4.71 Ϯ 1.64 5.04 Ϯ 1.65† HR (beat/min) 120 Ϯ 21 118 Ϯ 22 inhibitory functions of the central cardiorespiratory centers from MAP (mm Hg) 78 Ϯ 22 84 Ϯ 19 insufficient DO2 to the brain stem; (2) overactive, erratic, and Ϯ Ϯ SapO2 (%) 99 1983 marginally functional central cardiorespiratory centers; or (3) Ϯ Ϯ PtcCO2 (mm Hg) 48 22 48 21 greater therapeutic responsiveness in brain-dead patients than PtcO /FIO (mm Hg) 145 Ϯ 183 154 Ϯ 208 2 2 those with normally functioning brains. * p Ͻ 0.01 using paired Student’s t test. It should not be expected that mechanisms mediated by † p Ͻ 0.05 using paired Student’s t test. the CNS operate predictably in brain death.10 Erratic or un- expected behavior of these regulatory mechanisms may result creased from 3.5 L ⅐ minϪ1 ⅐ mϪ2 to 3.0 L ⅐ minϪ1 ⅐ mϪ2. from (1) primary damage to areas of the brain; (2) cerebral Similar sensitivity to vasopressors have been noted in dener- hypoxia caused by hypovolemia, systemic hypotension, low vated limbs suggesting that vasopressors should be avoided cerebral perfusion pressure; (3) regional hypoperfusion; or for maintaining MAP in the presence of hypovolemia. (4) secondary injury from cerebral edema, hemorrhage, or inflammation. With damage or dysfunction of the areas that regulate hemodynamic function, ineffective, inappropriate, DISCUSSION exaggerated, or uncontrolled attempts by malfunctioning response systems or failure of central inhibitory mechanisms The hemodynamic patterns in head injuries began with may produce hemodynamic deviations from the normal, in- a baseline of normal or low CI and reduced tissue perfu- cluding those that can be maladaptive or detrimental to re- sion, but with the onset of brain death these patterns covery. These include the episodic increases in CI and tissue changed to high CI with high tissue perfusion or oxygen- perfusion as determined by PtcO2/FIO2 values as well as coun- ation values. terintuitively muted patterns seen with severe head injuries. After head injury, the initial circulatory findings of nor- The inability of some brain-dead patients to respond mal or low flow and tissue perfusion values may be explained appropriately may require different therapeutic approaches as by circulatory responses to blood loss, tissue injury, pain, and the conventional parameters of MAP and HR may not be fear, which activate the sympathoadrenal axis, releasing epi- sufficiently sensitive to serve as guides to therapy. The use of nephrine and norepinephrine from the adrenal medulla and noninvasive hemodynamic monitoring for the measurement 33–38 sympathetic effector-neurons. These sympathetic stress of cardiac output and tissue perfusion beginning in the ED responses initially tend to increase cardiac output but may be provides early recognition of flow and perfusion deficiencies. limited by hypovolemia, exhaustion of the stress response, or More importantly, they provide criteria for selection of ther- direct injury to the central regulatory centers of the brain. apeutic modalities as well as for guides to titrate therapy to Evidence of sympathoadrenal axis activation by assay of achieve goals consistent with the short-term survival needed urinary catecholamines after trauma and with hypercarbia has for organ donation. been well-documented.12,16,33,34 A major limitation of this study is the timing of brain After brain death, the abrupt change to high flow and death, which is a clinical diagnosis based on the opinions of enhanced tissue oxygenation may be explained by the ab- two physicians not associated with the case, and who may or sence of central vasomotor regulation from brain death that may not be available immediately and may significantly de- leaves unopposed peripheral vasodilatory influences from lay the diagnosis. Further studies are necessary to elucidate local accumulation of CO2, hydrogen ions, and lactic acid in temporal relationships between head injury, brain death, and the peripheral tissues. These local influences, in the absence the underlying hemodynamic mechanisms.

1040 November 2007 Circulatory Patterns After Brain Death

Dopamine µg/kg/min Prbc 2 units ␮ ⅐ Ϫ1 ⅐ Ϫ1 Fig. 6. An example of the effect of dopamine 5 g kg min on a brain-dead patient with high PtcO2/FIO2 and evidence suggestive of hypovolemia. The sudden pronounced deterioration in PtcO2/FIO2 from over 400 mm Hg to less than 50 mm Hg with lesser reductions in CI and MAP, and increased PtcCO2 after the onset of dopamine infusion.

Therapy for brain-dead patients awaiting organ donations The therapeutic goals in brain-dead patients with head in- may differ from that of other late stage trauma patients who may juries are to maintain cardiac, pulmonary, and tissue perfusion have low flow, hypotension, and poor tissue perfusion that functions until organ donation can be accomplished. These were require circulatory resuscitation with transfusions, fluids, and not the goals of high-risk surgical and trauma patients where vasopressors. The hypotension of brain death is more often hemodynamic optimization was shown to improve outcome if caused by the absence of central vasoconstriction than hypovo- performed early, but not if performed late.39–45 In the conven- lemia, particularly when CI and tissue perfusion are higher than tional approach to head injuries, fluid therapy may be limited by normal. Of course, transfusions and fluids are indicated for low intracranial pressure.46–49 However, brain-dead patients had flow and poor tissue perfusion. Mild hypotension, which is mild hypotension presumably from the absence of central vaso- characteristic of brain-dead patients (Table 3), is tolerated if constriction and this was associated with high CI and PtcO2/FIO2. accompanied by high flow and tissue perfusion. Severe hypo- If this hypotension is misinterpreted as hypovolemic shock, and tension (MAP Ͻ60 mm Hg) associated with hypovolemia and dopamine is given, an adverse circulatory response may occur. low flow should be treated with transfusions and fluids. However, mild hypotension should not be overtreated with REFERENCES vasopressor therapy, because in the presence of hypovolemia, 1. Brown RS, Mohr PA, Carey JS, Shoemaker WC. Cardiovascular changes after cranial cerebral injury and increased intracranial vasopressors may lead to circulatory deterioration (Fig. 6). Pro- pressure. Surg Gynecol Obstet. 1967;125:1205–1211. spective studies are needed to evaluate the relative effectiveness 2. Brown RS, Shoemaker WC. Sequential hemodynamic changes in of various therapies when organ donation is desired. patients with head injury. Ann Surg. 1973;177:187–192.

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1042 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Treatment Strategies for Complex Fractures of the Tibial Plateau With External Circular Fixation and Limited Internal Fixation Maurizio A. Catagni, MD, Giulia Ottaviani, MD, PhD, and Massimiliano Maggioni, MD

Background: We intended to evalu- were used: (1) the frame is confined to the Results: The results were evaluated ate the technique of treatment of complex tibia when the external fixation is stable as excellent in 30 patients (50.85%), good fractures of the tibial plateau using exter- enough to allow knee bending; (2) the frame in 27 patients (45.76%), fair in 1 patient nal circular fixation combined with lim- is extended onto the distal femur, with the (1.695%), and poor in another 1 (1.695%). ited internal fixation, and to evaluate the proximal tibial ring located at the level of The patients’ satisfaction was significantly treatment outcomes. the tibial plateau when the joint surface is related with the functional results. Methods: From 1992 to 2002, we severely unstable; and (3) the frame is ex- Conclusions: Our hybrid Ilizarov treated 59 patients (40 men, 19 women) tended onto the distal femur, with the method combined with minimal internal fix- ranging in age from 23 to 63 years with the proximal tibial ring located more distally, ation enables excellent to good results in external circular fixation. All the cases were bypassing the fracture, when the skin and most cases of complex tibial plateau fractures. classified preoperatively as Schatzker types soft tissue are compromised and within Key Words: Complex tibial plateau V, VI/Orthopedic Trauma Association 41- the fracture there is no bone suitable to fractures, Schatzker types V and VI, C1.3, C2.3, C3.1, C3.3. Five fractures were place wires and pins for the external fix- Ilizarov method, Circular external fixa- open. Three different strategies of treatment ation construct. tion, Limited internal fixation. J Trauma. 2007;63:1043–1053.

omplex fractures of the tibial plateau, types V and VI invasiveness because of the additional trauma caused by according to the Schatzker classification,1 are difficult operative soft tissue stripping and dissection.10,17 Medial and Cto treat and represent one of the most challenging prob- lateral plate stabilization of comminuted bicondylar tibial lems in orthopedic surgery. To achieve good results, the plateau fractures with dual incisions is a useful treatment fractures should be anatomically reduced and adequately sta- method; however, residual dysfunction is common.9 External bilized, but the optimal treatment of complex proximal tibial fixation has been gaining increasing interest and application fractures has remained controversial.2–17 Nonoperative mea- during the past 20 years,2,4,6,8,12–14,18,19 to decrease the rate of sures such as closed reduction and casting have yielded poor complications related with plating.1,10,17 The external circular results and are not recommended for complex fractures of the fixator, originally introduced by Ilizarov,20 is being widely tibial plateau.8,9 used today in the management of open fractures, multiple Methods of acute open reduction and internal fixation closed and comminuted fractures, pseudoarthrosis, and in the with plates and screws of complex fractures of the tibial correction of various contractures and deformities. The Ilizarov plateau have an high rate of complications, mainly infections, frame has undergone several modifications over the years with posttraumatic deformities, inability to obtain a reduction, the purpose to decrease both complications and the time required wound breakdown, poor outcome despite articular reduction for treatment.8,21,22 because of stiffness, pain, deformity, wound problems, insta- Although current research focuses on devices and tech- 1,16 bility, and soft tissue problems. The major concern is their niques to increase the mechanical stability of the Ilizarov implant bone construct,3,23 and provide more biocompatibil- Preliminary results have been reported in abstract form at World ity and stability to metal-bone interface,24 there is little agree- Congress on External Fixation; May 26–28, 2005; Lima, Peru`. Abstract n. ment in the literature about which type of external fixators WC352EF. should be used for the treatment of complex fractures of the Submitted for publication February 11, 2007. 3,5,6–8,13,15,20,23 Accepted for publication May 21, 2007. tibial plateau. Copyright © 2007 by Lippincott Williams & Wilkins The purpose of this study is to evaluate the technique of From the Association for the Study and Application of the Method of treatment of complex fractures of the tibial plateau (Schatzker Ilizarov (ASAMI) (M.A.C., M.M.); Department of Orthopedics and Ilizarov types V, VI/Orthopedic Trauma Association [OTA] 41-C1.3, Unit (M.A.C., M.M.), “Alessandro Manzoni” Hospital, Lecco; and Institute C2.3, C3.1, C3.3) using the circular Ilizarov fixation modi- of Pathology (G.O.), University of Milan, Italy. 8,21,22,25–29 Address for reprints: Maurizio A. Catagni, MD, Department of Ortho- fied by Catagni and Cattaneo combined with lim- paedics and Ilizarov Unit, “Alessandro Manzoni” Hospital, Via dell’Eremo ited internal fixation, as well as to evaluate the treatment 9/11, 23900 Lecco, Italy; email: [email protected]. outcomes according to the herein newly introduced scoring DOI: 10.1097/TA.0b013e3181238d88 criteria of the Association for the Study and Application of

Volume 63 • Number 5 1043 The Journal of TRAUMA௡ Injury, Infection, and Critical Care the Method of Ilizarov (ASAMI) Italy. We questioned if this Table 1 Preoperative Classification of the 59 Patients method would be a preferable treatment option compared With Complex Fractures of the Tibial Plateau According with other treatments, in particular other types of external to the Schatzker1 and AO/OTA30 Classifications fixations described in similar cases. Preliminary results had been previously reported in abstract form.18 Schatzker Orthopaedic Trauma Association Classification Classification PATIENTS AND METHODS V VI C1.3 C2.3 C3.1 C3.3 Patients N 20392117183 From 1992 through 2002, 59 consecutive patients (40 Total 59 59 men, 19 women), ranging in age from 23 to 63 years, with complex tibial plateau fractures were treated using the circular Among the 59 cases, 39 (66.10%) fractures were isolated external fixation devised by Catagni and Cattaneo.8,21,22,25–29 to the tibial plateau, 12 (20.34%) extended beyond to the Most of the patients sustained high energy trauma with se- metaphysis, diaphysis, and tibial pilon, eight (13.56%) were verely compromised soft tissues in association with multiple concomitant to ipsilateral femoral fractures. Five (8.47%) injuries. The mechanisms of fracture were as follows: 69.49% fractures were open, types II (one case) and III (four cases) of cases were caused by traffic crash, 27.12% of cases were according to the Gustilo classification.31 The soft tissue in- because of falls from a height, and 3.39% of cases were juries in closed fractures were classified according to the caused by sport injury. We retrospectively reviewed their Tscherne classification.32 medical records and radiographs. Details such as patients’ age, sex, injury severity, type of fracture, whether the fracture Surgical Interventions and Treatment Strategies was closed or open, length of the segment, method of fixa- All the 59 patients were treated by the first author with an tion, incidence of delayed union, the time to union, necessity hybrid Ilizarov fixator, a modification of the classic Ilizarov for additional procedures, complications, and hospital stay technique20 combining Kirschner wires with half-pins and were recorded. full rings, half-rings with proximal arches, as previously At the time of hospital admission, all patients underwent devised by Catagni and Cattaneo8,21,22,25–29 (Figs. 1 and 2). thorough clinical and radiographic evaluation to assess fully Based on the severity of the trauma and soft tissue their injuries. A computerized axial tomography scan was compromise,1,30–32 40 patients (67.79%) underwent limited obtained to assess the degree of damage to the articular open reduction with temporary wires or screws, 10 (16.95%) surface, the size and orientation of the fracture fragments. patients underwent closed reduction by ligamentotaxis (calca- neal traction), and 9 (15.25%) patients underwent extended open Classification of Tibial Plateau Fractures reduction with screw fixation according to the AO technique.33 Schatzker Classification All fractures were stabilized with the technique of hybrid The cases were classified according to the gravity of the Ilizarov frame, with three strategies of treatment. The decision to fractures proposed by Schatzker et al.1 in 1979, describing six apply each strategy was based not only on the complexity of types of fractures of the tibial plateau: type I, pure cleavage fracture, but also on the severity of the soft tissue injury. fracture; type II, cleavage fracture combined with depression; First strategy of treatment. The preassembled frame is type III, pure central depression; type IV, fracture of medial confined to the tibia and the external fixation is stable enough condyle–split off as a single wedge or comminuted and de- to allow knee bending. The preassembled tibial frame con- pressed; type V, bicondylar fracture; type VI, plateau fracture sisted of three-sized rings. The proximal ring was placed at with dissociation of the tibial metaphysis and diaphysis. We the level of fibular head. Another ring was placed approxi- selected for this study only complex fractures, classified as mately 2 cm to 3 cm proximal to the ankle joint. The last ring Schatzker types V and VI, resulting from high-energy trauma was placed 2 cm to 3 cm distally to the fracture. To centralize with soft tissue compromise. Twenty (33.90%) Schatzker frame on every ring, wires were attached, through the tibia, type V fractures and 39 (66.10%) type VI fractures were transversely and perpendicular to the long axis of the tibia, or recorded (Table 1). parallel to the ankle or knee joint. Distally the frame was strengthened with two wires. A 5-mm half-pin was inserted AO/OTA Classification System on intermediate ring from anteromedial to posterolateral. The The cases were classified according to the gravity of the frame was strengthened by two half-pins proximally; one from fractures proposed by the AO/OTA classification, describing anteromedial to posterolateral, and the second from anterolateral for the 41 ϭ proximal tibia, the groups A ϭ extra-articular, to posteromedial (Figs. 1A and B, 2A, 3, and 4).8 Additional B ϭ partial articular, C ϭ complete articular, subdivided into application of hinges allowed progressive angulation to cor- the 1, 2, 3 subgroups.30 According to the AO/OTA system,30 rect deformity of the fractured tibia whenever deemed nec- there were 21 (35.59%) type 41-C1.3 fractures, 17 (28.81%) essary (Fig. 4). type 41-C2.3 fractures, and 21 (35.59%) type 41-C3 (18 C3.1 In case of extremely complex and unstable fractures, and 3 C3.3) fractures (Table 1). we extended the frame onto the distal femur with two

1044 November 2007 Complex Tibial Plateau Fractures

Fig. 1. Diagrammatic representations of a standard assemblies to treat complex tibial plateau fractures. (A) A diagram for serial insertion of wires and half-pins in Hybrid advanced system associated with internal osteosynthesis is shown: 1 ϭ open reduction, 2 ϭ centralization, 3 ϭ reduction, and 4 ϭ fixation. (B) Three-rings assembly for tibial plateau fracture. The number of wires and the position of olive wires depend upon the type of fracture. The frame is strengthened by three half-pins (strategy 1). (C) Assembly for tibial plateau fracture with extension to the femur. The femoral assembly consists of a distal ring and a proximal arch (strategy 2). (D) Detail of the knee assembly. The tibial and femoral rings are connected with hinges in line with the knee as center of rotation. The frame allows distraction of the knee joint to avoid compression and subsequent displacement of the fracture (strategy 2). (E) Frame extended onto the distal femur, with the proximal tibial ring located more distally, bypassing the fracture and the compromised soft tissue (strategy 3). levels of fixation. The femoral assembly consisted of a at the level of the tibial plateau (Figs. 1C and D, 2B, and ring distally and a proximal arch. Distally the frame was 5). The femoral frame was removed after 30 to 60 days, centralized by a wire through the mechanical axis of femur followed by the removal of the tibial one at variable and two half-pins. Proximally the frame was fixed by two intervals. or three half-pins. The tibial and femoral rings were con- Third strategy of treatment. When the skin and soft nected with connecting bars and hinges placed at the level tissue were compromised, the proximal tibial ring was placed of knee’s center of rotation (Fig. 1, C–E).8,21,25–29 The more distally, bypassing the fracture, as the skin and soft knee hinges were locked or left loose as needed. The tissue were suffering and there was no place for wire and pins identification of the knee’s center of rotation, which varies in the fractured tibial plateau (Figs. 1E, 2C, and 6). with the knee flexion angle, was determined on lateral X-ray films as the intersection of the posterior cortical line of the femur and the Blumensaat line (parallel to the roof Postoperative Regimen and Follow-Up of the intercondylar notch). The hinges allowed an early Early knee motion and partial weight bearing were en- knee motion, which was gradually increased as tolerated; couraged postoperatively. Patients with knee bridging were they did not allow a range of motion (ROM) greater than allowed an immediate weight bearing of 20 kg to 30 kg, as 40 degrees. In complex cases with severe comminution of the fracture is stabilized and the load is bypassed by the the tibial metaphysis, the Ilizarov frame allowed to distract external fixator, with the possibility of a controlled joint the knee joint (ligamentotaxis), to avoid compression and motion through the hinges. In patients without knee bridging, subsequent displacement of the fracture. the weight bearing starts with 10 kg and, based on the clinical Second strategy of treatment. In cases with severely and radiographic signs of healing, generally advances to 25 unstable joint surface, the proximal tibial ring was located kg to 30 kg after one month. In all cases, the weight bearing

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score given by the physician and the patient during the follow-up, the outcome was classified as poor (score Ͻ59), fair (score ϭ59–69), good (score ϭ 70–79), and excellent (score ϭ 80–90). The patients’ satisfaction was evaluated through an in- terview in which they subjectively reported their level of satisfaction (from full satisfaction to dissatisfaction) (Table 2). We investigated the subjective effects of the tibial plateau fracture, 1 year after its occurrence, on the patients’ physical and emotional health as well as on their health-related quality of life. The patients’ level of satisfaction was assessed by asking them (1) how they felt after the surgical procedure compared with that they felt before the operation; (2) if they would go through the procedure again; and (3) if they would recommend it to other people who sustained a similar fracture. The first author or someone under his direct supervision observed all the clinical and radiographic measures. RESULTS Fig. 2. Three different strategies to treat a complex fracture of the A total of 59 patients (40 men, 19 women) with complex tibial plateau: (A) First strategy, the preassembled frame is con- tibial plateau fractures (Schatzker types V–VI)1 were in- fined to the tibia when the external fixation is stable enough to allow cluded in this study. All cases were documented according to knee bending. This is a diagram of the standard three-ring assembly clinical and radiographic aspects (Figs. 3–6). The average for tibial plateau fracture. The number of wires depends upon the age of patients was 43 (range, 23–63 years). In 40 (67.79%) type of fracture; the frame is strengthened by three half-pins. (B) cases with extremely complex and unstable fracture, the Second strategy, the frame is extended onto the distal femur, with the frame was extended to the distal femur and connected to tibial proximal tibial ring located at the level of the tibial plateau when the frame with hinges (Figs. 1C–E, and 2B and C). All fractures joint surface is severely unstable. (C) Third strategy, the frame is healed, with an average time of treatment with the frame of extended onto the distal femur, with the proximal tibial ring located 115 days (range, 65–153 days), without significant differ- more distally, bypassing the fracture, when the skin and soft tissue ences among the three strategies of treatment. The patients are compromised and within the fracture there is no bone suitable for were evaluated with an average follow-up after frame re- the placement of wires and pins for the external fixation construct. moval of 21 months (range, 11–60 months). Prophylactic antibiotics were administered intravenously is allowed by incremental progression as subjectively toler- in all cases. In the open fracture cases, antibiotics were ated up to full weight bearing at the end of the treatment. prescribed as necessary for the first days and subsequently Pin care started at the first postoperative day with replaced according to the cultures results. All open fractures hydrogen peroxide and betadine and performed daily in were treated emergently with irrigation, debridement, intra- hospitalized patients. The patients were discharged with venous antibiotics, and tetanus prophylaxis. Associated me- the instruction of a biweekly pin site care.22,29 X-ray films niscal lesions were found in four (6.78%) cases and were all and clinical evaluations were conducted every 30 to 40 repaired by wall suture. days. The tibial alignment was checked radiographically, There were no systemic complications attributable to our adjusting the ring connection rods to obtain an articular align- surgical treatments. In 23.73% of cases pin site infections ment of the knee and to correct the abnormal translational and were observed. These infections were superficial or limited to rotational axis. If solid bone healing was confirmed clinically the soft tissue and in no cases were extended to the bone. and radiologically, the frames were dynamized and then re- None of the patients required hospital admission for a pin site moved in our clinic, usually without anesthesia. Long leg infection. Most of these infections responded to local pin-site brace with hinges at the level of the knee was applied for an care and oral antibiotics. In five cases, wires or half-pins needed average period of 4 weeks after frame removal. to be removed in the outpatient clinic, without compromising the The follow-up continued at least every 3 months for the stability of the frame. The infected pin tracts healed few days first year after injury and then every 2 years and included after pin removal without further complications. There was no evaluation of radiologic results, knee ROM, pain, and paring sequestrum or sign of infection at the following radiologic tient’s satisfaction. A postoperative score was recorded for evaluation (within 40 days after pin removal). each patient 1 year after the onset of the fracture according to There were no cases of wound infection, osteomyelitis, the herein newly introduced scoring criteria of the ASAMI, or septic arthritis postoperatively. Postinjury soft tissue swell- Italy (Table 2). Based on these parameters and the inherent ing did not influence the timing or technique of external

1046 November 2007 Complex Tibial Plateau Fractures

Fig. 3. A 56-year-old woman sustained a comminuted fracture of the tibial plateau of the left leg after a domestic fall. (A) Comminuted fracture of the tibial plateau, type V according to the Schatzker classification,1 at hospital admission. (B, C) Treatment with the hybrid advanced Ilizarov technique (strategy 1) two months after injury. No complications occurred during the treatment. (D, E) Successful bone healing at removal of the hybrid advanced Ilizarov fixator after 3 months and 18 days of treatment. The cannulated screws were left in place. The patient was able to bear full weight and had excellent joint motion. fixation application. As all patients were operated as soon as nipulation of the patient’s injured knee after frame removal possible, the early fracture stabilization avoided the develop- was performed by the physical therapists to improve ROM ment of severe edema. and did not require anesthesia. A knee flexion of Յ90 degrees There were two cases of deep peroneal nerve palsy was considered satisfactory in patients Ն60 years of age who caused by the trauma. One case resolved spontaneously 6 did not think the need to continue the physical therapy to months after frame removal, and in the other patient, the foot increase the ROM. In our eight patients with a concomitant drop caused by persistent impairment of the deep peroneal ipsilateral femoral fracture, the final knee ROM was not signif- nerve is addressed with a Codivilla’s spring during walking. icantly reduced compared with the patients suffering from iso- There were two cases of deep venous thrombosis, which lated tibial plateau fracture. Overall, the patients’ knee ROM were treated with low molecular weight heparin for 6 weeks. was always increasing at consecutive clinical evaluations. Clinical observation at 1-year follow-up revealed a range Based on the parameters considered at the follow-up of knee flexion from 60 degrees to 135 degrees with a mean (radiologic results, knee ROM, pain, ability to sport activities, of 119 degrees. A total of 46 (77.96%) patients regained and patient’s satisfaction), according to our herein introduced functional use of the limb and full flexion (135 degrees) and ASAMI Italy scoring criteria (Table 2), the results were extension (0 degrees) of the knee joint, good axis, without evaluated as excellent in 30 patients (50.85%), good in 27 pain or instability during an average follow-up of 11 months. patients (45.76%), fair in 1 patient (1.695%), and poor in 1 The remaining 13 (22.04%) patients achieved a limited knee (1.695%) (Table 3). The patients’ satisfaction was signifi- flexion Յ90 degrees. Of these 13 patients, in two cases cantly related with the functional results. arthroscopic arthrolysis was performed, and in one case Ju- det’s quadricepsplasty34 was performed. Indication for quad- DISCUSSION ricepsplasty was restriction less than 60 degrees in knee The tibial plateau fractures that are a result of high flexion, which was incompatible with a normal gait.34 Ma- energy injuries, especially types V and VI according to the

Volume 63 • Number 5 1047 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Fig. 4. A 40-year-old woman sustained a comminuted fracture of the tibial plateau of the left leg in a road traffic crash. (A) Comminuted fracture of the tibial plateau, type V according to the Schatzker classification.1 (B, C) Treatment with the hybrid advanced Ilizarov technique (strategy 1) 1 month after injury. Hinges applied to the tibial frame allowed correction of the traumatic deformity. (D, E) Results at removal of the hybrid advanced Ilizarov fixator after 3 months and 21 days of treatment showed bone healing. The patient was able to bear full weight and had excellent joint motion.

Schatzker classification,1 have been at high incidence of The more severe and complex fractures of the tibial severe complication when treated with internal fixation tech- plateau usually are because of high energy injuries with nique alone.1,10,17 The risk to not obtain good reduction and severely compromised soft tissues.4,5,14 The “complex” frac- stability and the risk to result in malunion are related to the tures of the tibial plateau fractures have been described in comminution of the fracture, to the compromise of soft tis- different ways. We classified fractures as complex, according sues, and of the correct realignment and stability of the to types V and VI proposed by Schatzker et al.,1 if either fracture.4 To prevent nonunion as well as posttraumatic bicondylar involvement or plateau fracture with dissociation arthrosis,16 or arthritis,11 joint congruity and axial alignment of the tibial metaphysis and diaphysis were involved. Kumar need to be reestablished. and Whittle5 reported 57 complex fractures of the tibial

1048 November 2007 Complex Tibial Plateau Fractures

Fig. 5. A 34-year-old man sustained a comminuted fracture of the tibial plateau of the left leg in a motorcycle crash. (A) Comminuted fracture of the tibial plateau, type V according to the Schatzker classification,1 at Hospital admission. (B, C) Treatment with the hybrid advanced Ilizarov technique (strategy 2). The distal tibial ring was located at the level of the tibial plateau. (D, E) Successful bone healing and joint motion at removal of the hybrid advanced Ilizarov fixator after 3 months and 20 days of treatment. plateau treated with external fixation, belonging to the with an intra-articular fracture, or a tibial condylar fracture of Schatzker type VI group. Recently, El Barbary et al.4 reported the medial plateau, as well as a severe associated soft tissue 29 cases of complex tibial plateau fracture (Schatzker type injury. VI) treated with Ilizarov external fixators. Differently, Methods of open reduction and internal fixation have an Watson and Coufal14 described the treatment with the Il- high rate of complications, such as infections and posttrau- izarov technique of 14 complex high energy fractures of the matic deformities.14,16,17 Only recently, treatment with open tibial plateau, belonging to the groups of Schatzker types I reduction and medial and lateral plate using two incisions and and II. Marsh et al.35 reserved the application of external proper soft tissue handling may contribute to a lower wound fixation to complex fractures consisting of a bicondylar fracture, complication rate than previously reported.11 The introduc- a dissociation of the shaft from the condyles in conjunction tion of the Ilizarov external fixation has decreased the rate of

Volume 63 • Number 5 1049 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Fig. 6. A 31-year-old man sustained a comminuted fracture of the tibial plateau of the left leg in a motor vehicle crash. (A) Comminuted fracture of the tibial plateau, type V according to the Schatzker classification.1 (B, C) The frame extended onto the distal femur with two levels of fixation. The proximal tibial ring was located more distally, bypassing the fracture (strategy 3). (D, E) Results at the time of frame removal after 3 months and 11 days of treatment showed bone healing. (F) Final radiographic results after removal of the cannulated screws 4 years after the crash. complications related with plating, being more respectful of bicondylar tibial plateau fractures, avoiding the application of the biology of bone and soft tissue.2,4,6,8,12–14,19 Besides its plates and soft tissue dissection. many advantages, the Ilizarov method has theoretical risks There is debate about the use of classical Ilizarov that may occur even in experienced hands, including pins fixator6,20 or what type of hybrid Ilizarov frame3,7,8,15,23 for infection or loosening, neurovascular injury, infection, mus- the treatment of complex fractures of the tibial plateau. Ac- cular damage, articular injury and deep venous thrombosis, cording to Watson,13 the definition of hybrid fixation is persistent pain, algodystrophy, and scar problems.21,36 ambiguous and denotes no single or universally accepted The surgical technique suggested by Ilizarov20 is unique treatment strategy or device. There are a variety of hybrid because of its many indications and advantages.22,25,27–29 The frames available and adopted to treat complex fractures of the safe placement of proximal transfixion wires with respect to tibial plateau.3,5,7,8,15,21,23 Ali et al.23 fixed simulated frac- anatomic neurovascular structures have been well described21,37 tures of the tibial plateau using a two-ring hybrid fixator with and the major advantage of the external fixation is the ability interfragmentary screws, a ring-bar hybrid fixator with inter- to stabilize the short periarticular segments encountered in fragmentary screws, lateral plate, and medial monolateral

1050 November 2007 Complex Tibial Plateau Fractures

differed from the conventional Ilizarov frames20 in the use of Table 2 Scoring Criteria and Classification of Results cortical bone pins rather than wires through the distal rings for Complex Fractures of the Tibial Plateau, Evaluated for the fixation of the diaphysis. Mueller et al.7 tested the 1 Year After the Fracture. Association for the Study and stability of various forms of osteosynthesis in the treatment of Application of the Method of Ilizarov (ASAMI), Italy fractures of the proximal tibia using external and hybrid Variables Score fixators, depicted in figures but not otherwise described. Bone results The treatment in the complex tibial plateau fractures Union without infection 30 firstly consisted on restoring the articular surface as much as Nonunion or infection 0 possible by either mini-open or open techniques and partially Radiologic results stabilizing the fracture with minimal internal fixation with Good joint line 10 33 Malalignment Ͻ2mm 8 wires or screws, according to the AO techniques. An hybrid 11,18,25 Malalignment 2–4 mm 6 Ilizarov circular external fixation was then applied Malalignment Ͼ4mm 0 (Figs. 1 and 2A–C). The decision to apply our strategies of Knee range of motion external circular fixation was based not only on the complex- Ͼ130 degrees 10 110 degrees–130 degrees 8 ity of fracture, but also on the severity of the soft tissue injury 80 degrees–109 degrees 6 in an effort to avoid soft tissue complications. Our hybrid Ͻ80 degrees 4 Ilizarov circular fixator, which uses a combination of half- Leg length discrepancy pins and wires on the Ilizarov ring construct8,18,21,25–29 (Figs. No leg discrepancy 10 1–6), has been described to be more stable than the conven- Ͻ1cm 8 20 1–2 cm 6 tional external Ilizarov fixator including only wires. This 2–4 cm 3 type of external fixator has been widely reported to be more Ͼ4cm 1 comfortable for the patients, having substituted some full Pain rings with arches, especially in the proximal portions of the Absent 10 limbs near movable joints,8,21,25–29 i.e., the knee joint in case After sport activity 9 After long walking 8 of fracture of the tibial plateau (Figs. 1–6). Weather related only 7 Our three strategies of treatment included the possibility After short walking 4 to extend the frame onto the distal femur with two levels of Mild activity related 2 fixation in case of extremely complex and unstable fracture. Night pain at rest 1 In such cases, the tibial and femoral frames were connected Sporting activity Full return to previous sport activity 10 with hinges. In cases with severely unstable joint surface, the Decreased sport performance 8 proximal tibial ring was located at the level of the tibial Poor sport performance 4 plateau (Figs. 1C and D; 2B; and 6B and C). The proximal No sport ability 0 tibial ring was placed more distally, bypassing the fracture, Subjective patient satisfaction when the skin and soft tissue were suffering and there was no Full satisfaction 10 Mild dissatisfaction 8 place for wire and pins in the fractured tibial plateau (Figs. Medium dissatisfaction 4 1E; 2B; and 5B and C). The double femoral and tibial frames Dissatisfaction 0 allowed to obtain distraction of articular surface (ligamento- Excellent: score ϭ 80–90; good: score ϭ 70–79; fair: score ϭ taxis) and more stability (Figs. 1C–E; 2B and C; 5B and C; 59–69; poor: score Ͻ59. and 6B and C). Parameswaran et al.38 observed pin tract infection rates of up to 20% with traditional external fixators when com- Table 3 Overall Results of 59 Patients With Complex pared with 12.9% for unilateral fixators and 3.9% for circular Fractures of the Tibial Plateau (Schatzker Types V and ring fixators. Recently, we demonstrated for our circular VI) Treated by the Hybrid Advanced Ilizarov Fixation Ilizarov fixation with conical half-pins and wires,8,21,22,25–29 Combined With Limited Internal Fixation an infection rate of 3.11% with the half-pins when compared Results No. (%) Patients with 4.73% for the Ilizarov wires. Moreover, the infection Excellent 30 (50.85) rate in pins with threads inside or outside the skin was 3.11% Good 27 (45.76) and 3.32%, respectively, without statistically significant Fair 1 (1.695) differences.29 Poor 1 (1.695) Morandi et al.6 described the need for bone grafting of Scoring criteria and classification of results are listed in Table 2. the tibial plateau in case of complex fractures. Recently, El Barbary et al.4 reported bone grafting in 5 of 30 cases external fixators. Bal et al.3 used anterior T-frame external (16.67%) to support the elevated articular surface after re- fixation combined with percutaneous internal fixation. Ku- duction. In this study, the bone grafting was not performed mar and Whittle5 applied hybrid Ilizarov fixators, which since the fracture reduction and stabilization, followed by an

Volume 63 • Number 5 1051 The Journal of TRAUMA௡ Injury, Infection, and Critical Care appropriate ligamentotaxis as needed, allowed a good bone REFERENCES consolidation in all cases. 1. Schatzker J, McBroom R, Bruce D. The tibial plateau fracture. The According to the present results and to other authors’ Toronto experience 1968–1975. Clin Orthop Relat Res. 1979; reports,4,6,12,13 we are convinced that the Ilizarov circular 138:94–104. external fixation method is the treatment of choice for com- 2. Ali AM, Burton M, Hashmi M, Saleh M. Outcome of complex plex fractures of the tibial plateau, especially when extensive fractures of the tibial plateau treated with a beam-loading ring fixation system. J Bone Joint Surg Br. 2003;85:691–699. dissection and internal fixation are contraindicated because of 3. Bal G, Kuo RS, Chapman JR, Henley MB. The anterior T-frame the bony comminution and soft tissue compromise. The use external fixator for high-energy proximal tibial fractures. Clin of hybrid Ilizarov external fixation8,18,25–29 for complex Orthop Relat Res. 2000;80:234–240. (Schatzker types V and VI)1 tibial plateau fractures offers the 4. El Barbary H, Abdel Ghani H, Misbah H, et al. Complex tibial advantages of1 greater fracture stability allowing early post- plateau fractures treated with Ilizarov external fixator with or operative joint mobilization with partial weight bearing;2 without minimal internal fixation. Int Orthop. 2005;29:182–185. 3 5. Kumar A, Whittle AP. Treatment of complex (Schatzker Type VI) respect of bone vascularity with less fragment devitalization; fractures of the tibial plateau with circular wire external fixation: less soft tissue stripping and dissection, wound complications retrospective case review. J Orthop Trauma. 2000;14:339–344. and minimal blood loss, and operative general risk;4 possi- 6. Morandi MM, Landi S, Kilaghbian V. Schatzker type VI tibial bility to obtain ligamentotaxis as well as compression across plateau fractures and the Ilizarov circular external fixator. Bull Hosp the site of bone loss, without additional bone grafting;5 pos- Jt Dis. 1997;56:46–48. 7. Mueller CA, Eingartner C, Schreitmueller E, et al. Primary stability sibility to enhance fracture consolidation through dynamiza- 6 of various forms of osteosynthesis in the treatment of fractures of tion of the frame during the treatment; possibility to easily the proximal tibia. J Bone Joint Surg Br. 2005;87:426–432. modify the circular external frame by temporarily removing 8. Catagni MA. Tibial fractures. In: Bianchi Maiocchi A, ed. Treatment during the treatment if secondary procedures are required, of Fractures, Nonunions and Bone Loss of the Tibia With the such as soft tissues coverage or bone grafting;7 possibility of Ilizarov Method. Milan, Italy: Il Quadratino; 1998:31–64. deformity correction by hinges (Fig. 4C). Among the disadvan- 9. Barei DP, Nork SE, Mills WJ. Functional outcomes of severe bicondylar tibial plateau fractures treated with dual incisions and medial tages of the external circular fixation, difficulty of achieving and lateral plates. J Bone Joint Surg Am. 2006;88:1713–1721. adequate reduction by closed or minimally invasive methods 10. Bennett WF, Browner B. Tibial plateau fractures: a study of and intensive postoperative management of the Ilizarov frame associated soft tissue injuries. J Orthop Trauma. 1994;8:183–188. for both patients and surgeons have been described.22,25,29,37 11. Barei DP, Nork SE, Mills WJ. Complications associated with internal Recently, the less invasive stabilization system using fixation of high-energy bicondylar tibial plateau fractures utilizing a extramedullary internal fixation with anatomically precon- two-incision technique. J Orthop Trauma. 2004;18:649–657. 12. Tucker HL, Kendra JC, Kinnebrew TE. Management of unstable toured plates has offered a minimally invasive approach with open and closed tibial fractures using the Ilizarov method. Clin improved healing rates and restoration of the articular surface Orthop Relat Res. 1992;280:125–135. in the treatment of complex fractures of the tibial plateau.39,40 13. Watson JT. Hybrid external fixation for tibial plateau fractures. Am J A disadvantage is that the precontoured shape of the plate Knee Surg. 2001;14:135–140. must fit a variety of tibia sizes and morphology leading to a 14. Watson JT, Coufal C. Treatment of complex lateral plateau fractures risk of implant-associated pain and the risk of infection is still using Ilizarov techniques. Clin Orthop Relat Res. 1998;353:97–106. 15. Watson JT, Ripple S, Hoshaw SJ. Hybrid external fixation for tibial a possibility. plateau fractures: clinical and biomechanical correlation. Orthop Clin Based on our experience of more than 16 years (since North Am. 2002;33:199–209. 1990), we suggest that the external fixation, according to our 16. Weiss NG, Parvizi J, Hanssen AD, Trousdale RT, Lewallen DG. technique of hybrid frame,8,18,21,22,25–29 accompanied by Total knee arthroplasty in post-traumatic arthrosis of the knee. minimal internal fixation, has indication for open types II and J Arthroplasty. 2003;18:23–26. 17. Young MJ, Barrack RL. Complications of internal fixation of tibial III fractures, according to the Gustilo classification,31 com- plateau fractures. Orthop Rev. 1994;23:149–154. plex fractures with severe displacement or comminution of 18. Catagni MA. Results in the treatment of complex tibial plateau 1 the fracture types V to VI by Schatzker et al., especially in fractures with the Ilizarov method. In: Proceed. World Congress on case of extensive soft tissue compromise. In conclusion, the External Fixation, Lima, Peru`, May 26–28th, 2005. Abstract n. hybrid Ilizarov method8,18,21,25–29 combined with minimal inter- WC352EF. nal fixation enables excellent to good results in most cases of 19. Sen C, Kocaoglu M, Eralp L. Bifocal compression-distraction in the acute treatment of grade III open tibia fractures with bone and soft- complex tibial plateau fractures (Table 3) when applied with tissue loss: a report of 24 cases. J Orthop Trauma. 2004;18:150– good indications, planning, and surgical experience. 157. 20. Ilizarov GA. The principles of the Ilizarov method. Bull Hosp Jt Dis Orthop Inst. 1988;48:1–11. ACKNOWLEDGMENTS 21. Catagni MA. In: Bianchi Maiocchi A, ed. Atlas for the Insertion of We thank Dr. Francesco Guerreschi, MD, and Dr. Luigi Lovisetti, MD, Transosseous Wires and Half-Pins Ilzarov Method. 2nd revised ed. for their precious help in treating and evaluating the cases herein described. Milan, Italy: Medi Surgical Video; 2003. Appreciation is extended to the entire staff and to all the national and 22. Catagni MA, Lovisetti L, Guerreschi F. Cosmetic bilateral leg international fellows visiting the Department of Orthopedics and Ilizarov lengthening: an experience of fifty-four cases. J Bone Joint Surg Br. Unit, “Alessandro Manzoni” Hospital, Lecco, Italy. 2005;87:1402–1405.

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23. Ali AM, Saleh M, Bolongaro S. The strength of different fixation 32. Oestern HJ, Tscherne H. Pathophysiology and classification of soft techniques for bicondylar tibial plateau fractures–a biomechanical tissue injuries associated with fractures. In: Tscherne H, Gotzen L, study. Clin Biomech. 2003;18:864–870. eds. Fractures With Soft Tissue Injuries. Berlin, Springer-Verlag; 24. Piza G, Caja VL, Gonzalez-Viejo MA. Hydroxyapatite-coated 1984:1–9. external-fixation pins. The effect on pin loosening and pin-track 33. Mu¨ller ME, Allgo¨wer M, Scheider R, et al. Manual of Internal infection in leg lengthening for short stature. J Bone Joint Surg Br. Fixation. 3rd ed. Berlin: Springer-Verlag; 1991:142–143. 2004;86:892–897. 34. Ali AM, Villafuerte J, Hashmi M. Judet’s quadricepsplasty, surgical 25. Catagni MA, Bolano L, Cattaneo R. Management of fibular technique, and results in limb reconstruction. Clin Orthop Relat Res. hemimelia using the Ilizarov method. Orthop Clin North Am. 1991; 2004;415:214–220. 22:715–722. 35. Marsh JL, Smith ST, Do TT. External fixation and limited internal 26. Cattaneo R, Catagni M, Johnson EE. The treatment of infected fixation for complex fractures of the tibial plateau. J Bone Joint nonunions and segmental defects of the tibia by the methods of Surg Am. 1995;77:661–667. Ilizarov. Clin Orthop Relat Res. 1992;280:143–152. 36. Paley D. Problems, obstacles and complications of limb 27. Catagni MA, Camagni M, Combi A. Medial fibula transport with the lengthening by the Ilizarov technique. Clin Orthop Relat Res. Ilizarov frame to treat massive tibial bone loss. Clin Orthop Relat 1990;250:81–104. Res. 2006;448:208–216. 37. Reid JS, Van Slyke MA, Moulton MJ, Mann TA. Safe placement of 28. Ottaviani G, Randelli P, Catagni MA. Segmental cement extraction proximal tibial transfixation wires with respect to intracapsular system (SEG-CES) and the Ilizarov method in limb salvage procedure after total knee cemented prosthesis removal in a former penetration. J Orthop Trauma. 2001;15:10–17. osteosarcoma patient. Knee Surg Sports Traumatol Arthrosc. 2005; 38. Parameswaran AD, Roberts CS, Seligson D. Pin tract infection with 13:557–563. contemporary external fixation: how much of a problem? J Orthop 29. Catagni MA, Ottaviani G, Combi A. External circular fixation: a Trauma. 2003;17:503–507. comparison of infection rates between wires and conical tapered 39. Stannard JP, Wilson TC, Volgas DA. The less invasive stabilization half-pins with threads outside or inside the skin. J Trauma. 2006; system in the treatment of complex fractures of the tibial plateau: 61:1186–1191. short-term results. J Orthop Trauma. 2004;18:552–558. 30. Orthopaedic Trauma Association Committee for Coding and 40. Krupp R, Malkani AL, Seligson D, et al. Treatment of bicondylar Classification. Fractures and Dislocations Compendium. J Orthop tibial plateau fractures using locking plates versus external fixation. Trauma. 1996;10(Suppl 1):46–50. In: Proceedings of 2006 Annual Meeting of the American Academy 31. Gustilo RB, Kyle RF, Templeman D. Fractures and Dislocations. of Orthopaedic Surgeons; March 22–26, 2006; Chicago, Illinois. Vol II. St. Louis: Mosby Year Book; 1993:945–979. Abstract n. 481.

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Proximal Femoral Nail for the Treatment of Reverse Obliquity Intertrochanteric Fractures Compared With Gamma Nail Woo-Kie Min, MD, Shin-Yoon Kim, MD, Tae-Kong Kim, MD, Kyu-Bong Lee, MD, Myung-Rae Cho, MD, Yong-Chan Ha, MD, and Kyung-Hoi Koo, MD

Background: The reverse obliquity were treated with the GN. The two groups satisfactory functional outcome was found fracture of the proximal femur (AO/OTA were comparable with regard to demo- in eight patients in the PFN group and 31-A3) is mechanically different from graphic and injury variables. The duration also in eight patients in the GN group. most intertrochanteric fractures. The pur- of follow-up averaged 18 months (range, There was one osteonecrosis of femoral pose of this study was to compare the 12–67 months). Radiographic changes dur- head in the PFN group. There was one results of proximal femoral nail (PFN) fix- ing the follow-up, clinical outcome, and cutting out of lag screw, one nonunion, ation with those of gamma nail (GN) fix- complications of the PFN group were com- and one varus deformity in the GN group. ation for these fractures. pared with those of the GN group. Conclusion: There was no differ- Methods: Between 1993 and 2003, Results: Reverse obliquity intertro- ence in clinical outcome between the 635 of the fractures were classified as inter- chanteric fractures accounted for 4.3% of PFN and GN groups. However, the PFN trochanteric or subtrochanteric. Clinical intertrochanteric and subtrochanteric demonstrated better results biomechani- and radiographic records were retrospec- fractures. Bone union time averaged 16.5 cally than the GN did in terms of less tively reviewed, and 22 fractures with re- weeks in the PFN group and 17.9 weeks in sliding of lag screw, less change of neck- verse obliquity pattern were identified. the GN group. Average sliding of lag shaft angle, and less complications for The patients were divided into two treat- screw was 2.5 mm in the PFN group and the treatment of reverse obliquity inter- .trochanteric fractures .(0.046 ؍ ment groups and were followed up for a 3.1 mm in the GN group (p minimum of 1 year (range, 12–67 months). Change of the neck-shaft angle was 2.45 Key Words: Reverse obliquity, Inter- Eleven patients in group I were treated degrees in the PFN group and 3.75 de- trochanteric, PFN, GN. A .(0.032 ؍ with the PFN, and 11 patients in group II grees in the GN group (p J Trauma. 2007;63:1054–1060.

ractures about the trochanteric area are classified accord- of A3 fractures have been recognized by numerous investi- ing to the Orthopedic Trauma Association classification gators, who have variably referred to these injuries as unsta- Fsystem as AO/OTA 31-A,1 which delineates them as ble intertrochanteric fractures, as subtrochanteric fractures, or extracapsular fractures of the hip. These fractures are subdi- as some combination of intertrochanteric and subtrochanteric vided into groups A1, A2, and A3 fractures. A1 fractures are fractures. A sliding hip screw is the most commonly used simple, two-part fractures, whereas A2 fractures have multi- implant for fixation of intertrochanteric fractures. However, ple fragments. A3 fractures include reverse oblique and trans- many investigators have reported that this device is not suit- verse fracture patterns. The distinctive characteristic of A3 able for AO/OTA 31-A3 reverse oblique or transverse fractures is a fracture line that extends through the lateral fractures,2,3 and several alternative methods of fixation have femoral cortex distal to the vastus ridge of the greater tro- been advocated for this more difficult fracture pattern.2,4–6 chanter. The unique anatomic and mechanical characteristics The gamma nail (GN) (Stryker Howmedica, Rutherford, NJ) has been available since 1988 and was designed specifically Submitted for publication February 13, 2006. for the treatment of unstable trochanteric fractures to combine Accepted for publication July 20, 2006. the advantages of semiclosed intramedullary nailing, a dynamic Copyright © 2007 by Lippincott Williams & Wilkins femoral neck screw, and early postoperative weight-bearing. From the Department of Orthopedic Surgery (W.-K.M., S.-Y.K., The advantages of the GN over dynamic hip screw in these T.-K.K., K.-B.L.), College of Medicine, Kyungpook National University, 7–13 Daegu, Korea; Department of Orthopedic Surgery (M.-R.C.), College of unstable fractures remain to be demonstrated clinically. Medicine, Daegu Catholic University, Daegu, Korea; Department of Ortho- Moreover, serious GN implant-related complications have pedic Surgery (Y.-C.H.), College of Medicine, Kyungsang National Univer- been described, such as a fracture of the femoral shaft in up sity, Jinju, Korea; and Department of Orthopedic Surgery (K.-H.K.), College to 17%, failure of fixation in up to 7%, and complications of of Medicine, Seoul National University, Sungnam, Korea. Address for reprints: Shin-Yoon Kim, MD, Department of Orthopedic distal locking in up to 10%, requiring reoperation with sub- 10,11,14,15 Surgery, College of Medicine, Kyungpook National University, Samduck 2 sequent morbidity and even mortality. Because of Ga 50, Jung-Gu, Daegu 700-721, Korea; email: [email protected]. the well-described and persistent problems, however, other DOI: 10.1097/01.ta.0000240455.06842.a0 intramedullary fixation devices have been introduced. The

1054 November 2007 PFN Versus GN in Treatment of AO/OTA 31-A3 proximal femoral nail (PFN) (Mathys, Bettlach, Switzerland) Table 1 Salvati and Wilson Score was developed to improve the rotational stability of the proximal fracture fragment, combining the features of an unreamed Pain intramedullary femoral nail with a sliding, load-bearing, fem- 0. All the time, unbearable, strong medication frequently oral neck screw.6 Furthermore, the tip of the nail was rede- 2. All the time but bearable, strong medication occasionally, salicylates frequently signed to decrease the risk of intraoperative and postoperative 4. None or little at rest, with activities, salicylates frequently fractures of the femoral shaft by a significant reduction in 6. When starting, then better, or after a certain activity. bone stress. Since its introduction in 1997, several clinical Salicylates occasional studies have shown good results with few intraoperative prob- 8. Occasional and slight lems and a low rate of complications.4,8 The clinical relevance 10. No pain Walking of the presumed advantages and lower complication rates are 0. Bedridden still to be established and compared with a standard method 2. Wheel chair, transfer activities with walker of treatment. In recent reports in the literature, the PFN has 4. No support—house bound or Markedly restricted been compared with the GN for the treatment of unstable One support—less than one intertrochanteric fractures.14 However, there is no report block Bilateral support—unrestricted comparing the PFN with the GN for AO/OTA 31-A3 reverse 6. No support—less than one Moderately restricted obliquity intertrochanteric fractures. We therefore performed block the present study to compare the results of PFN fixation with One support—up to 5 blocks those of GN fixation for these intertrochanteric fractures. Bilateral support—unrestricted 8. No support—limp Mildly restricted One support—no limp PATIENTS AND METHODS Muscle power (MP) and motion* Twenty-two patients with AO/OTA 31-A3 fractures 0. Ankylosis with deformity among 635 patients who were treated as intertrochanteric or 2. Ankylosis with good functional position subtrochanteric between March 1993 and September 2004 4. MP-poor to fair, are of flexion less than 60 degrees. were enrolled in this study. From March 1993 to April 1998, Restricted lateral and rotary movement 6. MP-fair to good, are of flexion up to 90 degrees. Fair† we implanted 83 GNs for unstable intertrochanteric fractures. lateral and rotary movement From May 1998 to September 2004, we implanted 98 PFNs 8. MP-good or normal, are of flexion over 90 degrees. for unstable intertrochanteric fractures. Each fracture was Good‡ lateral and rotary movement classified according to the Orthopedic Trauma Association 10. MP-normal. Motion-normal or almost normal scheme. A total of 27 consecutive patients with AO/OTA Function 0. Completely dependent and confined 31-A3 fractures were evaluated retrospectively from the chart 2. Partially dependent review and questionnaire. All AO/OTA 31-A3 fractures were 4. Independent limited housework, shops limitedly included. We excluded five patients: one pathologic fracture, 6. Most housework, shops freely, desk type work one fracture that extended 10 cm distal to the level of the 8. Very little restriction, can work on feet lesser trochanter, and three fractures treated with a dynamic 10. Normal activities compression screw. * Precedence in rating was given to active movement, but usu- Twenty-two patients with AO/OTA 31-A3 fractures of ally both active and passive movement were the same. † Fair lateral movement: 10 degrees abduction, 10 degrees ad- the femur were divided into two treatment groups; 11 patients duction. Fair rotary movement: internal rotation 10 degrees, external were treated with a 130-degree PFN, and 11 patients were rotation 20 degrees. treated with a 130-degree GN. All patients were followed up ‡ Good lateral movement: 20 degrees abduction, 20 degrees until the fracture united or a revision operation was per- adduction. Good rotary movement: internal rotation 20 degrees, ex- formed. Our local Institutional Review Board provided ap- ternal rotation 40 degrees. proval for this retrospective study. Follow-up evaluations were performed at 6 weeks; at 3, 6, and 9 months; and yearly fair when it is 16 to 23, and poor when it is 15 or less. thereafter. No patient was lost to follow-up until a minimum Intraoperative and postoperative complications were also in- of 1 year. Two independent observers (W.K.M., T.G.K) investigated. Radiologically, reduction status, displacement, terviewed and examined all patients. We clinically reviewed tip-apex index, sliding, position of the lag screw, changes of the age, sex, presurgical day, body mass index, operative neck-shaft angle, and union time were analyzed and com- time, transfusional requirements, length of hospital stay, prepared in each group. Anteroposterior and lateral radiographs operative and final follow-up, and clinical and functional of the affected hip were made postoperatively while the outcome according to the Salvati and Wilson score system,16 patient was in the hospital and at each follow-up visit. We which was based on the following four parameters: pain, classified the quality of reduction of the fracture as anatomic walking, motion and muscle power, and function (Table 1). (5 degrees of varus, valgus, anteversion, or retroversion), The results have been classified as excellent when the sum of acceptable (5–10 degrees), or poor (Ͼ10 degrees).5 Bone the four evaluations is 32 or more, good when it is 24 to 31, mineral density of total femur was determined using the DPX

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Table 2 Comparison of Various Factors

PFN Group GN Group p Age (yr) 67 (46–79) 65 (37–70) Ͼ0.05 Male:female 5:6 6:5 Ͼ0.05 Presurgical stay (d) 3 (1–7) 3 (1–7) Ͼ0.05 Operation time (min) 55 (45–75) 60 (40–82) Ͼ0.05 Blood transfusion (No) 3 5 Ͼ0.05 TAD (mm) 27.2 29.6 Ͼ0.05 Union time (wk) 16.5 (12–40) 17.9 (12–43) Ͼ0.05 Sliding of lag screw (mm) 2.5 (0–11) 3.1 (1–15) 0.046 Change of NSA (degrees) 2.45 (0–13) 3.75 (1–15) 0.032 BMI (kg/m2) 25.2 Ϯ 3 24.6 Ϯ 2.9 Ͼ0.05 BMD (g/cm2) 0.54 Ϯ 0.09 0.58 Ϯ 0.14 Ͼ0.05 Hospital stay (d) 13 Ϯ 418Ϯ 7 0.028 Charlson score 26.4 24.9 Ͼ0.05 SWS (No. excellent ϩ good, preoperative) 0 0 Ͼ0.05 SWS (No. excellent ϩ good, follow-up) 8 8 Ͼ0.05 No. complication 1 3 Ͼ0.05 PFN, proximal femoral nail; GN, gamma nail; TAD, Tip apex distance; NSA, neck-shaft angle; BMD, bone mineral density; SWS, Salvati and Wilson score system; BMI, body mass index.

(Prodigy, GE Lunar, WI) within 7 to 10 days after operation radius fracture in the PFN group, and scaphoid fracture and in all patients. We assessed that the fracture had healed if the multiple contusions in the GN group, respectively. The duration patient did not feel pain or motion at the fracture site clini- of follow-up averaged 18 months (range, 12–60 months) in the cally and when the fracture site was filled with bridging PFN group and 21 months (range, 12–67 months) in the GN callus or when the trabuculae had continued across the frac- group. The treatment groups were comparable with regard to ture site radiographically. all demographic and injury variables including preoperative The surgical procedure was performed with the patient in functional status, Charlson comorbidity index score, and the supine position on a fracture table and with the injured body mass index (Table 2). Average number of presurgical extremity slightly adducted to facilitate insertion of the nail. days was 3 days (range, 0–7 days) in both groups. Regional All patients were treated with closed reduction and internal anesthesia was administered to all patients. The mean oper- fixation except one patient who was treated with open reduc- ative time averaged 55 minutes (range, 45–75 minutes) for tion in the PFN group. The used PFN was of titanium alloy, the PFN group and 60 minutes (range, 40–82 minutes) for with a diameter of 10, 11 mm and a neck-shaft angle of 130 the GN group (p Ͼ 0.05). degrees. The implanted GN also had a diameter of 11, 12 mm In the PFN group, patients presented an average hemat- and a neck-shaft angle of 130 degrees. If we cannot achieve ocrit of 37.6%, which decreased to 30.3% 24 hours after the an acceptable working length (at least 5 cm from distal operation. Transfusion of packed erythrocytes was necessary fracture line), a long GN and a long PFN were used (one in three patients, with an average requirement of 1.8 units. In patient in each group, respectively). Two interlocking screws the GN group, the preoperative hematocrit of 38.1% de- were inserted in all 22 patients because we considered these creased to 29.8% postoperatively, with an average require- fractures as unstable. Statistical analysis was performed with ment of 1.6 units of transfusion needed in five patients. use of Student t test and Fisher exact test. Differences were Statistical comparison of these figures also showed no dif- considered significant when the p value was Ͻ0.05. ference (p Ͼ 0.05). There was acceptable reduction in both groups. The RESULTS position of lag screw was eight middle-middle and three Twenty-seven reverse obliquity intertrochanteric frac- inferoposterior in the PFN group, and six middle-middle, one tures (AO/OTA 31-A3) accounted for 4.3% of the 635 inter- inferoposterior, four slightly superoposterior in the GN group trochanteric and subtrochanteric hip fractures. The mean age according to anteroposterior and lateral radiographs. There of patients was 67 years (range, 46–79 years) in the PFN was no significant difference between the groups. Average group and 65 years (range, 47–76 years) in the GN group at bone healing time was 16.5 weeks (range, 12–40 weeks) for the time of fracture. There were five male and six female the PFN group and 17.9 weeks (range, 12–43 weeks) for the patients in the PFN group, and six male and five female GN group (p Ͼ 0.05). Average sliding of lag screw was 2.5 patients in the GN group. Nine fractures in the PFN group mm (range, 0–11 mm) in the PFN group and 3.1 mm (range, and seven fractures in the GN group were caused by a fall and 1–15 mm) in the GN group (p ϭ 0.046). Changes of neck- others were caused by a motor vehicle crash. Four patients shaft angle were averaged 2.45 degrees (range, 0–13 degrees) had an associated injury with symphysis pubis fracture, distal in the PFN group and 3.75 degrees (range, 0–25 degrees) in

1056 November 2007 PFN Versus GN in Treatment of AO/OTA 31-A3

Fig. 1. (A) Anteroposterior hip radiograph shows a reverse obliq- Fig. 2. (A) Anteroposterior hip radiographs shows a reverse obliquity intertrochanteric femoral fracture, AO/OTA 31-A3 type. (B) uity intertrochanteric femoral fracture, AO/OTA 31-A3 type. (B) One-year follow-up radiograph treated with PFN shows complete One-year follow-up radiograph treated with GN shows complete union without deformity. union with slight varus deformity. the GN group (p ϭ 0.032). The mean shortening of the limb was 1.7 mm (range, 0–7.8 mm) in the PFN group and 2.2 mm GN group had higher complications and significantly longer (range, 0–10.6 mm) in the GN group (Table 2). The mean hospital stays (18 days Ϯ 7 days) than did the patients in the bone-mineral density of total femur (and SD) was 0.54 PFN group (13 days Ϯ 4 days) (p ϭ 0.028). Three patients in g/cm2 Ϯ 0.09 g/cm2 in the PFN group and 0.58 g/cm2 Ϯ 0.14 the GN group had a second major procedure: one had bone- g/cm2 in the GN group; this difference was not significant graft, one had removal of implant, and one had removal of (p Ͼ 0.05). implant with bone grafting. A satisfactory functional outcome was found in eight patients in the PFN group (Fig. 1) as well as eight patients in DISCUSSION the GN group (Fig. 2). In the PFN group, the result in five The incidence of AO/OTA 31-A3 reverse obliquity inpatients rated excellent, three good, and three fair. In the GN tertrochanteric fracture is very low. Haidukewych et al.17 group, five had excellent results, three good, two fair, and one retrospectively reviewed 2,472 hip fractures that were treated poor results. Statistical analysis did not reveal any significant during a 10-year period, 1,035 of which were classified as difference between the two groups with regard to the Salvati intertrochanteric or subtrochanteric. Fifty-five reverse and Wilson score system. No patient underwent elective oblique fractures (5.3%) were identified. In our study, 27 removal of hardware because of pain. One case of osteone- reverse obliquity intertrochanteric fractures (AO/OTA 31- crosis of the femoral head with femoral neck fracture was A3) accounted for 4.3% of the 635 intertrochanteric and found in the PFN group, which was treated with a cementless subtrochanteric hip fractures. A number of authors have com- calcar replacement hemiarthroplasty (Fig. 3). In the GN mented on the unsatisfactory results associated with the use group, one had cutting out of lag screw (Fig. 4), one had of a sliding hip screw for fixation of these fractures.2,8,9 In A1 nonunion, and one had varus deformity. The patients in the and A2 fractures, axial loading leads to fracture impaction. In

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Fig. 3. (A) One-year follow-up anteroposterior hip radiograph Fig. 4. (A) Anteroposterior hip radiographs shows a reverse obliquity shows nonunion with varus deformity treated with PFN. (B) Two- intertrochanteric femoral fracture, AO/OTA 31-A3 type. (B) Postoper- year follow-up radiograph shows osteonecrosis of the femoral head ative radiograph shows acceptable reduction treated with GN. (C) with femoral neck fracture. (C) Radiograph shows a cementless Two-year follow-up radiograph shows cutting out of lag screw. calcar replacement hemiarthroplasy. al.17 reported that the results of treatment with a sliding hip A3 fractures, such impaction does not occur and medial screw were compared with the results of treatment with a displacement of the distal fragment with instability of the 95-degree fixed-angle device (a blade-plate or a dynamic fracture is common.9 To eliminate the problem of medial condylar screw). The authors concluded that the overall fail- displacement and loss of fixation, a fixed-angle implant has ure rate associated with the sliding hip screw was higher been recommended for these fractures.18 Haidukewych et when the device was used for A3 fractures than when it was

1058 November 2007 PFN Versus GN in Treatment of AO/OTA 31-A3 used for “standard” (A1 and A2) fractures, and they suggested present in any of our cases. Besides, there is one osteonecrosis of that a 95-degree fixed-angle implant was the preferable alter- the femoral head in the PFN group. This may not be related to native for the treatment of reverse obliquity intertrochanteric the device but to the fracture severity at initial injury. fractures. However, Rosso et al.19 noted eight complications The present study had two limitations. First, this is a related to the implant (pull-out and plate breakage) among 30 retrospective study, which would not be a better comparative elderly patients who received a dynamic condylar screw for method than a prospective study. Second, there was a small the treatment of an unstable intertrochanteric fracture. They sample size for each group because the incidence of reverse concluded that unstable intertrochanteric fractures in elderly obliquity intertrochanteric fractures is very low. patients should not be treated with this implant. There have been numerous reports concerning the use of an intramedul- CONCLUSIONS lary implant for the treatment of unstable intertrochanteric Both the PFN and the GN are effective functionally for fractures.4,5,8,13,14,20 the treatment of reverse obliquity intertrochanteric fractures, In a recent prospective, randomized study comparing a but our study revealed better results of the PFN over the GN compression hip screw (Osteo Hip Screw; Osteo, Selzach, regarding shorter hospital stay, less changes of neck shaft Switzerland) with the Intramedullary Hip Screw (IMHS; angle, less sliding of lag screw, and fewer complications. Smith and Nephew Richards, Memphis, TN), Hardy et al.13 Therefore, for the treatment of reverse obliquity intertrochan- noted that the patients who had unstable (type III, IV, and teric fractures, the PFN would be a better device compared V)21 fractures treated with an IMHS were found to have a with the GN. greater mean mobility score at each follow-up interval than were those with a compression hip screw. Baumgaertner et al.7 reported the results of a prospective, randomized study in REFERENCES which 135 patients were treated with either a sliding hip 1. Fracture and dislocation compendium. Orthopaedic Trauma Association Committee for Coding and Classification. J Orthop screw or an IMHS. In the group of patients with unstable Trauma. 1996;10(Suppl 1):v–ix, 1–154. intertrochanteric fractures, the intramedullary device was as- 2. Babst R, Renner N, Biedermann M, et al. Clinical results using the sociated with 23% less surgical time and 44% less blood loss. trochanter stabilizing plate (TSP): the modular extension of the Two randomized trials compared extramedullary fixation de- dynamic hip screw (DHS) for internal fixation of selected unstable vices with the PFN in stable and unstable trochanteric intertrochanteric fractures. J Orthop Trauma. 1998;12:392–399. 8,13 3. Willoughby R. Dynamic hip screw in the management of reverse fractures. For unstable fractures, the PFN gave better obliquity intertrochanteric neck of femur fractures. Injury. 2005; results with few complications. In addition, the minimum 36:105–109. duration of follow-up in many studies has been only 6 months 4. Boldin C, Seibert FJ, Fankhauser F, et al. The proximal femoral nail and only a few authors have reported a follow-up period of at (PFN)—a minimal invasive treatment of unstable proximal femoral least 1 year. Wagner et al.22 prospectively reviewed the cases fractures: a prospective study of 55 patients with a follow-up of 15 months. Acta Orthop Scand. 2003;74:53–58. of 112 patients who were treated with one of two different 5. Schipper IB, Steyerberg EW, Castelein RM, et al. Treatment of intramedullary devices (classical nail and GN), both of which unstable trochanteric fractures. Randomized comparison of the were found to be equally effective for the treatment of inter- gamma nail and the proximal nail. J Bone Joint Surg Br. 2004; trochanteric fractures. Herrera et al.14 performed a compara- 86:86–94. tive study of trochanteric fractures treated with the PFN and 6. Simmermacher RK, Bosch AM, Van der Werken C. The AO/ASIF- proximal femoral nail (PFN): a new device for the treatment of GN, and showed better result in the PFN group. However, we unstable proximal femoral fractures. Injury. 1999;30:327–332. were unable to find any report in which the PFN device was 7. Baumgaertner MR, Curtin SL, Lindskog DM. Intramedullary versus compared with the GN device for the treatment of A3 frac- extramedullary fixation for the treatment of intertrochanteric hip tures specifically. Our study showed operating times and fractures. Clin Orthop Relat Res. 1998;348:87–94. perioperative blood loss were similar in both groups (p Ͼ 8. Bridle SH, Patel AD, Bircher M, et al. Fixation of intertrochanteric fractures of the femur. A randomised prospective comparison of the 0.05). The most common late complication was cutting out of gamma nail and the dynamic hip screw. J Bone Joint Surg Br. 1991; the screws from the femoral neck in both the PFN and the 73:330–334. GN. The PFN is mainly different because it has an additional 9. Hardy DC, Drossos K. Slotted intramedullary hip screw nails reduce antirotational hip screw that prevents rotation and collapse of proximal mechanical unloading. Clin Orthop Relat Res. 2003; the head-neck fragment and a specially shaped tip, which, 406:176–184. 10. Leung KS, So WS, Shen WY, et al. Gamma nails and dynamic hip together with a smaller distal shaft diameter, results in less screws for peritrochanteric fractures. A randomised prospective study 6 stress concentration at the tip. In our series, there were fewer in elderly patients. J Bone Joint Surg Br. 1992;74:345–351. changes of neck shaft angle, less sliding of lag screw, and less 11. Radford PJ, Needoff M, Webb JK. A prospective randomised cutting out with the PFN group, which supports that the PFN comparison of the dynamic hip screw and the gamma locking nail. device would be better than the GN device biomechanically. J Bone Joint Surg Br. 1993;75:789–793. 12. Wagner R, Weckbach A, Sellmair U, et al. [Extra-articular proximal The PFN can cause a higher incidence of external migration femur fracture in the elderly—dynamic hip screw or intramedullary of the femoral neck screw and antirotational screw with hip screw for fracture management?]. Langenbecks Arch Chir Suppl collapse of the fracture site. But, this phenomenon did not Kongressbd. 1996;113:963–966.

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13. Hardy DC, Descamps PY, Krallis P, et al. Use of an intramedullary 18. Gundle R, Gargan MF, Simpson AH. How to minimize failures of hip-screw compared with a compression hip-screw with a plate for fixation of unstable intertrochanteric fractures. Injury. 1995;26:611–614. intertrochanteric femoral fractures. A prospective, randomized study 19. Rosso R, Babst R, Marx A, et al. [Proximal femoral fractures. Is of one hundred patients. J Bone Joint Surg Am. 1998;80:618–630. there an indication for the condylar screw (DCS)?]. Helv Chir Acta. 14. Herrera A, Domingo LJ, Calvo A, et al. A comparative study of 1992;58:679–682. trochanteric fractures treated with the Gamma nail or the proximal 20. Saudan M, Lubbeke A, Sadowski C, et al. Pertrochanteric fractures: femoral nail. Int Orthop. 2002;26:365–369. is there an advantage to an intramedullary nail?: a randomized, 15. Rosenblum SF, Zuckerman JD, Kummer FJ, et al. A biomechanical prospective study of 206 patients comparing the dynamic hip screw evaluation of the Gamma nail. J Bone Joint Surg Br. 1992;74:352– and proximal femoral nail. J Orthop Trauma. 2002;16:386–393. 357. 21. Jensen JS, Michaelsen M. Trochanteric femoral fractures treated with 16. Salvati EA, Wilson PD Jr. Long-term results of femoral-head McLaughlin osteosynthesis. Acta Orthop Scand. 1975;46:795–803. replacement. J Bone Joint Surg Am. 1973;55:516–524. 22. Wagner R, Blattert TR, Weckbach A. [Solution to the problem of 17. Haidukewych GJ, Israel TA, Berry DJ. Reverse obliquity fractures extra-articular, femoral hip fracture by the “sliding screw-nail of the intertrochanteric region of the femur. J Bone Joint Surg Am. principle”. Results of 2 different systems (classical nail and gamma 2001;83:643–650. nail)]. Unfallchirurg. 1998;101:894–900.

1060 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Plating of Femoral Shaft Fractures: Open Reduction and Internal Fixation Versus Submuscular Fixation Michael Zlowodzki, MD, Dennis Vogt, MD, Peter A. Cole, MD, and Philip J. Kregor, MD

Background: The standard treat- techniques were used. No bone grafting Conclusions: A 2.5% incidence of ment for femoral shaft fractures is in- was used for either group. A comparison of nonunion and a 5% incidence of infection tramedullary nailing. However, there are reduction quality, union rates, secondary in- (2 of 40; both in type III open fractures) indications for which plating can be per- terventions, and infection rates between tra- were seen in this series of 40 femoral shaft formed either openly or in a submuscular ditional open reduction and internal fixation fractures treated with plate application. manner. and submuscular fixation was performed Although the theoretical advantages of Methods: Between June 1996 and (retrospective cohort study/evidence-based submuscular plating are well established, May 2002, two fellowship-trained ortho- medicine (EBM)-level III). its utilization in the femoral shaft did not pedic trauma surgeons treated 40 acute Results: In assessing reduction qual- have a clear clinical advantage. In addi- diaphyseal femoral fractures in 37 pa- ity, there were no malreductions in the tion, its use appears to be more technically tients with use of plating techniques. Tra- traditional plating group and six in the challenging, and is associated with a high ditional open plating with emphasis on submuscular plating group. There was rate of suboptimal reductions. preservation of soft tissue integrity was one infection and one nonunion in the Key Words: Femur, Femoral, Frac- performed exclusively before February open reduction or internal fixation group. ture, Shaft, Submuscular plating, Internal .After that time point, in all One infection was noted in the submuscu- Fixation, Bridge plating .(19 ؍ n) 1999 .submuscular plating lar group (21 ؍ but one case (n J Trauma. 2007;63:1061–1065.

he standard treatment for femoral shaft fractures is in- plate fixation experience for femoral shaft fractures by two tramedullary nailing and is associated with less than a orthopedic trauma surgeons in a 6-year period at a university T1% rate of infection or nonunion.1 However, there are trauma center. Specifically, a comparison of reduction qual- indications for plating. Relative indications include an asso- ity, union rates, infection rates, and secondary interventions ciated femoral neck fracture, an associated acetabular frac- between traditional plate fixation and submuscular fixation ture, a vascular injury, an associated spinal fracture, young was performed. age (i.e. adolescent), and multisystem trauma. Published series of traditional plate fixation of the femur note rates of up to 69% primary bone grafting, 28% infection, 23% nonunion, PATIENTS AND METHODS 2–14 and 22% secondary surgical procedures (Table 1). A shift Between June 1996 and May 2002, 40 diaphyseal fem- from traditional plating to submuscular plating has thus oral fractures in 38 patients aged 16 years or greater were 15 ensued. This series entails an all-inclusive review of the managed utilizing plating via a traditional technique with a formal lateral incision (n ϭ 19), or submuscular plate fixation utilizing only a proximal and distal incision (n ϭ 21). Tra- Submitted for publication November 30, 2004. ditional plating was exclusively performed before February Accepted for publication July 17, 2007. 1999. All but one fracture after that date was treated by Copyright © 2007 by Lippincott Williams & Wilkins submuscular fixation (n ϭ 21). No bone grafting was utilized From the Department of Orthopedic Surgery (M.Z., P.A.C.), University of Minnesota, St. Paul, Minnesota; Department of Orthopaedic Surgery for either group. Overall, indications for plate fixation in 38 (D.V.), Bundeswehrkrankenhaus Berlin, Berlin, Germany; and Department patients included: multisystem trauma in 16 cases, ipsilateral of Orthopedic Surgery (P.J.K.), Vanderbilt University, Nashville, Tennessee. femoral neck fracture in 7 cases, ipsilateral acetabular frac- Presented at the following meetings: 6th European Trauma Congress; ture in 4 cases, spinal fracture in 4 cases, adolescence in 4 May 16–19, 2004; Prague, Czech Republic; 6th Annual Meeting of Euro- pean Federation of National Associations of Orthopaedics and Traumatology cases, vascular injury in 1 case, and pregnancy in 2 cases. The (EFORT); June 6–10, 2003; Helsinki, Finland; 38th Congress of the Euro- mechanism of injury for the 38 patients included a motor pean Society for Surgical Research; May 28–31, 2003; Ghent, Belgium; 18th vehicle crash in 35 cases, a pedestrian versus motor vehicle Annual Meeting of the Orthopaedic Trauma Association; October 9–11, crash in 1 case, a fall in 1 case, and a ballistic injury in 1 case. 2002; Toronto, Canada. Address for reprints: Philip J. Kregor, MD, Vanderbilt Orthopaedic The treatment of the fracture was performed within 24 hours Institute, Medical Center East, South Tower, Suite 4200, Nashville, TN in 32 cases, within 48 hours in 5 cases, and within 72 hours 37232; email: [email protected]. in 1 case. In all cases, a 4.5-mm broad compression plate DOI: 10.1097/TA.0b013e318154c0b4 (Synthes, Paoli, PA) was utilized.

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Table 1 Results of Plating of the Femoral Shaft

Nonunion Significant Secondary Primary Bone Delayed Infection (Noninfected, Failure of Refracture Surgical Grafting Union (%) Intact HW) Fixation (%) Procedures (%) (%) (%) (%) (%) Magerl (1979) (n ϭ 67/ORIF)2 16 3 0 5 11 3 18 Ruedi (1980) (n ϭ 127/ORIF)3 Not reported (10 6077222 double plated) Loomer (1980) (n ϭ 46/ORIF)4 30 7 2 0 13 9 Not reported Sprenger (1983) (n ϭ 37/ORIF)5 19 5 5 11 3 0 19 Thompson (1985) (n ϭ 77)6 21 0 1 3 12 3 17 Cheng (1985) (n ϭ 32/ORIF)7 35 0 3 0 9 9 Not reported O’Beirne (1986) (n ϭ 56)8 25 4 0 0 4 2 7 Heitemeyer (1987) (n ϭ 39/ORIF)9 Not reported 28 23 49 6 8 Not reported Heitemeyer (1987) (n ϭ 32/Submusc)9 N/A 0 0 9 3 0 Not reported Bostman (1989) (n ϭ 102/ORIF)10 Exceptionally 9 5 5 9 0 21 Wildburger (1991) (n ϭ 107/ORIF)11 If unstable medially 2 0 0 5 0 7 Van Niekerk (1992) (n ϭ 20/ORIF)12 35 10 0 6 0 0 At least 6 Wagner (1994) (n ϭ 199/ORIF)13 18 3 5 3 11 0 Not reported Geissler (1995) (n ϭ 71/ORIF)14 69 0 3 0 1 3 7

Demographics of Two Groups Group II: Submuscular Fixation Group I: Open Reduction or Internal Fixation The patients undergoing fixation of the femoral shaft In the group treated with open reduction or internal fracture via submuscular fixation were under complete mus- fixation, there were 16 closed fractures and 3 open fractures cular relaxation. The reduction of the femoral shaft was (2 Gustilo type I open fractures, 1 type III-C open fracture). achieved through use of manual traction, and sagittal plane The AO/OTA classification of the “32” diaphyseal femoral deformities were corrected by use of towel bumps placed fracture was four A-2, seven A-3, five B-2, two B-3, and posterior to the leg to recreate the anterior curvature of the one C-3. femur. A proximal incision through the skin subcutaneous tissue, iliotibial band, and vastus lateralis was then made in the proximal femur. The plate was then slid in a submuscular Group II: Submuscular Fixation manner down the shaft of the femur. A distal incision was In the group treated with submuscular fixation, there then made in the midlateral line of the femur over the distal were 18 closed fractures, and 3 open fractures (1 type I open end of the plate. Longitudinal traction with proper rotational fracture, 1 type II open fracture, 1 type III-A open fracture). control afforded by manual traction was then provided. With The AO/OTA classification of the “32” diaphyseal femoral surgical control of the proximal and distal end of the plate, fracture was two A-2, seven A-3, six B-2, three B-3, one C-2, and after assurance of appropriate length and rotation, the two C-3. most proximal and distal screw was placed into the plate through the incisions. The placement of these screws would Surgical Technique of the Two Groups then “lock in” length and rotation of the femoral shaft. Sag- Group I: Open Reduction or Internal Fixation ittal plane deformities could then be addressed. Often, a For the fractures treated by open reduction or internal mallet on the anterior aspect of the proximal end of the femur fixation, a midline incision was utilized and was centered combined with adjustment of the bumps posterior to the over the fracture. The iliotibial band was divided, as was the femur was helpful to obtain appropriate reduction, as viewed posterior fascia of the vastus lateralis muscle. The vastus with lateral fluoroscopy. Once the sagittal plane deformity lateralis muscle belly was then elevated off its posterior was corrected, percutaneous screws were then placed proxi- fascia, and the perforating vessels were ligated. Reduction of mal and distal to the fracture. An average plate length of 11 the fracture was achieved through a combination of manual holes was used. traction and clamp application between the plate and the proximal and distal femoral shaft fragments. Attention was Postoperative Treatment paid to minimize soft tissue dissection. Fractures with a Immediate range-of-motion exercises with a continuous transverse or oblique fracture line amenable to compression passive motion machine were begun immediately postopera- underwent compression either through the plate or with use of tively. Toe-touch weight bearing was allowed, if a contralat- a lag screw. The anterior and medial muscular attachments to eral extremity injury did not prohibit this. Full weight the fracture fragments were maintained. An average plate bearing was initiated at the discretion of the treating at- length of nine holes was utilized. tending orthopedic trauma surgeon, based upon clinical

1062 November 2007 Plating of Femoral Shaft Fractures examination, the patient’s symptoms, and radiographic around the thigh, and a severe head injury. At 18 months analysis of callus formation. follow-up, his range of motion of the knee was 5 degrees to 95 degrees. Radiographs were initially significant for 12 mm Radiographic Analysis of Reduction Quality of anterior translation of the proximal femoral shaft, and the One observer (D.V.) performed blinded quantitative assess- eventual development of a large amount of heterotopic ossi- ment of reduction quality without knowledge of operative tech- fication along the anterior femoral shaft. A Judet quadricep- nique. Malreductions were defined as (1) greater than 3 degrees splasty was offered to the patient, but was declined. The of varus or valgus malalignment; and (2) greater than 10 mm of second patient (group II) was a 16-year-old boy who sus- translation in either the frontal or sagittal plane. No attempt was tained a left “T-type” acetabular fracture and an ipsilateral made to quantify malrotational deformities radiographically, as proximal one-third femoral shaft fracture. The patient ini- this would have required a CT scan. tially underwent open reduction or internal fixation of the posterior column component of his acetabular fracture, and Clinical Follow-Up submuscular plating of the femoral shaft fracture, all in a All patients were followed until union by the attending prone position. Postoperative radiographs revealed a 5-degree orthopedic trauma surgeon. Time to full weight bearing and valgus deformity, which was deemed unacceptable. There- the need for secondary interventions was noted. Infectious fore, at the time of his planned second-stage open reduction complications were defined as the need for any irrigation and and internal fixation of his anterior column acetabular frac- debridement or prolonged antibiotics. Average follow-up was ture, he underwent revision open reduction and internal 15 months (range, 3–48 months). Two patients were lost to fixation of the femur fracture. He developed significant follow-up after 3 months of follow-up. (Both of their frac- heterotopic ossification, with a knee motion of 5 degrees to tures had healed uneventfully.) 90 degrees. Therefore, at 6 months postinjury, he underwent removal of heterotopic ossification around the femur and hip. RESULTS At 1 year postinjury, he had a symmetrical knee range of Intraoperative Complications and Reduction Quality motion (0–135 degrees), and had returned to competitive There were no malreductions in group I (ORIF). There high-school soccer. were no intraoperative complications in group I. In group II Overall, the average time to full weight bearing was 15.5 (submuscular fixation), there were three cases of posterior weeks. There was no significant difference in time of full translation (Ͼ10 mm) of the distal shaft relative to the prox- weight bearing between the two groups: 16 weeks for group imal shaft, two cases of anterior translation (Ͼ10 mm) of the I (open reduction or internal fixation) and 15 weeks for group distal shaft relative to the distal shaft, and one case of 5 II (submuscular plating). The range of motion of the knee was degrees of valgus deformity. There were two cases of screw eventually at least 120 degrees of flexion and 0 degrees of breakage when a screw was utilized in an attempt to correct extension in all patients except two, who lacked 5 degrees of a frontal plane deformity (e.g. to “bring in” an adducted knee extension (group II). There were no malrotation defor- proximal femoral shaft fragment). mities detected on clinical examination in either group. How- ever, a radiographic assessment of malrotation would have Postoperative Complications, Fracture Union, and required a computed tomography scan and was therefore not Time to Full Weight Bearing performed. Thirty-nine of 40 femoral shaft fractures healed without need of a secondary procedure. The one nonunion occurred in DISCUSSION a patient with a distal one-third femoral shaft fracture and a Traditional open reduction or internal fixation of a fem- contralateral intertrochanteric hip fracture sustained from a oral shaft fracture is associated with rates up to 49% of 100-feet fall in a parachuting crash (group I). Both fractures delayed union, 28% infection, and 23% nonunion, despite the required further operative intervention for nonunions. The liberal use of bone grafting2–14 (Table 1). Because of this, patient had plate breakage on the femoral shaft fracture, and submuscular plating has gained clinical popularity, but there had removal of the hardware, bone grafting, and antegrade has been limited reports of it, especially for treatment of intramedullary nailing. The fracture went on to unite without femoral shaft fractures.9 Submuscular application of the plate difficulty. The infection rate was 2 of 40 fractures (5%). is associated with less soft tissue stripping and devascular- The infections occurred in the setting of a type III-C open ization of bony fragments. This “bridging” of the fracture site femoral shaft fracture (group I) and a type III-A open theoretically should promote fracture healing and decrease fracture (group II). the incidence of complications such as infection and refrac- Two patients in group II (submuscular fixation) devel- ture. Farouk et al. demonstrated in multiple human cadaver oped significant heterotopic ossification around the femoral studies that a minimally invasive percutaneous plating tech- shaft, which significantly impaired knee motion. The first nique (MIPPO) disrupts the femoral blood supply less than patient (group II) sustained a complex pelvic ring injury, a the traditional open method.16–18 The MIPPO technique was proximal one-third femoral shaft fracture, a degloving injury associated with a better periosteal and medullary perfusion

Volume 63 • Number 5 1063 The Journal of TRAUMA௡ Injury, Infection, and Critical Care than conventional plate osteosynthesis. Krettek et al. reported tures) was seen in this series of 40 femoral shaft fractures good results using MIPPO in the treatment of proximal and treated with plate application. Although the theoretical ad- distal femur fractures.19,20 It should be noted, however, that vantages of submuscular plating are well established, its a submuscular technique is not absolutely necessary to utilization in the femoral shaft did not have a clear clinical obtain desirable results. However, it does appear that advantage. In addition, its use appears to be more technically maintenance of the soft tissue environment around the challenging, and is associated with a high rate of suboptimal fracture is paramount for avoiding a high rate of non- reductions. unions. The advantage of “biologic plating” has been demonstrated in subtrochanteric femoral, femoral shaft, and supracondylar femoral fractures.21–25 REFERENCES Heitemeyer et al. compared the outcome of 39 severely 1. Winquist RA, Hansen ST Jr, Clawson DK. Closed intramedullary comminuted femoral shaft fractures treated in an open man- nailing of femoral fractures. A report of five hundred and twenty 9 cases. J Bone Joint Surg Am. 1984;66:529–539. ner with 32 treated with bridge-plating osteosynthesis. The 2. Magerl F, Wyss A, Brunner C, et al. Plate osteosynthesis of femoral outcome results were overwhelmingly better for the bridging- shaft fractures in adults. A follow-up study. Clin Orthop Relat Res. plate group. He reported no nonunions and no infections for 1979;138:62–73. fractures treated with bridge-plating osteosynthesis, com- 3. Ruedi TP, Luscher JN. Results after internal fixation of comminuted pared with 11 nonunions, 2 early infections, and 7 late infec- fractures of the femoral shaft with DC plates. Clin Orthop Relat Res. 1979;138:74–76. tions in the group treated in an open manner. 4. Loomer RL, Meek R, De Sommer F. Plating of femoral shaft The results of the current study represent the 6-year fractures: the Vancouver experience. J Trauma. 1980;20:1038–1042. experience of two orthopedic trauma surgeons in plating of 5. Sprenger TR. Fractures of the shaft of the femur treated with a the femoral shaft. This report is not intended to satisfy the single AO plate. South Med J. 1983;76:471–474. need for a randomized, prospective study of sufficient sam- 6. Thompson F, O’Beirne J, Gallagher J, et al. Fractures of the femoral shaft treated by plating. Injury. 1985;16:535–538. ple size to draw statistically significant conclusion. How- 7. Cheng JC, Tse PY, Chow YY. The place of the dynamic ever, the results may be useful to the surgeon in deciding compression plate in femoral shaft fractures. Injury. 1985;16:529– upon a method when faced with an indication for plating of 534. a femoral shaft fracture. 8. O’Beirne J, O’Connell RJ, White JM, et al. Fractures of the femur Overall, the nonunion rate in this series was 1 of 40 treated by femoral plating using the anterolateral approach. Injury. 1986;17:387–390. fractures (2.5%), without the use of primary bone grafting. As 9. Heitemeyer U, Kemper F, Hierholzer G, et al. Severely comminuted seen in Table 1, reported rates of bone grafting have ranged femoral shaft fractures: treatment by bridging-plate osteosynthesis. from 16% to 69%. As has been shown in the distal femur and Arch Orthop Trauma Surg. 1987;106:327–330. proximal femur, a high rate of union without bone grafting 10. Bostman O, Varjonen L, Vainionpaa S, et al. Incidence of local can be expected in the femoral shaft if the biology of the complications after intramedullary nailing and after plate fixation of femoral shaft fractures. J Trauma. 1989;29:639–645. fracture zone is minimally disturbed. This does not necessar- 11. Wildburger R, Mahring M, Hofer HP. [Experience with plate ily require submuscular techniques. For example, Bolhofner osteosynthesis in femoral shaft fractures]. Aktuelle Traumatol. 1991; et al. reported high union rates of supracondylar femur frac- 21:182–188. tures with open reduction or internal fixation utilizing “indi- 12. van Niekerk JL, Schoots FJ. Femoral shaft fractures treated with rect reduction” techniques.25 Thus, although a skin incision is plate fixation and interlocked nailing: a comparative retrospective study. Injury. 1992;23:219–222. made, which is relatively long, the soft tissue envelope 13. Wagner R, Weckbach A. [Complications of plate osteosynthesis of around the fracture is maintained. the femur shaft. An analysis of 199 femoral fractures]. There appears to be no striking difference between the Unfallchirurg. 1994;97:139–143. two methods in terms of nonunion, infection, or need for 14. Geissler WB, Powell TE, Blickenstaff KR, et al. Compression secondary interventions. Obviously, a larger prospective plating of acute femoral shaft fractures. Orthopedics. 1995;18:655– 660. study with significant power to investigate these issues is 15. Rozbruch SR, Muller U, Gautier E, et al. The evolution of femoral necessary to definitively make this statement. Anecdotally, shaft plating technique. Clin Orthop Relat Res. 1998;354:195–208. the technical challenge of performing submuscular fixation of 16. Farouk O, Krettek C, Miclau T, et al. Minimally invasive plate the femoral shaft is greater than that of an open reduction or osteosynthesis and vascularity: preliminary results of a cadaver internal fixation. This is especially seen in the difficulty in injection study. Injury. 1997;28:A7–A12. 17. Farouk O, Krettek C, Miclau T, et al. Minimally invasive plate obtaining an appropriate reduction in the sagittal plane. The osteosynthesis: does percutaneous plating disrupt femoral blood proximal segment was translated greater than 10 mm in 5 of supply less than the traditional technique? J Orthop Trauma. 1999; 21 fractures. The clinical significance of this is unknown. 13:401–406. Theoretically, anterior translation of the proximal fragment 18. Farouk O, Krettek C, Miclau T, et al. Effects of percutaneous and may lead to irritation of the quadriceps muscle and decreased conventional plating techniques on the blood supply to the femur. Arch Orthop Trauma Surg. 1998;117:438–441. range of motion of the knee. 19. Krettek C, Schandelmaier P, Miclau T, et al. Transarticular joint In conclusion, a 2.5% incidence of nonunion, and a 5% reconstruction and indirect plate osteosynthesis for complex distal incidence of infection (2 of 40; both in type III open frac- supracondylar femoral fractures. Injury. 1997;28:A31–A41.

1064 November 2007 Plating of Femoral Shaft Fractures

20. Krettek C, Schandelmaier P, Miclau T, et al. Minimally invasive 23. Baumgaertel F, Gotzen L. [The “biological” plate osteosynthesis in percutaneous plate osteosynthesis (MIPPO) using the DCS in multi-fragment fractures of the para-articular femur. A prospective proximal and distal femoral fractures. Injury. 1997;28:A20–A30. study]. Unfallchirurg. 1994;97:78–84. 21. Baumgaertel F, Buhl M, Rahn BA. Fracture healing in biological 24. Kesemenli C, Subasi M, Necmioglu S, et al. Treatment of plate osteosynthesis. Injury. 1998;29:C3–C6. multifragmentary fractures of the femur by indirect reduction 22. van Riet YE, van der Werken C, Marti RK. Subfascial plate (biological) and plate fixation. Injury. 2002;33:691. fixation of comminuted diaphyseal femoral fractures: a report of 25. Bolhofner BR, Carmen B, Clifford P. The results of open reduction three cases utilizing biological osteosynthesis. J Orthop Trauma. and internal fixation of distal femur fractures using a biologic 1997;11:57–60. (indirect) reduction technique. J Orthop Trauma. 1996;10:372–377.

Volume 63 • Number 5 1065 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

The Epidemiology of Pelvic Ring Fractures: A Population-Based Study Zsolt Balogh, MD, PhD, FRACS, Kate L. King, RN, MN, Peter Mackay, RN, Debra McDougall, RN, Stuart Mackenzie, BMed, BMedSc, Julie A. Evans, RN, Timothy Lyons, MBChB, MD, FRCS (Ed), FRCPATH, FRCPA, DMJ (Path), DipAvMed, and Stephen A. Deane, MB BS, FRACS, FACS, FRCSC

Background: The severity of pelvic low-energy pelvic fractures (LE-PRFs), and the PD-PRF group). The PRF-related ring fractures (PRFs) can range from mi- prehospital deaths (PD-PRFs). mortality was 7% (HE-PRF: 7%; LE- nor injury with low-energy mechanism to Results: The incidence of PRF in the PRF: 2%; PD-PRF: 33%), which was high-energy injury causing prehospital trauma system was 23 per 100,000 persons always attributable to bleeding. The inci- death. The purpose of this study was to (138 fractures). The incidences of HE- dence of demonstrated pelvic fracture- prospectively describe the comprehensive PRF and LE-PRF were each 10 per related arterial bleeding was 1.3 per pelvic fracture occurrence in an inclusive 100,000 persons, whereas there were 3 100,000 persons per year. trauma system. PD-PRFs per 100,000. HE-PRF compared Conclusions: LE-PRF and HE-PRF Methods: A 12-month prospective, with LE-PRF occurred predominantly in are equally frequent among hospital ad- population-based epidemiologic study was men (64% vs. 20%, p < 0.05), younger missions. They represent two distinct de- performed in the Hunter Region, New persons (41 ؎ 3 vs. 83 ؎ 1 years, p < mographic groups with similar mortality South Wales, Australia (population of 0.05), those who had a higher Injury Se- rate. Most PRF-related deaths occur preserved by one Level I trauma verity Score (23 ؎ 3 vs. 6 ؎ 1, p < 0.05), hospitally. Bleeding remains the primary ,600,000 center and 7 referring hospitals). Patient and those with lower blood pressure cause of PRF-related mortality in all .demographics, mechanism, injury sever- (111 ؎ 1 mm Hg vs. 153 ؎ 1mmHg,p < groups ity, shock parameters, and outcomes were 0.05), but the inhospital mortality rate was Key Words: Pelvic fracture, Epide- recorded prospectively. The database in- not statistically different (15% vs. 8%, miology, Hemorrhagic shock, Pelvic NS). The overall mortality of the co- fixation, Acute pelvic fixation, Pelvic ؍ cluded all pelvic fractures from the region: p high-energy pelvic fractures (HE-PRFs), hort was 23% (60% of those were from angiography. J Trauma. 2007;63:1066–1073.

elvic ring fracture (PRF) is a common injury with occurrence of low-energy PRFs (LE-PRFs), but studies do significant morbidity and mortality.1–5 Severity can indicate the growing significance of this subgroup.12,13 The Prange from minor injury, causing pain and inconve- trauma registries are primarily not focused to collect all nience, to high-energy injury, causing prehospital death. LE-PRFs.14 Some studies indicated that the current estimates The publications on pelvic fractures infrequently re- of the mortality of pelvic fractures may be faulty because flect this wide variation in severity. Most of the available most critical PRF patients die during the prehospital phase literature is concerned with the inhospital management and (prehospital deaths with PRF [PD-PRF]).15,16 The incidence outcomes of patients who have suffered high-energy PRF of these injuries and its magnitude when compared with (HE-PRF).6–11 The data collection is often retrospective and inhospital-treated HE-PRFs are poorly understood. The com- trauma registry based, and only the Level I trauma center prehensive (HE-PRF, LE-PRF, and PD-PRF), population- admissions are considered. Less data are available on the based prevalence of pelvic fractures is largely unknown. The purpose of this study was to prospectively and com- Submitted for publication September 25, 2006. prehensively describe the population-based prevalence of pel- Accepted for publication August 16, 2007. vic fracture in an inclusive trauma system, with special focus Copyright © 2007 by Lippincott Williams & Wilkins on issues relevant to clinical management such as hemor- From the Department of Trauma (Z.B., K.L.K., P.M., D.M., J.A.E.), Department of Orthopaedics (S.M.), Department of Forensic Pathology rhagic shock, associated injuries, and short-term outcomes. (T.L.), and Division of Surgery (S.A.D.), John Hunter Hospital and Univer- sity of Newcastle, Newcastle, New South Wales, Australia. Presented at the 65th Annual Meeting of the American Association for METHODS the Surgery of Trauma, September 28–30, 2006, New Orleans, Louisiana. Address for reprints: Zsolt Balogh, MD, PhD, FRACS, Department of A 12-month population-based prospective epidemiologic Trauma, Division of Surgery, John Hunter Hospital, Locked Bag 1, Hunter study was performed from April 1, 2005 to March 31, 2006. Region Mail Centre, Newcastle NSW 2300; email: zsolt.balogh@hnehealth. The study was observational only; the State Coroner of New nsw.gov.au. South Wales and the Hunter New England Area Health Ser- DOI: 10.1097/TA.0b013e3181589fa4 vice Ethics Committee provided a waiver for this research

1066 November 2007 Epidemiology of Pelvic Ring Fractures and publication. The population of the Hunter Region (12,000 In the prehospital death group, only patients who lived long square miles and a population of 600,000) of the Hunter New enough to develop massive retroperitoneal hematoma were England Area Health Service, New South Wales, Australia defined as PRF-related deaths. was studied. This region is served by the John Hunter Hos- Data are presented as percentages, means, and SEM. For pital (JHH), a University of Newcastle-affiliated Level I statistical analysis, ␹2 test was used for nonparametric scale trauma center, and seven referring hospitals. The JHH is the assessment, and t test (unpaired, two-tailed) was used to busiest trauma center in the state of New South Wales, with compare parametric quantities. PRF groups were compared 4,500 annual trauma admissions including 420 trauma admis- with the whole cohort, HE-PRF versus LE-PRF, LE-PRF sions with an Injury Severity Score (ISS) greater than 15. versus PD-PRF, and HE-PRF versus PD-PRF. Significance The JHH has evidence-based PRF guidelines in place. was established at p Ͻ 0.05. These guidelines include emergency pelvic binding (Ͻ15 minutes of arrival), pelvic radiography (Ͻ10 minutes), blood RESULTS gas analysis (Ͻ30 minutes), emergency abdominal diagnosis During the 12-month study period, 157 fractures were (focused abdominal sonography for trauma [FAST]; or diag- prospectively identified in the trauma system on pelvic bones; nostic peritoneal aspiration or lavage [DPA/DPL]) (Ͻ15 min- of those, 138 were acute traumatic PRFs (23 PRFs per utes), laparotomy if significant hemoperitoneum is found 100,000 persons per year) and were further evaluated (Fig 1). (Ͻ45 minutes), massive transfusion protocol, pelvic angiog- The incidences of HE-PRF and LE-PRF in the Hunter Region raphy or embolization (Ͻ90 minutes), and minimally in- were shown to be each 10 cases per 100,000 persons per year, vasive pelvic fixation (Ͻ12 hours).17 The guidelines were whereas the incidence of PD-PRF was 3 per 100,000 persons prospectively evaluated and found to be highly effective in per year. the Australian environment.18 The JHH criteria for pelvic The demographics, ISS, SBP, and fracture classification angiography are (1) hemorrhagic shock on arrival with are summarized in Table 1. The HE-PRF patients were pre- base deficit (BD) worse than -6 mmol/L caused by pelvic dominantly male, younger, more severely injured, and have a bleeding; (2) expanding pelvic retroperitoneal hematoma lower SBP than the LE-PRF patients did. The ISS of the diagnosed in patients requiring urgent laparotomy for in- PD-PRF group was significantly higher than the cohort’s ISS traperitoneal bleeding; or (3) contrast blush on pelvic computed tomography. A prospective pelvic fracture database was maintained for all pelvic fractures (HE-PRF, LE-PRF, and PD-PRF) in the trauma system (from all hospitals and all prehospital deaths). Acetabular fractures without PRF and sacral and pubic rami insufficiency fractures without falls were excluded, but pathologic fractures (pelvic metastases) were considered if trauma was in the history (low-energy fall). High-energy fractures were defined as road and traffic-related injuries, high falls, and industrial and agricultural injuries. Fractures were classified prospectively as type A, B, or C according to the Tile classification, which includes both mechanism and potential instability.19 Patient demographics, injury mechanism, ISS, injury pattern (based on the Abbre- viated Injury Scale [AIS]),20 intraperitoneal injuries, bladder and urethral injuries, systolic blood pressure (SBP), arterial BD, transfusion requirements, the presence of hemorrhagic shock, comorbidities of LE-PRF, length of stay (LOS), mortality, and PRF-related mortality were also recorded prospectively. Hemorrhagic shock was defined prospectively based on the patient’s metabolic status (BD worse than 6 mmol/L), transfusion requirements (2 or more units of packed red blood cell transfusion during the first 6 hours after admission), and clinical signs of inadequate organ perfusion, which was consistent with the source(s) of bleeding on clinical examination, imaging, during surgery, or at postmortem examination. PRF- related mortality was defined if a patient had hemorrhagic shock caused primarily by the pelvic injury and had no significant head injury and no other life-threatening injuries. Fig. 1. Study population.

Volume 63 • Number 5 1067 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Table 1 Demographics, Injury Severity, and Fracture Pattern of Pelvic Ring Fracture Patients

Patient Group N Male (%) Age (yr) ISS SBP (mm Hg) Tile A/B/C% All 138 43 59 Ϯ 220Ϯ 2 NA 61/26/13 High-energy 59 64*† 41 Ϯ 3*† 23 Ϯ 3 111 Ϯ 1† 41/41/18 Low-energy 61 20 83 Ϯ 16Ϯ 1*† 153 Ϯ 1 98/2/0 Prehospital death 18 50 41 Ϯ 6*‡ 61 Ϯ 4*‡§ NA 0/53/47 * p Ͻ 0.05, compared with the cohort; † p Ͻ 0.05, HE-PRF versus LE-PRF; ‡ p Ͻ 0.05, LE-PRF versus PD-PRF; and § p Ͻ 0.05, HE-PRF versus PD-PRF were considered significant. ISS, Injury Severity Score; SBP, systolic blood pressure; Tile A/B/C%, percentage of patients having types A/B/C fractures based on the Tile classification. and the HE-PRF group’s ISS. The most frequent fracture There were seven isolated PRFs in the high-energy group pattern was the Tile type A rotationally and vertically stable (12%). HE-PRF patients suffered 349 AIS-coded injuries, PRFs (84 of 139 [61%]) followed by the rotationally unstable which is equivalent to 5.9 Ϯ 0.5 AIS-coded injuries per Tile type B PRFs (36 of 138 [26%]) and the rotationally and patient. In the LE-PRF group, only three patients (5%) had vertically unstable Tile type C PRFs (18 of 138 [13%]). The associated injuries: two head injuries and one chest injury. occurrence of more type B and C fractures in the high-energy The distribution of associated injuries of the HE-PRF and group and prehospital mortality groups is obvious. There PD-PRF patients is depicted in Figure 4. PD-PRF patients were three open PRFs among the high-energy injury mech- had significantly more injuries to the face AIS region (61% anism patients and one in the PD-PRF group, which is an vs. 5%, p Ͻ 0.05) and in the chest AIS region (89% vs. 44%, incidence of 4 of 138 (3%) in all PRF patients and 0.67 per p Ͻ 0.05). 100,000 persons per year in the region. Nine (15%) patients in the HE-PRF group and seven The age distribution of the cohort (Fig. 2) shows that the (39%) in the PD-PRF group had intraperitoneal organ inju- HE-PRF patients and the PD-PRF group had a similar pattern ries. There were five (8%) bladder injuries in the HE-PRF with peaks between the ages of 10 and 40 years, whereas 72% group and two (11%) in the PD-PRF group. Considering the of the LE-PRF group was more than 80 years old. Of the 61 LE-PRF patients, 5 (8%) had no comorbidities, 5 (8%) patients had at least one comorbidity, and 51 (84%) had multiple comorbidities. Sixteen (26%) of the LE-PRF patients required acute involvement of other medical or surgical teams, other than orthopedics and geriatrics, to manage their comorbidities. There were eight pediatric patients (younger than 16 years) in the HE-PRF group and three in the PD-PRF group, and thus, 11 of the 138 (8%) in the entire cohort were children. The mechanism of injury among the LE-PRF patients was exclusively fall from less than 1 m. The predominant mechanism in both the high-energy and the prehospital mortality group was road and traffic related, with 31% motorbike Fig. 3. Mechanism of injury in patients with pelvic ring injuries. crashes, 27% car crashes, and 22% pedestrians hit by car (Fig. 3).

Fig. 4. Frequency of injuries in the six Abbreviated Injury Scale Fig. 2. Age distribution of the pelvic ring fracture patients. categories of pelvic ring fracture patients (*p Ͻ 0.05).

1068 November 2007 Epidemiology of Pelvic Ring Fractures

Table 2 Transfusion Requirements and Outcomes of Pelvic Ring Fracture Patients

Patient Group N PBRCs (Units) LOS (days) Mortality PRF-Related All 138 NA 10 Ϯ 1 32 (23%) 10 (7%) High-energy 59 3 Ϯ 0.7† 15 Ϯ 3 9 (15%) 3 (7%) Low-energy 61 0.5 Ϯ 0.2 8 Ϯ 1 5 (8%) 1 (2%) Prehospital death 18 NA 0 18 (100%) 6 (33%)*‡§ * p Ͻ 0.05, compared the cohort; § p Ͻ 0.05, HE-PRF versus LE-PRF; ‡ p Ͻ 0.05, LE-PRF versus PD-PRF; and § p Ͻ 0.05, HE-PRF versus PD-PRF were considered significant. PRBCs, packed red blood cells; LOS, hospital length of stay; PRF-Related, pelvic ring fracture related mortality. whole cohort, the incidence of pelvic fracture-associated (4 external fixators, 5 symphyseal plates, and 7 percutaneous bladder injury was 5% (7 of 138). One patient had intraperi- iliosacral screw fixations). toneal bladder rupture, and four had extraperitoneal injuries. The mean length of stay and mortality data are listed in There were three (5%) urethral injuries in the HE-PRF group, Table 2. The overall mortality was 32 of 138 (23%). The which is 2% when considering all pelvic fractures. mortality rates of the HE-PRF patients (15%) and the LE- There were 11 (19%) HE-PRF patients and one (2%) LE- PRF patients (8%) were not statistically different. PRF was PRF patient with initial SBP of 90 mm Hg or less. Arterial blood found to directly contribute to death in 10 of the 138 patients gas samples were analyzed in 29 (49%) HE-PRF patients; their (7%); this constitutes 31% of the total mortality of the cohort. mean BD was Ϫ8 Ϯ 2 mEq/L. Twenty-five (42%) of the Mortality was attributable to PRF in 3 of 9 (33%) of the high-energy and one (2%) of the low-energy patients received HE-PRFs, 1 of 5 (20%) of the LE-PRFs, and 6 of 18 (33%) blood transfusion during the first 24 hours (first 24-hour of the prehospital deaths. Of the three PRF-related deaths in transfusion in Table 2). Thirteen of the HE-PRF patients the high-energy group, all had significant pelvic bleeding (22%) had hemorrhagic shock (SBP: 98 Ϯ 11 mm Hg; BD: identified on imaging. All three patients presented in pro- Ϫ13 Ϯ 2 mm Hg; transfusion: 11 Ϯ 2 units), and the hem- found shock and had multiple injuries. No patients had pul- orrhagic shock was caused primarily by pelvic bleeding in monary embolism. One LE-PRF patient had a low-risk type eight cases (14% of all HE-PRF patients, 62% of the shocked A fracture and developed massive retroperitoneal hematoma. patients). Other causes of hemorrhagic shock were abdominal The four other LE-PRF deaths were caused by cardiac failure bleeding in two cases, thoracic bleeding in two cases, and (2 cases), closed head injury (1 case), and pneumonia secondary to chest injury (1 case). The six PD-PRF victims had multiple open long bone fractures with severe external bleed- major pelvic vessel injury and massive pelvic hematoma ing in one case. Only 6 of 13 (46%) of the hemorrhagic shock without major head injury or significant other sources of patients had SBP Ͻ90 mm Hg, and 5 of 11(45%) of the SBP bleeding. Ͻ90 mm Hg patients had no hemorrhagic shock, based on arterial blood gas analysis, clinical indicators of tissue per- DISCUSSION fusion, and resuscitation requirements, and no bleeding was The overall population-based incidence of PRF in the identified on their imaging. Hunter Region is 23 per 100,000 persons per year. Pelvic Six (10%) patients in the high-energy group underwent fractures are present in a very diverse group of trauma pelvic angiography (5 Tile C and 1 Tile B type injury), it patients.6,12,15 The spectrum of injury severity ranges from 1 revealed arterial bleeding or arterial injury in all of them. (minimally displaced, mechanically stable pelvic ring frac- There was one high-energy patient and one low-energy pa- ture after a simple fall in hemodynamically normal patients tient who could have potentially benefited from pelvic an- [LE-PRF, 10 per 100,000 persons per year]), through 2 (chal- giography; both of them were elderly patients (older than 80 lenging multiple injuries in patients with high-energy injury years) and had Tile type A and B mechanically stable frac- mechanism with potential hemorrhagic shock [HE-PRF, 10 tures. The overall incidence of arterial bleeding from pelvic per 100,000 persons per year]), to 3 (rapidly exsanguinating fracture patients is 1.3 per 100,000 persons per year who catastrophic pelvic ring disruptions in patients who do not reach the hospital. even reach the hospital [PD-PRF, 3 per 100,000 persons per Seven (12%) high-energy patients had laparotomy, and year). These three major categories correspond to very dis- three of the laparotomies were nontherapeutic. None of the tinct resources, needs, and strategies in injury prevention, nontherapeutic laparotomy patients underwent FAST or diagnostics, resuscitation, surgical management, and clinical DPA/DPL; the attending surgeon made this decision based on research. Our prospective, population-based study describes physical examination and vital signs. There were no compli- the comprehensive prevalence of PRFs and the characteristics cations related to the nontherapeutic laparotomies, and all of these three major categories. three patients survived. Nine (15%) high-energy patients had A seminal article from the Mayo Clinic aimed to evalu- emergency pelvic ring fixation within 12 hours of admission ate the population-based prevalence of PRFs more than 25

Volume 63 • Number 5 1069 The Journal of TRAUMA௡ Injury, Infection, and Critical Care years ago and identified retrospectively 198 PRFs during a proportion is expected to be 28% by the year of 2031.30 JHH decade in a population of 55,000 persons (35 pelvic fractures (the only Level I trauma center in the region) admitted 49% per 100,000 persons per year).21 This article did not comment of all LE-PRF patients as primary admission with an average on outcomes and on the relative incidence of each subgroups LOS of 8 days, which is not different from the HE-PRF we described. patients’ LOS (Fig. 1 and Table 2). Whether these patients Muir et al. retrospectively studied PRFs in trauma pa- should be admitted to the Level I trauma center or lower-level tients with an ISS Ͼ15 and all prehospital deaths during a facilities is beyond the scope of this study. This subgroup of 12-month period.22 The overall incidence of prehospital predominantly elderly patients (mean age of 83 years) with deaths in their region was 5 per 100,000 persons per year, and multiple comorbidities and low ISS (mean ISS of 6) is very 3.5 per 100,000 persons per year for PRF patients who sur- different from the rest of the PRF patients.28 Although vived to the hospital. In our region, the incidences according reported,31 the LE-PRF patients’ mortality is very infre- to these filters were 9 per 100,000 persons per year and 6 per quently attributable to pelvic bleeding (2% in this study). 100,000 persons per year, respectively. The discrepancy However, the elderly is at risk of associated significant head could be attributed to the different study designs (retrospec- and chest injuries (5% in this study). LE-PRF patients gen- tive vs. prospective) or to the potential differences between erally require geriatrics, specialized medical care and phys- the regions. Two North European studies investigated the iotherapy, ergotherapy, and so forth, after trauma-related prevalence of hospitalized PRF patients only. From a Swed- hemodynamic compromise and other injuries are excluded. ish County, the published incidence was 20 per 100,000 Our demographic and injury mechanism data further persons per year, and from all of Finland, the incidence was support the expected differences between the high- and low- 29 per 100,000 women and 20 per 100,000 men.23,24 The energy groups (Tables 1 and 2). It also shows LE-PRF and German Multicenter Study Group (pelvis) of the German HE-PRF as different diseases, with different spectrums of Trauma Society provided a very detailed description of 3,260 injuries and care needs. The PD-PRF group is demographi- PRF patients during a 3-year period from nine major centers, cally similar to the hospital-treated HE-PRF patients, and for but the admissions to the lower-volume centers as well as the purposes of trauma system planning and evaluation, these number of PD-PRF patients and the denominator (covered should be regarded as one group with a continuum of injury population) are unknown.25 severity. PRF is a frequent autopsy finding among high-energy After the exclusion of bleeding outside of the abdomi- trauma victims.26 To date, the relative incidence of PD-PRF nopelvic region, prompt performance of abdominal diagnostic is unknown. In our study, the incidence of PD-PRF was 3 per tests is essential in the HE-PRF group to triage them efficiently 100,000 persons per year, 13% of all PRFs and 23% of all toward pelvic (angio or packing with temporary fixation) or HE-PRFs occurred in patients who died prehospitally. abdominal hemorrhage control (laparotomy).17,18 However, Roughly, for every three pelvic fractures treated in the trauma only 15% of the HE-PRF patients had intraperitoneal injuries, bay, one does not reach the hospital. The current safety and only half of them required urgent laparotomy. Because measures in cars are not efficient enough to prevent cata- most of the trauma patients with major pelvic fractures have strophic pelvic injuries. Lateral and near-lateral impacts es- abdominal symptoms, a liberal approach to exploratory pecially create high-risk, even in newer cars with the latest laparotomy, based on that alone, could lead to a high non- safety technology mandated by federal law.27 In addition, we therapeutic laparotomy rate, as we demonstrated. However, identified in the PD-PRF group more injuries in the AIS chest sometimes surgeons have to deal with this option to rule out region (Fig. 4), which is consistent with rapidly fatal cardiac other significant surgical injuries. Our institution’s nonthera- and aortic lacerations. Only few studies investigated specif- peutic laparotomy rate in this group was three of seven ically the PD-PRF group and their unequivocal conclusion is (43%), whereas our general nontherapeutic laparotomy rate is that pelvic fracture in rapidly fatal trauma scenarios is a below 10% for blunt trauma. In each of these three cases, the marker of significant energy transfer.15,16 Our 23% incidence institutional protocol for management of hemodynamically of pelvic fractures in trauma victims who died prehospital unstable pelvic fracture patients was violated (no emergency with relevant injury mechanism is consistent with the 23% to abdominal diagnostic was performed). 25% incidence published previously.15,16 The management of patients with multiple blunt injuries The significance of the LE-PRFs is increasingly recog- with potential unstable pelvic fractures can be very challeng- nized worldwide.12,13,28,29 There is a documented sharp in- ing and is far from the well-established international crease of low-energy osteoporotic PRF incidence in Finland consensus.2,5,7,8,32–36 On the basis of clinically used indices, in the population that is older than 60 years (from year 1970, we prospectively identified that 22% of the HE-PRF patients 20 per 100,000 persons; to year 1997, 92 per 100,000 presented in hemorrhagic shock and 62% of the shock was persons).13 In the Hunter Region hospitals, we admitted as attributable to PRF. We found that SBP Ͻ90 mm Hg was a many LE-PRFs as we did HE-PRFs (10 per 100,000 persons very poor indicator of hemorrhagic shock (46% of the paper year). This incidence is expected to grow steadily because tients who had shock had SBP Ͼ90 mm Hg and 45% of 15% of the region’s population is older than 65 years, and this patient who had SBP Ͻ90 mm Hg had no signs of shock).

1070 November 2007 Epidemiology of Pelvic Ring Fractures

Most of the current knowledge on hemodynamically unstable LE-PRF group and 33% in the HE-PRF and PD-PRF groups PRF patients is unfortunately based on trauma registry data (all related to pelvic hemorrhage) are clinically significant where shock is defined by SBP Ͻ90 mm Hg. Our approach figures and require focused attention. was to define hemorrhagic shock prospectively, based on the metabolic status, organ perfusion, and resuscitation require- Summary ments. The other potential bias in the literature in studies in Low-energy and high-energy pelvic fractures are equally which hemodynamic instability is defined retrospectively is frequent among hospital admissions, but they represent two that it could be caused by extrapelvic sources of bleeding. very distinct demographic groups with mortality that is not Although our protocol allows a liberal approach to significantly different. Thirteen percent of all pelvic fracture pelvic angiography, obviously not all of the study patients patients do not reach the hospital and represent 60% of all had angiography. Therefore, the pelvic arterial bleeding of pelvic fracture-related mortality. Sixty-two percent of high- 1.3 per 100,000 persons per year could be a slightly un- energy pelvic fracture patients admitted to hospital present in derestimated figure. On the basis of the prospective nature shock caused by pelvic hemorrhage. Fifteen percent of HE- of the study and that all deaths had postmortem examina- PRF patients have intraperitoneal injuries, but only half of tion, we think that the clinically relevant pelvic arterial them require urgent laparotomy. Bleeding remains uni- bleeders were recognized. formly the primary cause of pelvic fracture-related mor- Thirty-three percent of all PD-PRF patients’ deaths was tality in both high- and low-energy groups. The incidence attributable to pelvic bleeding. Although there are no inter- of arterial bleeding of pelvic fracture origin is 1.3 per national figures available for comparison, this figure seems to 100,000 persons per year. be high. Injury prevention and more rapid access to the place Based on our population-based epidemiologic data, fu- of injury in remote areas are mandatory to increase survival. ture improvements in pelvic fracture management should The inhospital PRF-related mortality rates of 7% in the HE- focus on (1) injury prevention, prehospital care, and early PRF group and 2% in the LE-PRF group are acceptable transportation to decrease prehospital mortality; (2) further outcomes. Even with these very low percentages, further optimization of delivery of care for hemodynamically un- improvement might be achieved with increased awareness of stable pelvic fracture patients; (3) the development of a potential arterial bleeding among the low-risk fracture pat- prospective prediction model for high- and low-energy pel- terns in elderly patients. Two of the four hospitalized PRF- vic fractures to identify arterial hemorrhage; and (4) to ad- related deaths (1 in HE-PRF and 1 in LE-PRF) occurred in dress the very distinct needs of the increasing population of minimally displaced type A and B fractures and those patients elderly patients with low-energy pelvic fractures. probably could have benefited from angiography. Fifteen percent of the HE-PRFs required urgent pelvic ring fixation because of hemodynamic instability and signif- REFERENCES icant displacement; complying with our protocol, all of them 1. Poole GV, Ward EF. 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11. Blackmore CC, Cummings P, Jurkovich GJ, Linnau KF, Hoffer EK, pelvic fractures: report of two representative cases and a description Rivara FP. Predicting major hemorrhage in patients with pelvic of technique. J Trauma. 2005;59:1510–1514. fracture. J Trauma. 2006;61:346–352. 36. Dyer GS, Vrahas MS. Review of the pathophysiology and acute 12. Boufous S, Finch C, Lord S, Close J. The increasing burden of management of haemorrhage in pelvic fracture. Injury. 2006;37:602– pelvic fractures in older people, New South Wales, Australia. Injury. 613. 2005;36:1323–1329. 37. Shuler TE, Boone DC, Gruen GS, Peitzman AB. Percutaneous 13. Kannus P, Palvanen M, Niemi S, Parkkari J, Jarvinen M. iliosacral screw fixation: early treatment for unstable posterior pelvic Epidemiology of osteoporotic pelvic fractures in elderly people in ring disruptions. J Trauma. 1995;38:453–458. Finland: sharp increase in 1970–1997 and alarming projections for 38. Connor GS, McGwin G Jr, MacLennan PA, Alonso JE, Rue LW the new millennium. Osteoporos Int. 2000;11:443–438. 3rd. Early versus delayed fixation of pelvic ring fractures. Am Surg. 14. Bergeron E, Lavoie A, Moore L, Bamvita JM, Ratte S, Clas D. 2003;69:1019–1023. Paying the price of excluding patients from a trauma registry. J Trauma. 2006;60:300–304. DISCUSSION 15. Adams JE, Davis GG, Alexander CB, Alonso JE. Pelvic trauma in Dr. Andrew B. Peitzman (Pittsburgh, Pennsylvania): rapidly fatal motor vehicle accidents. J Orthop Trauma. 2003; It’s a pleasure to discuss this very well-written paper on the 17:406–410. epidemiology of pelvic ring fractures. 16. Papadopoulos IN, Kanakaris N, Bonovas S, et al. Auditing 655 fatalities with pelvic fractures by autopsy as a basis to evaluate The paper reports 12 months of prospective epidemio- trauma care. J Am Coll Surg. 2006;203:30–43. logical data from a population of 600,000 in New South 17. Heetveld MJ, Harris I, Schlaphoff G, Balogh Z, D’Amours SK, Wales in Australia. And the authors categorize the pelvic Sugrue M. Hemodynamically unstable pelvic fractures: recent care fractures, excluding isolated acetabular fractures, as high en- and new guidelines. World J Surg. 2004;28:904–909. ergy pelvic fractures, low energy pelvic fractures, and then 18. Balogh Z, Caldwell E, Heetveld M, et al. Institutional practice guidelines on management of pelvic fracture-related hemodynamic prehospital deaths with associated pelvic fractures. instability: do they make a difference? J Trauma. 2005;58:778–782. The authors report what I think we have all observed in 19. Tile M. Acute pelvic fractures. I. Causation and classification. JAm our trauma bays, that young people are injured in high energy Acad Orthop Surg. 1996;4:143–151. crashes with significant displacement of the pelvis based on 20. American Association for Automotive Medicine. The Abbreviated Tile classification. In this paper the average ISS was 23. Injury Scale, 1990 Revision. Des Plaines, IL: AAAM; 1990. Older patients fall from standing with resulting Tile Type 21. Melton LJ III, Sampson JM, Morrey BF, Ilstrup DM. Epidemiologic features of pelvic fractures. Clin Orthop Relat Res. 1981;(155):43–47. A pelvic fractures and the mean ISS in this group was only 6 22. Muir L, Boot D, Gorman DF, Teanby DN. The epidemiology of which confirms that these were low energy, isolated injuries. pelvic fractures in the Mersey Region. Injury. 1996;27:199–204. And also, as expected, the older population with these 23. Ragnarsson B, Jacobsson B. Epidemiology of pelvic fractures in a low energy pelvic fractures had disproportionately high mor- Swedish county. Acta Orthop Scand. 1992;63:297–300. tality in comparison to the low ISS. I have six questions for 24. Luthje P, Nurmi I, Kataja M, Heliovaara M, Santavirta S. Incidence of pelvic fractures in Finland in 1988. Acta Orthop Scand. 1995; Dr. Balogh. 66:245–248. Number 1, what proportion of the patients ultimately 25. Gansslen A, Pohlemann T, Paul C, Lobenhoffer P, Tscherne H. were transferred to the Level I trauma Center? Epidemiology of pelvic ring injuries. Injury. 1996;27(Suppl 1):A13– Two, your institution, as you mentioned, has previously A20. reported on the impact of institutional protocols on the out- 26. Tonge JI, O’Reilly MJ, Davison A, Johnston NG. Traffic crash come in patients with pelvic fracture. Were these protocols fatalities. Injury patterns and other factors. Med J Aust. 1972;2:5–17. 27. Stein DM, O’Connor JV, Kufera JA, et al. Risk factors associated followed at the other hospitals in your system or only at the with pelvic fractures sustained in motor vehicle collisions involving Level I trauma center? You had several patients who under- newer vehicles. J Trauma. 2006;61:21–30. went nontherapeutic laparotomies, and these patients did so 28. Bergeron E, Clement J, Lavoie A, et al. A simple fall in the elderly: without DPL or FAST beforehand, clearly a violation of your not so simple. J Trauma. 2006;60:268–273. own protocol. Please comment. 29. Henry SM, Pollak AN, Jones AL, Boswell S, Scalea TM. Pelvic fracture in geriatric patients: a distinct clinical entity. J Trauma. Number three, you utilized arteriography in only six 2002;53:15–20. patients, all of whom were positive for arterial bleeding. 30. Department of Infrastructure, Planning and Natural Resources, Based on other reports, this 100 percent yield implies that Transport and Population Data Centre. New South Wales Statistical you’re not performing arteriography often enough in these Local Area Population Projections 2001–2031. The 2004 Release. patients. Please comment. 31. Graham CP. Fatal haemorrhage following a low-energy fracture of Number 4, and really along the same line, your mortality the pubic ramus. J Bone Joint Surg Br. 2005;87:1700. 32. Mucha P Jr, Welch TJ. Hemorrhage in major pelvic fractures. Surg attributable to bleeding from pelvic fracture, 50 percent of the Clin North Am. 1988;68:757–773. deaths in the high energy fractures and 25 percent of the 33. Durkin A, Sagi HC, Durham R, Flint L. Contemporary management deaths in the low energy fractures is higher than several other of pelvic fractures. Am J Surg. 2006;192:211–223. reports. Are you really aggressive enough in your use of 34. Biffl WL, Smith WR, Moore EE, et al. Evolution of a arteriography and embolization in the use of early external multidisciplinary clinical pathway for the management of unstable patients with pelvic fractures. Ann Surg. 2001;233:843–850. fixation and the early use of limited ORF? Please comment. 35. Smith WR, Moore EE, Osborn P, et al. Retroperitoneal packing as a Fifth, we have heard several times this morning about the resuscitation technique for hemodynamically unstable patients with insensitivity of vital signs in predicting the need for transfu-

1072 November 2007 Epidemiology of Pelvic Ring Fractures sion or as confirmatory evidence of global hypoperfusion. With this, we had 100 percent positive angiographies. What do you use at your institution as your end points in And we potentially missed two patients, one in the elderly volume resuscitation? low-energy group and one is an elderly patient in the high And, sixth, again with the high mortality in the low energy group with very subtle fractures, and actually, the energy pelvic fractures please comment on the comorbid literature alludes that these patients have to be looked after diseases in these patients. better, and this is one of our future directions as we presented. Dr. Zsolt Balogh (Newcastle, NSW, Australia): Regard- The 50 percent hemorrhage related death in the high ing the inter-hospital transfers, some of the high energy energy group, it’s just a matter of how you look at it. Most of patients were transferred to the trauma center. There were 88 the papers which describe the mortality rate in this group persons of high energy patients admitted to the Level I trauma were retrospective and hemorrhagic shock was not defined in center, and only 2 additional patients were transferred to the a prospective fashion. Level I trauma center, because they required pelvic fixation, Actually, the pelvic fracture related to mortality was only but both of them were hemodynamically normal. 7 percent in this group but 50 percent were related to bleed- The second question was about the institutional guide- ing. These are three patients, two of them arrived in a critical lines in pelvic fracture management. They followed only the condition, and one died in angio (within 90 minutes of ar- Level I trauma center and not at the small centers. rival) when the pelvic fixation was already in place. The guidelines followed only the Level I trauma, because One arrived in pre-morbid exsanguinated state, basically the prehospital triage criteria include that these patients have declared within 15 minutes. The third one died on Day 5 from to be taken preferably to the trauma center. multiple organ failure after massive transfusion. This death Any patients with high energy trauma and vital signs was indirectly related to hemorrhage, but still I think it is indicating hemodynamic instability are taken to the Level I significant. And in all patients, the guidelines were followed trauma center. Since in the lower level centers, the availabil- properly. The next question is how do we define patients to go to ity of angiography, pelvic fixation is limited, we didn’t find angiography and that, as I said, we haven’t found any of the appropriate to implement the guidelines in those centers. previous recommendations for predicting arterial hemorrhage The comment about the non-therapeutic laparotomy, it in our prospective study. was a measure that was 42%, and it clearly indicates the need We tend to use, after exclusion of the other sources of for dedicated trauma surgical approach in Australia. bleeding, the hemodynamic instability defined by the meta- Most of the surgeons, who are providing trauma care in bolic status by the base deficit. Australia, are not necessarily trauma surgeons. They are on- Dr. Carl Hauser (Boston, Massachusetts): Like your- call general surgeons, and they are not in hospital, only their self, I’ve been struck that some of these people come in trainees (registrars) are in house. without frank hypotension. When a patient with hemodynamic instability arrives Perhaps, I’m a little more liberal than you are with my with distended abdomen, the traditional response was to go to base deficit going to angio, but I think that this is a very real the Operating Room for laparotomy. All of these cases are phenomenon. flagged and discussed in the trauma audit, and we have exten- I think that my hypothesis is that what they’re doing is sive measures in the trauma service to improve on these num- they don’t have true hypovolemia, but they have bleeding bers. I think the John Hunter Hospital experienced a huge from small arteries which is persistent and that what they improvement in the management of these critical patients really have is an open artery rather than a hypovolemia with the implementation of the protocol, the partnership with model, if you wish, of shock. the general and trauma surgeons is optimal and since this As such, they really ought to have some element of study concluded our non-therapeutic laparotomy rate in this tachycardia related to loss of systemic vascular resistance. So group exponentially decreased. I’m wondering whether you’ve looked at whether tachycardia Having said that, none of the non-therapeutic laparotomy in this group may be a better predictor than hypotension of patients had adverse outcomes in this group. tissue shock and the need for angiography. About the angiography indication, that was the fourth Dr. Zsolt Balogh: Our data at the moment is not statis- question, how would we identify those patients who require tically powerful to answer that question. Angiography? I think it’s more than a 20-year old question Looking at our prospective data base at the moment, the whether you have to go to the angiography or to the Operat- tachycardia doesn’t seem to be a powerful predictor. It acts ing Room with these critically-ill patients. pretty similar to the systolic blood pressure. What we, in our institution, find very helpful is to ini- At the moment, the exclusion of other bleeding sources and tially exclude other sources of bleeding, and if the bleeding is a significant metabolic acidosis seems to be the only valuable only from the pelvis, the patient requires transfusion and the clinical indicator. But, as I said, we need to collect some more base deficit is higher than six, we take those patients to the cases to prove that. Probably in the future we can come up with angiography. a prospectively developed prediction model for angiography.

Volume 63 • Number 5 1073 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Optimal Plaster Conformation Derived Using a Custom-Made Jig to Obtain Maximum Strength of Protective Plaster of Paris for Hand Surgery Christoph Theopold, MA, MRCS, James A. Bush, MRCS, Stuart W. Wilson, FRCS, FRCS (Plast.), and Ardeshir Bayat, MRCS, PhD

Background: Surgical repair of soft with 0, 1, or 2 ridges and 15-layered back- Conclusions: Backslabs can be tissue trauma in the upper limb frequently slabs without ridges. strengthened significantly by placement of requires postoperative immobilization to Results: We demonstrate that the ad- a single reinforcing ridge. This allows prevent tension across repaired tendons, dition of longitudinal reinforcing ridges plaster weight and thickness to be kept to vessels, or nerves. A plaster of Paris back- on the convex surface of backslabs can a minimum, reducing the setting time of slab, placed on either the volar or the dor- improve simple backslabs in terms of the plaster and contributing to patient sal surface, is frequently used, as it is breaking strength, plaster stiffness, and comfort. These findings demonstrate the inexpensive and easy to apply. failure load. The optimal design employs a ideal construction of angled plaster of Methods: In an effort to improve single, centrally placed ridge, which pro- Paris backslabs for the protection of soft upon the strength of plaster of Paris back- vides the maximum support in the axis of tissue repairs. slabs, we designed a custom-made jig to the net force acting across the angle, the Key Words: Plaster of Paris, Back- ,per fulcrum of angle backslabs. The forma- slab, Ridge, Reinforcement, Stiffness 5 ؍ subject angled backslabs (n group) of various designs to a torsional tion of two parallel longitudinal ridges Breaking point. force. We tested 10-layered backslabs does not offer any additional support. J Trauma. 2007;63:1074–1078.

n the management of upper limb traumatic injuries, it is strength characteristics.1–3 As long as their unit cost remains commonplace to protect repairs of tendons, nerves, and considerably higher than that of PoP, their use will probably Ivessels in the immediate postoperative period. This is be confined to the creation of large plaster casts that remain usually achieved by flexing or extending the appropriate in place for several weeks, rather than temporary immobili- joint, to prevent tension across the repair and limiting joint zation of soft tissue repairs.3 motion with an angled plaster of Paris (PoP) backslab, an Since Luck’s treatise on the application of PoP Casts, the incomplete cast placed on the dorsal or volar side, opposite to majority of reports investigating properties of casts have the site of the repair. In our unit, these backslabs are usually focused on complete tubular casts, particularly those made replaced by custom-made thermoplastic splints after several from synthetic materials.1–6 Although the majority of syn- days, when the initial postoperative swelling has subsided thetic casts do have a higher breaking strength than PoP, the sufficiently. fact that plaster is easily molded lends itself to strengthening PoP is widely used for immediate postoperative immo- by supporting laminations or ridges.6,7 Furthermore, up to a bilization of joints because of its low cost, ease of application, break point, plaster exhibits higher stiffness than synthetic and high strength once it has set. Fiberglass-impregnated materials, making it useful for immediate postoperative materials do offer advantages over PoP by virtue of their low immobilization.2 weight, rapid application, and setting time, as well as superior One report describes an increase in break strength in backslabs by the addition of two ridges, but it does not detail whether these were straight or angled backslabs and how the Submitted for publication March 1, 2006. experiments were performed.8 Previous evidence suggests Accepted for publication June 26, 2006. that testing of plasters has to be tailored to the type of plaster Copyright © 2007 by Lippincott Williams & Wilkins 4 From the Department of Hand, Plastic and Reconstructive Surgery being tested, to bear any clinical relevance. Angled back- (C.T., J.A.B., S.W.W., A.B.), South Manchester University Hospital Foun- slabs have an inherent point of weakness, as the angle in- dation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, creases the density of any force lines acting across it. In an Manchester, United Kingdom. effort to improve on this weakness of angled backslabs, we Address for reprints: Ardeshir Bayat, MRCS, PhD, Department of Hand, tested backslabs of different designs in a custom-made jig Plastic and Reconstructive Surgery, South Manchester University Hospital Foundation Trust, Wythenshawe Hospital, Southmoor Road, Wythenshawe, that allowed us to subject them to a torsional force, leading to Manchester M23 9LT, United Kingdom; email: ardeshir.bayat@manchester. fracture across the angle, the most common mode of failure ac.uk. clinically. Here we demonstrate that the strength of angled DOI: 10.1097/01.ta.0000236059.45353.af plaster backslabs can be significantly increased by the addi-

1074 November 2007 Optimal Plaster Conformation for Backslabs

Moment arm 20cm Backslab

Fulcrum

Fig. 1. Schematic representation of the custom-made apparatus used to subject backslabs to a torsional force, with the fulcrum of the moment arm being in line with the neutral axis of the backslab. The apparatus ensures a normal force component at all angles of plaster deformation. Fig. 2. Schematic representation of the backslabs produced in tion of longitudinal supporting ridges and show the best molds for testing. Either 10 or 15 layers of Gypsona Plaster of Paris design for this method of strengthening. This article demon- were immersed in water before shaping and molding in a thermo- strates the ideal conformation of ridged plaster design for the plastic form. Ridges were placed centrally for single-ridged plasters immediate postoperative immobilization of joints, to combine and at intervals of one-third of the width of the plaster for two- maximum strength with the highest strength attainable in the ridged plasters. shortest possible time.

MATERIALS AND METHODS load of 2 N (Newton) every 5 minutes, angle readings being A custom-made three-point bending apparatus was de- taken just before increasing load. The force acts perpendic- signed to test angled backslabs in their most common mode ular to each limb of the plaster, regardless of the degree of of failure, a fracture across the angle. The apparatus applied deformation. Five-minute intervals were chosen for incre- a bending force, the fulcrum being in line with the neutral mental loading, as this was deemed sufficient for full equil- axis of the angle that was incorporated into backslabs (Fig. 1). ibration, since plastic deformation of plaster backslabs occurs Backslabs were prepared using either 10 or 15 layers of gradually. This was repeated until complete backslab failure 15 cm wide Gypsona PoP (BSN Medical, Hull, UK). Fol- was evident. lowing the manufacturer’s recommendations, the PoP was Statistical analysis of results was performed using the immersed in water for 5 seconds, squeezed by hand for 3 statistics software package GraphPad Instat (V3.05). An anal- seconds to remove excess water and subsequently shaped in ysis of variation and a Tukey-Kramer multiple comparison a mold formed from thermoplastic material. This ensured that test were performed to analyze the statistical significance of all plasters within a group were constructed in as reproducible variation among group means. a fashion as possible. Plasters were 40-cm long and had a 60-degree angle incorporated at the midpoint of their longi- RESULTS tudinal axis. Five plasters were made per group. Some of the Ten-layered backslabs had a mean mass of 290 g, com- 10 layered backslabs were created with either one or two pared with 430 g for 15-layered slabs (p Ͻ 0.0001, unpaired longitudinal ridges of 1 cm height and 1.5 cm width by t test). PoP backslabs initially deformed in a linear, elastic folding them before laying them into their molds and allow- fashion with increasing torsional force (Fig. 3). All backslabs ing them to set (Fig. 2). Backslabs were dried for 5 days invariably failed at the angle incorporated into their design, before testing to ensure complete curing. All plasters were which also represents the fulcrum of the bending force. weighed to ensure standardization. When plaster deformation deviated from the initial elas- One limb of the angled backslab was clamped in the tic linear portion, the stiffness gradually changed to a much custom-made jig, so that the angle in the plaster lay in the lower magnitude. Further deformation was still reasonably axis of rotation of the jig. After setting the angle readout to linear against increasing load, though interspersed by sudden zero, the plaster was stressed by an incremental increase in deviations from linearity.

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10 layers, no ridge 10 layers, 1 ridge 10 10 layers, 2 ridges 9 15 layers, no ridge

8 7

4 Torque (Nm) 3 2

0 Fig. 3. Mean plaster deformation. The mean values for each plaster Fig. 4. Virtual break point (VBP). Plaster of Paris backslabs (n ϭ (n ϭ 5) and standard deviation are given throughout the range of 5 per group) were incrementally loaded with 2 N every 5 minutes deformation. and the angle of deformation read before each increase in load. The To arrive at a clinically relevant comparison of backslab VBP was derived from the intersection of best-fit lines of the elastic stiffness, a notional Plaster stiffness was defined as the portion of deformation preceding the VBP and the plastic portion of Ϯ amount of torque required per degree of Plaster deformation deformation between 5 degrees and 20 degrees. Values are mean through the fulcrum (the angle of the plaster). This was standard deviation. ANOVA with Tukey-Kramer postcomparison t Ͻ Ͻ determined for each plaster from a best-fit line of the test: p 0.0001; 10 layers, no ridge/1 ridge: p 0.001; 10 layers, Ͻ initial elastic portion of plaster deformation between 0 and no ridge/2 ridges: p 0.001; 10 layers, no ridge/15 layers, no Ͻ 2 degrees of deformation. Because clinically relevant plas- ridge: p 0.001. ter failure occurs early but gradually, precluding accurate 10 identification of a true break point, a virtual break point 9 10 layers, no ridge 10 l a y e r s, 1 r i d g e (VBP) was defined. This was derived from the intersection 8 10 layers, 2 ridges of best-fit lines for the initial elastic portion of deforma- 7 15 layers, no ridge tion with that of plastic deformation between 5 and 20 6 5 degrees. 4 For 10-layered PoP backslabs, the virtual breakpoint is 3 significantly increased by the addition of ridges to the back- 2 1 slabs. Although unridged backslabs had a mean VBP of 3.66 0 Nm (Newton meter, n ϭ 5), those with one ridge were Fig. 5. 2.4-fold stronger, breaking at 8.62 Nm (n ϭ 5). Unexpect- Plaster stiffness. This was derived from the best fit line of ϭ edly, the addition of a further ridge did not significantly backslab deformation between 0 degrees and 2 degrees, n 5. Ϯ increase the VBP further, with two-ridged backslabs Values are mean standard deviation. ANOVA with Tukey-Kramer ϭ Ͻ breaking at 7.82 Nm (n ϭ 5), a 2.1-fold increase over postcomparison t test: p 0.0003; 10 layers, no ridge/1 ridge: p Ͻ unridged backslabs. 0.001; 10 layers, 1 ridge/2 ridges: p 0.01; 10 layers, 1 ridge/15 Ͻ Fifteen-layered unridged backslabs were tested in the layers, no ridge: p 0.01. same fashion to investigate the contribution of multiple layers of PoP to the strength of the backslab. The VBP of 7.51 Nm again intermediate in strength, failing at a mean torque of (n ϭ 5) was almost identical to that of 10-layered 2-ridged 18.8 and 18.2 Nm, respectively, the difference between them backslabs (Fig. 4). not being statistically significant (Fig. 6). Plaster stiffness, defined as the amount of torque required per amount of deformation, was lowest for unridged 10-layered DISCUSSION backslabs (2.33 Nm/degree). The addition of one ridge increased Surgical repair of soft tissue injuries of the extremities backslab stiffness 3.1-fold to 7.19 Nm/degree. Again, two- frequently requires immediate postoperative limitation of ridged 10-layered plasters and unridged 15-layered plasters joint movement to prevent tension across tendons, nerves, or performed similarly, with values of 3.79 Nm/degree and 3.62 vessels that have been repaired primarily. Although synthetic Nm/degree, respectively (Fig. 5). materials generally set faster than PoP, they are not as easy to Ultimate failure load was also strongly influenced by the mold.3 Furthermore, their high unit cost means that they number of layers or ridges incorporated into backslabs. It was would generally be second choice for intermediate-term pro- lowest for 10-layered unridged backslabs (9.4 Nm) and high- tection of surgical repairs until a more lightweight option, est for one-ridged backslabs (27.9 Nm). Two-ridged 10- such as a thermoplastic splint, can be employed once post- layered backslabs and unridged 15-layered backslabs were operative swelling has subsided.3

1076 November 2007 Optimal Plaster Conformation for Backslabs

35 10 layers, no ridge group up to the VBP, and less well after the VBP. We also 10 layers, 1 ridge noted sudden increases or decreases in stiffness, as strands of 30 10 layers, 2 ridges 15 layers, no ridge cotton gauze took the strain and subsequently ruptured on the 25 side of the cast under tension. 20 Using the same amount of layers, the addition of a single 15 ridge to an unridged PoP backslab increased stiffness 3.1-fold

Torque (Nm) and the VBP 2.4-fold. Somewhat surprisingly, the addition of 10 a further ridge only led to a 1.6-fold increase in stiffness and 5 a 2.1-fold increase in VBP. 0 Simply increasing the number of layers in an unridged Fig. 6. Failure load. This represents the maximum torque sustained angled backslab by 50% will lead to a similar increase in by the backslab before complete failure, obvious as the backslab strength and stiffness as that achieved by the addition of two bent through its maximum arc of deformation. ANOVA with Tukey- equally spaced ridges. Kramer postcomparison t test: p Ͻ 0.0001; 10 layers, no ridge/1 These observations may be explained by virtue of the ridge: Ͻ0.001; 10 layers, no ridge/2 ridges: Ͻ0.001. 10 layers, thickness of the plaster: increasing plaster thickness from 10 no ridge/15 layers, no ridge: p Ͻ 0.01; 10 layers, 1 ridge/10 to 15 layers increases the volume by 50%, hence reducing the layers, 2 ridges: p Ͻ 0.01; 10 layers, 1 ridge/15 layers, no ridge: density of force acting across the cross section of the cast by p Ͻ 0.01. one third. A similar effect can be achieved without increasing the In 1944, Luck published a comprehensive treatise on the volume (and weight) of the plaster by folding it, thus forming principles of PoP application. Among other observations, he a longitudinal ridge on the concave surface of the plaster. showed that tubular casts could be strengthened using ante- Although the total cross-sectional area does not increase per riorly and posteriorly placed supports. Furthermore, he se, the moment arm across which the torsional force acts is showed that PoP reaches its maximum strength once all increased. excess water, which is not involved in the crystallization In a perfectly symmetrical cast, the bending force will act process of gypsum, has evaporated from the plaster.6 In this equally across the entire plaster; hence, the net force will act regard, the thickness of plaster influences how quickly it will through the center of the cross-sectional area of the cast. This attain maximum strength, as the distance for water to diffuse theory is supported by the observation that placement of two to the surface of the plaster, and therefore its rate of evapo- ridges does not necessarily lead to a further increase in ration, are directly affected. breaking strength. Again, the cross-sectional area is not in- Our experiments demonstrate that the addition of lon- creased compared with unridged or one-ridged backslabs, but gitudinal reinforcing ridges on the convex surface of the net force is acting on a part of the cast that is not directly angled PoP backslabs significantly increases breaking supported by a ridge. strength as defined by a VBP, and stiffness, as defined by It was also noticed that during increasing deformation, the amount of torque required per degree of deformation. only one-ridged plasters formed a curvature along their trans- We elected to test these angled backslabs with a custom- verse axis. This may also delay rupture of cotton gauze made jig that would allow us to apply a perpendicular threads, contributing to an increase in the VBP. Two parallel force to each limb of the cast throughout the range of ridges impart a certain rigidity on the backslab across its deformation, stressing the angle, as this is the point we transverse axis, which probably contributes to the fact that most commonly find has failed when patients return to us the additional ridge does not increase the VBP or plaster with fractured backslabs. stiffness. Bilinear characteristics previously described for tubular In summary, to achieve a rapid, light-weight protection PoP casts were confirmed for backslabs during our experi- of soft tissue repair using PoP, the best option is to use fewer ments. These likely result from the amorphous structure of layers of plaster with a reinforcing ridge. This is shown to be PoP casts, which are composed of a crystalline structure of superior to a larger number of layers, which would increase ⅐ CaSO4 2H2O around a lattice of cotton gauze. In the initial the time required for the plaster to cure and add to the weight phase of deformation, the crystalline structure deforms elas- of the plaster. Although counterintuitive, a single ridge that is tically and demonstrates a high stiffness. Once fractures ap- placed centrally offers a higher stiffness and ultimate failure pear in the crystalline structure, visible with the naked eye, load compared with the placement of two reinforcing ridges and always found around the VBP, the stiffness is signifi- that are equally spaced. These results indicate that the optimal cantly decreased and the plaster begins to deform plastically, design of a plaster includes the reinforcement using a single, its behavior strongly influenced by the cotton gauze. Plaster centrally placed ridge, to achieve rapid protection of soft stiffness correlated well between individual slabs within each tissue repair.

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ACKNOWLEDGMENTS 3. Bowker P, Powell ES. A clinical evaluation of plaster-of-Paris and eight synthetic fracture splinting materials. Injury. 1992; We thank Ms. Fiona Procter for the production of the thermoplastic molds used to form backslabs. We also thank BSN Medical for their gen- 23:13–20. erous provision of Gypsona Plaster of Paris used in this study. We would also 4. Callahan DJ, Daddario N, Williams S. Three experimental designs like to thank Mr. Bob Williams for construction of the custom-made jig used testing orthopedic casting material strength. Orthopedics. 1986; to test the plaster constructs. 9:673–675. 5. Callahan DJ, Carney DJ, Daddario N. A comparative study of REFERENCES synthetic cast material strength. Orthopedics. 1986;9:679–681. 1. Rowley DI, Pratt D, Powell ES. The comparative properties of 6. Luck J. Plaster of Paris casts. JAMA. 1944;124:23–29. plaster of Paris and plaster of Paris substitutes. Arch Orthop Trauma 7. Cimino WR, Skinner HB. The stiffness of cylindrical casts enforced Surg. 1985;103:402–407. with splint laminations: biomechanical considerations. J Orthop 2. Mihalko WM, Beaudoin AJ, Krause WR. Mechanical properties and Trauma. 1989;3:338–344. material characteristics of orthopaedic casting material. J Orthop 8. Khan R, MacDowell A, Mears S, et al. Ridged re-inforcement of the Trauma. 1989;3:57–63. plaster slab. Ann R Coll Surg Engl. 2002;84:359.

1078 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures Bijan S. Kheirabadi, PhD, Angel V. Delgado, PhD, Michael A. Dubick, PhD, Michael R. Scherer, MA, Chriselda G. Fedyk, MS, John B. Holcomb, MD, and Anthony E. Pusateri, PhD

Background: Recombinant activated respective temperatures by standard co- improved by rFVIIa addition and nor- factor VII (rFVIIa) is currently adminis- agulation tests and thrombelastography. mothermic values were restored in 31°C tered off-label to control diffuse coagulo- Results: The clot reaction time of and 34°C cold blood samples. rFVIIa pathic bleeding of patients with traumatic blood samples, measured as prothrombin did not affect maximum amplitude at injuries. These patients are often cold, ac- time, activated partial thromboplastin any temperature. idotic, and coagulopathic upon arrival time, and R time (thrombelastography Conclusions: Mild to moderate hy- and each responds differently to rFVIIa analysis), was significantly prolonged at pothermia delayed the initial clot reaction therapy. This study investigated the ef- 31°C or below compared with at 37°C. and reduced clot formation rate without fects of hypothermia on clotting and the The clot formation rate (␣ angle, maxi- affecting ultimate clot strength. FVIIa ef- potential benefit of rFVIIa administration mum clotting velocity ͓Vmax͔) was de- fectively compensated for the adverse ef- on blood coagulation at different hypo- creased at all cold temperatures. Maximum fects of hypothermia except in severe cases. thermic temperatures. clot strength (maximum amplitude) was These results suggest that administration of Method: Citrated blood samples only affected (reduced) at 28°C. Addition FVIIa should be beneficial in enhancing he- were collected from eight healthy volun- of rFVIIa shortened the prothrombin mostasis in hypothermic trauma patients teers (20–45 years old) and incubated at time, activated partial thromboplastin without the need for prior correction of the 37°C, 34°C, 31°C, and 28°C for 30 min- time, and R times at every temperature, patient’s body temperature. utes. rFVIIa (1.26 ␮g/mL equivalent to 90 surpassing the normal (37°C) temperature Key Words: Hypothermia, Recombi- ␮g/kg in vivo dose) or vehicle solution (sa- values in 31°C and 34°C cold samples. nant factor VIIa, Coagulation, Throm- line) was added to each blood sample, in- Similarly, clot formation rate parameters belastography (TEG), Human blood. cubated (10 minutes), and analyzed at the (clotting time, ␣ angle, Vmax) were also J Trauma. 2007;63:1079–1086.

ncontrollable bleeding accounts for 39% of trauma- Trauma with hypothermia has been shown to have sig- related deaths and is the leading cause of potentially nificantly worse prognosis than either trauma or hypothermia Upreventable death in patients with major trauma.1,2 A alone.7–9 Although isolated hypothermia (32°C) incidents led major contributing factor to bleeding-related mortality is co- to 23% mortality, hypothermia in conjunction with severe agulopathy, particularly when it is associated with metabolic trauma (Injury Severity Score, [ISS] Ն25) was associated acidosis and hypothermia, often referred to as the “lethal with 100% mortality in patients with core temperature below 3–5 triad”. Substantial increases in mortality of trauma patients 32°C.8,9 This critical temperature was identified as an omi- have been associated with profound hypothermia. Patients nous predictor of mortality independent of the ISS, presence with admission temperatures less than 35°C had significantly of shock, or the volume of fluid resuscitation. The mortality greater mortality (25.5% vs. 3.0%) than patients with tem- of hypothermic patients with comparable ISS, shock, and Ն 6 peratures 35°C. fluid resuscitation was significantly higher than that of those who remained warm.8,9 A major risk factor of hypothermia is inducing coagu- Submitted for publication May 21, 2007. lopathy with abnormal bleeding. Hypothermia can cause Accepted for publication August 15, 2007. coagulopathy over a range of temperatures in a temperature- Copyright © 2007 by Lippincott Williams & Wilkins 8 From the Division of Damage Control Resuscitation, US Army Insti- dependent fashion. Several mechanisms for the effect of tute of Surgical Research, Fort Sam Houston, Texas. hypothermia have been proposed, including reduced platelet The opinions or assertions expressed herein are the private views of the function, decreased activity of coagulation enzymes, and ac- authors and are not to be construed as official or as reflecting the views of tivation of fibrinolysis; however, the exact mechanism con- the US Department of the Army or the US Department of Defense. 10 Address for reprints: Bijan S. Kheirabadi, PhD, US Army Institute of tinues to be debated. Surgical Research, 3400 Rawley E. Chambers Avenue, Fort Sam Houston, Recombinant activated factor VII (rFVIIa) has been con- TX 78234-6315; email: [email protected]. sidered as a “universal hemostatic agent”.11 It was originally DOI: 10.1097/TA.0b013e31815885f1 developed for the treatment of bleeding complications in

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hemophiliac patients with inhibitors against factors VIII or were treated with rFVIIa or vehicle. rFVIIa (1.2 mg kit, IX12 and has been approved by the Food and Drug Admin- NovoSeven, Novo Nordisk, Denmark) was reconstituted in istration for these indications. Successful treatment with this sterile water (2.2 mL) and 13.6 ␮L of the solution was added drug has been widely reported in hemophiliacs as well as to each 6.5 mL blood sample. Normal saline (13.6 ␮L) was other patients with pre-existing hemostatic defects (i.e., factor added to control blood. The final concentration of rFVIIa in VIIa deficiency, acquired von Willebrand disease, uremia, blood was 1.26 ␮g/mL, equivalent to a bolus dose of 90 and liver disease) for controlling acute bleeding episodes ␮g/kg in patients. The calculated concentration was based on during surgical procedures.13,14 The off-label use of rFVIIa in the assumptions that rFVIIa will distribute evenly in 5 L a bleeding trauma patient, without preexisting hemostatic circulating blood volume of an average patient with 70 kg disorders, was first described in 1999.15 Since then, the emer- body weight. The blood samples were kept at their normal or gency use of rFVIIa as an adjunct therapy for surgical or hypothermic temperatures for an additional 10 minutes and trauma patients with massive hemorrhage and coagulopathy then assayed for coagulation function by the standard clinical has become an important new treatment option.16–25 It has tests and by thrombelastograph (TEG) analysis at their re- provided a safe and effective means for control of severe spective temperatures. bleeding when all other measures have failed. In a double- blinded, randomized controlled trial, rFVIIa treatment re- Coagulation Tests duced transfusion requirements and the incidence of multiple After treatment, portions of blood samples were centri- organ failure and acute respiratory distress syndrome in se- fuged at high speed, and the plasma collected for the standard vere blunt-trauma patients without increasing thromboem- clotting assays. Prothrombin time (PT), activated partial bolic adverse effects.26 The treatment, however, did not thromboplastin time (aPTT), and fibrinogen concentration change the patients’ mortality at either 48 hours or at 30 days were measured in plasma using automated BCS Coagulation after treatment.26 In a recent clinical study, it was reported Analyzer (Dade Behring, Marburg, Germany). All of the tests that rFVIIa may be able to improve early survival of mas- were performed at the corresponding experimental tempera- sively bleeding trauma patients.27 It is also suggested that the tures (28°C–37°C) in duplicate. For PT measurement, the correction of acidosis and thrombocytopenia may be impor- clotting was induced by the addition of recombinant human tant prerequisites for rFVIIa efficacy.27 The high cost asso- tissue factor and synthetic phospholipids (Innovin, Dade Be- ciated with this treatment and its questionable life-saving hring, Marburg, Germany) to the plasma in a 2:1 volume effect in trauma patients support the need for continued re- ratio. For aPTT measurement, purified soy phosphatides in search to identify better conditions for improving the efficacy ellagic acid (Actin FS Activated PTT Reagent, Dade Behring, of this drug. The purpose of this study was to investigate the Marburg, Germany) was added to plasma samples in a 1:1 effects of hypothermia on coagulation parameters of normal volume ratio and clotting time was measured. Fibrinogen in human blood and determine the efficacy of rFVIIa to enhance plasma was also determined based on a clotting assay in coagulation at different hypothermic temperatures. which a large excess of bovine thrombin (50 IU/mL) was added to plasma in a 2:1 volume ratio, and the clotting time PATIENTS AND METHODS was measured. The fibrinogen concentration, which largely Blood Sampling and Treatment depends on this clotting time, was estimated based on a The Institutional Review Board of the US Army Institute standard curve generated by the machine. Calcium was added of Surgical Research and Brooke Army Medical Center ap- to overcome the citrate anticoagulant according to standard proved this study. After obtaining informed consent, blood practice. was collected from eight adult healthy volunteers, (four men and four nonpregnant women), 20 years to 45 years old. None TEG Analysis of the participants had received medication with acetylsali- Coagulation of all blood samples was tested with a TEG cylic acid or any other nonsteroidal anti-inflammatory drugs Hemostasis Analyzer 5000 (Hemoscope, Niles, IL). The ac- for the 7 days before blood sampling. A smooth cubital curate measurement by the TEG machines was confirmed venipuncture was performed using 21-gauge needle and daily using quality control standards obtained from Hemo- blood (ϳ65 mL) was collected into citrated vacutainer tubes scope. Before testing, the machines were set at the selected (0.109 mol/L ϭ 3.2% sodium citrate), mixing one part of experimental temperatures of the blood samples. Disposable citrate with nine parts of blood. The first tube aspirated was cups and pins were then loaded and allowed to equilibrate to the discarded to minimize tissue thromboplastin contamination. selected temperatures for at least 15 minutes. Next, 10 ␮L ␮ Blood from the remaining tubes was pooled in a 250 mL Innovin (diluted 1:500 with saline), 20 L of 0.2 mol/L CaCl2, Nalgene PETG bottle (Fisher Scientific, Pittsburgh, PA) and and 4.3 ␮L of Corn Trypsin Inhibitor (19 ␮g/mL, Hematologic incubated at 37°C for 15 minutes. After initial equilibration, Technologies Inc., Essex Junction, VT), a contact activation the blood was aliquoted (6.5 mL) into small tubes and placed inhibitor, were added to each cup and allowed to equilibrate in temperature-controlled water baths at 37°C, 34°C, 31°C, or for an additional 5 minutes. To start the reaction, 336 ␮Lof 28°C for an additional 30 minutes. Next, blood specimens citrated blood was added to each cup and measurement

1080 November 2007 rFVIIa on Coagulation Properties of Human Blood

started. Blood samples were tested in triplicate and TEG 15.0 PT measurements continued until 30 minutes after maximum + amplitude (MA) was reached. The following variables were 12.5 + measured for each sample at the experimental temperatures: * * * reaction time (R, min, the time that the initial fibrin formation 10.0 * * * is detected and signaled bya2mmrise of amplitude); Seconds clotting time (K, min, indicates the speed of clot formation 7.5 and is the time from the beginning of clotting, R time, until a a clot with a fixed firmness is formed, 20 mm amplitude rise); 5.0 angle (␣ degree, represents the kinetics of clot development); 37 34 31 28 and MA (mm, measures the maximum strength or firmness of 50 aPTT the developed clot). The velocity of clot formation was also + calculated as the first derivative of the TEG tracings and 40 maximum clotting velocity (Vmax, mm/min) and time to + * + * + * reach Vmax (t-Vmax, min) were determined for each sample +* as described previously.28 Fibrinolysis was measured as per- 30 +

Seconds * cent clot lysis at 30 minutes after MA was reached. This is * Saline measured based on reduction of the area under the TEG 20 rFVIIa tracing between the two time points. b 10 Statistical Analysis 37 34 31 28 Temp. oC All statistical analyses were performed using the statis- Fig. 1. tical program SAS, version 8.1 (SAS Institute Inc. 1999, Prothrombin time (PT) (top) and activated partial throm- Cary, NC). Data were examined for heterogeneity of variance boplastin time (aPTT), (bottom) of saline or rFVIIa added human and non-normality. These conditions were not detected in the blood samples at normal or hypothermic temperatures. PT and data. The coagulation measurements such as PT, aPTT, fi- aPTT were significantly prolonged in cold blood compared with brinogen and TEG parameters were first compared among 37°C samples. rFVIIa accelerated the clotting process and reduced Ϯ temperatures within each treatment group using a mixed PT and aPTT at every temperature. Data represent mean SEM of ϩ Ͻ model of analysis of variance, allowing for temperatures as triplicate measurement of samples from eight subjects. p 0.05, fixed effects and replicate subject as a random effect. If there significantly different from the 37°C temperature in each group. Ͻ Ͻ was a significant temperature effect, Dunnett’s test was used *p 0.05, **p 0.01, significantly different from saline (control) to compare the normal (37°C) temperature with hypothermic group. temperatures. The parameters were then compared between the two treatment groups (rFVIIa vs. saline) at each temper- temperature effects measured in 31°C and 34°C blood sam- ature using a paired t test. Data are expressed as means Ϯ ples (no difference compared with 37°C controls). SEM in the graphs. Statistical significance was assigned at a Fibrinogen measurement was the least affected by cold greater than 95% confidence level (p Ͻ 0.05). temperature. This assay is also based on a clotting time measurement but it does not depend on endogenous thrombin RESULTS generation. The fibrinogen measurement was reduced (15%) Plasma Clotting Assays only at the lowest temperature (28°C) compared with 37°C. PT, which examines the in vivo (extrinsic) coagulation rFVIIa addition had no significant effect on these measure- process induced by tissue factor was significantly prolonged ments at any experimental temperature. in cold blood samples measured at 31°C and 28°C compared with 37°C (Fig. 1, top). The addition of rFVIIa to blood TEG Measurements accelerated the initial clotting reaction and shortened the PT Typical TEG traces and velocity graphs of analysis of at every tested temperature. As a result, the PT of all rFVIIa blood collected from a single subject at different temperatures treated samples was shorter than the value of untreated con- are shown in Figure 2. Each tracing represents the average trols at 37°C (Fig. 1, top). data obtained from triplicate tests. As seen in the figures, the aPTT, a measurement of contact activation clotting (in- cold temperatures adversely affected all aspects of clot for- trinsic) pathway, was more sensitive to low temperatures than mation except the clot strength. The detailed analysis of the PT (Fig. 1, bottom). The aPTT was prolonged at each hypo- TEG data, including the effect of rFVIIa at different temper- thermic temperature in a temperature-dependent manner. The atures, is as follows: addition of rFVIIa to blood samples accelerated the clotting The initial clotting reaction time (R) was prolonged sig- process and reduced aPTT at every temperature tested. The nificantly (ϳ1–2 minutes) at 31°C and 28°C compared with shortening of aPTT with rFVIIa compensated for the cold 37°C (Fig. 3). The addition of rFVIIa sped up the initial

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Fig. 2. Typical TEG traces (left) and calculated velocity profiles (right) of blood from a subject at different temperatures. Each TEG trace represents the average of triplicate measurement of a blood sample at specific temperature. Velocity graphs were constructed from the triplicate TEG data measured at each temperature. reaction and decreased the R times by ϳ2 minutes in all the The MA, which represents clot strength and depends on samples, irrespective of their temperatures. The clot propa- fibrinogen and platelet interaction, was the least affected by gation was more affected by the low temperatures than the low temperatures (Fig. 6). A significant decrease in MA was initial reaction time. These changes were reflected as longer measured only at the lowest temperature (28°C) in both clotting time (K) and smaller clotting rate (␣ angle) of cold untreated and rFVIIa-treated samples. The addition of rFVIIa blood samples compared with normothermic controls (Fig. had no effect on clot strength at any temperature. With regard 4). Again, the addition of rFVIIa was effective at every to fibrinolysis, only a small fraction (ϳ0.2%) of the clot lysed temperature, reducing the clotting times by 0.6 minutes to 0.9 30 minute post-MA (LY30) at 37°C. This reaction was also minutes and increasing the clotting rate by ϳ8° at every affected by cold temperatures and reduced to 0% at 31°C and temperature tested. The calculated clotting velocity values (Vmax and t-Vmax) also indicated slower clotting kinetics Clotting Time (K) 4 * under hypothermic conditions (Fig. 5). The decrease of Vmax * and increase of t-Vmax were significant at 31°C and 28°C * 3 + * compared with normal temperature. The addition of rFVIIa + * + + resulted in an increase in Vmax and a decrease in t-Vmax in 2 + all of the samples at every temperature tested. The improve- Minutes + ment achieved by adding rFVIIa compensated or surpassed 1 the changes caused by hypothermic temperatures. a 0 37 34 31 28

Reaction time (R) Clotting rate ( α angle)

10.0 Saline 80 FVIIa Saline * + rFVIIa 7.5 * + + * + + * 60 * + * 5.0 + Degree * * +

Minutes * * * + * * + 2.5 b 40 0.0 37 34 31 28 o 37 34 31 28 Temp. C Temp. oC Fig. 4. Clot formation time (K)(top) and clotting rate (␣ angle) Fig. 3. Initial clotting reaction time (R) of saline or rFVIIa added (bottom) of saline or rFVIIa added human blood samples at normal human blood samples at normal or hypothermic temperatures. R- or hypothermic temperatures. The K-time increased and ␣ angle time was prolonged significantly at 31°C and 28°C, compared with decreased progressively with the decreasing of temperatures. 37°C, and was shortened by addition of rFVIIa at each specific rFVIIa addition shorten K time and fasten the clotting rate at each temperature. See Figure 1 for notation of significance. specific temperature. See Figure 1 for notation of significance.

1082 November 2007 rFVIIa on Coagulation Properties of Human Blood

Max. Clotting Velocity (Vmax) ple, it is well recognized that, in general, for every 10°C 20 decrease in temperature the activity of an enzyme is reduced 31 * * by approximately 50%. This study investigated the effects 15 * of mild (34°C), moderate (31°C) and severe (28°C) * 29 +* hypothermia on the coagulation of human blood and the 10 + * + * mm/min + potential ability of rFVIIa to reverse the coagulopathy and + 5 restore normal clotting function in hypothermic blood. The low temperatures affected the kinetics of clot formation by a 0 slowing (1) the cascade reactions of coagulation factors lead- 37 34 31 28 ing up to the formation of initial fibrin strands, which was Time to Vmax 10.0 detected as prolongation of PT, aPTT, and R-time in TEG analysis; and (2) the build up and cross linking of fibrin

7.5 + (propagation of clot), as determined by K time and clotting + * velocity measurements (␣ angle and Vmax) by TEG analysis. * * 5.0 * + The observed effects were temperature-dependent and pro- * + Minutes * Saline portional to the severity of hypothermia. These findings were 2.5 FVIIa consistent with other studies in which blood samples were b collected from hypothermic patients and analyzed by TEG at 0.0 32–34 37 34 31 28 corrected temperatures. The prolongation of PT and Temp. oC aPTT of normal blood when measured at hypothermic tem- Fig. 5. Maximum clotting velocity (Vmax) (top) and time to reach peratures has been reported elsewhere.35,36 In clinics, these Vmax (t-Vmax) (bottom) values of human blood at different temper- laboratory tests are usually performed on plasma samples atures calculated from TEG measurements. The decrease of Vmax after warming to 37°C, which can falsely produce normal was significant at all hypothermic temperatures and t-Vmax was values and underestimate coagulopathy in hypothermic prolonged at 31°C and 28°C compared with 37°C. rFVIIa increased patients.36,37 Vmax and shortened t-Vmax in all the samples at every temperature. Our TEG data showed that clot strength (MA), which See Figure 1 for notation of significance. represents the contribution of platelets and fibrinogen and their interaction to form a hemostatic clot, was not influenced 28°C. There was no difference in clot lysis of rFVIIa-treated by moderate hypothermia. The fibrinogen measurements es- blood versus untreated samples. timated indirectly by adding excessive amounts of thrombin to plasma samples were also unaffected by hypothermia. DISCUSSION These results collectively suggest that the moderate hypother- Hypothermia occurs when the body core temperature mic temperatures slow down clot formation by decreasing falls below 35°C (95°F).29 It has profound effects on every enzymatic activity and reducing the thrombin generation rate system of the body including reducing metabolism and oxy- without affecting the final contribution of platelets or fibrin- gen demand, which may be beneficial, and decreasing the rate ogen to form the clot. The velocity profiles of hypothermic of temperature-dependent enzymatic function.30 For exam- blood (Fig. 4), which display patterns similar to endogenous thrombin potential of the samples,38 also suggested temperature-dependent decreases in thrombin generation. This Max. amplitute (MA) mechanism is supported by an in vitro study which has shown 70 that the monocyte tissue factor activities, measured as factor Saline Xa generation, as well as platelet thrombin generation were 65 FVIIa reduced by 38% and 26%, respectively, at 33°C.39 Watts et al. reported significant alterations in both enzy- mm 60 +

+ matic clotting reaction and platelet function (MA) of blood

55 collected from hypothermic trauma patients with temperature below 34°C.34 The TEG analysis also detected an acute

50 hypercoagulability in blood of patients whose temperatures 37 34 31 28 were Ն34°C. Other studies found no significant change in Te mp. oC MA of blood collected from hypothermic patients,32,33 con- Fig. 6. Maximum clot strength (MA) of saline or rFVIIa added sistent with the present in vitro findings. The differing results human blood samples at normal or hypothermic temperatures. MA reported among studies may be explained based on the dif- was least affected by hypothermia, it only decreased slightly at ference in the sources of blood samples. The data reported by severe cold temperature (28°C) compared with 37°C. rFVIIa addi- Watts et al.34 were obtained from blood samples collected tion had no effect on MA. See Figure 1 for notation of significance. from hypothermic patients with significant traumatic injuries

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(ISS Ն 9) that may have adversely affected fibrinogen status apy. In these situations, the drug reverses the coagulopathy and platelet function. The TEG analysis of blood collected and restores normal clotting function without increasing the from animals with moderate hypothermia also showed no risk of thrombosis.24,25,42,43 change in the clot strength as compared with blood from With regard to contribution of platelet and fibrinogen in normotherimic animals.40,41 forming strong clot, rFVIIa did not have any impact even In the present study, the in vitro addition of rFVIIa to the when it was added to normothermic blood. The effect of samples at a concentration considered to be the equivalent to rFVIIa on fibrinolysis was also insignificant. The lack of a90␮g/kg in vivo dose corrected the coagulopathic effect of effect of rFVIIa on clot strength (MA) was also reported in mild and moderate hypothermia (34°C and 31°C), but had another in vitro study44 and in an in vivo study28 in which less effect on severely hypothermic blood (28°C). rFVIIa swine were injected with increasing doses of rFVIIa (180– shortened PT and aPTT of hypothermic samples and brought 720 ␮g/kg) and their blood was analyzed by TEG. These these clotting times to the level of normothermic blood but observations appear to be inconsistent with the reported effect had no effect on fibrinogen measurements. This lack of effect of rFVIIa on increasing hemostatic strength of clot in an can be explained by the fact that fibrinogen determination uncontrolled arterial hemorrhage model.45 In that study, pre- does not directly measure the concentration of the fibrinogen treatment of pigs with rFVIIa increased the clot strength and molecules in plasma but rather estimates the protein level the pressure at which rebleeding occurred after fluid from the clotting time of the sample when an excess amount resuscitation.45 The addition of rFVIIa, factor X, and pro- of thrombin (an activated factor) is added. Thus, fibrinogen thrombin to washed platelets and red cell media (plasma free determination is not influenced by hypothermia because blood) was also shown to increase platelet adhesion and the clotting reaction bypasses the slowed coagulation activation on collagen- and fibrinogen-coated surfaces.46 process and delayed thrombin generation caused by hypo- These findings suggest that rFVIIa-mediated thrombin gen- thermia. rFVIIa addition would also have no effect on eration may enhance the hemostatic strength of clot and its fibrinogen determination by this technique because by attachment to injured tissues. However, this hemostatic im- adding exogenous thrombin in excess, the need for FVIIa provement cannot be measured by the TEG analysis of blood activity to propagate coagulation and enhance thrombin that evaluates only the cohesive strength and not the adhesive generation is totally circumvented. strength of clot to the tissues. To analyze the TEG findings, a summary of the changes The mechanism by which therapeutic doses of rFVIIa in TEG parameters induced by hypothermia and the improve- induce initial thrombin generation is still a matter of ments achieved by the addition of rFVIIa as compared with debate.47,48 According to a cell-based model, rFVIIa at phar- the values of untreated blood at normal temperature are pre- macological concentrations binds to activated platelets, ex- sented in Table 1. The effect of rFVIIa was temperature- posing negatively charged phospholipids, and activates factor dependent, improving both R-time and Vmax with greater X independently from tissue factor.49 This pathway of rFVIIa effect on R-time. rFVIIa was most effective when added to activity was not affected by the reduced temperature (33°C), mildly hypothermic blood; it not only corrected for the hy- suggesting rFVIIa should be effective in enhancing hemosta- pothermia effect but produced a clotting rate that surpassed sis in hypothermic patients.50 Indeed, the effectiveness of the normothermic blood by ϳ25%. The increased coagula- rFVIIa to correct coagulopathy and stop bleeding in trauma tion rate observed here, may suggest the risk of thrombosis in patients with hypothermia was reported in the guidelines for patients treated with rFVIIa. However, rFVIIa is not indicated the use of rFVIIa, and elsewhere.51,52 Experimental studies for treating hypothermic patient, it is rather targeted to the also showed that administration of rFVIIa in hemodiluted patients with significant coagulopathy and associated hypo- pigs improved coagulation parameters and reduced bleeding thermia and acidosis who are unresponsive to standard ther- from a severe liver injury in the presence of hypothermia.53,54

Table 1 Changes in TEG Parameters of Hypothermic Blood Samples With or Without rFVIIa Compared With Those of Untreated Blood at Normal Temperature (37°C)

Parameter Temperature (°C) Without rFVIIa p With rFVIIa p R-time (min) 34 18% slower NS* 27% faster 0.02 31 31% slower 0.02 17% faster 0.06 28 37% slower Ͻ0.01 4% slower NS Vmax (mm/min) 34 14% slower 0.02 24% faster 0.06 31 22% slower Ͻ0.01 3% slower NS 28 38% slower Ͻ0.01 20% slower Ͻ0.01 MA (mm) 34 1% reduced NS 0% change NS 31 2% reduced NS 2% reduced NS 28 4% reduced Ͻ0.05 3% reduced 0.03 *NS, not significant, defined as p Ͼ 0.1.

1084 November 2007 rFVIIa on Coagulation Properties of Human Blood

However, the decreases in the bleeding in these studies and 12. Hedner U, Glazer S, Pingel K, et al. Successful use of recombinant the subsequent investigation55 with a greater number of ani- factor VIIa in patient with severe haemophilia A during mals did not result in a reduction in mortality rate. synovectomy. Lancet. 1988;2:1193. 13. Hay CR, Negrier C, Ludlam CA. The treatment of bleeding in The limitation of this study is that the rFVIIa effect was acquired haemophilia with recombinant factor VIIa: a multicentre assessed in an isolated in vitro condition on blood collected study. Thromb Haemost. 1997;78:1463–1467. from healthy volunteers, apart from many other influencing 14. Shapiro AD, Gilchrist GS, Hoots WK, Cooper HA, Gastineau DA. factors (e.g. tissue injury, hemorrhage, and acidosis) that may Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in affect rFVIIa responses in trauma patients. On the other hand, haemophilia patients with inhibitors undergoing surgery. Thromb Haemost. 1998;80:773–778. this isolation is also the strength of this in vitro study that 15. Kenet G, Walden R, Eldad A, Martinowitz U. Treatment of allows exploring the direct effect of hypothermia and defin- traumatic bleeding with recombinant factor VIIa. Lancet. 1999; ing the effectiveness of rFVIIa under different hypothermic 354:1879. conditions apart from other confounding factors that makes 16. Eikelboom JW, Bird R, Blythe D, et al. Recombinant activated the interpretation of the findings very difficult. factor VII for the treatment of life-threatening haemorrhage. Blood Coagul Fibrinolysis. 2003;14:713–717. In summary, hypothermia at 34°C, 31°C, and 28°C af- 17. Gowers CJ, Parr MJ. Recombinant activated factor VIIa use in fected blood coagulation function by delaying the initial re- massive transfusion and coagulopathy unresponsive to conventional action process and decreasing the clot formation rate without therapy. Anaesth Intensive Care. 2005;33:196–200. impacting the final clot strength. Hypothermia alone, there- 18. Khan AZ, Parry JM, Crowley WF, et al. Recombinant factor VIIa fore, can be the cause of increased bleeding in trauma patients for the treatment of severe postoperative and traumatic hemorrhage. Am J Surg. 2005;189:331–334. who may have normal clotting values (PT and aPTT mea- 19. Kulkarni R, Daneshmand A, Guertin S, et al. Successful use of sured at 37°C). The addition of rFVIIa to hypothermic blood activated recombinant factor VII in traumatic liver injuries in compensated for the decreases and restored or increased the children. J Trauma. 2004;56:1348–1352. clotting reaction process above normothermic values in the 20. Martinowitz U, Kenet G, Segal E, et al. Recombinant activated cold blood samples. These data suggest that administration of factor VII for adjunctive hemorrhage control in trauma. J Trauma. 2001;51:431–438; discussion 438–439. rFVIIa should be beneficial in promoting hemostasis in hy- 21. Mayo A, Misgav M, Kluger Y, et al. Recombinant activated factor pothermic trauma patients without the need to correct the VII (NovoSeven): addition to replacement therapy in acute, uncontrolled patient’s body temperature before the treatment. and life-threatening bleeding. Vox Sang. 2004;87:34–40. 22. O’Neill PA, Bluth M, Gloster ES, et al. Successful use of recombinant activated factor VII for trauma-associated hemorrhage in a patient without preexisting coagulopathy. J Trauma. 2002; REFERENCES 52:400–405. 1. Hoyt DB, Bulger EM, Knudson MM, et al. Death in the operating 23. Udy A, Vaghela M, Lawton G, Sigston P. The use of recombinant room: an analysis of a multi-center experience. J Trauma. 1994; activated factor VII in the control of haemorrhage following blunt 37:426–432. pelvic trauma. Anaesthesia. 2005;60:613–616. 2. Sauaia A, Moore FA, Moore EE, et al. Epidemiology of trauma 24. Dutton RP, McCunn M, Hyder M, et al. Factor VIIa for correction deaths: a reassessment. J Trauma. 1995;38:185–193. of traumatic coagulopathy. J Trauma. 2004;57:709–718; discussion 3. Ferrara A, MacArthur JD, Wright HK, Modlin IM, McMillen MA. 718–719. Hypothermia and acidosis worsen coagulopathy in the patient 25. Haas T, Innerhofer P, Kuhbacher G, Fries D. Successful reversal of requiring massive transfusion. Am J Surg. 1990;160:515–518. deleterious coagulopathy by recombinant factor VIIa. Anesth Analg. 4. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, 2005;100:54–58. Galloway B. Predicting life-threatening coagulopathy in the 26. Boffard KD, Riou B, Warren B, et al. Recombinant factor VIIa as massively transfused trauma patient: hypothermia and acidoses adjunctive therapy for bleeding control in severely injured trauma revisited. J Trauma. 1997;42:857–861; discussion 861–862. patients: two parallel randomized, placebo-controlled, double-blind 5. Lynn M, Jeroukhimov I, Klein Y, Martinowitz U. Updates in the clinical trials. J Trauma. 2005;59:8–15; discussion 15–18. management of severe coagulopathy in trauma patients. Intensive 27. Rizoli SB, Nascimento B Jr, Osman F, et al. Recombinant activated Care Med. 2002;28(suppl 2):S241–S247. coagulation factor VII and bleeding trauma patients. J Trauma. 6. Martin RS, Kilgo PD, Miller PR, et al. Injury-associated 2006;61:1419–1425. hypothermia: an analysis of the 2004 National Trauma Data Bank. 28. Pusateri AE, Ryan KL, Delgado AV, et al. Effects of increasing Shock. 2005;24:114–118. doses of activated recombinant factor VII on haemostatic parameters 7. Danzl DF, Pozos RS, Auerbach PS, et al. Multicenter hypothermia in swine. Thromb Haemost. 2005;93:275–283. survey. Ann Emerg Med. 1987;16:1042–1055. 29. Forgey WW. The Basic Essentials of Hypothermia. Guilford, CT: 8. Jurkovich GJ, Greiser WB, Luterman A, Curreri PW. Hypothermia Pequot; 1999. in trauma victims: an ominous predictor of survival. J Trauma. 30. Fischer RP, Souba WW, Ford EG. Temperature-associated injuries 1987;27:1019–1024. and syndromes. In: Felician DV, Moore EE, Mattox KL, eds. 9. Peng RY, Bongard FS. Hypothermia in trauma patients. J Am Coll Trauma. 3rd ed. Stamford, CT: Appleton & Lange; 1996:951–952. Surg. 1999;188:685–696. 31. Segel IH. Enzyme Kinetics: Behavior and Analysis of Rapid 10. Kirkpatrick AW, Chun R, Brown R, Simons RK. Hypothermia and Equilibrium and Steady-State Enzyme Systems. Wiley classics library the trauma patient. Can J Surg. 1999;42:333–343. edition. New York: Wiley; 1993. 11. Hedner U. Recombinant activated factor VII as a universal 32. Douning LK, Ramsay MA, Swygert TH, et al. Temperature haemostatic agent. Blood Coagul Fibrinolysis. 1998;9(suppl 1): corrected thrombelastography in hypothermic patients. Anesth Analg. S147–S152. 1995;81:608–611.

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33. Kettner SC, Kozek SA, Groetzner JP, et al. Effects of hypothermia 45. Sondeen JL, Pusateri AE, Hedner U, Yantis LD, Holcomb JB. on thrombelastography in patients undergoing cardiopulmonary Recombinant factor VIIa increases the pressure at which rebleeding bypass. Br J Anaesth. 1998;80:313–317. occurs in porcine uncontrolled aortic hemorrhage model. Shock. 34. Watts DD, Trask A, Soeken K, Perdue P, Dols S, Kaufmann C. 2004;22:163–168. Hypothermic coagulopathy in trauma: effect of varying levels of 46. Lisman T, Adelmeijer J, Cauwenberghs S, Van Pampus EC, hypothermia on enzyme speed, platelet function, and fibrinolytic Heemskerk JW, De Groot PG. Recombinant factor VIIa enhances activity. J Trauma. 1998;44:846–854. platelet adhesion and activation under flow conditions at normal and 35. Reed RL II, Johnson TD, Hudson JD, Fischer RP. The disparity reduced platelet count. J Thromb Haemost. 2005;3:742–751. between hypothermic coagulopathy and clotting studies. J Trauma. 47. Butenas S, Brummel KE, Branda RF, Paradis SG, Mann KG. 1992;33:465–470. Mechanism of factor VIIa-dependent coagulation in hemophilia 36. Rohrer MJ, Natale AM. Effect of hypothermia on the coagulation blood. Blood. 2002;99:923–930. cascade. Crit Care Med. 1992;20:1402–1405. 48. Hoffman M, Monroe DM, Roberts HR. Platelet-dependent action of 37. Gubler KD, Gentilello LM, Hassantash SA, Maier RV. The impact high-dose factor VIIa. Blood. 2002;100:364–365; author reply 365. of hypothermia on dilutional coagulopathy. J Trauma. 1994;36:847– 49. Veldman A, Hoffman M, Ehrenforth S. New insights into the 851. coagulation system and implications for new therapeutic options with 38. Sorensen B, Johansen P, Christiansen K, Woelke M, Ingerslev J. recombinant factor VIIa. Curr Med Chem. 2003;10:797–811. Whole blood coagulation thrombelastographic profiles employing 50. Meng ZH, Wolberg AS, Monroe DM III, Hoffman M. The effect of minimal tissue factor activation. J Thromb Haemost. 2003;1:551– temperature and pH on the activity of factor VIIa: implications for 558. the efficacy of high-dose factor VIIa in hypothermic and acidotic 39. Wolberg AS, Meng ZH, Monroe DM III, Hoffman M. A systematic patients. J Trauma. 2003;55:886–891. evaluation of the effect of temperature on coagulation enzyme 51. Martinowitz U, Michaelson M. Guidelines for the use of activity and platelet function. J Trauma. 2004;56:1221–1228. recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a 40. Martini WZ. The effects of hypothermia on fibrinogen metabolism report by the Israeli Multidisciplinary rFVIIa Task Force. J Thromb and coagulation function in swine. Metabolism. 2007;56:214–221. Haemost. 2005;3:640–648. 41. Shimokawa M, Kitaguchi K, Kawaguchi M, et al. The influence of 52. Arnal D, Pineiro P, Garutti I, Olmedilla L, Sanz J, Lajara A. induced hypothermia for hemostatic function on temperature-adjusted Recombinant activated factor VII used in a man with refractory measurements in rabbits. Anesth Analg. 2003;96:1209–1213. bleeding from a stab wound injuring the liver and kidney. Rev Esp 42. Aiyagari V, Menendez JA, Diringer MN. Treatment of severe Anestesiol Reanim. 2004;51:284–288. coagulopathy after gunshot injury to the head using recombinant 53. Martinowitz U, Holcomb JB, Pusateri AE, et al. Intravenous rFVIIa activated factor VII. J Crit Care. 2005;20:176–179. administered for hemorrhage control in hypothermic coagulopathic 43. Levy JH, Fingerhut A, Brott T, et al. Recombinant factor VIIa in swine with grade V liver injuries. J Trauma. 2001;50:721–729. patients with coagulopathy secondary to anticoagulant therapy, 54. Schreiber MA, Holcomb JB, Hedner U, Brundage SI, Macaitis JM, cirrhosis, or severe traumatic injury: review of safety profile. Hoots K. The effect of recombinant factor VIIa on coagulopathic Transfusion. 2006;46:919–933. pigs with grade V liver injuries. J Trauma. 2002;53:252–257; 44. Gerotziafas GT, Chakroun T, Depasse F, Arzoglou P, Samama MM, discussion 257–259. Elalamy I. The role of platelets and recombinant factor VIIa on 55. Klemcke HG, Delgado A, Holcomb JB, et al. Effect of recombinant thrombin generation, platelet activation and clot formation. Thromb FVIIa in hypothermic, coagulopathic pigs with liver injuries. Haemost. 2004;91:977–985. J Trauma. 2005;59:155–161; discussion 161.

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Immunocompetence of the Severely Injured Spleen Verified by Differential Interference Contrast Microscopy: the Red Blood Cell Pit Test Mark Falimirski, MD, FACS, Amjad Syed, MD, and David Prybilla, MD

Objective: To determine the immuno- two control groups: patients with sple- with Satterthwaite’s method because of competence of the successfully nonopera- nectomies and those with normal splenic unequal variances, there was a statisti- .(0.0002 ؍ tively managed injured spleen warranting function. cally significant difference (p vaccinations for overwhelming postsplenec- Results: Forty patients were con- Comparing the same study group with tomy sepsis by differential interference contacted, consented, and volunteered blood those with normal splenic function using trast microscopy (DICM). samples: 10 patients with grade IV splenic t test with pooled variance, there was no Methods: Cull an urban Level I injuries, 1 patient with a grade V injury, statistical significant difference between .(0.489 ؍ trauma systems data bank for all patients 14 patients with splenectomies, and 15 groups (p with grade IV or V splenic injuries (those controls. Average RBC pit levels and IgM Conclusion: DICM, a commonly used with the greatest potential to compromise levels for patients sustaining injuries (15) test to evaluate splenic-based immunocom- immunologic function) successfully man- and successfully nonoperatively managed petence in patients with sickle cell anemia, aged nonoperatively and those who have were 0.6% (0%–2% nL) and 91 mg/dL hemoglobinopathies, and patients undergo- required splenectomies since 1996 and (46–304 nL), respectively. Patients with ing partial splenectomies, also confirms verify the Association for the Surgery of splenectomies had levels of 20.4% and 86 splenic immunocompetence in patients sus- Trauma grading. Contact or obtain writ- mg/dL whereas controls had levels of taining up to grade IV splenic injuries. IgM ten consent of these patients and acquire 0.7% and 110 mg/dL, respectively. The levels earlier thought to be low in patients a blood sample for DICM (red blood cell average time frame from injury to RBC after splenectomy normalize. [RBC] pit analysis) and IgM levels (as a pit test was 3.1 years. Comparing the suc- Key Words: Spleen,Immunocompetence. control). Compare values of those sus- cessfully nonoperatively managed group taining splenic injuries with those of with the splenectomy group using t test J Trauma. 2007;63:1087–1092.

he change in management of blunt splenic injury was cally reflected the survey publication of North American driven by the learned immunocompetent role of the trauma surgeons by Shatz.3 Although there was “remarkable Tspleen. King and Schumacher’s1 1952 publication cor- consensus” of physicians who immunize patients after splenic relating asplenia with overwhelming infection initiated a bet- injury, there were significant differences in timing, vaccines ter understanding of the role of the competent spleen and an used, and patient selection. The question of timing appears to evolution from splenectomy to splenorrhaphy and finally to a have been answered in two publications.4,5 However, in ref- nonoperative approach to splenic injuries. Nonoperative pro- erence to patient selection, Shatz found 15.7% of responders tocols are the mainstay of management for nearly all hemo- immunize patients who undergo splenorrhaphy and 8.4% dynamically normal patients sustaining blunt splenic injury immunize those managed nonoperatively, nearly 25%, regardless of injury grade. However, there exists a lack of “supported by no clinical or experimental data”.2 A second consistency regarding immunization protocols in this same more recent publication by Shatz reemphasized the still patient population. In 2002, Shaffle editorialized the vacci- unanswered questions pertaining to the immunologic func- nation practices patterns after splenic injury.2 This specifi- tion of the injured spleen after successful nonoperative management.6 “Another generation of splenic injury pa- Submitted for publication May 10, 2007. tients has been created with no available data regarding the Accepted for publication July 10, 2007. immunologic capacity, and therefore a need for vaccina- Copyright © 2007 by Lippincott Williams & Wilkins From the Department of Surgery (M.F., A.S.), Indiana University, tion of this group.” Indianapolis, Indiana; and the Department of Anesthesia (D.P.), the Mayo Many parameters of splenic function have been investigated Clinic, Minneapolis, Minnesota. most commonly related to the measurement of immunologic Presented at the 65th Annual Meeting of the American Association for components including antibody production,7,8 properdin,9 and the Surgery of Trauma, September 28–30, 2006, New Orleans, Louisiana. 10 Address for reprints: Mark Falimirski, MD, FACS, Indiana Univer- tuftsin. Further studies demonstrate the profound immunologic sity, 550 N University Blvd., UH6611, Indianapolis, IN 46202; email: response by way of antibody production the spleen is responsi- [email protected]. ble for when antigenically challenged.11,12 However, differential DOI: 10.1097/TA.0b013e3181507329 interference contrast microscopy (Nomarsky Optics) has been

Volume 63 • Number 5 1087 The Journal of TRAUMA௡ Injury, Infection, and Critical Care recognized as the predominant test as first described by Casper This would potentially allow appropriate and adequate blood et al. in 1976 correlating reticuloendothelial (RE) function in flow to the spleen to theoretically maintain enough splenic splenectomized patients to those at risk of developing severe mass for appropriate immunologic function. However, sig- infection namely overwhelming postsplenectomy infection/sep- nificant variability to parenchymal damage exists between sis (OPSI).13 This laboratory study is referred to as the red blood grade IV and V injuries. The definition of a completely cell pit test (RBCPT). Conclusions identified a correlation of shattered spleen or a hilar vascular injury, which devascular- sepsis and infection to “pit counts” greater than 15% in sickle izes the spleen (grade V), leaves a 75% window to interpret cell disease patients from encapsulated organisms. This publi- grade based on percentage of devascularization in grade IV cation was followed by others in which this technique was used injuries. For these reasons, patients with grade IV and V to evaluate RE competence specific to the spleen in patients with splenic injuries were considered for RBCPT testing. 14,15 16–18 19 splenic trauma, hemoglobinopathies, RE immaturity, An urban Level I trauma center database was culled for 20 21 malignancy, nephrotic syndrome, and most recently, partial all adult patients (Ͼ18 years of age) who had sustained grade 22,23 splenectomies. The test has spanned four decades of af- IV and V blunt splenic injuries successfully managed non- firmed use for RE function relating to the spleen. operatively after obtaining approval from the Institutional Clinically, the immune response has not been thoroughly Review Board. All abdominal computed tomographies were investigated in patients sustaining splenic injury although retrieved, reviewed, and injury grades were confirmed to infectious consequences of splenectomy have been well iden- identify potential candidates for an adequate sample size. All tified. Patients sustaining severe (grades IV and V) blunt potential participants required to have sustained injuries a splenic trauma and successfully managed nonoperatively the- minimal of 90 days before participating in the study to insure oretically are at greatest risk for OPSI because of injury to a maximal restoration of any possible “regainable” immune significant proportion of parenchyma, architecture, and blood function. Two control groups of 10 volunteers were tested for supply potentially necessitating vaccinations. It is our hy- comparison: (1) a “nontraumatized” immunocompetent group pothesis that (1) the RBCPT can reliably correlate immune function to grade of splenic injury warranting appropriate use (patients with no history of traumatic injury) and (2) a group of immunizations in patients successfully managed nonop- of patients who required splenectomy after traumatic injury. eratively and potentially rendered immunoincompetent and All participants were first screened for history of immune (2) patients sustaining severe splenic injuries and successfully deficiency using the Jeffrey Model Foundation’s 10 warning 25 managed nonoperatively will have the same immunocompe- signs of primary immunodeficiency. tence as patients with normal splenic function. After obtaining a list of potential participants, individuals were contacted randomly, consent was obtained, and a pe- PATIENTS AND METHODS ripheral blood sample was acquired for two tests: the RBCPT The Association for the Surgery of Trauma spleen injury and an IgM level also used as a control. Blood for the RBCPT scale was created to facilitate clinical investigation and out- was placed in a fixative of 25% glutaraldehyde, transported comes research.24 Our interpretation of grade III injuries by cold, and a wet slide was prepared for microscopy. A pitted definition reflected adequate perfusion to the spleen to not cell was described as any red cell appearing to have one or compromise immunologic function. Grade IV injuries are more discrete crater-like indentations on its surface (Fig. 1). described as ruptured intraparenchymal hematoma with ac- Approximately 500 cells were scanned to report a result. tive bleeding or laceration involving segmental or hilar ves- Normal values for the RBCPT are between 0% and 2% pitted sels producing major devascularization (Ͼ25% of spleen). red cells with abnormal figures typically Ͼ10%.

Fig. 1. (A) Normal adult red blood cells. (B) Red blood cells in a splenectomized patient.26

1088 November 2007 Red Blood Cell Pit Test

Analysis was done using SAS version 9 (SAS Institute, waite’s method because of unequal variances, there was a Cary, NC). Statistical tests were conducted as two-sided at statistically significant difference (p ϭ 0.0002). Comparing the ␣ ϭ 0.05 significance level. t test was used to separate RBCPT in the same study group with those with normal analyses to compare the splenectomy versus the grade IV/V splenic function using t test with pooled variance, there was groups and the control versus the grade IV/V groups. The no statistical significant difference between groups (p ϭ folded F method was used to test for equality of variances, 0.489). IgM levels in patients sustaining splenic injury either Satterthwaite’s method was used for unequal variance, and successfully nonoperatively managed or splenectomized was pooled method was used for equal variance. This required a similar, but 17% to 22% less than our controls. Although this minimal sample size of 10 subjects per group (4 groups). difference is significant, all levels in the successfully nonop- Immunoglobulin levels between controls and those sus- eratively managed group fell well within the normal range. taining splenic injury were compared using Student’s t test with significance being attributed to p Ͻ 0.05. Immunoglob- DISCUSSION ulin levels were then compared with RBCPT results for each Many markers have been investigated to determine of the groups (both controls, the noninjured, and splenectomy splenic function in multiple disease states.7–12 Immunoglob- group, as well as each of the graded injury groups, IV–V). ulin M (IgM) titers have been widely studied and shown to be Nontraumatized immunocompetent volunteers were made up decreased, unchanged, and increased in patients sustaining of medical students, surgical residents, and administrative splenectomy for assorted etiologies including trauma.7,8,27,28 staff. Again approximately 10 patients in each group were Downey et al. identified a 36% decreased IgM level (79 Ϯ 9 needed for statistical significance. mg/dL) in the traumatic asplenic patient compared with their controls (104 Ϯ 9 mg/dL), but all levels were within an RESULTS acceptable/normal range (45–300 mg/dL).7 Chaimoff et al. Nineteen patients were identified to have sustained grade also identified a decreased IgM level in the traumatic IV or V splenic injuries that were successfully managed postsplenectomy patient, but does not report a normal range.8 nonoperatively between 1996 and 2003. Eleven of these gave Koren et al. reports “no significant change” in IgM titers,27 consent and volunteered blood samples, the majority of whereas Demeter et al. identified an increase in IgM levels in which (10) sustained grade IV splenic injuries. These two a similar patient population.28 Obviously, there is great vari- groups were grouped as one for statistical analysis because ances in reports. Our mean IgM levels were within the normal the results of samples from the single grade V patient fell well range for all groups tested; however, the successfully nonop- within the parameters of patients with grade IV injuries and eratively managed splenic injury group had levels closer to for the lack of patients successfully managed nonoperatively the splenectomy group than the control group. They were with grade V injuries. Fourteen patients with splenectomies decreased by 17% compared with controls, which mirror the and 15 controls also consented and volunteered blood sam- Downey et al. experience. IgM as well as other opsonin levels ples. Gender, average age, and ISS are shown in Table 1. have yet to be consistently correlated to immunocompetence Average RBC pit counts and IgM levels for patients of OPSI and specifically in the successfully nonoperatively successfully managed nonoperatively sustaining injuries were managed trauma patient sustaining splenic injury. Other tests 0.6% Ϯ 0.53% (0%–2% nl) and 91 Ϯ 30 mg/dL (46–304 nl), attempting to confer general function have also been studied. respectively. Patients with splenectomies had levels of Although Howell-Jolly and Heinz bodies provides morpho- 20.4% Ϯ 15.1% and 86 Ϯ 46.6 mg/dL whereas controls had logic evidence of asplenia, there presence (1) has never been levels of 0.8% Ϯ 0.56% and 110 Ϯ 42.1 mg/dL, respectively consistently correlated to OPSI and (2) because only 1 in (Table 1). The average time frame from injury to RBCPT in 1,000 to 5,000 red cells bear these structures, “it is not those successfully managed was 3.1 years (range, 1.1–5.4) possible to make quantitative assessments of degrees of and 4.4 years (range, 1.2–8.4) in those splenectomized. Com- splenic activity on their basis of relative numbers”14 as is also paring RBCPT’s in the successfully nonoperatively managed concluded by Casper et al.13 group with the splenectomy group using t test with Satterth- In 1966, Nathan and Gunn were among the first to recognize “distortions” on RBCs in splenectomized patients 29 Table 1 Demographics using differential interference microscopy. Holroyde and Gardner further attempted to demonstrate the characteristics Grade IV/V Splenectomy Control of the pits as vacuoles through a set of very elegant tests (n ϭ 11) (n ϭ 15) (n ϭ 14) where even transfused “normal” blood acquired the charac- Age 24 43.6 32 teristics of pits in the splenectomized recipients.26 In 1976, Gender (M/F) 8/3 8/7 5/9 ISS 23 32 — Casper et al. was the first to correlate pit counts to splenic RBCPT (%) (0%–2% nL) 0.6 20.4 0.7 dysfunction and concludes “the determination of red cell IgM (mg/dL) (46–304 nL) 91 86 110 pitting appears to offer a simple means for clinical evaluation Time between injury and 3.1 4.4 — of splenic RE function in patients with sickle cell disease”.13 blood sampling (yr) Preliminary results suggested that “15% or greater pitted

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RBCs is an indication of significant splenic RE dysfunction deemed necessary; namely, source of splenic blood flow, how and may provide a warning signal in the young sickle cell much critical splenic mass, disease process necessitating disease patient that is at risk to develop a severe infection”. splenectomy, or interpretation of tests confirming immuno- Multiple publications have used and verified this technique as competence. It is well appreciated in animal studies that there the laboratory test that confers splenic immunocompetence. is a graded immunologic response to different percentages of Rogers et al. identified severe infections in all children with viable splenic tissue. Van Wyck et al. demonstrates this best raised pit counts greater than 10%.16 Traub et al. correlated in an animal model subjecting different groups with either an elevated “pocked-erythrocyte rate” greater than 18% in compromised blood flow or splenectomy to different immu- patients after total splenectomy.15 Lastly, Pearson et al. found nologic challenges.32 In clinical studies, Petroianu et al. has an RBCPT greater than 12% in 18 splenectomized children14 demonstrated that “preservation of the uppermost part of the and goes on to agree with others, “although the precise nature spleen vascularized only by the splenogastric vessels main- of the surface indentations or “pits” remains controversial, tains splenic function”.33,34 Although an RBCPT was not their presence appears to be a reliable indicator of decreased performed to validate their results, their favorable outcomes splenic function”.19,30 The RBCPT has also been used to in patients with compromise of blood flow from the hilum confirm immunocompetence in patients with nephrotic syn- again puts into question the need for splenic artery integrity drome, malignancy, and multiple other illnesses.17,18,20,21 to maintain immunocompetence.35 More recently, Rice et al.22 and Stoehr et al.23 both demon- If the RBCPT is a valid test that confers immunocom- strated the application of this test in publications where the petence in different disease states, then the application of this RBCPT was performed to assess splenic phagocytic function test should be able to characterize the immunocompetence of in partially splenectomized children. As previously stated, the the successfully nonoperatively managed injured spleen. RBCPT has spanned four decades of affirmed use correlating Based on our results, it appears that spleens sustaining grade RE function in asplenic patients to OPSI. IV injuries are immunocompetent and patients sustaining All patients with grade IV/V injuries successfully man- these injuries should not be vaccinated for the pathogens of aged nonoperatively and “pit tested” showed the same pit OPSI. Not enough data exists to apply this same conclusion counts as the group that had not sustained a traumatic injury to grade V injuries even though our single enrollment also conferring immunocompetence. When the same injury group had a normal pit count and the Pearson et al. experience was compared with the splenectomized control group, a sig- would expect a high probability for the same. It would be nificant difference was noted in pit counts. Of note, a single useful to identify any occurrences of OPSI in successfully patient in the splenectomy group had a normal pit count nonoperatively managed patients sustaining splenic injuries (0.5%) and a second had a near normal count (2.2%). Al- thought to contract an asplenic state and if possible perform though the possibility of an accessory spleen may have been an RBCPT. present, the more likely cause is splenosis. Pearson et al. described a difference in pit counts in patients sustaining splenectomies for trauma versus hematological diseases.14 REFERENCES All pit counts in the later group were elevated whereas a 1. King H, Schumacher HB. Splenic studies: I. Susceptibility to significant proportion in the former group were not elevated infection after splenectomy performed in infancy. Ann Surg. 1952; where a greater variance was noted. When Tc-99m sulfur 136:239–242. 2. Shaffle JR. A comprehensive practice guideline is needed to make colloid scans were performed in a selected portion of the vaccination practices more consistent. J Trauma. 2002;53:1026–1027. former group, all showed extrahepatic left upper quadrant 3. Shatz DV. Vaccination practices among North American trauma uptake of the radionucleotide in multiple small nodules of RE surgeons in splenectomy for trauma. J Trauma. 2002;53:950–956. tissue thought to be the result of splenosis. This explanation 4. Shatz DV, Schinsky MF, Pais LB, et al. Immune responses of of greater distribution reflects our wider SD in the splenec- splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after tomy group. Corazza et al. also concluded similar findings splenectomy. J Trauma. 1998;44:760–766. while attempting to identify a critical splenic mass to confer 5. Shatz DV, Romero-Steiner S, Elie CM, et al. Antibody responses immunocompetence.31 This would question the belief that in postsplenectony trauma patients receiving the 23-valent architecture, namely splenic blood flow is required to main- pneumococcal polysaccharide vaccine at 14 versus 28 days tain immunocompetency specifically against encapsulated postsplenectomy. J Trauma. 2002;53:1037–1042. 6. Shatz DV. Vaccination considerations in the asplenic patient. Expert organisms. It may also explain why persons sustaining trau- Rev Vaccines. 2005;4:27–34. matic splenectomies have a lesser incidence of OPSI than 7. Downey EC, Shackford SR, Fridlund PH, et al. Long-term depressed those undergoing elective nontraumatic splenectomies. immune function in patients splenectomized for trauma. J Trauma. Neither the integrity of splenic artery blood flow nor 1987;27:661–663. embolization procedures were specifically screened for upon 8. Chaimoff C, Douer D, Pick IA, et al. Serum immunoglobulin changes after accidental splenectomy in adults. Am J Surg. 1978; initial review of abdominal computed tomographies. Al- 136:332–333. though a critical mass is required to maintain splenic immu- 9. Carlisle HN, Saslaw S. Properdin levels in splenectomized persons. nocompetence, there is great variability as to what else is Proc Soc Exp Biol Med. 1959;102:150–154.

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10. Constantopoulos A, Najjar VA, Wish JB, et al. Defective 31. Corazza GR, Tarozzi C, Viara D, et al. Return of splenic function phagocytosis due to tuftsin deficiency in splenectomized subjects. after splenectomy: how much tissue is needed. Br Med J. 1984; Am J Dis Child. 1973;125:663–665. 289:861–864. 11. Baker PJ, Prescott B. Regulation of the antibody response to 32. Van Wyck DB, Witte MH, Witte CL, et al. Humoral immunity in pneumococcal polysaccharides by thymus-derived (T) cells: mode of experimental hyposplenism. Surg. 1978;84:134–139. action of suppressor and amplifier T cells. In: Rudbach JA, Baker 33. Petroianu A, Silva RG, Simal CJR. Late postoperative follow-up of PJ, eds. Immunology of Bacterial Polysaccharides, Proceedings of a patients submitted to subtotal splenectomy. Am Surg. 1997;63:735–740. Symposium Presented at the Annual Meeting of the American Society 34. Petroianu A. Subtotal splenectomy for treatment of patients with of Microbiology, Las Vegas, Nevada, 16 May 1978. Amsterdam: myelofibrosis and myeloid metaplasia. Int Surg. 1996;81:177–179. 35. Petroianu A, Resende V, Gomes de Silva R. Late postoperative Elsevier North Holland, Inc.; 1979:67. follow-up of patients undergoing subtotal splenectomy. Clinics. 12. Jones JM, Amsbaugh DF, Prescott B. Kinetics of the antibody 2005;60:473–478. response to type III pneumococcal polysaccharide: II. Factors influencing the serum antibody levels after immunogenic dose of antigen. J Immunol. 1976;116:52–64. DISCUSSION 13. Casper JT, Koethe S, Rodey GE, et al. A new method for studying Dr. David Shatz (Miami, Florida): In years past, any splenic reticuloendothelial dysfunction in sickle cell disease patients injury to the spleen resulted in that spleen in a bucket, on its and its clinical application: a brief report. Blood. 1976;47:183–188. way to the pathology department. 14. Pearson HA, Johnston D, Smith KA, et al. The born again spleen: More serious considerations of the potential lethal Return of splenic function after splenectomy for trauma. N Engl complications of the asplenic patient helped swing the J Med. 1978;298:1389–1392. 15. Traub A, Giebink GS, Smith C, et al. Splenic reticuloendothelial pendulum to such salvage maneuvers as splenorrhaphy and function after splenectomy, spleen repair, and spleen non-operative management. autotransplantation. N Engl J Med. 1987;317:1559–1564. As Dr. Falimirski pointed out, in a study published four 16. Rogers DW, Serjeant BE, Serjeant GR. Early rise in “pitted” red cell years ago by our own group, while virtually every trauma count as a guide to susceptibility to infection in childhood sickle cell surgeon in North American feels that pneumococcal vacci- anemia. Arch Dis Child. 1982;57:338–342. nation is indicated in splenectomized patients, only 16% have 17. Fetunde JF, Scott RB. Pitted red cell counts in sickle cell disease. the same feeling towards splenorrhaphy, and only 8% toward Am J Pediatr Hematol Oncol. 1986;8:329–333. 18. Sills R, Oski FA. RBC surface pits in the sickle hemoglobinopathies. non-operatively preserved spleens. Am J Dis Child. 1979;133:526–527. Why? Presumably, because we believe that the presence of 19. Holroyde CP, Oski F, Gardner FH. The “pocked erythrocytes”: red- any spleen, partial or scarred, is enough. And without evidence cell surface alterations in reticuloendothelial immaturity of the to the contrary, we find it difficult to challenge that practice. neonate. N Engl J Med. 1969;281:516–520. Dr. Falimirski and colleagues have attempted to justify 20. Buchanan GR, Holtkamp CA. Splenic reticuloendothelial function in our predominate practice, using a simple test of splenic children with cancer. J Pediatr. 1985;106:239–242. reticulo-endothelial function in the form of the red blood 21. Berns JS, Pearson HA, Gaudio KM, et al. Normal splenic function in children with the nephrotic syndrome. Pediatr Nephrol. 1988; cell pit test. 2:244–246. I have a question, comment and a caution. The question 22. Rice HE, Oldham KT, Hillery CA, et al. Clinical and hematologic regards the selection of your patients. You chose patients benefits of partial splenectomy for congenital hemolytic anemias in with CT-graded, Grade IV and V splenic injuries, finding 19 children. Ann Surg. 2003;237:281–288. such patients in seven years. 23. Stoehr GA, Stauffer UG, Eber SW. Near-total splenectomy: a new Those are the same patients, in which Dr. Peitzman and technique for the management of hereditary spherocytosis. Ann Surg. the EAST group found an 83 and 99% non-operative failure 2005;241:40–47. 24. Moore EE, Cogbill TH, Jurkovich GJ, et al. Organ injury rate, suggesting that your institution must see a lot of splenic scaling: spleen and liver (1994 revision). J Trauma. 1995;38: injuries to gather that many patients with high-grade injuries 323–324. successfully managed non-operatively. 25. Ten warning signs of primary immunodeficiency. National Primary Combine that with Dr. Barquist’s study showing inaccu- Immunodeficiency Resource Center. Available at http://npi. rate radiologist reading rates of up 68% in Grade IV splenic jmfworld.org. Accessed September 2006. injuries, and I have to wonder if you are really dealing with 26. Holroyde CP, Gardner FH. Acquisition of autophagic vacuoles by the group of patients that you think you are, and not with, human erythrocytes physiological role of the spleen. Blood. 1970; 36:566–575. perhaps, a lower grade. 27. Koren A, Haasz R, Tiatler A, et al. Serum immunoglobulin levels in That lower grade group may theoretically have preserved children after splenectomy. A prospective study. Am J Dis Child. enough of the splenic architecture to remove the pitted red 1984;138:53–55. cells and enough of the microcirculation to provide for ade- 28. Demeter J, Bohn U, Paloczi K, et al. Immunoglobulin profiles and quate antigen processing, which may or may not be present in antibacterial antibody levels in 50 patients a long time after the true high grade lesions. posttraumatic splenectomy. 1990;33:7–9. Along those same lines, I have to assume that since you 29. Nathan DG, Gunn RB. Thalassemia: the consequences of unbalanced hemoglobin synthesis. Am J Med. 1966;41:815–830. made no mention in your manuscript, that you did not eval- 30. Kent G, Minick OT, Volini FI, et al. Autophagic vacuoles in human uate your study patients with a CT or radionucleotide scan to red cells. Am J Pathol. 1966;48:831–857. look for splenosis.

Volume 63 • Number 5 1091 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

This could produce a normal pit test, but not necessarily However, I do have some quibbles with your methodol- confer immunoprotection. As for the caution; you stated in ogy to reinforce what exactly does the pit test mean? your manuscript that several studies used the RBC pit test to It usually means that more RBC’s are not being gotten rid verify splenic immunocompetence. of. We are looking at it in a slightly different way and looking In fact, the pit test is only indicative of the lack of a at D-4 subsets to look at the immunologic competence. spleen and says nothing to the presence or absence of anti- I would appreciate your comments on that because you bodies, or the prevention of disease, which is, after all, what did select the one particular test to look at competence. we are ultimately interested in. Dr. Mark Falmirski: Sure, the reasoning that these pits Only Rogers alluded to that, and that was in children who are supposedly present is because of the architectural integ- were immuno-incompetent by virtue of their age and immu- rity or disintegrity of the spleen. nologic immaturity. And for that reason, I submit to you that It is believed that these pits would almost also be asso- your conclusion to not vaccinate patients with preserved ciated with intracellular bacteria; hence, when pits are Grade IV splenic injuries is a big leap of faith and perhaps present, bacteria will be present. This comparison that James premature. It’s also only based on 10 patients. Casper comes up with, or alludes to in his papers as to why Overall, I would like to congratulate the authors for these pits are present, so they would essentially be somewhat adding another piece of information to our literature and similar to intercellular organisms. That’s why we used this helping to define the therapy required in this gray zone group portion as our hypothesis. of patients. Dr. Ari Leppaniemi (Helsinki, Finland): Did you at- Dr. Mark Falimirski (Indianapolis, Indiana): When we tempt to correlate the pit tests result with an anatomical initially ran the data, or ran and reviewed the CT scans of findings, such as estimated amount of viable, or perfused these patients, we were fairly critical of applying the AAST splenic tissue that could be a relevant question, for example, grading scale. after selective angio-embolization. We took out rulers and tried to identify the actual volume Dr. Mark Falimirski: Absolutely. We did not, and it’s a of the injured part of the spleen. So we believe we were fairly mistake on my part for not actually documenting in our data accurate. set. I’m kicking myself for not doing that. I knew I was going In cases of difficulty in differentiating injury grades, we to get this question. consulted another surgical colleague as to the potential grade I can only tell you that the one injured Grade V patient’s and showed him all the calculations. CT scan of the entire spleen was not perfused. So we believe that our Grade IV and V injuries were It was actually just a black hole, essentially, in the left upper accurate in a grading scale. We were a bit surprised to find quadrant. I was actually surprised. My first initial belief was that initially so few, but later we looked at the damage that was done Grade V injuries were going to be not immunocompetent. on these CT scans, we were surprised at how many there were. This is a preliminary study. I will state that from my When we had the one result, which, actually, had an review of the literature, I’ve yet to identify a single patient average less than all the other pit counts, I was really sur- with a normal pit count that had the diagnosis of overwhelm- prised. We obviously don’t know when was it re-established? ing postsplenectomy sepsis/infection. Was it established within days, hours, weeks? Our initial attempt to study this was to look at patients who It was a mistake on our part to not go back and actually had overwhelming postsplenectomy sepsis/infection and then go correlate and identify when perfusion, and even in some patients back and measure their pit counts and to apply it the way that the with sequential CT scans, to go back and identify those patients paper from James Casper did. There is not a diagnostic code where reperfusion would have been easy to identify. identifying this so it couldn’t be performed this way. Dr. John Hall (Kingsport, Tennessee): Dr. Purtelle and We actually had the luxury of having James Casper, Henshaw up in Rochester showed many years ago that with when at the Medical College of Wisconsin, at our disposal, so the splenic implant, you don’t have the Howell␥C¸oˆJolly bod- we had a great source of use of his expertise in this area. I ies, which they looked at. think, unfortunately, he probably would beg to differ with the The spleen has several functions, one by architectural, one comments about using this as a test to tell us whether there’s by synergistic helper production, one by antibody production. immuno-incompetence based on the grading of scale. Do you know what you’re testing in your immune function? So I think that there is still a degree of difference in Dr. Mark Falimirski: Actually, it’s a structural integ- opinion as to what this test actually means at this time. rity. So it’s not integrity of production of components, or a Dr. Ajai K. Malhotra (Richmond, Virginia): I think you compliment. I felt like when I showed the one slide of note of are addressing a question that’s really relevant, because there patients who had the splenosis, I was opening a can of worms are more and more attempts being made with angio-emboli- as to the integrity of splenic perfusion, architectural need, or zation and increasing use of non-operative management to percentage of actual tissue left behind. anatomically preserve the organ without good evidence that it But the test is not intended to measure an immunocompe- is functionally competent as well. tent marker, literally a structural integrity of the organ itself.

1092 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Predicting the Severity of Systemic Inflammatory Response Syndrome (SIRS)-Associated Coagulopathy With Hemostatic Molecular Markers and Vascular Endothelial Injury Markers Toshiaki Iba, MD, Satoshi Gando, MD, Atsuo Murata, MD, Shigeki Kushimoto, MD, Daizoh Saitoh, MD, Yutaka Eguchi, MD, Yasuhiro Ohtomo, MD, Kohji Okamoto, MD, Kazuhide Koseki, MD, Toshihiko Mayumi, MD, Toshiaki Ikeda, MD, Hiroyasu Ishhikura, MD, Masashi Ueyama, MD, Yuji Ogura, MD, Shigeatsu Endo, MD, Shuji Shimazaki, MD, and the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Study Group

Introduction: The changes in bi- measured and the data were compared ence was seen regarding the thrombin-AT omarkers of coagulation or fibrinolysis, between the severe group (patients with complex and total plasminogen activator anticoagulation, inflammation, and endo- a total maximum Sequential Organ Fail- inhibitor on both days. A comparison of thelial damage occur in patients with sys- ure Assessment score of 10 or more and the areas under the receiver operating -and the less- characteristic curve revealed the AT ac (25 ؍ temic inflammatory response syndrome nonsurvivors; n (SIRS). The purpose of this study is to severe group (Sequential Organ Failure tivity to be the best predictor of a progres- .sion of organ dysfunction .(41 ؍ assess the prognostic value of these mark- Assessment score <10; n ers in patients with SIRS-associated Results: Significant changes between Conclusion: The changes in some he- hypercoagulopathy. the groups were observed in platelet mostatic molecular markers and vascular Methods: Sixty-six SIRS patients count, fibrin or fibrinogen degradation endothelial markers were conspicuous in with a platelet count less than 15.0 ؋ products, interleukin-6, soluble thrombo- patients with organ dysfunction. The AT 104/mm3 in three university hospital in- modulin, antithrombin (AT) activity, and activity is considered to be the most useful tensive care units were enrolled in this protein C activity, both on day 0 and on predictor of organ dysfunction. prospective, comparative study. Blood day 2. In contrast, the D-dimer, soluble fi- Key Words: Systemic inflammatory samples were obtained on day 0 and day brin, plasmin-␣2-antiplasmin complex, and response syndrome, Organ dysfunction, 2. Twelve hemostatic, inflammatory, E-selectin levels were higher in the severe Hypercoagulopathy, Hemostatic molecu- and vascular endothelial indices were group only on day 2. No significant differ- lar markers, Antithrombin activity. J Trauma. 2007;63:1093–1098.

t is widely accepted that hypercoagulopathy is a univer- nostic criteria for disseminated intravascular coagulation sal event in systemic inflammatory response syndrome (DIC) in 2005.3 Based on both retrospective4 and prospec- I(SIRS). In addition, accumulating evidence has shown tive trials,3 four global parameters including the SIRS hypercoagulopathy to play a major role in the development criteria, the platelet count, the fibrin or fibrinogen degra- of organ dysfunction.1 Indeed, inflammation and activa- dation products (FDP) level, and the prothrombin time tion in the coagulation system are considered to be the two were selected for the new diagnostic criteria. Because DIC main factors for a progression from SIRS to severe sepsis.2 is a common complication of variety of diseases and it Because the importance of recognizing coagulopathy in requires immediate management, only global markers were SIRS patients has recently been advocated, the Japanese selected for the new criteria; however, to increase the Association for Acute Medicine has proposed new diag- Center; Department of Emergency Medicine and Intensive Care (T.M.), Submitted for publication June 17, 2006. Nagoya University School of Medicine; Department of Critical Care and Accepted for publication October 16, 2006. Emergency Medicine (T.I.), Tokyo Medical University Hachioji Medical Copyright © 2007 by Lippincott Williams & Wilkins Center; Department of Emergency and Critical Care Medicine (H.I.), Na- From the Division Acute and Critical Care Medicine, Department of tional Hospital Organization, Kyoto Medical Center; Shakaihoken Cyukyo Anesthesiology and Critical Care Medicine (S.G.), Hokkaido University Hospital (M.U.); Department of Traumatology and Acute Critical Care Graduate School of Medicine; Department of Trauma & Critical Care Med- Medicine (H.O.), Osaka University Medical School; Department of Critical icine (A.M.), Kyorin University School of Medicine; Department of Emer- Care Medicine (S.E.), School of Medicine, Iwate Medical University; and gency & Critical Care Medicine (S.K.), Nippon Medical School; Department Department of Trauma & Critical Care Medicine (S.S.), Kyorin University of Traumatology and Critical Care Medicine (D.S.), National Defense Med- School of Medicine. ical College; Critical and Intensive Care Medicine (Y.E.), Shiga University Supported by the Japanese Association for Acute Medicine. of Medical Science; Department of Critical Care and Traumatology (Y.O.), Address for reprints: Toshiaki Iba, MD, Department of Surgery, Jun- National Disaster Medical Center; Department of Surgery 1 (K.O.), School tendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu Chiba 279- of Medicine, University of Occupational and Environmental Health; Emer- 0021, Japan; email: [email protected]. gency and Critical Care Medicine (K.K.), Kawaguchi Municipal Medical DOI: 10.1097/01.ta.0000251420.41427.d3

Volume 63 • Number 5 1093 The Journal of TRAUMA௡ Injury, Infection, and Critical Care sensitivity and specificity, new markers should be selected (APACHE) II score was assessed at the time of enrollment.6 for the next generation of diagnostic criteria. For this The Sequential Organ Failure Assessment (SOFA) score7 purpose, the Japanese Association for Acute Medicine DIC except for coagulation (platelet count) was determined daily, study group planned a prospective multicenter study. The and the total maximum SOFA (TMS) during the first week primary purpose of this study is to identify the best single was calculated. For the diagnosis of DIC, we used the diag- predictor for the severity of SIRS with hypercoagulopathy. nostic criteria of the Japanese Ministry of Health and Welfare for DIC.8 PATIENTS AND METHODS Patients who were admitted to surgical or medical inten- Statistical Analysis sive care units in three university hospitals and fulfilled the The Mann-Whitney U test was applied for two-group criteria of SIRS5 were eligible in this study. The institutional unpaired comparison. Receiver operating characteristic review board of each institution approved the protocol and curves were constructed for TMS (Ն10), Japanese Ministry the informed consent from all patients or next of kin was of Health and Welfare DIC score (Ͼ7), and outcome (non- obtained. survivors). The areas under the receiver operating character- The first blood samples were obtained when their platelet istic curve (AUC) were examined by a significance test for counts decreased to less than the lower limit of the normal AUC. Correlation was examined by the Spearman’s rank range (15.0 ϫ 104/mm3) (day 0). Next, the second blood correlation coefficient. For all reported results, p Ͻ 0.05 was samples were collected 48 hours after the first sample (day 2). considered to indicate a statistically significant difference. Immediately after the samples were taken, the platelet counts, prothrombin time, fibrinogen, and FDP levels were measured RESULTS daily using established standard laboratory techniques to cal- Trauma, peritonitis, and pneumonia were the common culate the DIC score up to day 7. After the enrollment, the underlying diseases in the study subjects. Among 66 subjects, interleukin 6 (IL-6), D-dimer, soluble fibrin (SF), thrombin- 25 (37.9%) had a TMS of 10 or more and were divided into antithrombin (AT) complex (TAT), plasmin-␣2-antiplasmin a severe group, whereas the TMS did not reach 10 in 41 complex (PAP), E-selectin, soluble thrombomodulin (sTM), (62.1%) subjects, and they were classified as the less-severe AT activity, protein C (PC) antigen, and total plasminogen group (Table 2). Anticoagulation therapy with either heparin, activator inhibitor (total-PAI) were measured as summarized low-molecular weight heparin, or protease inhibitors (gabex- in Table 1. The patients who had chronic renal failure requir- ate mesilate, nafamostat mesilate) was administered to 19 ing hemodialysis, cirrhosis, or chronic hepatitis were elimi- patients (76.0%) in the severe group and 10 patients (24.4%) nated. In addition, any patients who had immune suppression in the less-severe group before day 2. Substitution therapy and chronic malnutrition (albumin Ͻ3.0 mg/dL) were also using fresh frozen plasma or AT concentrate was performed excluded from the study. Neither anticoagulative therapies, in 18 patients (72.0%) in the severe group before day 2. including the prophylactic use of heparin, nor substitution The median of the platelet counts on day 0 in the severe therapy was administered to any patients until day 0. How- group was 9.3 ϫ 104/mm3, which was significantly lower ever, such treatments were not restricted thereafter. than that in the less-severe group (13.5 ϫ 104/mm3)(p Ͻ All patients were followed up for 28 days after enroll- 0.01). The median platelet counts decreased more on day 2 in ment and then were assessed for the 28-day all-cause mor- both groups, and the difference was still significant (p Ͻ tality. The Acute Physiology and Chronic Health Evaluation 0.01). Among the other hemostatic markers, the median FDP

Table 1 Assay Procedure

Test Kit Name Company Assay Procedure Coagulation/fibrinolysis markers FDP LPIA FDP-P Mitsubisi-Kagaku-Iatron Latex agglutination D-dimer LPIA Ace D-D dimer Mitsubisi-Kagaku-Iatron Latex agglutination SF Iatro SF Mitsubisi-Kagaku-Iatron Latex agglutination TAT LPIA-F ⅐ TAT test Mitsubisi-Kagaku-Iatron Latex agglutination PAP LPIA Ace PPI Mitsubisi-Kagaku-Iatron Latex agglutination Endothelial damage markers/others IL-6 Human interleukin-6 immunoassay kit R&D Systems EIA E-selectin Human sE-selectin immunoassay kit R&D Systems EIA STM TM panacela Fuji Rebio EIA AT activity Chromorate ATIII Mitsubisi-Kagaku-Iatron Chromogenic assay PC activity LPIA Ace PC Mitsubisi-Kagaku-Iatron Latex agglutination Total PAI LPIA ⅐ tPAI test Mitsubisi-Kagaku-Iatron Latex agglutination EIA, enzyme linked immunoassay.

1094 November 2007 Severity Markers for Septic Hypercoagulopathy

level was significantly higher in the severe group than in the Table 2 Patient Demographics less-severe group both on day 0 and on day 2 (p Ͻ 0.05, 0.01 Less-Severe Severe respectively), whereas the median D-dimer, SF, and PAP N ϭ 41 (62.1%) N ϭ 25 (37.9%) levels were significantly higher only on day 2 in the severe Ϯ Ϯ Ϯ Age (mean SD) 56.3 20.9 57.1 19.3 group (p Ͻ 0.01, 0.05, 0.05, respectively). In contrast, the Sex (male/female) 24/17 20/5 Underlying disease median TAT level did not differ between the groups both on Pneumonia 5 (12.2) 6 (24.0) day 0 and on day 2 (Fig. 1). Trauma 16 (39.0) 5 (20.0) The median IL-6 and sTM were significantly higher in Burn 2 (4.9) 4 (16.0) the severe group than in the less-severe group on days 0 and Peritonitis 7 (17.1) 3 (12.0) Ͻ Meningitis 5 (12.2) 2 (8.0) 2(p 0.01, respectively). Conversely, the median AT ac- Abdominal abscess 1 (2.4) 2 (8.0) tivity on day 0 (53.0%) was significantly lower in the severe Others 5 (12.2) 3 (12.0) group than in the less-severe group (71.9%), and the differ- Ϯ Ϯ APACHE II score 13.51 6.83 23.56 6.55 ence was significant (p Ͻ 0.01). The median activity in- (mean Ϯ SD) TMS score (mean Ϯ SD) 5.10 Ϯ 2.14 11.40 Ϯ 2.48 creased in both groups and the difference was still significant DIC score (mean Ϯ SD) 4.07 Ϯ 1.92 6.44 Ϯ 2.47 on day 2 (p Ͻ 0.01). A similar tendency was also recognized Survivor (%) 41 (100) 14 (56) in PC activity. Among the vascular endothelial markers, E-selectin showed a significant difference between the groups

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Volume 63 • Number 5 1095 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

SJPO᧥ QJPO᧥ 8PO᧥

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QJPO᧥ ᧦᧦ WRWDO3$, 3&DFWLYLW\ $7DFWLYLW\ ᧦᧦ ᧦ ᧦᧦ 'D\ 'D\ 'D\ 'D\ 'D\ 'D\ Fig. 2. Changes in the inflammation or endothelial damage markers in the less-severe and severe patients. The interleukin 6 (IL-6) and soluble thrombomodulin (sTM) levels were significantly higher in the severe patients both on day 0 and on day 2, whereas the antithrombin (AT) activity and protein C (PC) activity were both significantly lower in the severe patients on both days. The E-selectin levels were significantly higher in the severe cases only on day 2. In contrast, there was no difference in the total plasminogen activator inhibitor (t-PAI) level on both days. on day 2 (p Ͻ 0.05), whereas no difference was seen in the DISCUSSION total PAI on both days (Fig. 2). A recent subgroup analysis of the large scale phase 3 trial When the AUCs for TMS Ն10 on day 0 were compared, has elucidated that naturally derived anticoagulant, AT III is the AT activity showed the greatest value (0.84, p Ͻ 0.01) effective only in the population with hypercoagulopathy.9 In followed by PC activity (0.78, p Ͻ 0.01). Neither the AUCs addition, clinical trials using recombinant human activated in the AT activity nor the PC activity for TMS Ն10 showed a better value on day 2 (0.80, 0.73, respectively). To predict PC (rhAPC), such as ENHANCE trial, demonstrated rhAPC to be effective only when it is administered an early stage of the onset of DIC, platelet count, total PAI, and AT activity 10 were thought to be useful. The AUCs (ability to distinguish disease, and the ADDRESS trial revealed that rhAPC has the population whose DIC score reaches 7 or more within 7 beneficial effects only when it is applied to the severe cases Ͼ 11 days) of the platelet count, the total PAI, and the AT activity with an APACHE II score 25. Along with these advances were 0.81, 0.79, and 0.73, respectively (p Ͻ 0.01, respec- in treatment and accumulated knowledge, it is now becoming tively). When The AUCs were compared among the variables more important to evaluate the severity of illness quicker and regarding mortality, the AT activity and IL-6 showed the more precisely. The primary objective of the current study highest value (0.86, 0.79, respectively) on day 0 (Table 3). was thus to examine the usefulness of measuring the endo- In comparing any correlations, the TMS and APACHE II thelial and hemostatic molecular markers in SIRS patients revealed the highest correlation (R2 ϭ 0.53) followed by the with coagulopathy. TMS and AT activity (R2 ϭ 0.35), and then the TMS and Ferreira et al.12 reported TMS to be a good predictor of IL-6 level (R2 ϭ 0.16). the outcome in critically ill patients, and they also demon-

1096 November 2007 Severity Markers for Septic Hypercoagulopathy

Table 3 Comparison of Spearman’s Rank Correlation

TMS Ͼ10 DIC Score Ն7 Outcome (Mortality) Day 0 Day 2 Day 0 Day 2 Day 0 Day 2 AUC p AUC p AUC p AUC p AUC p AUC p Platelet count 0.77 Ͻ0.01 0.67 0.06 0.81 Ͻ0.01 0.94 Ͻ0.01 0.64 0.18 0.83 Ͻ0.01 FDP 0.61 0.17 0.65 0.06 0.68 0.02 0.66 0.04 0.76 Ͻ0.01 0.87 Ͻ0.01 D-dimer 0.60 0.18 0.62 0.12 0.68 0.02 0.67 0.03 0.73 0.02 0.85 Ͻ0.01 SF 0.59 0.33 0.57 0.32 0.67 0.03 0.59 0.21 0.58 0.39 0.73 0.02 TAT 0.58 0.29 0.62 0.11 0.67 0.03 0.61 0.13 0.38 0.16 0.73 0.02 PAP 0.61 0.15 0.67 0.04 0.61 0.15 0.55 0.48 0.56 0.55 0.62 0.21 IL-6 0.68 0.03 0.74 Ͻ0.01 0.64 0.07 0.68 0.02 0.79 Ͻ0.01 0.86 Ͻ0.01 E-selectin 0.65 0.07 0.65 0.06 0.54 0.63 0.62 0.12 0.59 0.35 0.70 0.04 sTM 0.69 0.02 0.64 0.07 0.71 0.01 0.75 0.01 0.66 0.09 0.66 0.11 AT activity 0.84 Ͻ0.01 0.80 Ͻ0.01 0.73 Ͻ0.01 0.86 Ͻ0.01 0.86 Ͻ0.01 0.86 Ͻ0.01 PC antigen 0.78 Ͻ0.01 0.73 Ͻ0.01 0.64 0.07 0.60 0.18 0.70 0.04 0.73 0.02 Total PAI 0.70 0.01 0.64 0.07 0.79 Ͻ0.01 0.68 0.02 0.67 0.09 0.75 0.02 strated a poor outcome of the patients whose TMS exceeded 0.86), which was even better than that of IL-6 or the platelet 11. In this study, because the patients were eligible if the count. From the AUC calculated in this study, APACHE II is platelet number was less than 15.0 ϫ 104/mm3 (SOFA score superior to AT activity. However, as a diagnostic parameter, in coagulation disorder is Ͼ1 with this count) the patients single blood marker is much more preferable. were thought to be severe if TMS was 10 or more. As a result, Another purpose of this study was to examine the 11 of 25 (44%) did not survive in the severe group, whereas usefulness of the second measurement performed 48 hours all survived in the less-severe group. after the first sampling. Former studies revealed that a Systemic inflammation and a procoagulant host response decrease in the AT activity to be recognized at a very early are closely related. For example, inflammatory cytokines phase and the degree of depletion often indicates an unfa- such as tumor necrosis factor and IL-6 are capable of acti- vorable prognosis.23,24 Mesters et al.25 reported a signifi- vating coagulation and inhibiting fibrinolysis. Conversely, cant decline occurred within the first few hours after the thrombin is capable of stimulating multiple inflammatory onset of fever. In our study, we found the decrease of AT 13 pathways, including IL-6 production. As a result, these activity was already significant on day 0 and the degree systems form a vicious cycle in the progression of organ reflected the severity. In addition, a second sample did not damage. A numbers of studies have shown a rapid rise in IL-6 show any better AUC than the first according to many of levels at the onset of septic episodes, and the increase in IL-6 the indices. Dhainaut et al.26 reported that a worsening of 14–17 was related to the severity of septic events. So, IL-6 has the coagulopathy during the first day of sepsis was asso- been recognized to be one of the best markers for the eval- ciated with the outcome and the clinical usefulness of uation of disease severity. In the present study, AUC for TMS information gained from the day 2 values appeared to be of IL-6 was 0.68 and higher than that of the other hemostatic negligible. Similar to their findings, we think the day 2 markers except platelet count. The platelet counts showed the data were very limited. highest AUC for DIC, however, because the diagnosis of DIC is partially dependent on the platelet counts, and the present study enrolled the patients with platelet counts of less than CONCLUSION 15.0 ϫ 104/mm3, considerable inclusion bias might thus have AT activity is considered to be the best single marker existed. because it correlated well with the severity and mortality in The depletion of the AT activity in critically ill patients SIRS-associated coagulopathy. We therefore recommend this is a well-known event. In a large-scale phase 3 trial of parameter be included in the future diagnostic criteria for high-dose AT treatment for severe sepsis, a higher mortality DIC. rate was found in patients with baseline AT activity of less than 60%.18 The decrease of AT activity is the result of the following: an enhanced coagulative state,19 impaired liver synthesis,19,20 the degradation by neutrophil elastase,21,22 and ACKNOWLEDGMENTS leakage from the endovascular space. In the present study, The author contributions are as follows: Satoshi Gando and Atsuo among all the coagulative, anticoagulative, inflammatory, Murata participated in the study setting. Shigeki Kushimoto, Daizoh Saitoh, Yutaka Eguchi, Yasuhiro Ohtomo, Kohji Okamoto, Kazuhide Koseki, Toshi- and vascular damage markers, AT activity correlated best to hiko Mayumi, Toshiaki Ikeda, Hiroyasu Ishikura, Masashi Ueyama, Hiroshi the clinical severity with a very high prognostic value for the Ogura, Shigeatsu Endo, and Shuji Shimazaki contributed to the data analysis prediction of TMS Ն10 (AUC ϭ 0.84) and death (AUC ϭ and writing.

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REFERENCES 13. Johnson K, Choi Y, DeGroot E, et al. Potential mechanisms for a proinflammatory vascular cytokine response to coagulation 1. Levi M, Cate HT. Disseminated intravascular coagulation. N Engl activation. J Immunol. 1998;160:5130–5135. J Med. 1999;341:586–592. 14. Hack CE, De Groot ER, Felt-Bersma RJ, et al. Increased plasma 2. Matthay MA. Severe sepsis-a new treatment with both levels of interleukin-6 in sepsis. Blood. 1989;74:1704–1710. anticoagulant and antiinflammatory properties. N Engl J Med. 15. Reinhart K, Menges T, Gardlund B, et al. Randomized, placebo- 2001;344:759–762. controlled trial of the anti-tumor necrosis factor antibody fragment 3. Gando S, Iba T, Eguchi Y, et al. A multicenter, prospective afelimomab in hyperinflammatory response during severe sepsis: the validation of disseminated intravascular coagulation diagnostic RAMSES study. Crit Care Med. 2001;29:765–769. criteria for critically ill patients: comparing current criteria. Crit Care Med. 2006;34:625–631. 16. Presterl E, Staudinger T, Pettermann M, et al. Cytokine profile and 4. Gando S, Wada H, Asakura H, et al. Evaluation of new Japanese correlation to the APACHE III and MPM II scores in patient with diagnostic criteria for disseminated intravascular coagulation in sepsis. Am J Respir Crit Care Med. 1997;156:825–832. critically ill patients. Clin Appl Thromb Hemost. 2005;11:71–76. 17. Ostermann H, Kratz-Albers K, Mesters RM, et al. Reciprocal 5. Members of the American College of Chest Physicians/Society of changes in circulating interleukin-6 and its soluble receptor during Critical Care Medicine Consensus Conference Committee. American evolving sepsis in leukocytopenic patients. J Infect Dis. 1997; College of Chest Physicians/Society of Critical Care Medicine 176:825–828. Consensus Conference. Definition for sepsis and organ failure and 18. Warren BL, Eid A, Singer P, et al. High-dose antithrombin III in guidelines for the use innovative therapies in sepsis. Crit Care Med. severe sepsis. JAMA. 2001;286:1869–1878. 1992;20:864–874. 19. Rodeghiero F, Mannucci PM, Vigano S, et al. Liver dysfunction 6. Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity rather than intravascular coagulation as the main cause of low classification system. Crit Care Med. 1985;13:818–829. protein C and antithrombin III in acute leukemia. Blood. 1984; 7. Vincent JL, de Mendonca A, Cantraine F, et al. Use of the SOFA 63:965–969. score to assess the incidence of organ dysfunction/failure in intensive 20. Sie P, Letrenne E, Caranobe C, et al. Factor II related antigen and care units: results of a multicenter, prospective study. Crit Care antithrombin III levels as indicators of liver failure in consumption Med. 1998;26:1793–1800. coagulopathy. Thromb Haemost. 1982;47:218–220. 8. Kobayashi N, Maekawa T, Takada M, et al. Criteria for diagnosis of 21. Jordan RE, Kilpatrick J, Nelson RM. Heparin promotes the DIC based on the analysis of clinical and laboratory findings in 345 inactivation of antithrombin by neutrophil elastase. Science. 1987; DIC patients collected by the Research Committee on DIC in Japan. 237:777–779. Bibl Haematol. 1987;49:848–852. 22. Seitz R, Wolf M, Egbring R, et al. The disturbance of hemostasis in 9. Kienast J, Juers M, Wiedermann CJ, et al. Treatment effects of septic shock: role of neutrophil elastase and thrombin, effects of high-dose antithrombin without concomitant heparin in patients antithrombin III and plasma substitution. Eur J Haematol. 1989; with severe sepsis with or without disseminated intravascular 43:22–28. coagulation. J Thromb Haemost. 2006;4:90–97. 23. Lorente JA, Garcia-Frade LJ, Landin L, et al. Time course of 10. Vincent JL, Bernard GR, Beale R, et al. Drotrecogin alfa hemostatic abnormalities in sepsis and its relation to outcome. Chest. (activated treatment in severe sepsis from the global open-label 1993;103:1536–1542. trial ENHANCE: further evidence for survival and safety and 24. Fourrier F, Chopin C, Goudemand J, et al. Septic shock, multiple implications for early treatment. Crit Care Med. 2005;33:2266– organ failure, and disseminated intravascular coagulation. Chest. 2277. 1992;101:816–823. 11. Abraham E, Laterre PF, Garg R, et al. Drotrecogin alfa (activated) 25. Mesters RM, Mannucci PM, Coppola R, et al. Factor VIIa and for adults with severe sepsis and a low risk of death. N Engl J Med. antithrombin III activity during severe sepsis and septic shock in 2005;353:1332–1341. neutropenic patients. Blood. 1996;88:881–886. 12. Ferreira FL, Bota DP, Bross A, et al. Serial evaluation of the SOFA 26. Dhainaut JF, Shorr AF, Macias WL, et al. Dynamic evolution of score to predict outcome in critically ill patients. JAMA. 2001; coagulopathy in the first day of severe sepsis: relationship with 286:1754–1758. mortality and organ failure. Crit Care Med. 2005;33:341–348.

1098 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

The Effects of Gammahydroxybutyrate on Hypermetabolism and Wound Healing in a Rat Model of Large Thermal Injury Kevin D. Murphy, MD, MCh, MMS, FRCSI, Mary W. Rose, PsyD, David L. Chinkes, PhD, Walter J. Meyer III, MD, David N. Herndon, MD, FACS, Hal K. Hawkins, MD, PhD, and Arthur P. Sanford, MD

Background: Growth hormone (GH) Methods: Body composition in male Conclusions: GHB sufficiently ele- improves wound healing and ameliorates Sprague-Dawley rats with >40% total body vated serum GH and IGF-1 levels to sig- pediatric postburn tissue catabolism associ- surface area scald burn, receiving incre- nificantly improve epithelialization rates ated with deficient endogenous GH/IGF-1 mental GHB doses orally, was assessed by and layer thickness at high doses. Sub- levels. Expense, parenteral administration, Dual Energy X-Ray Absorptiometry. Se- stantially greater elevations of serum GH and compliance have limited widespread rum GH and IGF-1 levels were measured. and IGF-1 levels are required in the rat usage. Gammahydroxybutyrate (GHB), Wound cross sections were scored semi- burn model than for humans. GHB may an upstream neuromodulatory gamma- quantitatively for wound healing variables. improve postburn hypermetabolism in amino butyric acid (GABA) derivative, is Results: Incremental elevation in GH humans by elevating endogenous GH lev- known to increase slow wave sleep and and IGF-1 were associated with signifi- els, though only improved epithelializa- stimulate endogenous GH secretion. In cantly improved wound edge epithelialization was demonstrated in this study. this study, improvement in GH levels in tion and cell-layer thickness at high doses Key Words: Burns, Hypermetabolism, turn has been shown to accelerate wound (p < 0.005). However, body composition Gammahydroxybutyrate, Wound healing, healing. was similar to that of burned controls. Growth hormone, Sleep, Anabolic. J Trauma. 2007;63:1099–1107.

evere burns cause more profound systemic dysregula- lation, and water and electrolyte balance are also severely tion than other trauma does. Control of sepsis by early altered. Consequentially, vast amounts of energy are ex- Sburn eschar excision and early wound closure, and pended to deliver glucose to the healing burn wound at the topical antimicrobial dressings, have markedly reduced mor- expense of other tissues.10 Elevated catecholamine, cortico- tality during the last 25 years.1–5 steroid, and proinflammatory cytokine levels mediate these Burn-associated hypermetabolism affects carbohydrates, profound effects,11–13 exacerbated by resistance or suppres- lipids, and structural and functional proteins. Concentrations sion of circulating anabolic hormones such as insulin, growth of the proinflammatory cytokines, interleukin (IL)-1, IL-6, hormone (GH),14 and IGF-1;15 extreme loss of body weight ␣ 6–9 and tumor necrosis factor- , are increased. Thermoregu- and musculoskeletal wasting ensue.16 Acute administration of exogenous recombinant human Submitted for publication December 13, 2005. GH markedly reduces loss of essential and nonessential Accepted for publication August 8, 2007. amino acids from muscle, which reduces net muscle protein Copyright © 2007 by Lippincott Williams & Wilkins From the Northern Ireland Plastic and Maxillofacial Service (K.D.M.), degradation, promotes protein synthesis, and doubles IGF-1 17 The Ulster Hospital, Dundonald, Belfast, Ireland; Breast Care Center and IGF binding protein 3 (IGF-BP3) levels. Metabolic (M.W.R.) and Pulmonary, Critical Care, and Sleep Medicine Section rates for burn survivors, measured as resting energy expen- (M.W.R.), Department of Medicine, Baylor College of Medicine, Houston, diture, are related primarily to total body surface area burned Texas; Departments of Surgery (D.L.C., D.N.H., A.P.S.), Psychiatric and (TBSAB). Adults and children with greater than 40% TBSAB Psychological Services (W.J.M.), and Pathology (H.K.H.), Shriners Burns Hospital for Children, Galveston, Texas; and Departments of Surgery- have metabolic rates that are elevated to 150% to 180% of (D.L.C., D.N.H., A.P.S.), Psychiatry and Behavioural Sciences (W.J.M.), those predicted by patient age.18 Adequate enteral nutritional and Pathology (H.K.H.), University of Texas Medical Branch at Galveston, supplementation only partially reduces the acute wasting. GH Galveston, Texas. effectively increases weight in severely burned pediatric Presented at the 36th Annual Meeting of the American Burn Associa- ⅐ Ϫ1 ⅐ Ϫ1 tion, Vancouver, B.C., Canada on March 24–26, 2004. (J Burn Care Reha- patients. Low doses (GH 0.05 mg kg d ) for 1 year bil. 2004;24(Suppl):378–381). significantly increase height and weight, attributable to in- Supported by Shriners Hospitals for Children grant 8010, National Insti- creased lean body mass (LBM), bone mineral content (BMC), tutes for Health Training grant 5T32GM08256-07, and The Shriners Hospitals and bone mineral density (BMD)18–20 and additional benefi- for Children project 8460, the Special Shared Facility for Electron Microscopy. Address for reprints: Kevin Murphy, MD, MCh, MMS, FRCSI, Northern cial modulatory effects on acute phase protein and inflam- 21–26 Ireland Plastic and Maxillofacial Service, The Ulster Hospital, Dundonald, matory cytokine function. Belfast BT 16 1RH, Northern Ireland; email: [email protected]. Improvements in donor site wound healing occur be- DOI: 10.1097/TA.0b013e318157d9d0 cause of increased serum IGF-1 levels when recombinant

Volume 63 • Number 5 1099 The Journal of TRAUMA௡ Injury, Infection, and Critical Care human GH is administered acutely at doses of 0.2 drug administration. Environmental enrichment was introduced mg ⅐ kgϪ1 ⅐ dϪ1. Hospital stay per percentage TBSAB is with 10-cm PVC “dens” and Nylabones (Nylabone products, decreased27 with implications for cost containment and im- Neptune, NJ). Food and water were allowed ad libitum in easily proved outcomes in mortality and rehabilitation. Accelerated accessible containers. The temperature was controlled within the donor site healing achieves earlier coverage, minimalization 68°C to 73°C range and humidity was controlled at 55% to 60%. of septic risk, and mortality. Stimulation of protein synthesis All aspects of the study were performed under a protocol that the occurs through enhanced hepatic production and elevated circu- Institutional Animal Care and Use Committee of the University lating serum IGF-1.28 Consequentially, increased deposition of of Texas Medical Branch approved. structural proteins including collagen IV and VII, laminin, and Animals were maintained in a time reversed 12:12 hour cytokeratin-14 accelerates healing.29 light to dark cycle to reverse their nocturnal circadian rhythm. Several limiting factors adversely impact the benefits of Red-light conditions were kept during the day when person- subcutaneous administration of GH and its mediators. Re- nel were active in the vivarium environment. Animals were combinant technology results in drug costs of $10,000 to observed to respond behaviorally to this cycle as planned. $35,000 per year for low doses in children. IGF-1 and its The drug was administered before sleep, after which person- binding proteins are difficult to obtain, expensive, and may be nel left the vivarium for the evening. These steps were critical associated with long-term complications such as neuropathies in to assist normalization of GH and cytokine expression circa- adults. Alternative safe and less expensive therapies such as dian patterns.42–44 GHB effects are optimized when timed insulin, oxandrolone, and propranolol are under investigation. closely with sleep onset.35–37. Administration by gastric ga- Gammahydroxybutyrate (GHB) is an endogenous neu- vage is a more customary and accurate drug delivery method romodulator with therapeutic applications in anesthesia, sleep than ad libitum oral drug administration, but would have disorders, and drug or alcohol addiction. GHB is a hydroxy- introduced a significant timing error in controlling for sleep. lated metabolite of the inhibitory central nervous system (CNS) Oral administration of GHB disguised in Vanilla Resource neurotransmitter GABA, and acts on GABAB and specific GHB (Novartis Nutrition Corporation, Freemont, MI) proved ideal receptors along the hypothalamopituitary axis.13,21,30 As a result as it was consistently consumed entirely. Before the study, of its euphoric and sedative qualities, GHB has been abused Resource without drug was delivered to animals to habituate recreationally and remains a Class I controlled substance by them. The drug was mixed with Resource in a petri dish each the United States Drug Enforcement Agency,31 but uniquely evening and the animals were observed. No animals regurgi- is simultaneously licensed as a schedule III drug for treatment tated or vomited the meal, and all were observed to sleep of narcolepsy (Xyrem, Jazz Pharmaceuticals, Palo Alto, CA). shortly thereafter. Its simple chemical structure is inexpensively synthesized, readily absorbed enterally, and stable at room temperature. Evaluation of Body Composition GHB’s analgesic and hypnotic properties and its ability to A global rat body scan was performed to assess meta- increase slow wave sleep (SWS) are all beneficial adjuncts in bolic variables including BMC, BMD, Fat Mass, and LBM, burned patients,32–38 especially as the majority of endoge- Spine BMC, and Spine BMD using a Hologic model QDR- nous GH is emitted as cyclical pulses during SWS.25,39–41 4500A Dual Energy X-Ray Absorptiometer (DEXA; Ho- We hypothesized that GHB, when administered imme- logic, Waltham, MA). This was calibrated before scanning diately before sleep onset, would promote increased secretion using the Rat Step Phantom (Hologic P/N 010-0758 rev. A). of endogenous GH during SWS, resulting in improved met- Individual pixel calibrations determined density measure- abolic endpoints and wound healing. GHB would signifi- ments corresponding to bone, fat, lean tissue, or air for each cantly improve GH secretion after burn trauma, consequently rat under anesthesia before burn and at 15 days and 30 days reducing muscle protein losses. Our aim was to test this after burn. Animal weights were simultaneously recorded. inexpensive oral drug with potential to stimulate the im- Daily weights were not taken as previous studies in our labora- proved wound healing and metabolic benefits that have been tory have demonstrated that repeated daily handling stress demonstrated with GH. alone deters metabolic recovery in hypermetabolic animals. Sixty male Sprague-Dawley rats were randomized to METHODS receive either a 40% total body surface area (TBSA) full A prospective randomized placebo-controlled trial in a thickness scald burn or a “sham” burn. Six experimental rodent model of large thermal injury was conducted as fol- groups differing with regard to burn or sham and drug dose lows. Sixty juvenile white male Sprague-Dawley rats (Harlan were developed. Groups included Burn No Drug; Burn ϩ 100 Labs, Indianapolis, IN) weighing 325 g to 381 g, were accli- mg/kg GHB; Burn ϩ 200 mg/kg GHB; Burn ϩ 1,000 mg/kg mated in a vivarium for 1 week before the experiment, and GHB; Sham No Drug; Sham ϩ 100 mg/kg GHB. Animals housed separately in transparent microisolators during the were anesthetized using 2% to 4% isoflurane induction for 4 study. Rats remained in visual contact with one another to minutes and anesthesia was maintained by immediate intra- maximize socialization but separated to prevent cross-infection peritoneal injection of butorphanol 5 mg/kg to 10 mg/kg and and debridement of wounds by other animals, and to facilitate 25 mg/kg to 50 mg/kg pentobarbital (ϳ40 mg/kg IP). Bu-

1100 November 2007 Gammahydroxybutyrate Enhances Burn Wound Healing prenorphine (0.1–1.0 mg/kg) was administered subcutane- Statistical Analysis ously twice daily for 3 days after the procedure. Data were analyzed using the paired two-tailed Student’s Animals in all groups were anesthetized, weighed, t test within groups to evaluate the effect of time and using shaved, and secured with elastic bands at the wrists and the unpaired two-tailed Student’s t test with unequal variance ankles, in a mold designed to expose 20% TBSA when to evaluate the effects of treatment between groups for met- immersed. Rats were placed on their backs and the mold was abolic variables. A two-way analysis of variance was used to partially immersed in a water bath for 10 s. Animals were evaluate the overall effects of time and treatment followed by resuscitated with an intraperitoneal injection of 60 mL/kg Tukey’s post hoc test where appropriate. The unpaired Stu- lactated Ringer’s solution, which also acts as a heat sink to dent’s t test (two-tailed, unequal variance) was used to ana- prevent visceral injury during the subsequent ventral burn. lyze histologic data. Reproducibility of the semiquantitative Animals were turned, secured and reimmersed to expose 20% scoring system used to evaluate histologic specimens was of the ventral skin for 2 seconds, creating a 40% TBSA evaluated using a modified version of Fleiss modified Co- third-degree burn of consistent depth. Rats randomized to hen’s [kappa] score. burn were immersed in large water baths at 98°C to 100°C and sham animals to water at room temperature (21°C). RESULTS Animals were recovered on a warming pad until awake and There were no observable side effects in any group. returned to their isolators. Apathy, loss of body weight Pair-feeding, physical activity, and food and water intake greater than 20%, or inability to ambulate, feed, or drink were were not controlled or monitored in this study. However, in considered signs for which animals were considered for hu- humans, GHB use has not been associated with increased mane euthanasia. No animals required euthanasia. appetite, food intake, or physical activity level.

Evaluation of Hormonal Variables Hormonal Variables: GH and IGF-1 Animals were killed at 30 days by cervical decapitation GH levels were not significantly different between the Ϫ Ϫ under anesthesia. Blood was collected immediately in a se- Sham ϩ low dose GHB (100 mg ⅐ kg 1 ⅐ d 1) and the Sham ϩ rum gel tube, centrifuged for 10 minutes to ensure plasma No Drug groups. Interestingly, GH levels in the Burn ϩ No separation, and stored at Ϫ20°C in the laboratory freezer for Drug group were not significantly lower than in the sham analysis. Analysis was performed using an Enzyme Immu- groups. Despite this, incremental elevations in serum GH levels noassay kit for rat GH (Cayman Chemicals, MI) and rat were seen in burned animals that received increasing drug doses. IGF-1 (DSL Laboratories, Clear Lake, TX). Rat IGFBP-3 This was significantly greater in the Burn ϩ high dose GHB Ϫ1 Ϫ1 was not assayed because of the lack of a commercial kit. (1,000 mg ⅐ kg ⅐ d ) group than in either the Burn ϩ No Hind-limb gastrocnemius muscle was harvested for wet or Drug or Sham groups (p Ͻ 0.03) (Fig. 1). dry muscle weight ratio to validate DEXA scanning measure- The Sham ϩ GHB group had serum IGF-1 levels 20% ments of LBM. higher than the Sham ϩ No Drug group (p Ͻ 0.04). Serum IGF-1 levels for burned animals were ϳ20% less than in sham animals not receiving drug (p Ͻ 0.04). Increasing doses Evaluation of Burn Wound Morphology of GHB incrementally increased IGF-1 levels in burned an- Morphology of the healing burned wounds was scored imals with normalization of levels that were equivalent to ⅐ Ϫ1 ⅐ Ϫ1 semiquantitatively in a masked fashion by an experienced pa- sham animals at the highest dose (1,000 mg kg d ). thologist, using light microscopy of coded H&E cross-sections Despite these incremental elevations in serum IGF-1 levels, ϩ of paraffin-embedded dorsal rat skin. Slides were not identified the increase above normal values observed in Sham low dose GHB (100 mg ⅐ kgϪ1 ⅐ dϪ1), was not achieved in burned ani- as to experimental group. The scoring system assigns a value mals even with high doses (1,000 mg ⅐ kgϪ1 ⅐ dϪ1) (Fig. 2). between zero and four for the perceived degree of presence of a histologic variable. Cells in the base of the demarcating full thickness burn wound, consisting of a mixture of spindle cells, Metabolic Variables: Body Weight fibroblasts, and myofibroblasts, acute and chronic polymorpho- To simulate the clinical scenario, juvenile rats that had nuclear cells, but not keratinocytes were assigned a total cellu- not attained full adult body mass (325–381 g individually) larity score. The rate of re-epithelialization was measured using were used. The average weight was 340 g/rat to 346 g/rat in a graduated graticule superimposed on the microscopic field. each group after randomization. Sham animals continued to The nearest viable skin appendage (sebaceous gland, hair folli- gain weight at an average rate of approximately 3 g/d. Sham cle) was deemed to constitute the edge of the burn wound. animals given low doses of GHB (100 mg ⅐ kgϪ1 ⅐ dϪ1) con- The epithelial extension from that point over the surface of the tinued to gain weight at a slightly greater rate than Sham burned wound was measured. The average thickness of the animals. Weight gain between groups of sham animals was keratinocyte layer was also measured. not significantly different despite elevated GH levels, sug-

Volume 63 • Number 5 1101 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

rat. During the latter half of the study, the animals gained weight at a reduced rate of approximately 1.5 g/d. There was no difference in the weight lost or regained in groups of burned rats given different GHB doses, suggesting that differences relative to sham groups were because of the effects of burn alone.

Lean Body Mass Changes in metabolic variables were expressed as mean averages of individual changes in each group at time points versus baseline. There was no difference in LBM between groups at baseline. Sham animals continued to gain LBM in proportion to increasing BW. Burned animals gained almost no additional LBM during the study period, despite some increase in BW latterly. This was independent of the drug dose (including no drug) indicating that the late increase in BW was because of increased fat mass only, which is consistent with the observations made in hypermetabolic burned Fig. 1. Graph demonstrating incremental elevations in rat serum pediatric subjects. growth hormone levels with increasing doses of GHB after 30 days. Bone Mineral Content There was no significant difference in BMC between groups at baseline. Sham animals continued to accrue BMC at rates similar to increases in BW and LBM (normal juvenile animal growth). There was no difference between sham animals and sham animals receiving low dose GHB. Burned animal groups increased their respective BMCs at similar rates to LBM during the entire period of study, which was substantially less than for sham burned groups. There was no significant difference between groups of burned animals treated with various doses of GHB or no drug, indicating that GHB has no effect at these doses on BMC and the differences between groups are because of the effects of burn alone.

Bone Mineral Density Burned animals continued to improve their BMD at similar rates to sham animals for the initial 2 weeks. There- after, the BMDs of burned animals remained static until the day 30, reflecting the delayed deterioration seen clinically. Surprisingly, the group of burned animals receiving high dose GHB was an exception, showing no improvement in BMDs Fig. 2. Figure demonstrating incremental increases in serum IGF-1 after burn at all, with an additional minor deterioration evi- levels in rats with increasing doses of GHB after 30 days. High dent in the latter 2-week period until day 30. Despite this, the doses of GHB achieved similar IGF-1 levels to sham burned ani- percentage change in BMD was not significantly different mals. Even low levels of GHB in sham burned animals achieved between sham groups or between burn groups, indicating no similar elevations. effect of the drug on BMD in healthy or burned rats. gesting no clinical drug effect on body weight in uninjured Wound Healing animals. Total cellularity scored in hematoxylin and eosin (H&E) In contrast to sham burned animals, burned animals did cross-sections of the dorsal burn wound (spindle, fibroblasts, not gain weight for the first 2 weeks after burn. During this myofibroblasts, and polymorphonuclear cells) was not signif- time, the ventral burn wound healed almost completely in icantly different between groups of burned animals (Student’s most animals because of wound contraction assisted by an unpaired t test, unequal variance). No significant differences excess of loose skin found in the ventrum and flanks of the were found in collagen content, neutrophilia, or vascularity.

1102 November 2007 Gammahydroxybutyrate Enhances Burn Wound Healing

Fig. 3. Figure demonstrating epithelial extension from the last viable skin adnexal structure to the edge of healing dorsal burn wound Fig. 5. Animal tissue of sham burn ϩ no dose. in rats. (Hematoxylin and Eosin stained microscopic sections on day 30). Significant differences were demonstrated between untreated burned animals (Burn ϩ No Drug) and those receiving high dose GHB (Burn ϩ 1,000 mg ⅐ kgϪ1 ⅐ dϪ1 GHB) (p ϭ 0.005).

Fig. 6. Animal tissue sham burned ϩ 100 mg/kg dose.

keratinocyte layer was thinner in these groups relative to the Burn ϩ GHB 0 groups. Low drug doses appeared to diminish epithelialization thickness, which was significantly decreased in animals receiving GHB at a dose of 200 mg ⅐ kgϪ1 ⅐ dϪ1 (p ϭ 0.03). In contrast, the Burn ϩ GHB 1,000 group not only had a significantly longer epithelial extension (p ϭ Fig. 4. Average thickness of keratinocyte layer formed over healing 0.005, Student’s t test), but the new epithelial layer was also dorsal burn wounds in rats administered increasing doses of GHB significantly thicker than in the Burn ϩ GHB 0 group (p ϭ for 30 days. 0.002, Student’s t test). Accordingly, the estimated new keratinocyte mass was also significantly greater than either The score for foreign body reaction to dead hair was signif- untreated burned animals (p Ͻ 0.005) or burned animals icantly less in the burn ϩ GHB 1,000 group (p ϭ 0.01). receiving lower doses of the drug (p Ͻ 0.001) (Fig. 4). Dorsal full thickness wounds healed by a combination of Figures 5 to 10 provide tissue examples for all treatment wound contraction (minimal) and epithelialization from the groups. wound edge. Clinically, burn wounds treated with GHB 1,000 epithelialized significantly more rapidly than in the DISCUSSION Burn ϩ GHB 0 group (Fig. 3). Histologically, although The hypermetabolic response to burn injury can neither the rate of epithelial migration was substantially greater in the be prevented nor abated by early definitive burn wound Burn ϩ GHB 100 and Burn ϩ GHB 200 groups, the new closure or nutritional supplementation alone.45

Volume 63 • Number 5 1103 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Fig. 7. Animal tissue of burned ϩ no dose. Fig. 9. Animal tissue of burned ϩ 200 mg/kg dose.

Fig. 8. Animal tissue of burned ϩ 100 mg/kg dose.

Fig. 10. Animal tissue of burned ϩ 1,000 mg/kg dose. Although the precise mechanism of GHB is uncertain, current evidence indicates that it acts as a ligand at both (8%), somnolence (8%), vomiting (8%), and urinary incon- GABAB and specific GHB receptors along the hypothalamo- 51 pituitary axis. Maximal cyclical GH release from the pituitary tinence (7%). Largely because of liability risk consequent is associated with the onset of SWS,25,46 and GH secretion is to abuse of GHB, no published research has been performed quantitatively related to the duration of SWS.47 Inhibitory with GHB in children. GHB is a CNS depressant and there- GHRIF control over GHRH is dissociated at the onset of fore, care to demonstrate absence of upper airway compro- SWS, and the lack of inhibition facilitates pulsatile large mise is critical before it can be safely administered. amplitude GH secretion in normal individuals.48,49 GHB in- Administration of an orally active upstream modulator of creases the amplitude and duration of the initial GH pulses for endogenous GH secretion is a novel approach that has not up to 2 hours after SWS onset in normal men,29 suggesting been previously attempted in burn management. The GHB that GHB and perhaps other pharmacologic SWS stimulants receptor (GHB-R) is a transmembrane protein that is highly may represent a novel class of GH secretagogues. We believe conserved between rats and humans. No significant homol- that stimulation of SWS in trauma patients will improve the ogy exists with other receptors, including GABAB. Its several disruption of diurnal rhythm and the decrease in secretion subtypes are normally located in the CNS38 (although it was of anterior pituitary hormones that are common in these recently identified peripherally in cardiomyocytes),52 sug- patients.50 GHB in its controlled form, Xyrem, may have gesting that the mode of action is central rather than a direct several side effects; in narcoleptic adults these included head- effect on myocytes, osteocytes, or keratinocytes peripherally. ache (22%), nausea (21%), dizziness (17%), nasopharyngitis Stimulation of appetite is an unlikely mode of action as

1104 November 2007 Gammahydroxybutyrate Enhances Burn Wound Healing nutritional supplementation is clinically incapable of dimin- supranormal elevations of IGF-1 are required to improve ishing hypermetabolism associated with major burns.53 metabolic variables after burns, normalization may be suffi- GH and IGF-1 levels taken 60 minutes to 90 minutes cient to improve keratinocyte proliferation and migration. after GHB administration on the day of sacrifice were elevated Postburn signal transduction aberrations and IGF-1 receptor in treated burned rats. Increasing GHB doses incrementally up-regulation may be differentially expressed in different cell elevated endogenous GH above sham levels, demonstrating populations. Physiologic effects may therefore occur at dif- that sufficient drug is absorbed to promote adequate GH fering serum IGF-1 levels in different cell populations. Mech- secretion in the burn altered hormonal milieu despite enteral anistic studies into the mode of action of GH as an anabolic administration. GHB doses required to double GH secretion agent in postburn hypermetabolism have demonstrated that in this burned rodent model are 20 times those in normal IGF-1 receptors are upregulated on donor site keratinocytes human subjects (ϳ50 mg/kg). This is most likely because of in addition to elevated GH and IGF-1 levels.29 Accelerated interspecies differences in the threshold drug stimulus required healing may be facilitated despite deficient responses at other to evoke a response at the pituitary level. GH administered at target organs that may require supranormal IGF-1 levels to doses of 0.05 mg ⅐ kgϪ1 ⅐ dϪ1 is sufficient to improve meta- achieve a physiologic effect. bolic variables in severely burned children whereas doses up IGF-1 plays an essential role in epidermal homeostasis to 50 times larger are routinely required to show improve- under normal conditions. IGF-1 is produced by both dermal ments in juvenile rodent models.54,55 fibroblasts and keratinocytes of the stratum granulosum. Al- The half-life of GH is short (ϳ20 minutes), and secretion though epidermal basal keratinocytes do not produce IGF-1, usually occurs as a single pulse (pulse width ϳ30 minutes). they are IGF-1 surface receptor positive,56 indicating that Plasma IGF-1 levels provide a better indicator of drug effect. basal keratinocyte mitogenesis is regulated by paracrine Circulating GH binds receptors in hepatocytes where release IGF-1 sequestration, probably predominantly by dermal fi- of its secondary messenger IGF-1 propagates the signal at the broblasts. Stratum granulosum keratinocytes may jointly reg- target organ. IGF-1 levels were modestly decreased in burned ulate basal keratinocyte proliferation with dermal fibroblasts animals (20%) and increased 20% in sham animals after or control autocrine regulation of keratinocyte differentiation receiving low doses of GHB versus untreated sham animals as they migrate superficially. In hair follicles, IGF-1 is mor- (p Ͻ 0.04). IGF-1 levels were incrementally improved with phogenic rather than mitogenic, since differentiating cells but increasing GHB doses in burned animals with normalization not proliferating cells express surface IGF-1R. Therefore, it is of IGF-1 levels at high doses. Increases above untreated sham likely that improved serum IGF-1 levels in GHB treated rats animals did not occur even with high doses. We had expected provide basal keratinocytes with IGF-1 concentrations suffi- that sufficiently high GHB doses might stimulate the dou- cient to stimulate keratinocyte mitogenesis and migration in bling of IGF-1 levels that is sufficient to improve metabolic full thickness burn wound edges in this study. variables (LBM and BMD) in human subjects. Relative re- Although the signal transduction pathway is still insuffi- sistance to GH in hypermetabolic rats rendered the drug ciently elucidated, it is probable that a GHB stimulus might incapable of elevating endogenous GH levels sufficiently to stimulate not only mitogenesis but also the differentiation or demonstrate improvements in metabolic variables that were migration pattern. The transduced signal that regulates this previously achieved with huge doses of exogenously admin- may be dose dependent. We observed that the product of istered GH. It is doubtful that sufficient drug could be ad- epithelial extension and keratinocyte layer thickness, to esti- ministered in the rat to double IGF-1 levels associated with mate the total keratinocyte mass, was greater with higher improved metabolic variables. Nevertheless, it is probable drug doses. that GHB would promote improved metabolic variables in GHB also has useful adjunctive analgesic properties for human subjects where significantly lower exogenous GH burned patients, but these are mediated independently of ␮, ␬, doses are required than in the rodent model. Although no and ␦ opioid receptors. It may act through the prodynorphin metabolic variables were improved in this model, IGF-1 and proenkephalin57 systems since chronic GHB exposure levels demonstrated significant improvements in wound heal- (10 days) induces significant increases in proenkephalin (PE) ing. For this to occur, keratinocytes are potentially required to and prodynorphin rat brain mRNAs, suggesting that these are receive and transduce a stimulatory mitogenic signal from modulated by the endogenous GHBergic system.58 GHB itself, GH, or the secondary mediator IGF-1. This must We acknowledge several weaknesses in our current initiate and maintain mitogenesis and migration in the basal study. Nutrient intake was not measured in animals, nor was layer keratinocyte subpopulation that predominantly governs pair-feeding conducted. The former would have helped us to proliferation and migration in wound healing. The mecha- control the possibility that animals in different groups had nism of accelerated re-epithelialization of the burn wound by differential oral caloric intake, the later to have controlled it. GHB is unclear. It may be mediated through the GH/IGF-1 Likewise, physical activity was not monitored. pathway or by a direct effect of GHB on basal layer keratin- Changes to IGF-1, GH, and wound epithelialization levels ocytes. The latter is improbable, since neither GABAB-R nor were not linearly improved in the GHB treated groups. As our GHB-R is known to be expressed on keratinocytes. Although doses were chosen based on information on human dosing

Volume 63 • Number 5 1105 The Journal of TRAUMA௡ Injury, Infection, and Critical Care typically used to treat narcoleptics, the doses were likely not 12. Klein GL, Herndon DN, Goodman WG, et al. Histomorphometric ideal. Before we can understand the optimal doses for improve- and biochemical characterization of bone following acute severe ment of GH, IGF-1, and wound re-epithelialization, we will need to burns in children. Bone. 1995;17:455–460. 13. Takahara J, Yonoki S, Hosogi H, et al. Concomitant increases in gather more information on animals dosing. Whether or not serum growth hormone and hypothalamic somatostatin in rats after these dosing issues are unique to GHB is unknown at this time. injection of gamma-aminobutyric acid, aminooxyacetic acid, or This is the first study of its kind to attempt to use a novel gamma-hydroxybutyric acid. Endocrinology. 1980;106:343–347. upstream CNS neuromodulator of the GH/IGF-1 system to 14. Ghaemi SN, Irizarry MC. Parasomnias as neuropsychiatric promote enhanced secretion of endogenous GH in a severe complications of electrical injury. Psychosomatics. 1995;36:416. 15. Jefferies MK, Vance ML. Growth hormone and cortisol secretion burn model. The study demonstrated accelerated keratinocyte in patients with burn injury. J Burn Care Rehabil. 1992;13:391– proliferation and migration in full thickness burn wound with 395. high GHB doses. GH and IGF-1 levels were elevated and 16. Hart DW, Wolf SE, Chinkes DL, et al. Determinants of skeletal normalized respectively by drug treatment from subnormal muscle catabolism after severe burn. Ann Surg. 2000;232:455– levels consequent to severe burn injury. Improvements in 465. metabolic variables were not observed, likely because of 17. Klein GL, Wolf SE, Langman CB, et al. Effect of therapy with recombinant human growth hormone on insulin-like growth factor deficiencies in the model, although these are more likely to system components and serum levels of biochemical markers of occur in human subjects. If effective in human subjects, GHB bone formation in children after severe burn injury. J Clin would provide an orally active, inexpensive alternative to Endocrinol Metab. 1998;83:21–24. restore depressed levels of endogenous GH, an effective 18. Hart DW, Wolf SE, Ramzy PI, et al. Anabolic effects of anabolic hormone necessary for healing acute donor sites and oxandrolone after severe burn. Ann Surg. 2001;233:556–564. 19. Ramirez RJ, Wolf SE, Barrow RE, et al. Growth hormone treatment meshed split thickness autografts and possibly in metabolic in pediatric burns: a safe therapeutic approach. Ann Surg. 1998; rehabilitation in severe pediatric burns. Adjunctive analgesic 228:439–446. and hypnotic properties would help to restore the perturbed 20. Low JFA, Barrow RE, Mittendorfer B, et al. The effect of short-term pattern sleep pattern that is prevalent in major burns. growth hormone treatment on growth and energy expenditure in burned children. Burns. 2001;27:447–452. 21. Takagi K, Suzuki F, Barrow RE, et al. Recombinant human growth ACKNOWLEDGEMENT hormone modulates Th1 and Th2 cytokine response in burned mice. We would like to acknowledge Cynthia Villarreal, RPI for her guidance Ann Surg. 1998;228:106–111. with administration and reconstitution of the GHB during the study. 22. Jeschke MG, Barrow RE, Herndon DN. Insulinlike growth factor I plus insulinlike growth factor binding protein 3 attenuates the proinflammatory acute phase response in severely burned children. REFERENCES Ann Surg. 2000;231:246–252. 1. Herruzocabrera R, Fernandezarjona M, Garciatorres V, et al. 23. Spies M, Wolf SE, Barrow RE, et al. 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33. Chaminov M, Bahar M, Cohen ML, et al. Spinal anaesthesia with 46. Sassin JF, Parker DC, Mace JW, et al. Human growth hormone gamma hydroxybutyrate. A study in a rat model. Eur J Anaesthesiol. release: relation to slow-wave sleep and sleep-waking cycles. 2003;16:330–338. Science. 1969;165:513–515. 34. Scharf MB, Hauck M, Stover R, et al. Effects of gamma hydroxy- 47. Van Cauter E, Kerkofs M, Caufriez A, et al. A quantitative estimation butyrate on pain, fatigue, and the alpha sleep anomaly in patients of GH secretion in normal man: reproducibility and relation to sleep and with fibromyalgia. J Rheumatol. 1998;25:1986–1990. time of day. J Clin Endochrinol Metab. 1992;74:1441–1450. 35. Lammers GJ, Arends J, Declerck AC, et al. Gammahydroxybutyrate 48. Van Cauter E, Latta F, Nedeltcheva A, et al. Reciprocal interactions and narcolepsy: a double-blind placebo-controlled study. Sleep. between the GH axis and sleep. Growth Horm IGF Res. 2004; 1993;16:216–220. 14(Suppl):S10–S17. 36. Scharf MB, Brown D, Woods M, et al. The effects and effectiveness 49. Jarrett DB, Greenhouse JB, Miewald JM, et al. A reexamination of of gamma-hydroxybutyrate in patients with narcolepsy. J Clin the relationship between growth-hormone secretion and slow-wave Psychiatry. 1985;46:222–225. sleep using delta-wave analysis. Biol Psychiatry. 1990;27:497–509. 37. Van Cauter E, Plat L, Scharf MB, et al. Simultaneous stimulation of slow- 50. Rose M, Sanford A, Thomas C. Factors altering the sleep of burned wave sleep and growth hormone secretion by gamma-hydroxybutyrate children. Sleep. 2001;24:45–51. in normal young men. J Clin Invest. 1997;100:745–753. 51. Clinical Trials.gov identifier NCT00244465. Post-Marketing Non- 38. Andriamampandry C, Taleb O, Viry S, et al. Cloning and characterization Interventional Pharmacoepidemiology Study to evaluate long-term of a rat brain receptor that binds the endogenous neuromodulator safety, tolerability and compliance in administration of Xyrem gamma-hydroxybutyrate. FASEB J. 2003;17:1691–1693. (sodium oxybate) in regular clinical practice. Clinical Trials.gov 39. Van Cauter E, Plat L. Physiology of growth hormone secretion identifier NCT00244465; 2006. during sleep. J Pediatr. 1996;128:S32–S37. 52. Lorente P, Lacampagne A, Pouzeratte Y, et al. Gamma-aminobutyric 40. Brandenberger G, Gronfier C, Chapotot F, et al. Effect of sleep acid type B receptors are expressed and functional in mammalian deprivation on overall 24 h growth-hormone secretion. Lancet. 2000; cardiomyocytes. Proc Natl Acad SciUSA.2000;97:8664–8669. 356:1408. 53. Hart DW, Wolf SE, Chinkes DL, et al. Effects of early excision and 41. Davidson JR, Moldofsky H, Lue FA. Growth hormone and cortisol aggressive enteral feeding on hypermetabolism, catabolism, and secretion in relation to sleep and wakefulness. J Psychiatry Neurosci. sepsis after severe burn. J Trauma. 2003;54:755–761. 2002;16:96–102. 54. Jeschke MG, Wolf SE, DebRoy MA, et al. The combination of 42. Czeisler CA, Klerman EB. Circadian and sleep-dependent growth hormone with hepatocyte growth factor alters the acute phase regulation of hormone release in humans. Recent Prog Horm Res. response. Shock. 1999;12:181–187. 1999;54:97–132. 55. Jeschke MG, Herndon DN, Wolf SE, et al. Recombinant human 43. Weyerbrock A, Timmer J, Hohagen F, et al. Effects of light and growth hormone alters acute phase reactant proteins, cytokine chronotherapy on human circadian rhythms in delayed sleep phase expression, and liver morphology in burned rats. J Surg Res. 1999; syndrome: cytokines, cortisol, growth hormone, and the sleep-wake 83:122–129. cycle. Biol Psychiatry. 1996;40:794–797. 56. Rudman A, Feller AG, Nagraj HS. Effect of human growth hormone 44. Holzheimer RG, Curley P, Saporoschetz IB, et al. Circadian Rhythm in men over 60 years old. N Engl J Med. 1990;323:1–6. of cytokine secretion following thermal injury in mice: implications 57. Pearlman CA, Greenberg R. Medical-psychological implications of for burn and trauma research. Shock. 2002;17:527–529. recent sleep research. Psychiatry Med. 1970;1:261–276. 45. Noordenbos J, Hansbrough JF, Gutmacher H, et al. Enteral 58. Schmidt-Mutter C, Gobaille S, Muller C, et al. Prodynorphin and nutritional support and wound excision and closure do not prevent proenkephalin mRNAs are increased in rat brain after acute and postburn hypermetabolism as measured by continuous metabolic chronic administration of gamma-hydroxybutyrate. Neurosci Lett. monitoring. J Trauma. 2000;49:667–671. 1999;262:65–68.

Volume 63 • Number 5 1107 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Packed Red Blood Cell-Associated Arginine Depletion is Mediated by Arginase Andrew Bernard, MD, Cynthia Meier, MS, Nicholas Lopez, MD, John May, BS, Phillip Chang, MD, Bernard Boulanger, MD, and Paul Kearney, MD

Background: Packed red blood cells units were isolated and processed by an plasma؉RBC, but with plasma؉RBC (PRBCs) transfusion is associated with accredited blood bank and stored at 4°C. this did not reach statistical significance. immune suppression, but these mecha- Leukoreduced PRBCs or supernatant ali- Arginine levels were decreased and or- nisms are incompletely understood. PRBCs quots were withdrawn every 5 days to 7 nithine levels increased in cultures con- contain arginase, an enzyme that converts days for 42 days. Cell cultures were cre- taining either supernatant or PRBC, as arginine to ornithine, and is known to ated with standard Roswell Park Memo- compared with control media. Addition limit arginine availability and suppress rial Institute media, controlling the of nor-N-␻-OH-L-arginine significantly cellular immunity. We sought to deter- arginine level at 80 ␮mol/L (approximat- decreased cell culture arginase activity, mine whether PRBC arginase causes ar- ing human serum), and adding 20% restored arginine levels, and diminished .ginine depletion, potentially contributing plasma or plasma؉RBC. An irreversible ornithine synthesis to immunosuppression. arginase blocker (nor-N-␻-OH-L-arginine) Conclusions: Arginase is present in Methods: A model of transfusion was was added to selected cultures. After 24 PRBC units and causes arginine deple- designed by adding either centrifuged hours, culture arginase activity was mea- tion. Depletion of arginine by PRBC argi- acellular supernatant from the PRBC unit sured by ornithine synthesis, and amino nase is a potential novel mechanism for (plasma) or total fluid from the unit acid levels were measured using mass immunosuppression. ,plasma؉RBC [red blood cells]) to cell spectroscopy. Key Words: Arginine, Arginase) culture media. Through an institutional Results: Culture arginase activity Ornithine, Red blood cell, Transfusion, review board-approved protocol, PRBC was increased by both plasma and Immunosuppression. J Trauma. 2007;63:1108–1112.

ransfusion of blood components is associated with im- depletion is associated with suppressed T-cell function, nitric mune suppression in critically ill and injured patients, oxide synthesis, and macrophage bactericidal function.7–9 Tbut the mechanisms for this effect are incompletely Mechanisms by which clinical arginine depletion occurs understood.1 Increased infections and risk of organ failure remain unclear. We sought to determine whether PRBC ar- have been reported in transfused patients, with risk correlat- ginase may cause arginine depletion, thus potentially contrib- ing with number of transfused units.1 Packed red blood cells uting to postinjury immune suppression. (PRBCs) contain large amounts of arginase, a catabolic enzyme that converts arginine to ornithine, and is known to PATIENTS AND METHODS 2–5 limit arginine availability. Arginine is an amino acid im- Through an institutional review board-approved protocol portant for a competent immune system in injury, infection, and after informed consent, allogeneic blood donation was ob- and stress,2 and as such, arginine-enriched nutritional thera- 6 tained from each of three healthy humans (1 per subject) at the peutics have been developed. Central Kentucky Blood Center using the standard procedure at Arginine depletion is known to play a role in clinical that accredited facility. After routine processing, including leu- infections and outcome in some patient groups. Arginine koreduction, the PRBC units designated for research were delivered to our laboratory by the blood center courier and stored Submitted for publication December 30, 2005. at 4°C for the remainder of the protocol. Accepted for publication July 2, 2007. Cultures were created using standard Roswell Park Me- Copyright © 2007 by Lippincott Williams & Wilkins From the Department of Surgery (A.B., C.M., N.L., P.C., B.B., P.K.), morial Institute (RPMI) media, controlling the arginine level College of Medicine; and Environmental Research and Training Labora- at 80 ␮mol/L, approximating human serum. Aliquots from tory (J.M.), College of Engineering, University of Kentucky, Lexington, PRBC units (20–25 mL) were withdrawn using sterile tech- Kentucky. nique in laminar flow conditions every 5 days to 7 days for 42 Supported by a grant from the Southern Medical Association (to N.L.). days. Two groups were created from each aliquot. The first Presented at the 19th Annual Meeting of the Eastern Association for the ϭ Surgery of Trauma January 10–14, 2006, Orlando, Florida. group (n 3) consisted of unmodified fluid from the PRBC Address for reprints: Andrew C. Bernard, MD, C222 Division of unit, containing cells and plasma (plasmaϩRBC [red blood General Surgery, University of Kentucky College of Medicine, 800 Rose cells]). The second group (n ϭ 3) consisted of the acellular Street, Lexington, KY 40536-0298; email: [email protected]. supernatant (plasma) from the centrifuged PRBC sample. DOI: 10.1097/TA.0b013e31814b2b17 Each was added to respective media cultures at 20% by

1108 November 2007 Red Blood Cell Arginase Depletes Arginine

volume to simulate transfusion.10 An irreversible arginase blocker (nor-N-␻-OH-L-arginine [nor-NOHA] 50 ␮mol/L) was added to media before addition of plasma and plasmaϩRBC (n ϭ 3 each). After 24 hours of incubation, media was withdrawn from the well. Wells containing RBCs were briefly centrifuged for removal of cells, and all samples frozen at Ϫ80°C until analysis. Arginase activity was measured in the plasma fraction of PRBC aliquots and in media as conversion of arginine to ornithine by a modification of the technique of Konarska and Tomaszewski as described.7,11,12 Unless otherwise specified, all chemical reagents were obtained from Sigma Aldrich (St. Louis, MO). Culture samples (25 ␮L) were added to 25 ␮L

of 10 mmol/L MnCl2. Incubation at 55°C for 10 minutes was performed and followed by addition of 150 ␮Lof100 Fig. 1. mmol/L carbonate buffer to each sample. Arginine (50 ␮L, Arginase activity in plasma. Arginase activity in the plasma 100 mmol/L) was added, allowed to incubate at 37°C, and the fraction of PRBC units was measured as ornithine production dur- reaction halted at 10 minutes with 750 ␮L of glacial acetic ing controlled enzyme assay. Arginase activity increased through ϭ acid. Ninhydrin solution (250 ␮L, 0.35 mol/L in phosphoric the 42-day study period (p 0.0008). and glacial acetic acids) was added and the samples were RESULTS boiled for 60 minutes. Ornithine production was measured by Arginase Activity spectrophotometry (Molecular Devices, Sunnyvale, CA) at a Arginase activity in the plasma fraction of the PRBC unit wavelength of 515 nm. increased over time (p ϭ 0.0008; Fig. 1). Media cultures also Media and plasma amino acid levels were measured showed a significant difference in arginase activity between using mass spectroscopy. Amino acids were extracted and treatment groups (p Ͻ 0.0001). PlasmaϩRBC cultures dem- ␮ derivatized from media and PRBC supernatant (25–100 L) onstrated increased arginase activity, though not significantly using the EZ:faast LC/MS kit for amino acid analysis from (p ϭ 0.09). However, addition of plasma alone showed a Phenomenex (Torrance, CA). In-house standards of arginine, significant increase in arginase activity (p Ͻ 0.0001) when ornithine, and citrulline were run as controls. Internal stan- compared with media and plasmaϩRBC cultures (p Ͻ dards of homo-Arginine, methionine-d3, and homophenylala- 0.0001; Fig. 2). These plasma cultures also showed decreased nine were incorporated into each sample and processed with activity by the addition of the arginase blocker nor-NOHA high-pressure liquid chromatography (HPLC-Varian ProStar (p ϭ 0.03). Pumps, Model 210) and mass spectrometry (MS-Varian 1200L Quadrupole MS/MS) using a Phenomenex EZ:faast 4 ␮m AAA-MS column (250 ϫ 2.0 mm). The LC program (10 mmol/L ammonium formate in water, 10 mmol/L ammonium formate in methanol) was used in a gradient fashion, with a flow rate of 0.25 mL/min over a total time of 21 minutes to optimize amino acid “separation” on the high-pressure liquid chromatography column. The MS condition was as follows: electrospray ionization (ESI) positive ion mode, scan range 280 m/z to 351 m/z with 200°C drying gas.

Statistical Analysis Parametric data are expressed as means Ϯ SEM unless Fig. 2. Culture arginase activity—day 21. Culture arginase activity specified. In this experimental model, three endpoints were was measured as ornithine production during controlled enzyme considered: arginine, ornithine, and arginase levels. The lin- assay after adding either plasmaϩRBC or plasma alone. Culture ear mixed model was fitted, and F tests associated with mixed arginase activity did not change significantly over time, and so the model analysis were used to check the treatment effect, time 21-day time point is shown above, as representative of the entire effect, and treatment-by-time interaction. After determining experiment. Arginase blocker nor-NOHA alone had no effect on the treatment or time effect, post hoc comparisons were arginase activity. Plasma increased arginase activity significantly applied to deduce statistical significance between treatment compared with media and with plasmaϩRBC (p Ͻ 0.0001). groups. A reduced linear regression model based on F statis- PlasmaϩRBC did not significantly increase culture arginase activ- tics was used to analyze arginase activity over time. Signif- ity (p ϭ 0.09). Nor-NOHA significantly reduced plasma-induced icance was set at p Ͻ 0.05. arginase activity (p ϭ 0.03).

Volume 63 • Number 5 1109 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Fig. 3. Citrulline, arginine, and ornithine in plasma and plasmaϩRBC Fig. 4. Culture arginine levels—day 21. Media samples were ana- samples. Published normal ranges for human serum amino acids are lyzed using mass spectroscopy. Arginine level was 80 ␮mol/L in all shown in comparison with measured plasma and total plasmaϩRBC wells at start of experiment (approximating human plasma). There was levels from these experiments. Citrulline and arginine levels in PRBC no significant change in arginine levels within groups over time, and so units, whether in total fluid (plasmaϩRBC) or acellular supernatant data from the 21-day time point is shown above, as representative of the (plasma), are well below the published normal human serum ranges. entire life of the unit. Arginine levels in plasma or plasmaϩRBC- Conversely, ornithine levels are at or above normal human serum treated wells were significantly lower than those in wells with media levels. Statistical analyses of these data were not performed. alone (p Ͻ 0.0001). Effect of plasmaϩRBC on arginine depletion was significantly greater than that seen with plasma alone (p Ͻ 0.0001). Baseline Amino Acid Levels Nor-NOHA abrogated plasma and plasmaϩRBC induced arginine ϩ Arginine, citrulline, and ornithine levels in plasma RBC depletion (p ϭ 0.001 and Ͻ0.0001, respectively). and in plasma alone are shown in Figure 3. Published values 13 for normal human serum are shown in comparison. Argi- greater ornithine levels than those in plasma cultures (p Ͻ ϩ Ϯ ␮ nine levels are low in both plasma RBC (6.0 2.5 mol/L) 0.0001), though these levels did not change over time. Ϯ ␮ and in plasma (3.2 2.4 mol/L) when compared with the Addition of nor-NOHA significantly diminished ornithine Ϯ normal range for human plasma arginine (86 16 synthesis in both plasma and plasmaϩRBC-treated cul- ␮ 13 mol/L). Likewise, citrulline levels are low in both tures (p ϭ 0.008 and Ͻ0.0001, respectively; Fig. 5). ϩ Ϯ ␮ plasma RBC (14.4 5.2 mol/L) and in the plasma frac- Citrulline levels were measured in all samples. Standard Ϯ ␮ tion (4.0 1.5 mol/L) when compared with the normal RPMI media contains no measurable citrulline levels and Ϯ ␮ range for human plasma citrulline (34 7 mol/L). Con- citrulline levels are very low in units of transfused blood as versely, ornithine in plasma alone (50.3 Ϯ 14.8 ␮mol/L) approximates normal human plasma ornithine (66 Ϯ 20 ␮mol/L) whereas plasmaϩRBC ornithine is elevated (134 Ϯ 42.5 ␮mol/L). These data indicate that arginase is active during PRBC storage, depleting arginine and producing ornithine in the stored unit.

Amino Acid Levels in Cultures of Plasma or Plasma؉RBC Arginine levels in culture media were controlled at 80 ␮mol/L (similar to human serum) and were not significantly changed by addition of nor-NOHA (Fig. 4). Arginine levels were decreased in cultures containing either plasma or plasmaϩRBC when compared with control media (p Ͻ Fig. 5. Culture ornithine levels—day 21. Media samples were ana- 0.0001 and Ͻ0.0001, respectively). PlasmaϩRBC reduced lyzed using mass spectroscopy. No measurable ornithine is present in culture arginine to levels significantly lower than those in control media. Ornithine was present at all time points in media treated plasma cultures (p Ͻ 0.0001). Addition of nor-NOHA sig- with plasmaϩRBC or plasma. There was no significant change in nificantly increased culture arginine levels compared with ornithine levels within groups over time, and so data from the 21-day those in cultures treated with either plasma or plasmaϩRBC time point is shown above, as representative of the entire life of the unit. alone (p ϭ 0.001 and Ͻ0.0001, respectively). PlasmaϩRBC cultures had significantly greater ornithine levels than There is no measurable ornithine in RPMI media alone those in plasma cultures (p Ͻ 0.0001). Addition of nor-NOHA signif- but ornithine was present in all cultures created with plasma icantly diminished ornithine levels in both plasma and plasmaϩRBC or plasmaϩRBC. PlasmaϩRBC cultures had significantly cultures (p ϭ 0.008 and Ͻ0.0001, respectively).

1110 November 2007 Red Blood Cell Arginase Depletes Arginine shown above. There were no significant differences in these levels and increases ornithine levels throughout the 42-day very low levels between treatment groups (data not shown) or life span of the unit. Arginase activity in the fluid fraction over the life spans of the units. increases over time in our model. Increasing arginase levels over time has been previously reported in PRBC units and CONCLUSIONS attributed to RBC lysis that is known to occur with storage.3 The negative effects of transfusion on human immunity An important novel discovery in this investigation is that and outcome are clear, though the mechanisms are incom- arginine depletion and ornithine synthesis were greater in pletely understood.1 Data shown here show that arginase cultures containing plasmaϩRBC compared with those con- depletes arginine in a PRBC model. Based on previous evi- taining plasma alone. A previous report of free arginase in dence that arginine depletion impairs lymphocyte prolifera- PRBC units suggested an effect of free arginase on arginine tion, we speculate that arginine depletion by arginase may availability but amino acids were not measured.3 Here, we contribute to transfusion-associated immunosuppression.1,8 have shown arginine depletion resulting from free arginase Arginine depletion is one mechanism for injury-induced im- but more importantly, an even more pronounced effect on mune dysfunction.6,14 Arginine is depleted from the serum of arginine depletion when intact RBC are present. This is likely trauma and surgical patients and arginine repletion has proven the result of a greater metabolic effect from living cells beneficial in some studies.6,15,16 However, the clinical benefit of compared with plasma alone. During storage, arginase is routine arginine supplementation in injured patients has been elaborated into the plasma from RBCs. Although plasma questioned because of inconsistent clinical trial outcomes.17 arginase activity in PRBCs is measurable, intracellular argi- Clinical and in vitro studies have established arginine’s nase in RBCs is not measurable without a cell lysis step, role in immune competence. Nitric oxide synthases (NOS) which we did not perform. Despite this discrepancy in mea- metabolize arginine to nitric oxide, which in turn, participates surable arginase activity between the two groups, the intact in generation of reactive nitrogen species and bacterial PRBC (plasmaϩRBC) culture model is more clinically rele- killing.18 Arginine has other effects on the response to injury vant than “plasma” alone, given the fact that PRBC are that are independent of NOS. Arginine supplementation in commonly transfused to patients. animals increases wound hydroxyproline levels and restores Alternative pathways for arginine catabolism in this normal levels of collagen I synthesis that are depressed after model include leukocyte arginase and RBC NOS. We have trauma or hemorrhage.19 Arginine also directly promotes previously reported significant upregulation of arginase in wound healing and T-lymphocyte clonal expansion and func- peripheral leukocytes.7 However, quality control data from tion in humans and in animals.2 our institution indicate that leukocyte counts in PRBC units Arginase is an enzyme that catabolizes arginine and is are between 0 and 1 million per bag, most of them Ͻ30,000 present in many cell types. Although it was initially described per bag and many below detectable levels. Thus, based on as a urea cycle enzyme, it is now known to exist in at least these data and the small volume of the bag withdrawn in each two isoforms and without other urea cycle enzymes.20 Argi- aliquot, leukocytes are unlikely to have produced significant nase plays an important role in arginine catabolism by reduc- arginase contamination. ing arginine availability in tissue beds, and thus, limiting RBCs also express NOS and recent evidence indicates arginine consumption for other metabolic processes.9 For that NOS is active in RBCs. However, nor-NOHA has no example, arginase-producing monocytes and granulocytes effect on NOS activity. Therefore, differences between control arginine availability in the extracellular environment, groups treated with nor-NOHA and those without nor-NOHA impairing T-cell receptor expression and function.21,22 The are exclusively because of activity of arginase.23 effect of this arginine depletion has been shown to suppress Citrulline levels in our experiments were low in tumoricidal activity, and thus, accelerate tumor growth.21 plasmaϩRBC and plasma samples and in all cultures. Citrul- Data shown here suggest that a similar catabolism of line is the metabolic precursor to arginine and is converted to arginine by arginase may occur after exposure to PRBC, arginine in liver and kidney. This amino acid has been shown implying a role in arginine depletion that occurs in many to provide salvaging characteristics for T-cell function in clinical conditions, including trauma, surgery, critical illness, vitro where elevated levels of arginase and thus low levels of and cancer. Arginase is present in erythrocytes4 and catabo- arginine exist.24 This model, which demonstrates low levels of lizes arginine in this model of PRBC culture. Enzyme activity arginine and citrulline in PRBC cultures, suggests a novel mech- is a proven method of quantifying arginase.7,11,12 Although anism of immunosuppression, and the potential for citrulline and plasma-treated cultures had higher measurable arginase, arginine supplementation as a novel therapeutic target to reduce plasmaϩRBC-treated cultures had higher arginine metabolic the immunosuppressive effects in transfused patients. activity. This discrepancy is because of the extracellular REFERENCES location of arginase in plasma-treated cultures. Arginase ac- ϩ 1. Silliman CC, Moore EE, Johnson JL, et al. Transfusion of the tivity in plasma RBC-treated cultures did not account for injured patient: proceed with caution. Shock. 2004;21:291–299. enzyme within intact RBC. The plasma fraction from PRBC 2. Bronte V, Zanovello P. Regulation of immune responses by units contains free arginase that actively decreases arginine L-arginine metabolism. Nat Rev Immunol. 2005;5:641–654.

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3. Prins HA, Houdijk APJ, Nijveldt RJ, et al. Arginase release from Many of these studies indicate that increased metabolism red blood cells: possible link in transfusion induced immune of L-arginine by myeloid cells can result in impairment of suppression? Shock. 2001;16:113–115. lymphoid responses to antigen during immune responses. 4. Kim PS, Iyer RK, Lu KV, et al. Expression of the liver form of arginase in erythrocytes. Mol Genet Metab. 2002;76:100–110. There are two enzymes that compete for L-arginine as a 5. Cederbaum SD, Yu H, Grody WW, et al. Arginases I and II: do substrate and they are arginase, as studied in this current their functions overlap? Mol Genet Metab. 2004;81:S38–S44. report, and nitric-oxide synthase. Both are crucial compo- 6. Daly JM, Lieberman MD, Goldfine J, et al. Enteral nutrition and nents of the lymphocyte suppression pathway. This leads me supplemental arginine, RNA, and omega-3 fatty acids in patients to ask you several questions. after operation: immunology, metabolic, and clinical outcome. Surgery. 1992;112:56–67. You used packed cells and plasma from donated blood 7. Ochoa JB, Bernard AC, O’Brien WE, et al. Arginase I expression that underwent leukocyte reduction. How did you assess for and activity in human mononuclear cells after injury. Ann Surg. residual leukocytes in the cells used for culturing? 2001;233:393–399. In other words, is the arginase activity that you’re mea- 8. Zea AH, Rodriguez PC, Culotta KS, et al. L-arginine modulates suring really from the erythrocytes or are there some white CD3zeta expression and T cell function in activated human T lymphocytes. Cell Immunol. 2004;232:21–31. cells in the samples that were used in the in vitro cultures? 9. Buga GM, Singh R, Pervin S, et al. Arginase activity in endothelial Second, because the arginase is also a substrate for nitric- cells: inhibition by NG-hydroxy-L-arginine during high-output NO oxide synthase, how did you assess for NOS activity in your production. Am J Physiol. 1996;271:H1988–H1998. cultures? Is the decrease in arginine levels really representa- 10. Biffl WL, Moore EE, Offner PJ, et al. Plasma from aged stored red tive of increased arginase activity or is it representing NOS blood cells delays neutrophil apoptosis and primes for cytotoxicity: abrogation by poststorage washing but not prestorage leukoreduction. activity in the background? J Trauma. 2001;50:426–431. You used quantities of erythrocytes and supernatant rep- 11. Konarska L, Tomaszewski L. A simple quantitative micromethod for resenting 20% of the volume in the cell-cultured system to arginase assay in blood spots dried on filter paper. Clin Chim Acta. simulate a transfusion in a patient. Why not perform a dose- 1986;154:7–17. response curve with different volumes of cells and superna- 12. Corraliza IM, Campo ML, Soler G, et al. Determination of arginase activity in macrophages: a micromethod. J Immunol Methods. 1994;174:231–235. tant to identify a maximal dose response? 13. Filho JCD, Barany P, Stehle P, et al. Free amino-acid levels You performed repeat cultures during 7-day intervals for simultaneously collected in plasma, muscle and erythrocytes of 42 days and you presented the data at day 21, and you didn’t uraemic patients. Nephrol Dial Transplant. 1997;12:2339–2348. notice any increase in the arginase activity. I’d like to hear 14. Bansal V, Ochoa JB. Arginine availability, arginase and the immune your comments on why you think that occurred in this study. response. Curr Opin Clin Nutr Metab Care. 2003;6:223–228. 15. Tseui BJ, Bernard AC, Shane MD, et al. Surgery induces human In your results, the maximal activity of arginase was seen mononuclear cell arginase I expression. J Trauma. 2001;51:497–502. in the supernatant and not in the red cells. Is this again a 16. Tsuei BJ, Bernard AC, Barksdale AR, et al. Supplemental enteral reflection of residual arginase from the leukocyte reduction arginine is metabolized to ornithine in injured patients. J Surg Res. process or is it actually leached from the RBCs? 2005;123:17–24. Dr. Andrew C. Bernard (Lexington, KY): First, we 17. Stechmiller JK, Childress B, Cowan L. Arginine supplementation and wound healing. Nutr Clin Pract. 2005;20:52–61. didn’t assess for the presence of white blood cells. 18. Griffith OW, Stuehr DJ. Nitric oxide synthases: properties and That data is available preliminarily from our blood bank, catalytic mechanism. Annu Rev Physiol. 1995;57:707–736. but that’s something I should examine in my own laboratory. 19. Shi HP, Efron DT, Most D, et al. L-arginine enhances diabetic And, likewise, we did not assess for NOS activity, but that would healing. Surg Forum. 2000;51:613–614. would be a straightforward analysis, as you indicated. 20. Wu G, Morris SM. Arginine metabolism: nitric oxide and beyond. Biochem J. 1998;336:1–17. We used the 20% transfusion model that has been pre- 21. Rodriguez PC, Quiceno DG, Zabaleta J, et al. Arginase I production viously described by Dr. Moore’s group at Denver in their in the tumor microenvironment by mature myeloid cells inhibits transfusion-associated immunosuppression basic science work. T-cell receptor expression and antigen-specific T-cell responses. A dose-response curve is an excellent idea and again would Cancer Res. 2004;64:5839–5849. be straightforward to do. 22. Munder M, Schneider H, Luckner C, et al. Suppression of T cell functions by granulocyte arginase. Blood. 2006;108:1627–1634. The fact that we did not see in the final data analysis a 23. Kleinbongard P, Schulz R, Rassaf T, et al. Red blood cells express a difference in arginase over time is probably a result of a lack functional endothelial nitric oxide synthase. Blood. 2006;107:2943–2951. of specificity in my assay, quite frankly. 24. Bansal V, Rodriguez P, Wu G, et al. Citrulline can preserve In the data reported in the abstract booklet, that was a proliferation and prevent loss of CD3 zeta chain under conditions of more limited sample set, and I grouped other data sets to- low arginine. JPEN J Parenter Enteral Nutr. 2004;28:423–430. gether for the final data analysis for the study and lost some specificity because of variability between assays. DISCUSSION And, finally, the fact that we didn’t see elevated arginase Dr. Fred A. Luchette (Maywood, IL): Search the Na- activity to as great a degree in the red cell-treated wells as the tional Library of Medicine and you will see over 20 publi- supernatant-only wells, but yet we saw important impacts cations since New Year on the topic of arginase and its role upon arginine depravation, is that I didn’t measure the intra- in immune suppression. cellular arginase that is active in those red cell wells.

1112 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Resuscitation From Hemorrhagic Shock Comparing Standard Hemoglobin-Based Oxygen Carrier (HBOC)-201 Versus 7.5% Hypertonic HBOC-201 Fernando A. Rivera-Chavez, MD, Sergio Huerta, MD, Ronnie Brown, BS, Gregory B. York, MD, and Joseph P. Minei, MD

؍ PVR (p ,(0.001 ؍ Background: Hemoglobin-based ox- HBOC) when compared with standard Results: SVR (p -were signifi (0.01 ؍ ygen carrier (HBOC) resuscitation has HBOC resuscitation. 0.001), and MPAP (p been associated with increased systemic Methods: Thirty-two domestic cross- cantly reduced in the HT-HBOC group and pulmonary vascular resistances bred pigs (50–60 kg) were hemorrhaged to compared with the standard HBOC group. (SVR, PVR), which may result in re- a mean arterial pressure (MAP) of 35 mm Conclusion: In this model of hem- duced blood flow and severe pulmonary Hg ؎ 5 mm Hg for 45 minutes and resus- orrhagic shock, hypertonic HBOC-201- hypertension. The physiologic and im- citated to a baseline mean arterial pressure resuscitated pigs had significantly reduced munologic properties of 7.5% hyper- using the following groups: (1) sham, no SVR and PVR, as well as mean pulmonary -tonic saline solution (HTS), such as hemorrhage; (2) shed blood ؉ lactated artery pressure (MPAP) and increased car reduction of SVR and PVR, as well as Ringer’s solution; (3) standard HBOC-201; diac output. HT-HBOC may be beneficial in inhibition of neutrophil and endothelial (4) hypertonic saline 7.5%; (5) hypertonic reducing the undesirable effects of standard activation may be beneficial in reducing 7.5% HBOC-201. After resuscitation, ob- HBOC-201. The mechanisms of these bene- some of these undesirable effects of servation was continued for 4 hours. Hemo- ficial effects need to be investigated. HBOCs. The aim of this study was to dynamic variables, oxygen consumption, Key Words: HBOC-201, Small vol- evaluate the hemodynamic effects of the and arterial blood gases were monitored ume, Resuscitation, Hypertonic solution, HBOC and HBOC-201 suspended in continuously. Data were analyzed using Hemorrhagic shock, Hemoglobin-based 7.5% hypertonic saline solution (HT- analysis of variance. oxygen carriers. J Trauma. 2007;63:1113–1119.

ypertonic saline (HTS) solutions have been studied for polymorphonuclear leukocytes (PMN) activation.17,19,20 several years. Data from human and animal studies However, because HTS does not carry oxygen, increased Hhave shown HTS to be safe and effective low-volume oxygen delivery is limited by improvements in CO. Thus, resuscitation fluids.1–6 Some of the beneficial properties of HTS by itself, particularly in the setting of trauma and blood HTS include rapid volume expansion,2,7,8 restoration of mi- loss, may not achieve or maintain adequate oxygen delivery crocirculatory blood flow by capillary reopening,9,10 in- to the compromised tissues. creased cardiac output (CO),11,12 correction of acid-base Recently, significant clinical and laboratory information has 13,14 disturbances, and decreased systemic vascular resistances accumulated regarding the efficacy of low-volume resuscitation 15 (SVR). In addition, data suggest that HTS has some immu- fluids as therapeutic agents for hemorrhagic shock.21,22 Exper- 16 nomodulating properties. For example, HTS resuscitation imental data obtained by several research groups have suggested prevents endothelial vascular dysfunction and the generation that among low-volume strategies, hemoglobin-based oxygen 17,18 of reactive oxygen species, as well as abrogation of carriers (HBOCs)23,24 seem to have significant potential. Along with HTS, HBOCs have been proposed as an effective low- 23,25,26 Submitted for publication May 10, 2007. volume resuscitation solution for hemorrhagic shock. The Accepted for publication July 20, 2007. bovine polymerized HBOC-201 has been shown to be more Copyright © 2007 by Lippincott Williams & Wilkins effective in restoring mean arterial pressure (MAP) to normal From the Department of Surgery, Division of Burn/Trauma/Critical values,27,28 while requiring significantly less fluid volume when Care, The University of Texas Southwestern Medical Center, Dallas, Texas. Presented as a poster at the 64th Annual Meeting of the American compared with other low-volume and standard resuscitation 29–31 Association for the Surgery of Trauma, September 22–24, 2005, Atlanta, fluids. Moreover, HBOC-201 resuscitation increased sur- Georgia. vival in animal models of controlled and uncontrolled hemor- This study was partially supported by the Biopure Corporation via the rhage, and provided better tissue oxygenation for survival with donation of Hemopure (HBOC-201). Fernando A. Rivera-Chavez was sup- no long-term organ dysfunction.24,29–34 Additionally, clinical ported by NIH Grant K08 GM071646. Address for reprints: Fernando A. Rivera, MD, Department of Surgery, studies have shown that HBOC-201 reduces transfusion require- 35 University of Texas Southwestern Medical Center, 5323 Harry Hines Bou- ments in 35% to 40% of adult surgical patients. levard, Dallas, TX 75390-9160; email: [email protected]. However, one of the main concerns that have limited the DOI: 10.1097/TA.0b013e3181561157 clinical use of HBOCs is the associated vasoconstriction/

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hypertension and its limited plasma expansion capacity. The 10 mL/kg; FIO2, 50%. Tidal volume was adjusted to maintain vasoconstrictive effect is reflected by increases in systemic aPCO2 of approximately 40 mm Hg and maintained at that and pulmonary vascular resistance, which results in de- volume for the rest of the experiment. Electrocardiogram creased CO and pulmonary hypertension. Studies have shown leads, pulse oxymeter, and an esophageal temperature probe that the HBOC-induced hypertension is directly correlated to were placed. Body temperature was maintained at 37.5°C Ϯ vasoconstriction of the vascular arterioles.36 The mechanisms 1.0°C by using a forced air warmer (BAIR Hugger, Augus- by which this vasoconstriction occurs remain unclear. tine Medical, Eden Prairie, MN). A Foley catheter was in- Based on this evidence, both HTS and HBOC-201 have serted into the urinary bladder, and urine output was recorded significant potential benefits and limitations as low-volume hourly. resuscitative solutions for clinical use. Interestingly, HTS restores microcirculatory blood flow by capillary reopening, Surgical Procedures whereas HBOC-201 causes vasoconstriction. Thus, the com- A small incision was made on the left lower extremity bination of both solutions may prove beneficial. For example, and a 5F catheter introduced into a superficial branch of the the plasma-expanding and vasodilator capacity of HTS 7.5% femoral artery, threaded proximally into the iliac artery, se- may attenuate the vasoconstrictive effect of HBOC, and the cured in position, and used for continuous arterial pressure. oxygen-carrying capacity of HBOC may improve and pro- While supine, the neck was prepped, an incision was made, long the hemodynamic effects of HTS. To our knowledge, the and a 9F vascular introducer was placed into the right internal combination of HBOC-201 with HTS 7.5% has not been jugular vein. A Swan-Ganz catheter (SW) was inserted and investigated. The aim of this study was to evaluate the phys- flow directed into the pulmonary artery for hemodynamic iologic and hemodynamic effects of HBOC-201 in a hyper- monitoring and physiologic evaluation (Vigilance Monitor, tonic saline 7.5% carrier (HT-HBOC), and compare it with Edwards Lifesciences, Irving, CA). A catheter was positioned standard HBOC-201 and HTS 7.5% alone. We hypothesized in the carotid artery and was used for controlled hemor- that the prevention of endothelial dysfunction and the vaso- rhage and blood draws. Animals were allowed to stabilize dilator and cardiac effects of HTS 7.5% combined with the for 15 minutes, and baseline measurements of hemody- oxygen-carrying capacity of HBOC-201 may work synergis- namic and physiologic variables were taken, and values tically and be a more effective small-volume resuscitative repeated throughout the experimental protocol (Marquette fluid. model 8000 mol/L, GE/Marquette, Milwaukee, WI). Ani- mals were maintained under general anesthesia for the MATERIALS AND METHODS duration of the protocol. Animal Preparation This study was approved by the University of Texas Hemorrhage and Resuscitation Procedures Southwestern Medical Center at Dallas Institutional Animal After the stabilization period, the animals were rapidly Care and Use Committee. All animals used in this study were hemorrhaged via the carotid artery for 5 minutes to 10 min- cared for and handled according to the Guide for the Care and utes until the MAP was decreased to 35 mm Hg Ϯ 5mmHg Use of Laboratory Animals. Thirty-two domestic crossbred (Fig. 1). Animals were maintained hypotensive with a MAP pigs (50–60 kg) obtained from a single provider source were of 35 mm Hg Ϯ 5 mm Hg for a total of 45 minutes (including used in this experiment. Animals were fasted overnight be- the 5 minutes to 10 minutes rapid hemorrhage period) by fore surgery and only received water ad libitum. Sedation was continued intermittent hemorrhage (Fig. 1). No intervention induced with an intramuscular injection of Telazol (Fort was made if the MAP decreased below 35 mm Hg during Dodge Animal Health, Fort Dodge, Iowa) (4 mg/kg) and the shock period. Shed blood was collected in standard atropine (0.04–0.4 mg/kg). General anesthesia was induced donor bags containing citrate phosphate dextrose (Baxter with mask ventilation using isoflurane (2.5%–3.0%) in 40% Corp., Deerfield, IL) and kept at room temperature until oxygen. used for reinfusion in the LR/shed blood group. Net weight of the donor blood bags was used to calculate volume of Maintenance Fluids hemorrhage. Before, and during anesthesia induction and prepara- At the end of the 45-minute shock period, animals were tion surgical procedures, an 18-gauge intravenous catheter randomized to receive one of four resuscitation fluids. A was placed in an ear vein, and intravenous fluids [lactated separate Sham group (n ϭ 3) underwent surgical procedures Ringer’s (LR) solution] were administered to maintain but was not hemorrhaged. MAP greater than 80 mm Hg, heart rate less than 120 bpm. The average maintenance fluid rate was 6 mL ⅐ kgϪ1 ⅐ hrϪ1 Experimental Groups to8mL⅐ kgϪ1 ⅐ hrϪ1 during the experiment. The groups were as follows: group 1 (LR)—standard Each animal underwent endotracheal intubation followed resuscitation of LR solution (33 mL/kg), followed by shed by mechanical ventilation. The following parameters were blood, infused rapidly; group 2 (HBOC)—standard HBOC- used: respiratory rate, 10 to 12 bpm; tidal volume, 7 mL/kg to 201 (6 mL ⅐ kgϪ1 ⅐ 5 minϪ1); group 3 (HTS)—hypertonic saline

1114 November 2007 Resuscitation From Hemorrhagic Shock

Fig. 1. Schematic diagram of experimental timeline in swine undergoing hemorrhage and resuscitation.

7.5% (4–5 mL ⅐ kgϪ1 ⅐ 5minϪ1); group 4 (HT-HBOC)— minutes, and 240 minutes of resuscitation. Analysis and cal- hypertonic 7.5% HBOC-201 (4–5 mL ⅐ kgϪ1 ⅐ 5 minϪ1). culations were made using a Marquette monitor 8000 mol/L The HT-HBOC solutions was prepared in our labora- (GE/Marquette). tory by removing 80 mL from the 250 mL bag of HBOC- 201 (13 g/dL of hemoglobin) and replacing this volume Statistical Analysis with pharmaceutical-grade stock solution of 23% NaCl Data are reported as mean Ϯ SE for each group. Statis- (Baxter Corp.) to a final concentration of 7.5%-hypertonicity tical analysis was performed using SPSS for Windows ver- HBOC-201 (10.4 g/dL of hemoglobin). The HTS solution sion 12.0 (SPSS, Inc., Chicago, IL). Comparisons included (250 mL) was similarly made by diluting the 23% stock repeated measures and one-way analysis of variance followed saline solution to 7.5% with sterile water. by post hoc analysis (Tukey’s multiple comparison test) The LR group was included to provide a familiar control where appropriate. Significance was defined as p Ͻ 0.05. reference and the HTS 7.5% to have a hypertonic control. An observation period of 4 hours followed the initial resuscita- RESULTS tion. Maintenance fluids were resumed, and additional bo- There were no differences in the groups with respect luses of 5 mL/kg were given at 30 minutes, 60 minutes, 120 to weight, estimated blood volume, hemorrhage volume, minutes, and 180 minutes, if MAP was Ͻ60 mm Hg. At the and percentage of estimated blood volume hemorrhaged end of the observation (4 hours) tubes were removed, inci- (Table 1). sions closed, and animals were allowed to awake from the anesthetic before taken to their cages. Hemodynamic Parameters Animals were followed for survival for 24 hours or 72 There were no significant hemodynamic changes in the hours. At these time points, half of each group of pigs sham animals. Statistical comparisons included only the LR, underwent the same previously mentioned procedures for HBOC, HTS, and HT-HBOC groups. The sham group data monitoring; a Swan-Ganz catheter was reintroduced and are included in the graphics to present a reference for com- physiologic and hemodynamic data, as well as blood and parison. Because the aim of this study was to compare the tissue samples, were obtained. Animals were then killed with standard HBOC-201 versus HT-HBOC-201 and HTS 7.5%, an overdose of barbiturate. the statistical analysis is between these groups. Baseline measurements and physiologic responses to Blood Samples hemorrhage were comparable in all groups. Hemorrhage de- Blood was taken serially during the experiment at the creased MAP and CO pulmonary capillary wedge pressure following time points: at baseline; at 30 minutes and 45 (PCWP) and increased heart rate equally in all groups. minutes (completion) of shock; and at 30 minutes, 60 min- The following differences were found during the resus- utes, 120 minutes, 180 minutes, and 240 minutes of resusci- citation and observation periods: the HT-HBOC- and HBOC- tation. Arterial and mixed venous blood samples were drawn resuscitated animals required significantly less fluid volume from the external carotid artery and the distal port of the (Fig. 2). Swan-Ganz catheter, respectively, for blood gas and chemistry analysis. Blood gas analysis was performed on an ABL (Radiometer, Copenhagen, Denmark). Serum chemistry Table 1 Group Characteristics (Mean ؎ SD) 725 measurements were performed on an OSM3 (Radiometer). Hemorrhage Estimated Blood Experimental Group Weight (kg) Physiologic and Hemodynamic Measurements Volume (mL) Volume (%) ϭ Ϯ Pulmonary and arterial pressures, body temperature, ox- Sham (n 3) 56.5 1.7 NA NA LR (n ϭ 6) 56.1 Ϯ 1.3 2,130 Ϯ 400 38.2 Ϯ 7.7 ygen saturation, and vital signs were measured continuously HBOC (n ϭ 8) 56.6 Ϯ 0.7 2,198 Ϯ 308 39.1 Ϯ 1.3 throughout the experiment. Cardiac and oxygenation profiles HTS 7.5% (n ϭ 6) 56.3 Ϯ 2.3 2,125 Ϯ 343 38.4 Ϯ 3.3 were measured at the following time points: at baseline; at 15 HT-HBOC (n ϭ 8) 56.2 Ϯ 7.3 2,268 Ϯ 399 40.06 Ϯ 0.5 minutes, 30 minutes, and 45 minutes (completion of shock); p 0.999 0.719 0.753 and at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 NA, not assayed.

Volume 63 • Number 5 1115 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

The HBOC and HT-HBOC groups had a more sustainable MAP response (Fig. 3A).

Cardiac Output CO returned to near baseline in the LR and HT-HBOC groups, remained significantly lower in the HBOC group, and was not sustained in the HTS group (Fig. 3B).

Pulmonary Capillary Wedge Pressure PCWP was slightly lower in the HBOC group during the observation period, but this did not reach statistical significance. However, by the end of the 4-hour observation period, PCWP was similar in all groups. Heart rate returned to near-baseline levels in all groups by the end of the observa- Fig. 2. Resuscitation fluids; the LR group required significantly tion period (Fig. 3C). more fluids when compared with the rest of the groups (*p Ͻ 0.001). Similarly, the HTS group required more fluids when compared with Systemic and Pulmonary Vascular Resistances the HBOC and HT-HBOC groups (*p Ͻ 0.001). There were no (SVR/PVR) differences between the HBOC and HT-HBOC groups (Ͼ0.05). Hemorrhage did not cause significant changes in SVR. However, resuscitation with standard HBOC significantly Mean Arterial Pressure increased SVR when compared with the other groups. PVR By the end of the observation period (4 hours), MAP was similarly increased in all groups at the end of hemor- returned to near baseline in the HBOC and HT-HBOC rhage. Upon resuscitation, PVR returned to near-baseline groups, whereas it remained low in the HTS and LR groups. levels in the HT-HBOC and HTS groups, and remained

Fig. 3. (A) MAP recovered faster (ϳ10–20 minutes) in the HTS, HT-HBOC, and HBOC groups, when compared with LR. However, the only significant difference was at 4 hours when the MAP in the HTS group was lower than that in all other groups (p ϭ 0.02). (B)COwas significantly lower in HBOC-resuscitated pigs at 1 hour, 2 hours, and 4 hours when compared with LR and HT-HBOC (p ϭ 0.001). This was not significantly different from HTS. (C) PCWP was similar in all groups after resuscitation, but PCWP was significantly lower in the HTS group when compared with the rest of the groups from 2 hours to 72 hours (p ϭ 0.03).

1116 November 2007 Resuscitation From Hemorrhagic Shock

Fig. 4. (A) Resuscitation with HBOC significantly increased PVR greater than that in the other groups (p Ͻ 0.001). (B) MPAP was significantly increased in the HBOC group at all time points (p Ͻ 0.01). slightly elevated in the LR group. Resuscitation with standard elevated in the HBOC and HTS groups. However, the HBOC further increased PVR and it remained significantly differences were not significant. Sodium levels increased elevated throughout the duration of the observation period upon resuscitation in the HBOC, HT-HBOC, and HTS when compared with the other experimental groups (Fig. 4A). groups. By the end of the observation period, sodium levels returned to baseline in the HBOC-resuscitated animals, and Mean Pulmonary Artery Pressure remained slightly elevated in both hypertonic groups. By the end of hemorrhage, MPAP was decreased in all groups. Upon resuscitation, MPAP gradually began to in- DISCUSSION crease, and by the end of the observation period, was slightly In this model of controlled hemorrhage, we demonstrated below baseline levels in both hypertonic groups, above base- for the first time that the HBOC-201 in a hypertonic saline line in the LR group, and significantly elevated in the HBOC carrier (HT-HBOC) improved hemodynamic parameters group (Fig. 4B). when compared with HTS alone. This combination also attenuated the vasoconstrictive effects observed with standard Mixed Venous Oxygen Saturation HBOC-201 resuscitation.

Mixed venous oxygen saturation (SvO2) decreased in re- Administration of 250 mL of HT-HBOC-201 signifi- sponse to hemorrhage and gradually increased during the begin- cantly improved CO and restored mixed venous oxygen sat- ning of resuscitation in the HT-HBOC, LR, and HTS groups. By uration (SvO2), when compared with administration of an the end of the observation phase, SvO2 was significantly de- equivalent volume of standard HBOC-201 or HTS 7.5%. creased in the HTS-resuscitated animals. Standard HBOC Additionally, HT-HBOC maintained hemodynamic parame- resuscitation did not restore SvO2, and throughout the obser- ters better than the HTS 7.5% and LR groups. vation period SvO2 values remained significantly lower as Furthermore, HT-HBOC-201 attenuated the increases in compared with the HT-HBOC and LR groups (Fig. 5). SVR and PVR as well as the pulmonary hypertension observed with standard HBOC-201 resuscitation. The vasocon- Metabolic Markers strictive effect of HBOC solutions is one of the potential Lactate increased during hemorrhage in all groups. limitations for its clinical use. Although several studies have Resuscitation with HT-HBOC and LR, similarly, returned reported this effect, the exact mechanism remains undefined. lactate levels to baseline. Lactate levels remained slightly Nitric oxide scavenging by polymerized hemoglobin has been

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Fig. 5. Mixed venous oxygen saturation (SvO2) was significantly decreased in the HBOC pigs when compared with all the other groups at all time points postresuscitation except HTS at 4 hours (p ϭ 0.03). suggested as the most probable mechanism. It has been fact that HTS solution does not have oxygen-carrying capac- previously shown that vasoconstriction was independent of ity. Thus, the oxygen-carrying capacity of HBOC-201 con- nitric oxide. Alternative mechanisms for HBOC-induced tributed to the sustained hemodynamic parameters in the vasoconstriction are those secondary to the interaction of HT-HBOC group. free hemoglobin with endothelium-derived factors, resulting Another concern is the increased sodium blood concentra- in endothelial dysfunction, and the subsequent production of tion caused by HTS. However, the increases were only transient reactive oxygen species, enhanced endothelin-1 production, and within clinically acceptable levels. We did not observe neutrophil activation, and increased permeability. hyperchloremic acidosis, which has been associated with HTS. In fact, several studies have previously demonstrated It is clear that the observed benefits in this study in the the effects of hypertonic saline in the mechanisms men- HT-HBOC cannot be attributed to only one solution. There- tioned above.16 For instance, HTS resuscitation prevents fore, we hypothesized that the beneficial effects observed leukocyte adhesion to the endothelium, abrogation of PMN with HT-HBOC are synergistic. activation17,19,20 as well as decreased generation of reactive However, one of the major the limitations of this study is oxygen species.17–19 the controlled hemorrhagic shock model. Although our fixed- Additionally, the cardiac effects of HTS resuscitation pressure model is good to study the acute and long-term such as increases in heart rate, cardiac contractility, venous effects of hypotension, on inflammatory responses as well as return (preload), and the reductions in peripheral and pulmo- the effects of our resuscitation strategies on organ function nary vascular resistance (after load)10–12,15 may explain the and outcome, this model does not actually resemble the increases in CO and the restored mixed venous oxygen uncontrolled hemorrhage situation observed in trauma pa- saturation (SvO2). tients. For example, studies using uncontrolled shock animal The effects of hypertonicity such as increased blood models have shown that raising MAP to normal or near- flow12 in the micro and peripheral circulation by arteriolar normal values resulted in delayed hemostasis, increased vasodilatation and the rapid induced reduction in blood vis- blood loss, and higher acute mortality from washout anemia. cosity by hemodilution10,22 might also contributed to the Therefore, further studies investigating the use of HT- reduction in PVR and SVR observed in the HT-HBOC group. HBOC-201 in a more clinically relevant model of uncon- Resuscitation with HTS 7.5% also has its limitations. trolled hemorrhage as well as the investigation of the For example, if administered rapidly, HTS 7.5% may cause cellular and molecular mechanisms should be performed. hypotension and arrhythmia, secondary to hypertonicity- Nevertheless, these findings suggest a potential benefit of induced vasodilatation and reduction in peripheral vascular this combination to be considered for the initial manage- resistances. There are concerns that these effects could over- ment of hemorrhage. come homeostatic mechanisms, such as vasoconstriction. Thus, there is potential risk for increased internal bleeding. CONCLUSION Interestingly, the vasoconstrictive capacity of HBOC-201 In conclusion, this study demonstrates for the first time may help to antagonize these effects. In addition, the inability that the combination of HBOC-201 with hypertonic saline of HTS to maintain hemodynamics could be secondary to the produces physiologic benefits. Both standard HBOC-201 and

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HT-HBOC-201 were superior to LR and HTS 7.5% in re- 17. Angle N, Hoyt DB, Cabello-Passini R, Herdon-Remelius C, Loomis storing and maintaining hemodynamics. However, the com- W, Junger WG. Hypertonic saline resuscitation reduces neutrophil bination of HBOC-201 with hypertonic saline further margination by suppressing neutrophil L selectin expression. J Trauma. 1998;45:7–12. improved hemodynamics and oxygenation, as indicated by 18. Pascual JL, Ferri LE, Seely AJ, et al. Hypertonic saline resuscitation restoration of CO and higher SvO2, respectively. More impor- of hemorrhagic shock diminishes neutrophil rolling and adherence to tantly, this combination attenuated the increases in pulmonary endothelium and reduces in vivo vascular leakage. Ann Surg. 2002; and systemic vascular resistance as well as pulmonary hyper- 236:634–642. tension, observed with standard HBOC-201. 19. Angle N, Hoyt DB, Coimbra R, et al. Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil activation after hemorrhagic shock. Shock. 1998;9:164–170. REFERENCES 20. Rizoli SB, Kapus A, Parodo J, Rotstein OD. Hypertonicity prevents 1. Dubick MA, Wade CE. A review of the efficacy and safety of 7.5% lipopolysaccharide-stimulated CD11b/CD18 expression in human NaCl/6% dextran 70 in experimental animals and in humans. neutrophils in vitro: role for p38 inhibition. J Trauma. 1999;46: J Trauma. 1994;36:323–330. 794–798. 2. Kramer GC. Hypertonic resuscitation: physiologic mechanisms 21. Dubick MA, Atkins JL. Small-volume fluid resuscitation for the far- and recommendations for trauma care. J Trauma. 2003;54: forward combat environment: current concepts. J Trauma. 2003; S89–S99. 54:S43–S45. 3. Terajima K, Aneman A, Haljamae H. Haemodynamic effects of 22. Rocha-e-Silva M, Poli de Figueiredo LF. Small volume hypertonic volume resuscitation by hypertonic saline-dextran (HSD) in resuscitation of circulatory shock. Clinics. 2005;60:159–172. porcine acute cardiac tamponade. Acta Anaesthesiol Scand. 2004; 23. Anbari KK, Garino JP, Mackenzie CF. Hemoglobin substitutes. Eur 48:46–54. Spine J. 2004;13(Suppl 1):S76–S82. 4. Wade C, Grady J, Kramer G. Efficacy of hypertonic saline dextran 24. Arnoldo BD, Minei JP. Potential of hemoglobin-based oxygen (HSD) in patients with traumatic hypotension: meta-analysis of carriers in trauma patients. Curr Opin Crit Care. 2001;7:431–436. individual patient data. Acta Anaesthesiol Scand Suppl. 1997;110: 25. Standl T. Haemoglobin-based erythrocyte transfusion substitutes. 77–79. Expert Opin Biol Ther. 2001;1:831–843. 5. Wade CE, Kramer GC, Grady JJ, Fabian TC, Younes RN. Efficacy of 26. Waschke KF, Frietsch T, Quintel M, Lenz C, Rebel A. Hemoglobin hypertonic 7.5% saline and 6% dextran-70 in treating trauma: a meta- solutions. Acta Anaesthesiol Scand Suppl. 1997;111:259–263. analysis of controlled clinical studies. Surgery. 1997;122:609–616. 27. Lee SK, Morabito D, Hemphill JC, et al. Small-volume resuscitation 6. Wade CE, Grady JJ, Kramer GC. Efficacy of hypertonic saline with HBOC-201: effects on cardiovascular parameters and brain dextran fluid resuscitation for patients with hypotension from tissue oxygen tension in an out-of-hospital model of hemorrhage in penetrating trauma. J Trauma. 2003;54:S144–S148. swine. Acad Emerg Med. 2002;9:969–976. 7. Mazzoni MC, Borgstrom P, Arfors KE, Intaglietta M. Dynamic fluid 28. Boura C, Caron A, Longrois D, Mertes PM, Labrude P, Menu P. redistribution in hyperosmotic resuscitation of hypovolemic Volume expansion with modified hemoglobin solution, colloids, or hemorrhage. Am J Physiol. 1988;255:H629–H637. crystalloid after hemorrhagic shock in rabbits: effects in skeletal 8. Mazzoni MC, Borgstrom P, Arfors KE, Intaglietta M. The efficacy muscle oxygen pressure and use versus arterial blood velocity and of iso- and hyperosmotic fluids as volume expanders in fixed- resistance. Shock. 2003;19:176–182. volume and uncontrolled hemorrhage. Ann Emerg Med. 1990; 29. Kasper SM, Walter M, Grune F, Bischoff A, Erasmi H, Buzello W. 19:350–358. Effects of a hemoglobin-based oxygen carrier (HBOC-201) on 9. Kreimeier U, Frey L, Dentz J, Herbel T, Messmer K. Hypertonic homodynamic and oxygen transport in patients undergoing saline dextran resuscitation during the initial phase of acute preoperative hem dilution for elective abdominal aortic surgery. endotoxemia: effect on regional blood flow. Crit Care Med. 1991; Anesth Analg. 1996;83:921–927. 19:801–809. 30. Katz LM, Manning JE, McCurdy S, et al. HBOC-201 improves 10. Rocha-e-Silva M, Negraes GA, Soares AM, Pontieri V, Loppnow L. survival in a swine model of hemorrhagic shock and liver injury. Hypertonic resuscitation from severe hemorrhagic shock: patterns of Resuscitation. 2002;54:77–87. regional circulation. Circ Shock. 1986;19:165–175. 31. Gurney J, Philbin N, Rice J, et al. A hemoglobin based oxygen carrier, 11. Constable PD, Muir WW III, Binkley PF. Effect of hypertonic saline bovine polymerized hemoglobin (HBOC-201) versus Hetastarch (HEX) solution on left ventricular afterload in normovolumic dogs. Am J in an uncontrolled liver injury hemorrhagic shock swine model with Vet Res. 1995;56:1513–1521. delayed evacuation. J Trauma. 2004;57:726–738. 12. Crystal GJ, Gurevicius J, Kim SJ, Eckel PK, Ismail EF, Salem MR. 32. Freitag M, Standl TG, Gottschalk A, et al. Enhanced central organ Effects of hypertonic saline solutions in the coronary circulation. oxygenation after application of bovine cell-free hemoglobin HBOC- Circ Shock. 1994;42:27–38. 201. Can J Anaesth. 2005;52:904–914. 13. Hannon JP, Wade CE, Bossone CA, Hunt MM, Coppes RI, Loveday 33. Standl T, Freitag M, Burmeister MA, Horn EP, Wilhelm S, Am Esch JA. Blood gas and acid-base status of conscious pigs subjected to JS. Hemoglobin-based oxygen carrier HBOC-201 provides higher and fixed-volume hemorrhage and resuscitated with hypertonic saline faster increase in oxygen tension in skeletal muscle of anemic dogs than dextran. Circ Shock. 1990;32:19–29. do stored red blood cells. J Vasc Surg. 2003;37:859–865. 14. Kolsen-Petersen JA, Nielsen JO, Tonnesen E. Acid base and electrolyte 34. Hughes GS Jr, Yancey EP, Albrecht R, et al. Hemoglobin-based changes after hypertonic saline (7.5%) infusion: a randomized controlled oxygen carrier preserves submaximal exercise capacity in humans. clinical trial. Scand J Clin Lab Invest. 2005;65:13–22. Clin Pharmacol Ther. 1995;58:434–443. 15. Marshall RJ, Shepherd JT. Effect of injections of hypertonic 35. LaMuraglia GM, O’Hara PJ, Baker WH, et al. The reduction of solutions on blood flow through the femoral artery of the dog. Am J the allogenic transfusion requirement in aortic surgery with a Physiol. 1959;197:951–954. hemoglobin-based solution. J Vasc Surg. 2000;31:299–308. 16. Staudenmayer KL, Maier RV, Jelacic S, Bulger EM. Hypertonic 36. Kavdia M, Tsoukias NM, Popel AS. Model of nitric oxide diffusion saline modulates innate immunity in a model of systemic in an arteriole: impact of hemoglobin-based blood substitutes. Am J inflammation. Shock. 2005;23:459–463. Physiol Heart Circ Physiol. 2002;282:H2245–H2253.

Volume 63 • Number 5 1119 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Range-of-Motion Restriction and Craniofacial Tissue- Interface Pressure From Four Cervical Collars Ann N. Tescher, RN, PhD, CNS, Aaron B. Rindflesch, PT, PhD, James W. Youdas, PT, Therese M. Jacobson, RN, CNS, Lisa L. Downer, RN, CNS, Anne G. Miers, RN, CNS, Jeffrey R. Basford, MD, PhD, Daniel C. Cullinane, MD, Susanna R. Stevens, MS, V. Shane Pankratz, PhD, and Paul A. Decker, MS

Background: Occipital pressure ul- mandibular pressures were mapped with were Philadelphia, Miami J, and Aspen cers are well-known complications for subjects in upright and supine positions. (p < 0.001). Philadelphia and Miami J col- trauma patients wearing cervical collars. Results: All collars significantly re- lars had significant collar-body mass index We assessed the effects of four commercial stricted CROM in all planes (p < 0.001). interaction effects on supine occiput mean .(0.04 ؍ cervical collars (Aspen, Philadelphia, Mi- The Philadelphia and standard Miami J col- pressure (p ami J, and Miami J with Occian back lars were the most restrictive. The Aspen Conclusions: Miami J and Philadel- [Miami J/Occian]) on cervical range of collar was the least restrictive for flexion phia collars restricted CROM to the motion (CROM) and mandibular and oc- and rotation. The Miami J/Occian back was greatest extent. Miami J and Miami J/Oc- cipital tissue-interface pressure (TIP). the least restrictive for extension and lateral cian back had the lowest levels of mandib- Methods: Forty-eight healthy volun- flexion. For supine measurements, Miami J ular and occipital pressure; these collars teers (24 men, 24 women; mean age, 38.9 and Miami J/Occian back had the lowest may markedly reduce the risk of occipital -years ؎ 10.5 years) were stratified by body mean TIP, whereas Aspen and Philadelphia pressure ulcers without compromising im mass index. CROM was measured in the collars had the greatest (p < 0.001). For mobilization. seated position without and with collars. upright measurements, the Miami J/Occian Key Words: Cervical collar, Pressure Sagittal, coronal, and rotatory CROM was back produced the smallest mean TIPs; the ulcer, Range of motion, Tissue-interface measured with a goniometer. Occipital and other collars, ranked by ascending TIP, pressure. J Trauma. 2007;63:1120–1126.

ccipital pressure ulcers are well-known complications that spine of trauma patients until fracture or ligamentous injury result from prolonged use of rigid cervical collars.1–4 can be excluded.5 However, if a patient cannot be evaluated OPressure on occipital tissue as a result of immobility, adequately because of an altered mental status or other inju- decreased level of consciousness, or hypoesthesia is the most ries, the collar is usually kept in place until a definitive crucial factor.2 Impaired perfusion, fluid shifts that occur evaluation can be performed. In a study by Davis et al.,3 55% with resuscitation, poor collar fit, shear forces, and diaphore- of patients who wore a cervical collar for 5 or more days had sis all may have an effect.2 Although many factors cannot be development of full-thickness occipital ulcers. controlled or eliminated, the pressure exerted against occip- The aims of our study were to compare the degree to ital tissue by the cervical collar may be ameliorated. which each of four commercially available hard cervical The American College of Surgeons Advanced Trauma collars restricted normal cervical range of motion (CROM) Life Support course for physicians recommends use of a rigid and to assess tissue-interface pressure (TIP) exerted by the cervical collar and backboard to immobilize the cervical collars in the upright and supine positions. Our goal was to determine which of these collars would have the minimum TIP and the most restriction of CROM. Submitted for publication June 19, 2006. Accepted for publication February 8, 2007. PATIENTS AND METHODS Copyright © 2007 by Lippincott Williams & Wilkins Subjects From the Department of Nursing (A.N.T., T.M.J., L.L.D., A.G.M.); Department of Physical Medicine and Rehabilitation (J.R.B.); Division of Fifty-three healthy volunteers between 18 and 60 years of Trauma, Critical Care, and General Surgery (D.C.C.); Division of Biostatis- age were recruited for the study after approval was obtained tics (S.R.S., V.S.P., P.A.D.), Mayo Clinic; and the Physical Therapy Program from the Mayo Clinic Institutional Review Board. Prospective (A.B.R., J.W.Y.), Mayo School of Health Related Sciences, Mayo Clinic subjects were screened for neck pain, history of spinal surgery, College of Medicine, Rochester, Minnesota. physical or chiropractic therapy to the neck, history of neck Nothing in this article implies endorsement of the products of Philadelphia Cervical Collar Company, Aspen Medical Products, or Jerome Medical. trauma requiring medical care, and history of cervical spondy- Address for reprints: Ann N. Tescher, RN, PhD, Department of Nurs- losis or osteoporosis. Five prospective subjects were excluded, ing, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; email: and the remaining 48 were stratified by body mass index (BMI) [email protected]. (20–24.9 kg/m2, 25–30 kg/m2,orϾ30 kg/m2) into three groups DOI: 10.1097/TA.0b013e3180487d0f of eight women and eight men each.

1120 November 2007 Evaluation of Four Cervical Collars

Orthoses Table 1 Protocol for Cervical Range-of-Motion We assessed four collars. The Philadelphia (Philadelphia (CROM) Measurements Cervical Collar Company, Thorofare, NJ), Aspen (Aspen Medical Products, Irvine, CA), and Miami J (Jerome Medi- 1. The subject was seated in an aluminum-frame chair. The cal, Moorestown, NJ) collars are designed to provide neck thoracic spine maintained contact with the chair’s backrest, and the lumbosacral spine filled the gap between the seat and the immobilization for long-term acute and rehabilitation phases backrest. The subject’s feet were flat on the floor, and the of patient care. The Miami J collar with Occian back (Miami subject’s arms rested freely on the sides. J/Occian) (Jerome Medical) is recommended for patients who 2. A nurse investigator measured and fit each subject with 4 require cervical immobilization, prolonged supine position- cervical collars, according to manufacturers’ instructions. Collars ing, and have a high risk of occipital skin breakdown.6 The were chosen in random order. The CROM device was mounted over the subject’s nose bridge and ears and secured to the Miami J/Occian back uses the anterior half of the Miami J head with a Velcro strap, according to the manufacturer’s collar, and the posterior Occian component is composed of instructions. materials that conform to the occiput, maximize the area of 3. As instructed by the physical therapist investigator, each subject skin contact, and soften when warmed by the patient’s own performed 3 repetitions of neck flexion, extension, left and right body heat.2,6 lateral flexion, and left and right rotation, in that order, to increase compliance of the soft tissues of the neck. The subject was instructed to move the head until the CROM in flexion, Measurements extension, lateral flexion to left and right, and rotation to the left Subjects were weighed, and their height was measured and right was stopped by muscle tightness, pain, or until a using a calibrated standing scale. Three nurses with expertise substitution movement occurred. in collar use measured and fit the subjects according to the 4. The tester measured the subject’s CROM in both directions manufacturer’s instructions. The four collars were assessed in within a cardinal plane using the CROM device. The starting and end points of the CROM were recorded. Immediately after the random order. first 6 measurements, the tester removed the CROM apparatus All CROM measurements were taken by the same expe- from the subject and repositioned it on the subject. The subject rienced physical therapist (J.W.Y.) using a CROM device repeated the series of movements, providing 2 sets of 6 (Hospeq, Miami, FL).7 The device consists of a plastic frame measurements. mounted over the subject’s nose bridge and ears and secured to the head with a Velcro strap. Neck flexion, extension, and Table 2 Protocol for Tissue-Interface Pressure lateral flexion movements are recorded by two gravity goni- Measurement ometers marked in two-degree increments. The cervical rotation was assessed in a similar manner with a compass 1. The subject was seated, and XSENSOR pads were placed on the anterior mandibles and occiput. The subject was fit with a goniometer that is used with a shoulder-mounted magnetic properly sized cervical collar by a nurse investigator. Collars yoke. Goniometric measurements correlate closely with were chosen in random order. roentgenographically determined cervical motion.8 The 2. While the subject was seated, pressure measurements and CROM device is accurate,9 easy to use, and has a high distribution of pressure (“pressure map”) on the anterior intraclass correlation coefficient (0.83–0.95)10 when com- mandibles and occiput were recorded by one of the physical therapist investigators. pared with a universal goniometer or visual estimation. The 3. The subject was placed in a supine position on a standard same device was used throughout the study in the manner hospital bed mattress without a pillow. Pressure measurements outlined in Table 1. CROM was measured only when patients and distribution of pressure (“pressure map”) at the mandibles were seated because the CROM device inclinometers for the and occiput were noted. Collars were evaluated in the same sagittal and frontal planes rely on gravity. order as the upright seated evaluation. The subject was instructed to notify investigators of any discomfort while supine. TIP was measured simultaneously over the occiput and both mandibles by a highly experienced physical therapist (A.B.R.) using three custom-sized pads of the XSENSOR X2 resistive ink technology systems such as the F-scan system.11 System (XSENSOR Technology Corporation, Calgary, Al- Calibration was performed before measuring each subject in berta, Canada). The XSENSOR system consisted of a square accordance with the manufacturers’ instructions.12 TIPs were grid of capactive pressure-sensing transducers (resolution, measured using the protocol described in Table 2. 0.64 cm2) embedded in three mats (7.5 ϫ 12.5 ϫ 0.1 cm) placed between the cervical collar and the subject’s mandible Data Analysis and occiput. Pressure between 0 mm Hg and 220 mm Hg may Data were analyzed using repeated-measures analysis of be sensed. The mats are connected to a laptop computer that variance. The univariate single-group repeated-measures analy- permits data viewing in two or three dimensions and in sis of variance used the Greenhouse-Geisser correction to nom- distribution histograms; data may be shown as mean pressure inal degrees of freedom with a sample size of six and p Ͻ 0.05. versus time, peak pressure versus time, and contact area This significance level had 80% power to detect a difference in versus time. For measuring pressure over curved surfaces, the means across the levels of the repeated measures factor and was system is highly accurate (2% error) when compared with characterized by an effect size of 4.3405. This scenario assumed

Volume 63 • Number 5 1121 The Journal of TRAUMA௡ Injury, Infection, and Critical Care a mean TIP of 95 mm Hg Ϯ 6 mm Hg without a collar and 125 Miami J. The difference in restrictiveness between the Philadel- mm Hg Ϯ 10 mm Hg with a collar. The data used in this phia and Miami J collars in all movement planes was not calculation were taken from the study by Bridges et al.12 statistically significant. The Aspen collar was the least restrictive of flexion and rotation, and the Miami J/Occian back was RESULTS the least restrictive of extension and lateral flexion move- CROM ments. The pairwise comparisons of the collars (to each other Baseline measurements without a collar showed that all and to CROM without a collar) are shown in Table 4. subjects had normal CROM in all directions.9,10,13 All collars produced a statistically significant restriction of movement TIP (p Ͻ 0.001). Measurement reliability was confirmed with TIP was measured along both mandibles and the occiput intraclass correlation coefficients greater than 0.6 in all with the subjects sitting upright and lying supine without a movement planes (Table 3). pillow on a standard hospital bed. The Aspen collar had the Of the four collars, the Philadelphia was the most restrictive highest mean TIP on both mandibles and occiput in the of CROM in all movement planes (p Ͻ 0.001), followed by the upright and supine positions (p Ͻ 0.001). The Philadelphia

Table 3 Intraclass Correlation Coefficients for Cervical Range-of-Motion Measurements

Miami J With No Collar Philadelphia Aspen Miami J Occian Back Flexion 0.859 0.790 0.609 0.939 0.902 Extension 0.981 0.928 0.876 0.973 0.980 Right lateral flexion 0.935 0.953 0.951 0.961 0.955 Left lateral flexion 0.955 0.963 0.973 0.957 0.966 Right rotation 0.874 0.953 0.973 0.942 0.970 Left rotation 0.977 0.959 0.951 0.962 0.946

Table 4 Extension, Flexion, Lateral Flexion, and Rotation With Four Cervical Collars

Collar Type Miami J With Movement No Collar* Aspen Philadelphia Miami J Occian Back Mean P Mean P Mean P Mean Extension, degrees† 70.98 Ϯ 10.00 26.87 Ϯ 13.71 0.03‡ 23.26 Ϯ 11.58 0.15§ 25.65 Ϯ 11.49 Ͻ0.001࿣ 31.40 Ϯ 12.99 0.46¶ Ͻ0.001# 0.007** Flexion, degrees† 48.92 Ϯ 7.91 16.97 Ϯ 8.74 Ͻ0.001‡ 11.67 Ϯ 6.53 0.44§ 12.57 Ϯ 6.79 0.57࿣ 13.22 Ϯ 6.86 Ͻ0.001¶ 0.18# 0.001** Lateral flexion, degrees† Right 39.89 Ϯ 6.01 24.50 Ϯ 9.90 0.03‡ 21.93 Ϯ 10.00 0.10§ 23.85 Ϯ 10.16 0.02࿣ 26.65 Ϯ 9.05 0.58¶ Ͻ0.001# 0.07** Left 39.76 Ϯ 6.64 23.42 Ϯ 9.24 0.03‡ 20.88 Ϯ 10.16 0.14§ 22.63 Ϯ 9.53 0.02࿣ 25.39 Ϯ 8.93 0.50¶ Ͻ0.001# 0.09** Rotation, degrees† Right 67.92 Ϯ 6.97 24.81 Ϯ 13.45 0.003‡ 20.09 Ϯ 12.31 0.05§ 23.08 Ϯ 11.38 0.96࿣ 23.00 Ϯ 11.59 0.26¶ 0.06# 0.24** Left 68.16 Ϯ 8.66 26.89 Ϯ 14.41 0.01‡ 22.59 Ϯ 13.01 0.10§ 25.40 Ϯ 11.76 0.58࿣ 26.34 Ϯ 13.56 0.38¶ 0.03# 0.75** * P Ͻ 0.001 for all pair-wise comparisons. † P Ͻ 0.001 for all overall comparisons. ‡ Aspen versus Philadelphia. § Philadelphia versus Miami J. ࿣ Miami J versus Miami J with Occian back. ¶ Aspen versus Miami J. # Philadelphia versus Miami J with Occian back. ** Aspen versus Miami J with Occian back.

1122 November 2007 Evaluation of Four Cervical Collars

Fig. 1. Tissue-interface pressure, mandible. Capillary closing pressure is 32 mm Hg (solid line). (A) Mean right mandible pressure, upright position. (B) Mean left mandible pressure, upright position. (C) Mean right mandible pressure, supine position. (D) Mean left mandible pressure, supine position. collar had the highest maximal TIP on the occiput in the American Association of Neurologic Surgeons, Nashville, supine position (p Ͻ 0.001). The Miami J/Occian back had TN, 1990), Mosenkis,14 and Lunsford et al.15 compared the the lowest mean TIP on the occiput in the upright and supine restrictive ability of cervical collars. These investigators positions, and on both mandibles in the supine position. The found that all collars were restrictive when compared with mean and maximal pressures exerted by each collar in the reference values but reached different conclusions about the upright and supine positions are shown in Figures 1 and 2. comparative restrictiveness of individual collars. The most We categorized the 48 subjects by BMI and sex to likely reason for the different conclusions is that different control for the effect of body size on mobility and TIP. We measurement devices were used with each study. Our choice found a significant association between BMI and the mean of the CROM device was made on the basis of its ease of use supine occiput pressure overall (p ϭ 0.04). and measurement reliability.10 With three video cameras, Lunsford et al.15 measured DISCUSSION cervical motion in 10 subjects using a pointer attached to a CROM mouth stick. The fit of each collar (Philadelphia, Miami J, To our knowledge, no studies have combined measure- Malibu, and Newport extended wear) was standardized with ments of restrictiveness (i.e. CROM) and tissue pressures an elastic tensiometer. Zhang et al.16 compared four collars when examining cervical collars. Ducker (Ducker TB, read at (Aspen, XTW, C-Breeze, and Miami J) with 20 subjects.

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Fig. 2. Tissue-interface pressure, occiput. Capillary closing pressure is 32 mm Hg (solid line). (A) Mean occiput pressure, upright position. (B) Mean occiput pressure, supine position.

They used a sophisticated three-camera motion analysis sys- 32 mm Hg. However, the mean supine occiput pressures in all tem in a biomechanics laboratory to obtain three-dimensional collars (range, 26.92–38.56 mm Hg [Miami J/Occian back kinematic data from each subject. Although measurements in and Aspen, respectively]) were much lower because mean that study were precise, we chose a technique that would be pressure is a function of total surface area of contact. Several more readily used by clinicians. authors have associated wearing a cervical collar with occipital Mosenkis14 and an unpublished abstract by Ducker pressure ulcer formation,1,19–23 but their studies were descrip- (Ducker TB, read at American Association of Neurologic tive, predictive, or focused on the process of product change. Surgeons, Nashville, TN, 1990) used the CROM goniometer The ability to measure the effect of a hard cervical collar device to measure cervical motion restriction. Mosenkis stud- on occipital TIP clearly has been hampered by the lack of ied 20 subjects and compared the Philadelphia, Aspen, and measuring devices that were reliable but still small and pli- Miami J collars; Ducker studied five collars (soft foam, able enough to fit between the head and collar. We are aware Philadelphia, Stifneck, NecLoc, and Miami J) in 35 subjects. of only two studies that examined the effect of pressure One limitation of the Mosenkis study is that the degrees of exerted by cervical collars on the skin.2,8 One by Fisher et al.8 lateral flexion and axial rotation to the left and right were included eight subjects and used an infant sphygmomanom- summed rather than reported separately, which precluded eter at the chin and occiput to measure pressure during flex- testing of motion symmetry. ion and extension. The Fisher study aimed to determine whether a cervical collar could be fitted to more tolerable TIP pressures while still providing adequate immobilization. Although cervical collar TIP was the variable of most Plaisier et al.2 compared four collars (Stifneck, Philadelphia, interest in the formation of pressure ulcers, collar restrictive- Newport, and Miami J) with 20 subjects and used one elec- ness was the outcome variable of utmost importance for tropneumatic sensor that needed to be repositioned to mea- clinical practice. Although individual factors may have some sure skin-collar interface pressures on the occiput, mandible, aggravating or relieving influence, an external pressure of 25 and chin. Despite the differences in measurement techniques, mm Hg to 32 mm Hg generally causes capillary compression.12 their TIP findings for the Philadelphia and Miami J collars Bader and Gant17 and Colin and Saumet18 showed a direct were similar to ours. association between vascular perfusion and tissue oxygen The mapping system used in our study provided several tension by measuring a 50% decrease in transcutaneous ox- advantages. First, the pressure mapping pads were small and ygen after applying external pressure as low as 22 mm Hg. pliable enough to fit easily inside each collar. Second, the Whether external pressure is of low intensity and long dura- sensor pads were able to cover the occiput and mandibles tion or high intensity and short duration, unrelieved pressure simultaneously and repositioning was unnecessary. Third, the ultimately may cause tissue ischemia and cell necrosis. The sensor pads reliably measured pressure over curved surfaces. maximal supine occiput pressure for all collars (range, 44.21– BMI had a significant effect on TIP only for the Phila- 103.7 mm Hg [Miami J/Occian back and Philadelphia, re- delphia and Miami J collars (Fig. 3). The association between spectively]) was well above the capillary closing pressure of BMI and TIP was contrary to the findings of other pressure

1124 November 2007 Evaluation of Four Cervical Collars

2. Plaisier B, Gabram SG, Schwartz RJ, et al. Prospective evaluation of craniofacial pressure in four different cervical orthoses. J Trauma. 1994;37:714–720. 3. Davis JW, Parks SN, Detlefs CL, et al. Clearing the cervical spine in obtunded patients: the use of dynamic fluoroscopy. J Trauma. 1995; 39:435–438. 4. Agency for Health Care Policy and Research. Preventing Pressure Ulcers. Rockville, MD: US Department of Health and Human Services Public Health Service; 1992. AHCPR Publication No. 92- 0048. [cited May 18, 2006]. Available at: www.woundheal.com/healing/patientGuideMain.htm. 5. Chendrasekhar A, Moorman DW, Timberlake GA. An evaluation of the effects of semirigid cervical collars in patients with severe closed head injury. Am Surg. 1998;64:604–606. 6. Jerome Cervical Spine System [homepage on the internet]. Continuum of Care Products: Occian Back. Moorestown, NJ: Jerome Medical Inc; c2000–2005 [cited Dec 14, 2005]. Available at: www.jeromemedical.com/occianback.php. Fig. 3. Effects of body mass index (BMI) on mean supine occiput 7. rehaboutlet.com [homepage on the internet]. Range of Motion pressure. The interaction effect of the collar and BMI was signifi- Measurement. Miami: Hospeq Inc; c1999–2006 [cited Nov 18, ϭ 2004]. Available at: www.rehaboutlet.com/range_of_motion_ cant (p 0.04). measurement.htm. 8. Fisher SV, Bowar JF, Awad EA, et al. Cervical orthoses effect on mapping studies24–27 that often show lower BMIs associated cervical spine motion: roentgenographic and goniometric method of with higher TIPs, usually because of lack of muscle or adi- study. Arch Phys Med Rehabil. 1977;58:109–115. pose tissue mass over bony prominences. In our study, sub- 9. Youdas JW, Garrett TR, Suman VJ, et al. Normal range of motion 2 of the cervical spine: an initial goniometric study. Phys Ther. 1992; jects with BMI more than 30 kg/m had higher average TIP, 72:770–780. which we attribute to greater weight without greater tissue 10. Youdas JW, Carey JR, Garrett TR. Reliability of measurements of mass on the skull. cervical spine range of motion: comparison of three methods. Phys Our study had several potential limitations. Use of Ther. 1991;71:98–104. ambulatory adults as a model for CROM and TIP may have 11. Fergenbaum M, Hadcock L, Stevenson J, et al. Pressure limited application for acutely injured trauma patients. The measurement applications for humans. Available at: www.anatomicsitt.com/produkter/xsensor/queensstudy.pdf. Accessed traumatic inflammatory response leads to retention of fluid May 18, 2006. and tissue edema, which further exacerbate the effects of 12. Bridges EJ, Schmelz JO, Mazer S. Skin interface pressure on the pressure on tissue ischemia. Also, factors such as moisture, NATO litter. Mil Med. 2003;168:280–286. poorly fitting collars, and shear forces that may increase 13. Schoen DC. Adult Orthopaedic Nursing. Philadelphia, PA: the risk of pressure ulcer formation were not examined. Lippincott; 2000. 14. Mosenkis R. Comparison of Three Cervical Collars in Restricting CONCLUSION Cervical Spine Motion [CITECH test report]. Moorestown, NJ: Jerome Medical; 2001:CITECH: 490–421. The results of our study of uninjured, healthy adults 15. Lunsford TR, Davidson M, Lunsford BR. The effectiveness of four indicate that the Philadelphia and Miami J collars effec- contemporary cervical orthoses in restricting cervical motion. J tively reduced cervical movement, and the Miami J collar Prosthet Orthot. 1994;6:93–99. with and without the Occian back provided superior pres- 16. Zhang S, Wortley M, Clowers K, et al. Evaluation of efficacy and sure relief. Consequently, the Miami J collar may be the 3D kinematic characteristics of cervical orthoses. Clin Biomech (Bristol, Avon). 2005;20:264–269. orthosis of choice for trauma patients who are admitted to 17. Bader DL, Gant CA. Changes in transcutaneous oxygen tension as a the hospital. Because the Miami J/Occian back was the result of prolonged pressures at the sacrum. Clin Phys Physiol Meas. least restrictive in cervical extension, we use it for occip- 1988;9:33–40. ital support for patients with strict spine precautions and 18. Colin D, Saumet JL. Influence of external pressure on patients who are exclusively bedridden. transcutaneous oxygen tension and laser Doppler flowmetry on sacral skin. Clin Physiol. 1996;16:61–72. 19. Webber-Jones JE, Thomas CA, Bordeaux RE Jr. The management ACKNOWLEDGMENTS and prevention of rigid cervical collar complications. Orthop Nurs. We thank the Section of Scientific Publications, Mayo Clinic, for 2002;21:19–25. editing, proofreading, and reference verification. 20. Black CA, Buderer NM, Blaylock B, Hogan BJ. Comparative study of risk factors for skin breakdown with cervical orthotic devices: Philadelphia and Aspen. J Trauma Nurs. 1998;5:62–66. REFERENCES 21. Liew SC, Hill DA. Complication of hard cervical collars in multi- 1. Blaylock B. Solving the problem of pressure ulcers resulting trauma patients. Aust NZ J Surg. 1994;64:139–140. from cervical collars. Ostomy Wound Manage. 1996;42:26–28, 22. Powers J. A multidisciplinary approach to occipital pressure ulcers 30, 32–33. related to cervical collars. J Nurs Care Qual. 1997;12:46–52.

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23. Watts D, Abrahams E, MacMillan C, et al. Insult after injury: index, and seating position. Arch Phys Med Rehabil. 2003; pressure ulcers in trauma patients. Orthop Nurs. 1998;17: 84:405–409. 84–91. 26. Colin D, Loyant R, Abraham P, et al. Changes in sacral 24. Kernozek TW, Wilder PA, Amundson A, et al. The effects of body transcutaneous oxygen tension in the evaluation of different mass index on peak seat-interface pressure of institutionalized mattresses in the prevention of pressure ulcers. Adv Wound Care. elderly. Arch Phys Med Rehabil. 2002;83:868–871. 1996;9:25–28. 25. Stinson MD, Porter-Armstrong A, Eakin P. Seat-interface 27. Garber SL, Campion LJ, Krouskop TA. Trochanteric pressure pressure: a pilot study of the relationship to gender, body mass in spinal cord injury. Arch Phys Med Rehabil. 1982;63:549–552.

1126 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Use of a Pediatric Cohort to Examine Gender and Sex Hormone Influences on Outcome After Trauma Herb A. Phelan, MD, Shahid Shafi, MD, MPH, Jennifer Parks, MPH, R. Todd Maxson, MD, Naveed Ahmad, MD, MPH, Joseph T. Murphy, MD, and Joseph P. Minei, MD

Background: Animal studies suggest and ventilator days were examined. To a higher mean ISS for women at these that female gender imparts a protective control for the effect of sex hormones, greater magnitudes of injury. The cause of effect on outcome after trauma, and im- patients were divided into three groups by this effect could not be explained by mech- plicate sex hormones as the cause. Human age: prepubertal (birth to 8 years), anism of injury, ventilator days, or intensive studies have yielded mixed results. These peripubertal (8.1–14.5 years), and postpu- care unit days. results are confounded by postmenopausal bertal (14.6–20 years). We calculated Conclusion: Female gender was as- hormone replacement and the difficulty of survival rates for age group ISS subsets sociated with improved survival rates for controlling for pretrauma comorbidities. overall and by mechanism of injury. patients demonstrating sex hormone pro- The pediatric population is a better model to Results: The prepubertal and peripu- duction (i.e. postpubescent patients) in a determine the impact of gender and sex hor- bertal age groups had equivalent survival manner that was directly proportional to mones on outcome after trauma. rates between genders across all severities of their severity of injury. No protective ef- Methods: The National Trauma Data injury. The sex hormone-containing postpu- fect of gender was seen in the prepubes- Bank was queried for all patients from bertal cohort had a significantly improved cent or peripubertal age groups. birth to 20 years of age. Age, gender, In- survival rate for women across all ISS sub- Key Words: Gender, Trauma, jury Severity Score (ISS), mechanism of groups, and the effect was more pronounced Outcomes. injury, mortality, intensive care unit days, with increasing ISS. This effect was despite J Trauma. 2007;63:1127–1131.

lthough a fairly convincing body of evidence exists for categorization and consequent tainting of any results based on the influence of gender on outcomes after trauma in sex hormone status may contribute to the conflicting study Aanimal studies, the relationship in humans is less clear. results seen in the literature. Studies can be found that either support1–6 or contradict7–10 Another model for examining the effect of gender and the hypothesis that sexual dimorphism impacts outcome after sex hormone status on outcome after trauma is the pediatric undergoing trauma. In the animal literature, the cause seems population, as the progression from prepubescence to sexual to be the increased estrogen:testosterone ratio. Although hu- maturity would seem to function as an adequate control for man studies have concentrated on outcomes, they frequently any estrogen or androgen effect. The primary goal of this study address the question of sex hormone influence by breaking was to examine gender-specific differences in survival by cal- the study populations into premenopausal and postmeno- culating outcomes in age groups which were clearly prepubertal, pausal age groups. The difficulty with this approach is that it peripubertal, and postpubertal. A secondary goal was to examine takes into account neither the variability of the age of meno- the impact of mechanism of injury on gender outcomes. pause, nor the hormonal fluctuations seen in the years-long perimenopausal period. The potential for difficulty with mis- MATERIALS AND METHODS We queried the American College of Surgeons’ National Submitted for publication January 25, 2007. Trauma Data Bank (NTDB) (version 5.0) and requested data Accepted for publication July 17, 2007. for patients from birth until 20 years of age. Our study Copyright © 2007 by Lippincott Williams & Wilkins population consisted of 218,474 patients. We requested the From the Department of Surgery (H.A.P.), University of South Ala- following data points for each patient: age, gender, Injury bama Medical Center, Mobile, Alabama; University of Texas-Southwestern Medical Center (S.S., J.P., J.P.M.), Dallas, Texas; Children’s Hospital of Severity Score (ISS), discharge status, mechanism of injury, Austin (R.T.M.), Austin, Texas; Children’s Medical Center Research Insti- number of days spent on the ventilator (VD), and number of tute (N.A.), Dallas, Texas; and Children’s Medical Center (J.T.M.), Dallas, days spent in the intensive care unit (ICU). We chose to look Texas. at the differences between men and women in three distinct Presented as a poster at the 63rd Annual Meeting of the American age groups: birth to 8 years of age, 8.1 to 14.5 years of age, Association for the Surgery of Trauma, September 29–October 2, 2004, Maui, Hawaii. and 14.6 to 20 years of age based on the latest trends in onset 11 Address for reprints: Herb A. Phelan, MD, Department of Surgery, of puberty in the United States as reported by Lee et al. University of South Alabama Medical Center, 2451 Fillingim St., MSTN From their data, we chose to examine children under 8 years 708, Mobile, AL 36617; email: [email protected]. of age to limit any potential effects of secondary sex hormone DOI: 10.1097/TA.0b013e318154c1b8 production on outcomes. We chose also to compare children

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between 14.6 and 20 years of age to include a majority that PREPUBERTAL SURVIVAL clearly would have secondary sex hormone production. The 100 middle group, those children aged 8.1 to 14.5 years, were 90 deemed peripubescent. They are statistically in the range of male 80 first production of sex hormones, but are much less uniform female in this respect. All patients were grouped within ISS subsets % SURVIVAL 70 of 1 to 14, 15 to 23, and Ն24. Comparisons were then made between men and women for ISS subgroup overall survival, 60 ISS subgroup survival by mechanism of injury, ISS subgroup ISS 1-14 ISS 15-23 ISS >24 VD, and ICU. Fig. 1. Prepubertal survival comparison between genders by ISS Univariate analyses and independent samples t tests were subsets. conducted to determine significant differences among the groups. A p value Յ0.05 was considered statistically signif- PERIPUBERTAL SURVIVAL icant for all analyses. Clinically significant differences in ISS 100 were defined as being a difference in ISS between groups of 90 greater than or equal to one point. SPSS (SPSS Inc., Chicago, male IL) was used for all statistical analyses. 80 female

RESULTS % SURVIVAL 70

Table 1 shows the size, mean ISS, and survival rate for 60 each age group’s ISS subset. When survival rates were cal- ISS 1-14 ISS 15-23 ISS >24 culated for prepubertal patients, they were equivalent be- Fig. 2. Peripubertal survival comparison between genders by ISS tween genders across all ISS subgroups (Fig. 1). In the subsets. peripubescent group, survival rates were again equivalent across all ISS subgroups (Fig. 2). Mortality in the postpubes- POSTPUBERTAL SURVIVAL cent age group is displayed in Figure 3. Female survival was 100 * # higher across all ISS subgroups, and the benefit was more pronounced with higher severity of injury. 90 male Statistically significant differences in mean ISS scores 80 were noted in the prepubertal ISS 1 to 14 comparison, pre- * female pubertal ISS 1 to 14, and ISS Ͼ24 comparison, and all % SURVIVAL 70 postpubertal ISS subset comparisons. The only difference 60 which reached the definition of clinical significance (i.e. a ISS 1-14 ISS 15-23 ISS >24 difference between ISS scores of Ն1) was in the peripubertal Fig. 3. Postpubertal survival comparison between genders by ISS age group in which the female mean ISS of 33.4 Ϯ 11.6 was subsets. *p Ͻ 0.001, #p ϭ 0.001. higher than the male value of 32.2 Ϯ 10.7. Each age group’s ISS subsets were then compared for survival based on mechanism of injury. These results are seen found between genders for various age group ISS subsets. in Tables 2 to 4. No association was found between type of However, all of the ISS differences were within one point of injury mechanism and survival by gender. Again, several each other, and therefore the groups were deemed clinically statistically significant differences in mean ISS scores were equivalent based on our definition.

Table 1 Survival by Gender Irrespective of Mechanism of Injury

n ISS Survival Age Group ISS Group Male Female Male Female p Value Male (%) Female (%) p Value Prepubertal 1–14 33,528 22,067 5.1 Ϯ 3.4 5.0 Ϯ 3.4 0.029 99.7 99.7 0.378 15–23 3,272 2,250 17.3 Ϯ 1.8 17.2 Ϯ 1.8 0.169 97.0 96.8 0.785 Ͼ24 1,978 1,325 32.0 Ϯ 11.7 31.8 Ϯ 11.4 0.649 71.0 70.2 0.624 Peripubertal 1–14 30,142 13,699 5.5 Ϯ 3.5 5.3 Ϯ 3.5 Ͻ0.001 99.7 99.7 0.736 15–23 2,914 1,380 17.7 Ϯ 2.0 17.9 Ϯ 2.0 0.064 97.9 98.3 0.395 Ͼ24 1,883 952 32.2 Ϯ 10.7 33.4 Ϯ 11.6 0.009 75.7 75.0 0.692 Postpubertal 1–14 56,948 23,962 5.7 Ϯ 3.8 5.4 Ϯ 3.9 Ͻ0.001 99.4 99.6 Ͻ0.001 15–23 8,042 3,018 18.2 Ϯ 2.1 18.6 Ϯ 2.2 Ͻ0.001 95.3 96.8 0.001 Ͼ24 8,017 3,097 33.4 Ϯ 11.4 34.3 Ϯ 11.0 0.001 70.7 76.2 Ͻ0.001

1128 November 2007 Pediatric Gender Outcomes

Table 2 Survival by Gender—Penetrating Mechanism of Injury

n ISS Survival Age Group ISS Group Male Female Male Female p Value Male (%) Female (%) p Value Prepubertal 1–14 1,893 1,164 3.03 Ϯ 2.92 3.10 Ϯ 3.09 0.539 99.5 99.7 0.586 15–23 77 47 16.86 Ϯ 1.18 17.04 Ϯ 1.57 0.456 96.1 91.5 0.280 Ͼ24 74 42 32.65 Ϯ 15.58 36.12 Ϯ 17.26 0.270 55.4 47.6 0.420 Peripubertal 1–14 2,167 756 3.66 Ϯ 3.27 3.21 Ϯ 3.16 0.001 99.4 99.7 0.323 15–23 109 48 17.19 Ϯ 1.62 17.02 Ϯ 1.51 0.534 89.9 95.8 0.215 Ͼ24 144 40 31.01 Ϯ 13.46 33.05 Ϯ 16.76 0.423 47.2 55.0 0.384 Postpubertal 1–14 11,821 1,646 4.97 Ϯ 4.02 4.24 Ϯ 3.80 Ͻ0.001 98.3 98.9 0.054 15–23 1,354 115 17.66 Ϯ 1.73 17.35 Ϯ 1.53 0.059 87.3 86.1 0.711 Ͼ24 1,773 159 33.51 Ϯ 14.78 32.45 Ϯ 13.48 0.384 46.0 52.2 0.131

Table 3 Survival by Gender—Blunt Mechanism of Injury

n ISS Survival Age Group ISS Group Male Female Male Female p Value Male (%) Female (%) p Value Prepubertal 1–14 28,538 18,893 5.39 Ϯ 3.39 5.29 Ϯ 3.32 0.002 99.7 99.7 0.551 15–23 3,051 2,102 17.32 Ϯ 1.84 17.24 Ϯ 1.78 0.118 97.0 97.1 0.998 Ͼ24 1,787 1,204 31.92 Ϯ 11.09 31.72 Ϯ 10.93 0.627 71.1 70.4 0.707 Peripubertal 1–14 25,929 12,208 5.76 Ϯ 3.48 5.51 Ϯ 3.53 Ͻ0.001 99.8 99.7 0.896 15–23 2,684 1,303 17.80 Ϯ 2.02 17.92 Ϯ 2.03 0.071 98.2 98.4 0.749 Ͼ24 1,681 896 32.38 Ϯ 10.23 33.27 Ϯ 10.99 0.041 78.0 76.0 0.252 Postpubertal 1–14 43,212 21,804 5.91 Ϯ 3.76 5.55 Ϯ 3.90 Ͻ0.001 99.7 99.6 0.940 15–23 6,524 2,869 18.31 Ϯ 2.14 18.62 Ϯ 2.20 Ͻ0.001 96.9 97.1 0.559 Ͼ24 6,119 2,913 33.43 Ϯ 10.18 34.32 Ϯ 10.73 Ͻ0.001 77.7 77.6 0.964

Table 4 Survival by Gender-Thermal Mechanism of Injury

Age Group by Male Female ISS Group Male (n) Female (n) Male ISS Female ISS ISS p Value Survival p Value Mechanism Survival (%) Survival (%) Thermal 1–14 1,664 1,142 2.96 Ϯ 3.08 3.2 Ϯ 3.22 0.050 99.6 99.9 0.155 prepubertal 15–23 84 60 16.15 Ϯ 0.61 16.25 Ϯ 0.88 0.443 98.8 98.3 0.810 Ͼ24 70 52 35.13 Ϯ 19.56 31.08 Ϯ 15.13 0.200 81.4 78.8 0.723 Thermal 1–14 584 227 3.13 Ϯ 2.92 3.18 Ϯ 3.07 0.833 99.7 98.7 0.110 peripubertal 15–23 23 9 16.17 Ϯ 0.49 16.44 Ϯ 1.33 0.400 95.7 88.9 0.477 Ͼ24 25 8 32.04 Ϯ 16.58 37.75 Ϯ 23.00 0.446 80.0 62.5 0.315 Thermal 1–14 589 159 3.14 Ϯ 3.02 3.61 Ϯ 3.30 0.090 99.7 99.4 0.608 postpubertal 15–23 30 8 16.50 Ϯ 1.36 17.38 Ϯ 2.33 0.337 100 100 — Ͼ24 47 12 32.64 Ϯ 17.16 40.67 Ϯ 21.90 0.177 85.1 66.7 0.143

Comparisons between genders were then performed for tosterone receptor antagonists can ameliorate the depressed VD and ICU (Table 5). The only significant differences function of male rat endothelial cells after trauma or found were for postpubertal women in the ISS 1 to 14 sub- hemorrhage.13 Bench investigations have shown a role for group who spent a slightly shorter period of time on the female sex hormones in improving gut perfusion,14 augmen- ventilator, and for postpubertal women in the ISS Ն24 sub- tation of splenic immune function,15 and regulation of mac- group who stayed in the ICU half a day longer than their male rophage function after trauma or hemorrhage.16 Other studies counterparts did. have shown that progesterone administration after hemorrhagic shock can augment the cardiovascular response to DISCUSSION resuscitation,17 and can attenuate liver injury.18 A wealth of basic science work has seemed to show a Although bench research has uniformly shown an out- benefit to an increased estrogen:androgen ratio. Knoferl and come effect of gender dimorphism, attempts to investigate associates showed that removing the ovaries of proestrus this relationship in the clinical sphere have met with mixed females blunted their immune responses after hemorrhagic results. Various research has shown an overall female sur- shock, and that administering 17-␤ estradiol restored immune vival benefit,1,4 improved female outcomes after blunt trauma function.12 Other studies have shown that administering tes- only,2,5 and improved male outcomes after penetrating

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Table 5 Analysis of Ventilator Days and ICU Days by Gender

Age Group ISS Group Male (n) Female (n) Male VD Female VD VD p Value Male ICU Female ICU ICU p Value Prepubertal 1–14 33,528 22,067 0.31 Ϯ 9.87 0.13 Ϯ 1.06 0.070 0.66 Ϯ 2.44 0.62 Ϯ 2.07 0.128 15–23 3,272 2,250 1.63 Ϯ 19.72 1.54 Ϯ 5.88 0.907 2.72 Ϯ 5.29 2.78 Ϯ 5.34 0.691 Ͼ24 1,978 1,325 3.90 Ϯ 9.48 6.77 Ϯ 40.29 0.078 5.74 Ϯ 9.38 6.00 Ϯ 10.19 0.259 Peripubertal 1–14 30,142 13,699 0.30 Ϯ 10.64 0.30 Ϯ 10.89 0.982 0.56 Ϯ 1.82 0.56 Ϯ 1.85 0.912 15–23 2,914 1,380 1.29 Ϯ 3.95 1.24 Ϯ 3.59 0.825 2.60 Ϯ 4.12 2.74 Ϯ 4.35 0.346 Ͼ24 1,883 952 5.99 Ϯ 34.70 6.56 Ϯ 34.21 0.772 6.00 Ϯ 9.66 6.84 Ϯ 10.41 0.055 Postpubertal 1–14 56,948 23,962 0.32 Ϯ 9.73 0.14 Ϯ 0.95 0.011 0.57 Ϯ 1.95 0.54 Ϯ 1.95 0.119 15–23 8,042 3,018 2.71 Ϯ 27.73 1.96 Ϯ 18.98 0.353 2.92 Ϯ 5.19 2.91 Ϯ 4.99 0.920 Ͼ24 8,017 3,097 6.22 Ϯ 27.91 6.95 Ϯ 35.82 0.395 6.60 Ϯ 10.08 7.14 Ϯ 10.29 0.018 injury.5 Other investigators have found no gender differences 1.5%. The survival advantage of female gender then becomes either overall,7,9 or in blunt trauma only.8,19 a more pronounced effect of 5.5% when the injuries are most The issue with the question of causality in most clinical severe (i.e. ISS Ն24). Further, these survival advantages for gender-related investigations is that the presence of sex hor- postpubertal women in the ISS 15 to 23 and Ն24 subgroups mones is usually central to the discussion, and the sex hor- were despite having significantly higher mean ISS scores. mone status of most patients is not something that is tracked Although the male and female mean ISS scores in these in large trauma databases. Given that the necessary data on subgroups were within one point of each other (and therefore sex hormone status is not tracked directly, assumptions must clinically equivalent severities of injury by our definition), at be made about the study populations based on age. This is a minimum it cannot be argued that the females were less problematic in its own right because the ubiquity of hormone severely injured than their male counterparts. We think that replacement (37.6% of postmenopausal women in one these results argue persuasively that not only is there a sex review20), variability in age of onset of menopause, and hormone-dependent effect of gender dimorphism, but that frequency of medical comorbidities in this age group all act this effect becomes more apparent with increasing severity of as confounding variables. Taken together, it is easy to under- injury. stand the difficulty in clearly defining the sex hormone status The cause of this effect seems to be independent of of adult populations from database reviews, and may explain mechanism of injury and time spent on the ventilator. In an ad why the uniformity of basic science data has not been re- hoc analysis, we also examined whether there was a potential flected in clinical investigations. difference in the rates of gunshot wounds versus stab wounds Using a pediatric cohort to examine the question of between genders in the penetrating, postpubertal cohort with gender and sex hormone influence circumvents many of these an ISS Ն24. None was found. Severely injured postpubertal problems. We have broken our patient groups into those women were found to have spent about half a day longer in which would predictably be hormonally naive (prepubescent) the ICU. This would seem to speak to a better tolerance for and sexually mature (postpubescent). We also collected data the physiologic stressors associated with a protracted ICU on a peripubertal subset about which less can be said with course, and is a consistent reflection of the fact that these confidence. Although this approach still requires making as- women were staying alive longer. sumptions based on patient age, this structure allows them to An intriguing possibility for this apparent estrogen effect be made with a higher degree of confidence in the homoge- lies in the red cell and its response to oxidative stress. It has neity of the sex hormone status in the study population. An been shown that red blood cells have a decrease in their additional benefit of using a pediatric cohort is that children ability to elongate and consequently negotiate the narrow tend to have a healthier baseline, so preinjury comorbidities lumen of capillaries after trauma or hemorrhage.21 This de- should be less common with minimal confounding effects. crease in red cell deformability could lead to impaired oxygen The present study suggests that gender does play a role in delivery and tissue hypoxia. Studies have shown that preser- outcome after injury, that this effect is mediated by sex vation of normal red cell morphology in sepsis is associated hormones, and the protective effect of female gender is pro- with a lower incidence of multiorgan dysfunction,22 and de- portional to the magnitude of injury. In the hormonally naive creased deformability heralded infectious complications in prepubertal and peripubertal patient groups, survival rates trauma patients by a matter of days.23 Machiedo and associ- were equivalent between genders across all levels of injury ates showed that female rats with high estrogen levels had severity. These results stand in stark contrast to patients who preserved red blood cell deformability after trauma or hem- clearly have sex hormones present, however. If one considers orrhage, whereas males and low estrogen females had de- ISS differences of less than one to be clinically equivalent, creased indices of deformability.24 The authors postulated the data show that a very small survival benefit for postpu- that this may be because of an inhibitory influence of estro- bertal women of 0.2% in the ISS 1 to 15 subgroup becomes gen on lipid peroxidation. This mechanism is consistent with a modest advantage of 1.5% in the ISS 15 to 23 subgroup of our findings of a protective gender effect that is proportional

1130 November 2007 Pediatric Gender Outcomes to the severity of injury. As the magnitude of injury rises, so 6. Croce MA, Fabian TC, Malhotra AK, et al. Does gender difference would the degree of oxidative stress as well as the protective influence outcome? J Trauma. 2002;53:889–894. effect of estrogen. 7. Bowles BJ, Roth B, Demetriades D. Sexual dimorphism in trauma? A retrospective evaluation of outcome. Injury. 2003;34:27–31. This investigation is not without its weaknesses. These 8. Rappold JF, Coimbra R, Hoyt DB, et al. Female gender does not are largely those of any large retrospective database re- protect blunt trauma patients from complications and mortality. view. As previously discussed, assumptions regarding age J Trauma. 2002;53:436–441. and hormonal status had to be made to define the param- 9. Gannon CJ, Napolitano LM, Pasquale M, et al. A statewide eters of this study. Given that these assumptions were data population-based study of gender differences in trauma: validation driven11 this effect would hopefully be minimized, but its of a prior single-institution study. JACS. 2002;195:11–18. 10. Coimbra R, Hoyt DB, Potenza BM, et al. Does sexual dimorphism magnitude is unknowable. Because multiple institutions influence outcome of traumatic brain injury patients? The answer is contribute to the NTDB, data quality may be variable. no! J Trauma. 2003;54:689–700. Indeed, given limitations in the presence or accuracy of 11. Lee PA, Guo SS, Kulin HE. Age of puberty: data from the United data points we were not able to examine comorbidities, States of America. APMIS. 2001;109:81–88. resuscitation endpoints, transfusion requirements, and sep- 12. Knoferl MW, Jarrar D, Angele MK, et al. 17-beta estradiol tic complications. These concerns should be balanced normalizes immune responses in ovariectomized females after trauma-hemorrhage. Am J Phys Cell Phys. 2001;281:C1131–C1138. against the very large sample size of the study population, 13. Zheng FB, Wang P, Koo DJ, et al. Attenuation of vascular which allows adequate powering to pick up any effect of endothelial dysfunction by testosterone receptor blockade after small clinical differences. Finally, it is possible that the trauma and hemorrhagic shock. Arch Surg. 2001;135:1158–1163. different physiologic milieu (in ways beyond sex hor- 14. Kuebler JF, Jarrar D, Toth B, et al. Estradiol administration mones) of prepubertal patients does not allow for their improves splanchnic perfusion following trauma-hemorrhage and intergender comparisons to be juxtaposed against those of sepsis. Arch Surg. 2002;137:74–79. 15. Knoferl MW, Angele MK, Schwacha MG, et al. Preservation of adults. After all, this accounts for the training aphorism splenic immune functions by female sex hormones after trauma- that “kids are not little people”. Nevertheless, when hemorrhage. Crit Care Med. 2002;30:888–893. viewed in light of the basic science data suggesting sex 16. Knoferl MW, Angele MK, Diodato MD, et al. Female sex-hormones hormones as the key to a difference in sexual dimorphism, regulate macrophage function after trauma-hemorrhage and prevent it seems reasonable to conclude that the present study increased death rate from subsequent sepsis. Ann Surg. 2002; construct is valid. 235:105–112. 17. Kuebler JF, Jarrar D, Bland KI, et al. Progesterone administration In summary, our use of the NTDB to examine the impact after trauma and hemorrhagic shock improves cardiovascular of gender dimorphism on outcome after trauma in a pediatric responses. Crit Care Med. 2003;31:1786–1793. cohort suggests that there is a protective effect of female 18. Kuebler JF, Yokoyama Y, Jarrar D, et al. Administration of gender, which is proportional to the severity of injury and that progesterone after trauma and hemorrhagic shock prevents it is sex hormone mediated. The cause of this effect cannot be hepatocellular injury. Arch Surg. 2003;138:727–734. clearly explained by its association with mechanism of injury, 19. Napolitano LM, Greco ME, Rodriguez A, et al. Gender differences in adverse outcomes after blunt trauma. J Trauma. 2001;50:274– VD, or ICU length of stay. Future studies should be directed 280. at elucidating the mechanism of this effect. 20. Keating NL, Cleary PD, Rossi AS, et al. Use of hormone replacement therapy by postmenopausal women in the United REFERENCES States. Ann Int Med. 1999;130:545–553. 1. Wohltmann CD, Franklin GA, Boaz PW, et al. A multicenter 21. Zaets SB, Berezina TL, Morgan C, et al. Effect of trauma- evaluation of whether gender dimorphism affects survival after hemorrhagic shock on red blood cell deformability and shape. trauma. Am J Surg. 2001;181:297–300. Shock. 2003;19:268–273. 2. George RL, McGwin G, Metzger J, et al. The association between 22. Machiedo GW, Powell RJ, Rush BF, et al. The incidence of gender and mortality among trauma patients as modified by age. decreased red cell deformability in sepsis and the association with J Trauma. 2003;54:464–471. oxygen free radical damage and multiple system organ failure. Arch 3. McGwin G, George RL, Cross JM, et al. Gender differences in Surg. 1989;124:1386–1389. mortality following burn injury. Shock. 2002;18:311–315. 23. Langenfield JE, Livingston DH, Machiedo GW. Red cell 4. Mostafa G, Huynh T, Sing RF, et al. Gender-related outcomes in deformability is an early indicator of infection. Surgery. 1991; trauma. J Trauma. 2002;53:430–435. 110:398–404. 5. George RL, McGwin G, Windham ST, et al. Age-related gender 24. Machiedo GW, Zaets S, Berezina T, et al. Red blood cell damage differential in outcome after blunt or penetrating trauma. Shock. after trauma-hemorrhage is modulated by gender. J Trauma. 2004; 2003;19:28–32. 56:837–844.

Volume 63 • Number 5 1131 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Can Increased Incidence of Deep Vein Thrombosis (DVT) be Used as a Marker of Quality of Care in the Absence of Standardized Screening? The Potential Effect of Surveillance Bias on Reported DVT Rates after Trauma Elliott R. Haut, MD, Kathy Noll, MSN, David T. Efron, MD, Sean M. Berenholz, MD, Adil Haider, MD, MPH, Edward E. Cornwell III, MD, and Peter J. Pronovost, MD, PhD

Background: Deep vein thrombosis creases, the rate of DVT identification will reported increased 10-fold (0.7–7.0 per ,significantly ,(0.0024 ؍ DVT) is a significant cause of morbidity also increase. 1,000 admissions, p) and mortality in trauma patients, even Methods: Retrospective cohort study between the two periods. The pulmonary with appropriate prophylaxis. Many na- of 21,961 patients from an urban, univer- embolism rate increased almost fivefold ,(0.15 ؍ tional agencies (Agency for Healthcare sity-based Level I trauma center for more (0.7–3.2 per 1,000 admissions, p Research and Quality, Joint Commis- than 11 years (1995–2005). We grouped although this difference was not statistically sion, National Quality Forum) have sug- patients according to admission at the significant. gested DVT incidence as a measurement of trauma service either before or after im- Conclusions: Increasing the number health care quality, but none has recom- plementation of a written practice manage- of duplex screening exams resulted in an mended a standardized screening approach. ment guideline for DVT prophylaxis and increased rate of DVT identification. In Duplex ultrasound serves an important duplex ultrasound surveillance in 1998. the absence of standardized surveillance, role as a noninvasive diagnostic tool for We compared duplex, DVT, and pulmo- DVT rates may be more influenced by detection of DVT. However, screening of nary embolism rates per 1,000 trauma ad- how often caregivers look for these events asymptomatic patients for DVT is some- missions using Fisher’s exact test. rather than the quality of care provided. what controversial and these practices Results: The proportion of trauma pa- Key Words: Deep vein thrombosis, vary widely among trauma centers. We hy- tients having a duplex ultrasound increased Duplex surveillance, Quality of care, pothesized that as the number of screening significantly (20.9–81.5 per 1,000 trauma Screening, Trauma, Pay for performance, duplex examinations in trauma patients in- admissions, p < 0.0001). The rate of DVT Surveillance bias. J Trauma. 2007;63:1132–1137.

eep vein thrombosis (DVT) is a common occurrence Many trauma centers have implemented guidelines for and causes significant morbidity and mortality after DVT prophylaxis in an attempt to decrease morbidity and Dmajor trauma. The reported rate of DVT varies widely mortality associated with the development of potentially le- depending upon many factors. The rate of DVT is related to thal pulmonary emboli (PE). Guidelines often utilize risk injury severity and patient-specific variables.1 It may be as stratification to target those at highest risk for developing PE high as 58%2 or as low as 0.36%1 in trauma patients depend- for the most aggressive prophylaxis. However, even when ing upon how diligent clinicians are at looking for these often providers are diligent with prophylaxis regimens, trauma pa- clinically silent DVTs. tients are still at risk for developing DVT and PE. Duplex ultrasound is commonly used to detect DVT. The Eastern Association for the Surgery of Trauma guidelines suggest that “duplex ultrasound may be used to assess symptomatic Submitted for publication December 14, 2006. trauma patients with suspected DVT without confirmatory Accepted for publication June 25, 2007. venography” based upon Level I evidence.3 However, the data Copyright © 2007 by Lippincott Williams & Wilkins for screening of asymptomatic patients for DVT is somewhat From the Division of Trauma and Surgical Critical Care, Department of Surgery (E.R.H., K.N., D.T.E., S.M.B., A.H., E.E.C., P.J.P.); Department of conflicting and these practices vary widely among trauma cen- Anesthesiology and Critical Care Medicine (E.R.H., D.T.E., S.M.B., E.E.C., ters. Some authors have suggested that routine duplex screening P.J.P.), The Johns Hopkins University School of Medicine; and Department for DVT in asymptomatic high-risk trauma patients may have of Health Policy and Management (E.E.C., P.J.P.), Johns Hopkins University some utility.4–8 The goal of DVT detection in asymptomatic Bloomberg School of Public Health, Baltimore, Maryland. patients is to allow treatment of the DVT to prevent propagation Presented at the 20th Annual Meeting of the Eastern Association for the Surgery of Trauma, January 16–20, 2007, Fort Myers, Florida. or embolization of the clot and death from PE. Cippolle et al. Address for reprints: Elliott R. Haut, MD, FACS, Department of stressed that adherence to a prophylaxis protocol is more impor- Surgery, The Johns Hopkins Hospital, 600 N. Wolfe St., 625 Osler, Balti- tant than screening duplex at preventing thromboembolic more, MD 21287; email: [email protected]. complications.9 Others emphasize that the large expenditure to DOI: 10.1097/TA.0b013e31814856ad screen asymptomatic patients may be cost prohibitive.10–13

1132 November 2007 DVT Incidence and Screening in Trauma Patients

The DVT rate has been suggested as a marker of quality tation of the new written guideline, duplex ultrasounds were of care by various healthcare agencies. As such, it is impor- obtained as indicated by physical examination or at the dis- tant to ensure that these rates are valid and reliable. The cretion of the trauma attending. Agency for Healthcare Research and Quality (AHRQ) lists This study was a retrospective cohort review of prospec- postoperative DVT or PE as a hospital-level patient safety tively collected data from the adult trauma registry at The indicator.14 The Institute for Clinical Systems Improvement Johns Hopkins Hospital Level I Adult Trauma Center be- provides guidelines for DVT prevention and treatment aimed tween January 1995 and December 2005. Patients admitted to at improving quality of care and cost-effectiveness.15 The the Adult Trauma Service were divided into two groups, Joint Commission has identified DVT as a quality-of-care mea- those admitted before (1995–1997), and those admitted after sure and in collaboration with the National Quality Forum (1999–2005) implementation of guidelines for DVT prophy- (NQF) published the National Consensus Standards for Preven- laxis and duplex ultrasound screening. Data from the year tion and Care of Venous Thromboembolism.16 However, to our 1998 were excluded to allow for full adoption of the guide- knowledge, none of these organizations has recommended a line. However, all results are qualitatively the same if these standardized approach to surveillance for DVT or PE. In the data are included in the after group. The numbers of DVT and absence of standardized surveillance systems, providers who PE were identified from the trauma registry. The number of screen more aggressively by ordering more duplex ultra- patients who had at least one duplex examination was ob- sounds may identify more cases of DVT and appear to pro- tained from the hospital’s discharge billing database. Duplex vide worse quality of care than those providers who order ultrasound, DVT, and PE rates were calculated per 1,000 fewer duplex ultrasounds. Differences in reported DVT rates patient admissions for comparison purposes. We used Fisher’s might be more an issue of surveillance bias than true differ- exact test to compare proportions. Some basic demographics ences in quality of care. Surveillance bias (also known as (i.e., age, gender, percent penetrating, and Injury Severity ascertainment or detection bias) may occur when one group is Score [ISS]) for patient groups were also collected from the followed more closely than the other group. If we look harder registry and differences were examined by Student’s t test or for events in one group, rates of events identified and re- ␹2 test as appropriate. The Institutional Review Board of The ported may reflect how hard clinicians look. Johns Hopkins Medical Institutions granted exempt status for The purpose of this study was to examine the influence this retrospective review. of the rate of duplex scanning on the incidence of DVT identified and reported from our Level I trauma center. We RESULTS hypothesized that as we increase the number of duplex A total of 21,961 trauma visits were recorded during the screening exams in trauma patients, the rate of DVT identi- study period, of which 7,559 were admitted to the adult fication would also increase. trauma service (our study population). Five hundred eight patients had at least one duplex scan of the lower extremities PATIENTS AND METHODS were performed during this period. During the same period, In 1998, The Johns Hopkins Hospital Adult Trauma there were 41 diagnosed cases of DVT. There were 21 cases Center implemented a group of structural changes designed to of PE identified by either ventilation-perfusion scan or com- enhance the commitment to trauma patient care. These pro- puted tomography (CT) angiogram among patients admitted grammatic changes led to well-documented improvements in to the adult trauma service. There was one death in all both the process of care and patient outcomes.17 One specific patients studied (in the early group). Patient characteristics item implemented was a new written practice management varied significantly between the two periods. Patients in the guideline for DVT or PE prophylaxis and surveillance to help later group were slightly older, less likely to be male, less ensure that all trauma patients receive appropriate DVT or PE likely to be injured by penetrating trauma, and less severely prophylaxis. These evidence-based guidelines were developed injured based on ISS (Table 1). in accordance with the practice guidelines for the management The number of duplex scans per 1,000 patients admitted of venous thromboembolism published by the Eastern Associ- increased fourfold between the before and after periods ation for the Surgery of Trauma.3 The guideline suggests the (20.9–81.5 per 1,000 trauma admissions, p Ͻ 0.0001). The preferential use of enoxaprin (dosed 30 mg twice daily) for all number of DVTs recorded increased 10-fold between periods admitted trauma patients with thromboembolic risk factors. (0.7–7.0 per 1,000 admissions, p ϭ 0.0024). There was no The guideline suggests that asymptomatic trauma patients at difference in recorded PE rate (0.7–3.2 per 1,000 admissions, “high risk” for DVT undergo routine screening duplex ultra- p ϭ 0.15) (Table 2 and Fig. 1). sound surveillance. Patients were considered at “high risk” based upon the following risk factors: age Ͼ40 years, pelvic DISCUSSION or femur or tibial fracture, venous injury, femoral venous This study demonstrates that more aggressive surveillance catheter placement, spinal cord injury, severe traumatic brain for DVT results in higher rates of DVT and PE identified. A injury (Glasgow Coma Score Յ8), or anticipated need for 10-fold increase in the proportion of patients diagnosed with prolonged immobilization (Ͼ3 days). Before the implemen- DVT was identified during the time in which duplex ultrasound

Volume 63 • Number 5 1133 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

method to adjust for case mix. Surveillance becomes increas- Table 1 Comparision of Patient Demographics and ingly important when the events are clinically silent (not Characteristics Between Time Periods detected on routine examination), but have the potential for Time Period Before (1995–1997) After (1999–2005) devastating consequences.19 No. adult trauma admissions 1,389 5,561 The DVT rate may be more influenced by how often Age 32.1 33.6* caregivers look for these events rather than the quality of care Male (%) 84.4 79.4* provided. Higher DVT rates may not be a marker of quality Penetrating (%) 59.8 45.0* ISS (mean) 11.7 8.9* of care, but rather an outcome of improved screening prac- ISS Ͼ15 (%) 28.9 19.7* tices. In the absence of standardized surveillance systems, providers who look harder by ordering more duplex ultra- *p Ͻ 0.05. ISS, Injury Severity Score; GCS, Glasgow Coma Scale. sounds, may have higher rates of DVT, and appear to provide poorer quality of care than those providers who order fewer duplex ultrasounds. The effect of surveillance bias on esti- Table 2 Number of Duplex Ultrasounds, Deep Vein mates of the quality of care can result in misinformation and Thromboses (DVT), and Pulmonary Emboli (PE) Before cannot be ignored. We performed more duplexes per admis- Versus After Written Guideline for DVT Prophylaxis sion in the second period in which DVT screening was an and Screening emphasized philosophy. No. Adult Trauma No. Duplex No. No. It is unclear what explanation we can give for the non- Time Period Service Admissions Ultrasounds DVT PE statistically significant increase in rate of PE identified. It is Before (1995–1997) 1,389 29 1 1 possible that CT angiogram images have improved with the After (1999–2005) 5,561 453 39 18 current multidetector CT technology and we are now identifying smaller PEs than we found on older CT scan machines.20 An alternative theory is that clinicians have a lower threshold to perform CT angiography to evaluate for PE in patient with a known DVT and the higher rate of DVT actually directly influences the number of PEs identified. This preliminary study has some limitations. It was performed in a single institution, which may not see a representative population of trauma patients. The study was a retrospective analysis based on data from the trauma registry, which may not have recorded all DVT or PE diagnoses, and hospital discharge data that may have missed some duplex studies performed. There may be Fig. 1. The comparison of rates of trauma patients having a duplex some improvement in duplex technology, but this also ultrasound and diagnosed with deep vein thrombosis (DVT) per year does not explain the large DVT rate change. Patient char- increased significantly (p Ͻ 0.0001 and p ϭ 0.0024, respectively) acteristics are known to influence DVT rates. We cannot between the periods before versus after implementation of a written control for the differences between patient groups, but guideline for DVT surveillance. The PE rate was not statistically these small (albeit statistically significant) patient differ- significant (p ϭ 0.15). ences (age, gender, and penetrating rate) cannot fully explain a 10-fold increase in DVT rate. Our patients are less rates increased 4-fold. DVT surveillance with duplex ultrasound injured (lower mean ISS and lower percentage of higher may serve as an important adjunct to prophylaxis in the preven- ISS patients), which would predict a lower DVT rate, not tion of venous thromboembolism complications in asymptom- higher. atic high-risk trauma patients. However, our data show that more The guideline (and our practice philosophy) encouraged aggressive screening may influence rates of DVT identified. DVT screening for asymptomatic patients at risk for DVT, There are increased efforts to measure, and often reward but never explicitly mandated screening of all asymptomatic or punish providers for the quality of care they provide. Pay patients. Our rate of duplex ultrasound per trauma admission for performance and public reporting of quality are growing increased fourfold suggesting that out screening guideline exponentially.18 Yet, implicit in these systems is the assumed was followed. However, the exact indication for the duplex presence of a valid way to measure clinical quality. The use studies performed remains unknown. We do not know how of outcome measures to evaluate quality of care is challeng- many studies were actually done to screen asymptomatic ing. A valid outcome measure requires explicit definitions for patients as opposed to being directed by findings on physical the numerator (i.e., the number of events) and the denomi- examination. A policy that mandated screening and ordered nator (i.e., the number of patients at risk), a surveillance even more duplexes likely would have found more DVTs and system to capture all numerators and denominators, and a made the study findings even more robust. Additionally, there

1134 November 2007 DVT Incidence and Screening in Trauma Patients may have been different DVT prophylaxis measures in place 10. Meyer CS, Blebea J, Davis K Jr, Fowl RJ, Kempczinski RF. as well. The guideline suggested the use of low molecular Surveillance venous scans for deep venous thrombosis in multiple weight heparin (the current gold standard) instead of unfrac- trauma patients. Ann Vasc Surg. 1995;9:109–114. 11. Spain DA, Richardson JD, Polk HC Jr, Bergamini TM, Wilson MA, tionated heparin. Although we did not examine prophylaxis Miller FB. Venous thromboembolism in the high-risk trauma patient: regimens specifically, these most likely have improved over do risks justify aggressive screening and prophylaxis? J Trauma. time and certainly should not have gotten worse. Improved 1997;42:463–469. pharmacologic prophylaxis would be expected to lower 12. Satiani B, Falcone R, Shook L, Price J. Screening for major deep vein thrombosis in seriously injured patients: a prospective study. DVT rates. However, this is not borne out by the data as Ann Vasc Surg. 1997;11:626–629. the DVT rates in our registry are significantly higher, not 13. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous lower. DVT rates could actually have been even higher had thromboembolism: the seventh ACCP conference on antithrombotic this added benefit of chemical prophylaxis not occurred. and thrombolytic therapy. Chest. 2004;126(Suppl 3):338S–400S. However, this study does bring up a major point. If DVT 14. Patient Safety Indicators Overview. AHRQ Quality Indicators. Rockville, MD: Agency for Healthcare Research and Quality; 2006. and PE are going to be national quality measure then the Available at: http://www.qualityindicators.ahrq.gov/psi_overview.htm. specific patient populations to be screened should be delin- Accessed December 5, 2006. eated. We should specifically clarify the patient population, 15. Institute for Clinical Systems Improvement (ICSI). Health Care frequency, and methods for screening. In the absence of Guideline: Venous Thromboembolism. Bloomington, MN: Institute for standardized surveillance, DVT and PE rates may be influ- Clinical Systems Improvement; 2006. Available at: http://www.icsi.org/ display_file.asp?FileIdϭ187&titleϭVenous%20 Thromboembolism. enced more by how often caregivers look for these events Accessed December 5, 2006. rather than the quality of care provided, a classic example of 16. National Consensus Standards for the Prevention and Care of Venous surveillance bias. To be valid, outcome measures to evaluate Thromboembolism. National Quality Forum Project. Available at: http:// quality of care require standardized definitions, surveillance, www.jointcommission.org/PerformanceMeasurement/Performance ϩ ϩ ϩ ϩ ϩ ϩ and risk adjustment. In the absence of these, outcomes mea- Measurement/National Consensus Standards for Prevention and CareϩofϩVenousϩThromboembolismϩ%28VTE%29.htm. Accessed sures will likely be biased and may misinform. December 5, 2006. 17. Cornwell EE III, Chang DC, Phillips J, Campbell KA. Enhanced trauma program commitment at a level I trauma center: effect on the REFERENCES process and outcome of care. Arch Surg. 2003;138:838–843. 18. Rosenthal MB, Landon BE, Normand SL, Frank RG, Epstein AM. 1. Knudson MM, Ikossi DG, Khaw L, Morabito D, Speetzen LS. Pay for performance in commercial HMOs. N Engl J Med. 2006; Thromboembolism after trauma: an analysis of 1602 episodes from 355:1895–1902. the American College of Surgeons National Trauma Data Bank. Ann 19. Pronovost PJ, Miller MR, Wachter RM. Tracking progress in patient Surg. 2004;240:490–496. safety: an elusive target. JAMA. 2006;296:696–699. 2. Geerts WH, Jay RM, Code KI, et al. A comparison of low-dose 20. Schoepf UJ, Holzknecht N, Helmberger TK, et al. Subsegmental heparin with low-molecular–weight heparin as prophylaxis against pulmonary emboli: improved detection with thin-collimation multi- venous thromboembolism after major trauma. N Engl J Med. 1996; detector row spiral CT. Radiology. 2002;222:483–490. 335:701–707. 3. Rogers FB, Cipolle MD, Velmahos G, Rozycki G, Luchette FA. Practice management guidelines for the prevention of venous DISCUSSION thromboembolism in trauma patients: the EAST practice Dr. Ronald Sing (Charlotte, NC): Apropos to Dr. J Trauma management guidelines work group. . 2002;53:142–164. Pasquale’s presidential address yesterday, many organiza- Available at: http://east.org/tpg/dvt.pdf. Accessed December 12, 2006. tions, JCAHO being most prominent, are now beginning to 4. Burns GA, Cohn SM, Frumento RJ, Degutis LC, Hammers L. track and benchmark complications as a measure of quality of Prospective ultrasound evaluation of venous thrombosis in high-risk care, deep venous thrombosis, and pulmonary embolism be- trauma patients. J Trauma. 1993;35:405–408. ing high on this list. 5. Napolitano LM, Garlapati VS, Heard SO, et al. Asymptomatic deep Although I agree with the conclusions of this article, I do venous thrombosis in the trauma patient: is an aggressive screening protocol justified? J Trauma. 1995;39:651–659. have some questions and a couple of concerns about this 6. Piotrowski JJ, Alexander JJ, Brandt CP, et al. Is deep vein article. One, I would ask the authors why significant demo- thrombosis surveillance warranted in high-risk trauma patients? graphic information was not found in the article itself. We Am J Surg. 1996;172:210–213. know that there are a number of potential, additional high- 7. Brasel KJ, Borgstrom DC, Weigelt JA. Cost-effective prevention of risk factors, such as injury severity score, age, prior history of pulmonary embolus in high-risk trauma patients. J Trauma. 1997; 42:456–462. DVT, and pulmonary embolism. This information is lacking 8. Velmahos GC, Nigro J, Tatevossian R, et al. Inability of an in the article. aggressive policy of thromboprophylaxis to prevent deep vein Also importantly, there’s no mention of DVT prophylaxis thrombosis (DVT) in critically injured patients: are current methods during this time. What was your practice, the practice of your of current DVT prophylaxis insufficient? J Am Coll Surg. 1998; prophylaxis against deep venous thrombosis and PE, and did 187:529–533. 9. Cipolle MD, Wojcik R, Seislove E, Wasser TE, Pasquale MD. The role that change at any time during the study? Do you have any of surveillance duplex scanning in preventing venous guidelines and can you tell us whether patients that had the thromboembolism in trauma patients. J Trauma. 2002;52:453–462. DVTs or pulmonary embolism were being prophylaxed?

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The Surgical Care Improvement Project (SCIP) initia- or the structure of care. They want to know the outcome of tive actually looks more at this time the compliance with care and of those three things that we can look at, maybe prophylaxis and not necessarily outcomes, yet, although outcome of care isn’t the right thing to look at. Maybe the other organizations are, how have you addressed your not process of care or the structure is the right thing. giving prophylaxis to patients at high-bleeding risk, i.e., We also agree 100% that documentation is very impor- the patients with traumatic brain injuries or nonoperative tant. There are high-risk patients who can’t be anticoagulated management of solid organ injuries? I think the documen- who do get pulmonary embolism and DVT. The last patient tation there is a very critical thing to make sure that we are I had was a patient who had been at very high risk with a “compliant”. packed open pelvis that was still bleeding. Contraindication It’s kind of obvious that we know that many DVTs are to prophylaxis was documented on the day of his pulmonary asymptomatic and so the more you screen, the more you will embolism. find. For us, how are we going to define better care with Your next question was about asymptomatic patients and outcomes in this setting, particularly again, at my institution, I don’t know the answer. I would assume that most of these which may have a much larger blunt population versus your patients were asymptomatic. As we know, symptoms don’t population? Our DVT rates should be different and how are really necessarily indicate DVT. Physical examination is only we going to measure quality of care comparing those two about 50% reliable and so I think most of these patients were particular settings? indeed asymptomatic. Screening should pick up more asymptomatic DVTs. You also asked a question about is it really the more you Was there a change or an increase in your symptomatic DVT look the more you find and is it related to case mix or or pulmonary embolism rate? I would be very curious with demographics and I do think it may be something related to that outcome. case mix, that case mix may have changed somewhat, but I do Interestingly, you had a fivefold increase in your pulmo- think that it’s mostly these asymptomatic patients that we’re nary embolism as well. This was not to be picked up by finding. duplex, obviously, and so my question there is how would The next question you asked was why the rates of PE are up you explain why your pulmonary embolism rate increased? I as well and I had a little bit of difficulty trying to explain that. suspect the answer should be, again, a greater surveillance for What I came up with was maybe in these patients who that particular entity. we know have a DVT, at the first sign of pulmonary com- Again, probably the most important thing is better sur- promise we may want to be more aggressive in looking for veillance equals greater identification of this problem, as you PE in this patient population or it could be the other way stated. around, in patients who we identify PE, we look for DVT and Really, I think a strong definition on how you propose I don’t know. Maybe it’s one way or the other, but I’m not we define quality of care is going to be important for all of us, really sure in this retrospective analysis. because again, we’re all going to be graded on this in some Dr. David T. Harrington (Providence, RI): I think, and way by these organizations and as you’re stating, it’s proba- I think most of the audience would agree with me, that bly not going to look very fair and so maybe we should stop increased surveillance will increase your rate of DVT and so doing some of our screens. it’s difficult to hinge it on quality, but I think I have a solution Dr. Elliott R. Haut (Baltimore, MD): The first question to the idea of quality: if you screen, you might detect more, was about demographics and no, we didn’t include demo- but if you screen, you probably will be able to prevent more graphics, although I could go back and get some of that PEs and so how about if you look at the rate of fatal PEs in information. As we know, some of the risk for DVT is related your group before you started doing this protocol and after. to these patients’ specific demographics, but I don’t know The number of fatal PEs before study and after study would that that could account for a 10-fold increase in rate of DVT. be interesting. As far as prophylaxis changes, I don’t think we’ve had If you truly screened and picked them up and treated major changes in prophylaxis. I think we are pretty com- them appropriately, you should knock your fatal PE rate pliant with the EAST guidelines and we use enoxaparin down. pretty religiously on our service. I don’t know that we have Dr. Elliott R. Haut: I actually don’t have that number information specifically on which patients were or were off the top of my head. I do know that it’s a relatively small not prophylaxed. number in both groups. There were only 21 during the course The next question is about the SCIP initiative, with of this period, but I can go back and look at that number and which I agree. They are suggesting that maybe we should try to figure it out, although I do suspect that it’s a relatively look at compliance with guidelines and what percentage of low number of PEs that were fatal. patients who met specific criteria for being at high risk for Dr. Douglas J.E. Schuerer (St. Louis, MO): I have DVT or PE got appropriate prophylaxis. I would agree with two very quick questions. One, we’ve found as we’ve that idea 100%, but most of the agencies, such as AHRQ and studied this that our data collectors actually get a little bit The Joint Commission, are not looking at that process of care better at finding DVTs and PEs in the chart and also we

1136 November 2007 DVT Incidence and Screening in Trauma Patients found that more CT scans were performed where PEs were don’t record it, it’s still going to be the rate that they’re going found. Did you look at that at all or talk to your data to publish on the Internet, and so patients can go and look for collectors and see if they’re actually better at gleaning it. I don’t know which is the answer. I do think it’s the former those things from the record? and not the latter, but it’s certainly a possibility. Number two, as we started more screening for asymp- Your second question was how we get it paid for and first tomatic patients, our vascular laboratory started to get pretty of all, Maryland is a little different. All of our trauma patients mad at us, because Medicare doesn’t reimburse for asymp- are basically covered by universal health care by the State of tomatic scans. What have you done to address that at your Maryland and so if they’re uninsured, we can get paid for institution? them anyway, number one. Dr. Elliott R. Haut: The first question was that you Number two, sometimes patients who are at very high think we’re finding these better in the chart and getting it into risk will have both legs that are swollen and they’re in the the registry better and that’s clearly a potential problem and ICU and they’ve gotten massive resuscitation. So we put it goes to the question of can a registry be used as a marker on the duplex request form that they have bilateral swollen of quality of care. legs, which is true. It’s a little bit of fudging the duplex That’s the data they’re going to look at. They’re going to request, but I think a lot of people would end up doing the ask for your self-reported rate of DVT and whether you miss same thing. It’s not a lie. They do have two swollen legs it because you don’t look for it or you miss it because you and so that’s what the duplex indication is.

Volume 63 • Number 5 1137 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Ethnic Disparities Exist in Trauma Care Shahid Shafi, MD, MPH, Carlos Marquez de la Plata, PhD, Ramon Diaz-Arrastia, MD, PhD, Aaron Bransky, MD, Heidi Frankel, MD, Alan C. Elliott, MAS, MBA, Jennifer Parks, MPH, and Larry M. Gentilello, MD

Background: An estimated 5.3 mil- after discharge was studied in three likely to be placed in rehabilitation (odds lion people in the United States live with groups: non-Hispanic white (NHW 77%), ratio 0.85, 95% confidence interval 0.8– permanent disability related to traumatic African American (14%), and Hispanic 0.9, p < 0.0001). brain injury (TBI). Access to rehabilita- (9%). The two minority groups were com- Conclusions: Ethnic minority pa- tion after TBI is important in minimizing pared with NHW patients using logistic tients are less likely to be placed in reha- these disabilities. Ethnic disparities in ac- regression to control for differences in bilitation than NHW patients are, even cess to health care have been documented age, gender, overall injury severity (in- after accounting for insurance status, sug- in other diseases, but have not been stud- jury severity score), TBI severity (head gesting existence of systematic inequalities ied in trauma care. We hypothesized that abbreviated injury score and Glasgow in access. Such inequalities may have a access to rehabilitation after TBI is influ- Coma Scale score), associated injuries, disproportionate impact on long-term enced by race or ethnicity. and insurance status. functional outcomes of African American Methods: Retrospective analysis of Results: The three groups were sim- and Hispanic TBI patients, and suggest the National Trauma Data Bank patients ilar in injury severity score, TBI severity, the need for an in-depth analysis of this with severe blunt TBI (head abbreviated and associated injuries. After accounting disparity at a health policy level. -who sur- for differences in potential confounders, Key Words: Ethnic disparities, Reha (58,729 ؍ injury score 3–5, n vived the initial hospitalization was per- including injury severity and insurance bilitation, Trauma care, TBI. formed. Placement into rehabilitation status, minority patients were 15% less J Trauma. 2007;63:1138–1142.

here is growing recognition of the existence of ethnic or over 1 million Americans per year.17,18 After acute care of racial disparities in access to health care, quality of care their injuries, a large proportion of TBI patients require re- Tprovided, and outcomes in our health care system.1–4 For habilitation services to achieve optimal functional status.19 example, minorities have been shown to have lower access to Minorities are at disproportionate risk for TBI, as AAs have primary care providers, and are less likely to receive a referral a 35% higher incidence rate of emergency department visits for cardiac rehabilitation services than non-Hispanic whites for TBI than NHWs, and minorities account for nearly half of (NHWs) are.5 Hispanics (HIS) and African Americans (AAs) all brain injury hospitalizations.17,20,21 are more likely to report a “major” problem accessing spe- Racial or ethnic disparities, however, have not been cialty care.6 Minorities are less likely to undergo cardiac demonstrated in provision or outcome of trauma care. The catheterization, lytic therapy for acute coronary syndromes, purpose of the current study was to determine whether such coronary artery bypass grafting, and orthotopic liver and differences exist in the care of trauma patients in the United kidney transplantations, compared with NHWs.3,4,7–10 Signif- States. We specifically focused on acute rehabilitation of icant racial disparities in outcomes of certain diseases, including patients with TBI after discharge from initial hospitalization. surgical mortality rates, have also been demonstrated.7,11–13 The study hypothesis was that among TBI patients, access to Injuries are a leading cause of death and disability, and rehabilitation after discharge from the trauma centers was account for more years of potential life lost than heart disease influenced by their race or ethnicity. and stroke combined.14–16 Traumatic brain injury (TBI) is a major source of disability in modern societies, and affects PATIENTS AND METHODS

Submitted for publication September 27, 2006. This is a retrospective analysis of the National Trauma Accepted for publication July 25, 2007. Data Bank (version 4.0, 2004), the largest database of trauma Copyright © 2007 by Lippincott Williams & Wilkins inpatients in the country, which is maintained by the Amer- From the Departments of Surgery (S.S., A.B., H.F., J.P., L.M.G.), ican College of Surgeons. Patients with blunt TBI who sur- Neurology (C.M.P., R.D.-A.), and Clinical Sciences (A.C.E.), University of vived their initial hospitalization and who were NHW, AA, or Texas Southwestern Medical Center, Dallas, Texas. Presented as a poster at the 64th Annual Meeting of the American Asso- HIS were included in the study. Other minority groups were ciation for the Surgery of Trauma, September 22–24, 2005, Atlanta, Georgia. excluded from the study because of small numbers. Presence Address for reprints: Shahid Shafi, MD, MPH, 5323 Harry Hines Blvd., of TBI was determined using abbreviated injury score (AIS) Dallas, TX 75390-9158; email: [email protected]. for head and neck, and only those with head AIS 3, 4, or 5 DOI: 10.1097/TA.0b013e3181568cd4 were included. Head AIS of 1 and 2 were excluded because

1138 November 2007 Ethnic Disparities Exist in Trauma Care

Patients with incomplete information on initial GCS score, Table 1 Demographics, Injury Severity, and Insurance race, discharge disposition, and insurance status were excluded. Status The final study population consisted of 58,792 patients. African NHWs Hispanics The study population was divided into three groups: Americans NHWs (n ϭ 45,061, 77%), AAs (n ϭ 8,325, 14%), and HIS Age (yr) 38 Ϯ 24 32 Ϯ 20 27 Ϯ 18 (n ϭ 5,406, 9%). The HIS group included all persons of Gender (% male) 67 75 80 ISS 20 Ϯ 10 19 Ϯ 10 19 Ϯ 9 Hispanic origin, whether white or black. The proportion of GCS score 11.7 Ϯ 4.6 11.5 Ϯ 4.5 11.4 Ϯ 4.6 HIS in the study population was less than the national aver- Head AIS (%) age, and likely reflects the voluntary nature of trauma center AIS3 505450participation in National Trauma Data Bank. The two minor- AIS4 373438ity groups were compared with NHW patients using ␹2-tests AIS5 131212 t Insurance (%) for categorical variables, and Student’s test and analysis of Uninsured 16 27 36 variance for continuous variables. Logistic regression analy- Private 47 31 30 sis was used to determine the relationship between race and Government 28 36 22 rehabilitation placement while adjusting for differences in Workers compensation 4 2 6 potential confounding variables, such as age, gender, ISS, Others 5 4 5 head AIS, GCS score, associated injuries, and insurance status. ISS, injury severity score; GCS score, Glasgow Coma Scale The final model was a poor fit for the data (Hosmer-Lemeshow score; AIS, abbreviated injury score, NHWs, non-Hispanic whites. ␹2-statistic 760, p Ͻ 0.0001, C-statistic 0.8). Results are presented as means Ϯ SD, proportions, and odds ratios with 95% Table 2 Associated Injuries confidence intervals. Statistical Package for the Social Sciences for Windows version 11 (SPSS Inc. Chicago, IL) and Statistical NHWs African Americans Hispanics Analysis Software (SAS, Cary, NC) were used for statistical Abdomen (%) 13 11 13 analyses. To account for multiple comparisons, p Ͻ 0.01 was Chest (%) 26 22 24 Neck (%) 1 1 1 considered significant. Face (%) 43 46 45 Spine (%) 15 12 12 RESULTS Upper extremity (%) 29 22 27 Lower extremity (%) 27 23 24 The two minority groups were slightly younger, more likely to be men, and more likely to be uninsured than NHWs (Table 1). Overall injury severity (ISS), severity of head they represent minor extracranial injuries or concussions, and injuries (head AIS and GCS score), and distribution of asso- head injuries with AIS 6 were excluded as they are uniformly ciated injuries were similar in all three groups (Tables 1 and fatal. Patient data for analysis included age, race, overall 2). Compared with NHW, the two minority groups were less injury severity (injury severity score [ISS]), anatomic sever- likely to be placed in rehabilitation after discharge from ity of head injuries (head AIS), physiologic severity of head initial hospitalization (Table 3). Multivariate regression anal- injuries (Glasgow Coma Scale [GCS] score), presence or ysis showed that race was an independent predictor of reha- absence of associated injuries, and insurance status. The pri- bilitation placement for minority patients with the odds of mary outcome of interest was placement into a rehabilitation placement in rehabilitation 15% lower than NHWs, even after facility after discharge from initial hospitalization for trauma. taking severity of head injury and insurance status into ac-

Table 3 Rehabilitation Placement by Insurance Status and TBI Severity

NHWs African Americans p* Hispanics p* Rehabilitation placement—all patients (%) 23 20 Ͻ0.001 16 Ͻ0.001 Insurance status (%) Uninsured 17 13 Ͻ0.001 12 Ͻ0.001 Private insurance 25 24 0.138/NS 22 0.004 Government 24 21 0.004 17 Ͻ0.001 Workers compensation 30 27 0.375/NS 23 0.018/NS Other insurance 23 21 0.365/NS 11 Ͻ0.001 Head AIS AIS 3 11 9 0.08/NS 7 0.001 AIS 4 18 14 0.002 12 Ͻ0.001 AIS 5 41 35 0.137/NS 32 0.019/NS * p values compared with NHWs. NHWs, non-Hispanic whites; AIS, abbreviated injury score.

Volume 63 • Number 5 1139 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

insurance, the uninsured, and those with AIS 4 head injuries Table 4 Independent Predictors of Rehabilitation (Table 3). However, these differences did not persist in mul- Placement tivariate analysis suggesting that race was not an independent Predictors Odds Ratios 95% CI p predictor of rehabilitation placement among AAs after con- Race—minority* 0.850 0.800–0.900 Ͻ0.001 trolling for associated injuries, overall injury severity, age, Age (yr) 1.015 1.013–1.016 Ͻ0.001 and gender (Table 5). ISS 1.040 1.036–1.044 Ͻ0.001 GCS score 0.866 0.862–0.871 Ͻ0.001 Facial injuries 0.928 0.884–0.976 0.003 DISCUSSION Ͻ Spine injuries 1.655 1.550–1.767 0.001 This is the first study to suggest presence of racial dis- Upper extremity injuries 1.107 1.048–1.169 Ͻ0.001 Lower extremity injuries 1.430 1.351–1.513 Ͻ0.001 parities in trauma care at a national level. The primary finding Insurance of this study is that TBI patients from minority groups are less Private† 1.603 1.492–1.722 Ͻ0.001 likely to be placed in acute rehabilitation after discharge from Government† 1.459 1.350–1.578 Ͻ0.001 trauma centers, even after accounting for differences in inju- † Ͻ Workers compensation 2.307 2.034–2.616 0.001 ries, their severity, and insurance status. The study also dem- Others† 1.361 1.210–1.531 Ͻ0.001 onstrates that having health insurance of any type is an Nonsignificant variables include gender, abdominal injuries, and important, independent predictor of rehabilitation placement. thoracic injuries. * Compared with non-Hispanic whites. These findings suggest that minorities, who traditionally are † Compared with uninsured patients. less likely to be insured as shown in this study, bear a dispro- ISS, injury severity score; GCS score, Glasgow Coma Scale portionate financial and social burden of TBI in our society. score; CI, confidence intervals. Racial and ethnic disparities in health care have been well documented, but have not been previously shown in the count (Table 4, Fig. 1). Other independent predictors of care provided to trauma patients. We chose to look at reha- rehabilitation placement are listed in Table 4. Access to any bilitation placement as the outcome of interest as TBI is the type of insurance significantly improved the odds of rehabil- most common cause of disability in trauma patients, and itation placement. because access to rehabilitation is critical in achieving opti- The uninsured minority patients were less likely to be mal functional outcomes. Differential access to rehabilitation placed in rehabilitation compared with NHWs (Table 3). placement after acute care of injuries is likely multifactorial. Among HIS, lower rate of rehabilitation placement was Patients may not get placed in a rehabilitation center if their present even in the insured (except those with workers com- rehabilitation needs are not correctly identified before discharge pensation), and across most categories of head injuries, and from the trauma centers, if the cost is prohibitive because of persisted in multivariate analysis (Tables 3 and 5). Among lack of insurance or under-insurance, if geographic location AAs, there seemed to be differences in rehabilitation place- of rehabilitation centers is too far for the patients and their ment compared with NHWs in patients with government families, or if any special needs of the patient cannot be met

Minority status

Age

ISS

GCS

Spine injuries

Facial injuries

Upper Extremity

Lower Extremity Insurance - Private Insurance - Government Insurance - WC Insurance - Others

0.5 0.6 0.8 1 1.3 1.6 2 2.5 Adjusted Odds Ratio of Placement in Rehabilitation (95% C.I.) Fig. 1. Independent predictors of placement in rehabilitation.

1140 November 2007 Ethnic Disparities Exist in Trauma Care

Table 5 Odds of Rehabilitation Placement for Ethnic Minorities Compared With Non-Hispanic Whites

African Americans p* Hispanics p* Unadjusted 0.81 (0.77–0.86) 0.001 0.65 (0.60–0.70) Ͻ0.001 Adjusted for head AIS and GCS score 0.75 (0.71–0.80) 0.001 0.58 (0.53–0.63) Ͻ0.001 Adjusted for head AIS, GCS score, and insurance status 0.75 (0.65–0.86) 0.001 0.63 (0.54–0.74) Ͻ0.001 Adjusted for head AIS, GCS score, insurance status, age, 0.94 (0.88–1.01) 0.1/NS 0.73 (0.67–0.80) Ͻ0.001 ISS, gender, associated injuries† Values given are odds ratios and 95% confidence intervals. * p values compared with the NHW patient group. † Presence or absence of associated injuries to chest, abdomen, face, spine, and upper and lower extremities. AIS, abbreviated injury score; GCS score, Glasgow Coma Scale score; ISS, injury severity score; NS, not significant. by the rehabilitation centers available, such as multilingual patterns than NHW during the first 4 years after injury.32,33 therapists. Our data suggest that ethnic minorities may be at These findings underscore the importance of changes needed a systematic disadvantage in this entire process. However, it in our health care system to improve access for minorities. is unclear whether this is because of language and cultural In conclusion, this study demonstrates that ethnic minor- barriers, economic barriers, geographic locations, or true dis- ity patients are less likely to be placed in rehabilitation after crimination against minorities. It may simply be a reflection sustaining TBI compared with NHWs, even after accounting of poverty, but we do not have income data to support it. for injury severity and insurance status, suggesting the exis- Language barriers are often recognized as a significant tence of systematic multifactorial inequities in access to this challenge to effective health care delivery for non–English- specialized care. Such inequities may have a disproportionate speaking minorities, as patients may not adequately under- impact on long-term functional outcomes of AA and HIS TBI stand their diagnosis, treatment, and plan for follow-up patients, and suggest the need for an in-depth analysis of this care.22 Patients who speak Spanish as their predominant or disparity at a health policy level. Prospective studies are only language may perceive language as an insurmountable needed to determine reasons for disparities, such as language barrier for receiving effective treatment, and report that in- barriers, availability of rehabilitation centers in poor areas, ability to communicate with physicians in their native lan- inadequate reimbursements from third-party payors, etc. so guage detracts from the patient-provider relationship.23–28 that appropriate remedies may be developed. The changing Additionally, certain rehabilitation centers may recognize demographic of this country dictates that interventions to their limitation in communicating with these individuals (i.e., address racial disparities be devised and implemented as soon do not have a Spanish-speaking therapist or physician) and as possible to improve health care for all Americans. not offer rehabilitation services to this patient population for this practical reason. REFERENCES Ethnic minorities in this study were disproportionately un- 1. Healthy People 2010. Washington, DC: U.S. Department of Health insured compared with NHW, thereby creating an additional risk and Human Services; 2000. for not receiving needed rehabilitation care. We also found that 2. National Healthcare Disparities Report. Washington, DC: U.S. having any type of health insurance significantly improved the Department of Health and Human Services; 2005. 3. Bertoni AG, Goonan KL, Bonds DE, et al. Racial and ethnic disparities chances of rehabilitation placement. These findings are consis- in cardiac catheterization for acute myocardial infarction in the United tent with other reports that individuals who are uninsured have States, 1995–2001. J Natl Med Assoc. 2005;97:317–323. limited access to health care in general.29,30 One reason the 4. Barnhart JM, Fang J, Alderman MH. Differential use of coronary uninsured are less likely to be placed in rehabilitation is that they revascularization and hospital mortality following acute myocardial must compete for a limited number of charity (free) beds in infarction. Arch Intern Med. 2003;163:461–466. 5. Mochari H, Lee JR, Kligfield P, et al. Ethnic differences in barriers rehabilitation centers, and may ultimately not receive services and referral to cardiac rehabilitation among women hospitalized with because of an inability to pay. It is also possible that patients coronary heart disease. Prev Cardiol. 2006;9:8–13. without medical insurance and burdened by medical bills ac- 6. Collins K, Hall A, Euhaus C. U.S. Minority Health: A Chartbook. crued during acute hospitalization are inclined to refuse subse- New York: Commonwealth Fund; 1999. quent rehabilitation to avoid further financial debt. 7. Barnato AE, Lucas FL, Staiger D, et al. Hospital-level racial disparities in acute myocardial infarction treatment and outcomes. Whatever the reason for differential rehabilitation place- Med Care. 2005;43:308–319. ment, it places a disproportionate burden on ethnic minorities, 8. Reid AE, Resnick M, Chang Y, et al. Disparity in use of orthotopic and may explain disparities in post-TBI social and vocational liver transplantation among blacks and whites. Liver Transplant. outcomes. Hart et al. reported that AAs with moderate to 2004;10:834–841. severe TBI lost more income than NHWs 1-year postinjury.31 9. Venkat A, Hoekstra J, Lindsell C, et al. The impact of race on the acute management of chest pain. Acad Emerg Med. 2003;10:1199–1208. Employment outcomes are also disparate across racial lines, 10. Werner RM, Asch DA, Polsky D. Racial profiling: the unintended as fewer minorities are employed 1-year postinjury, and mi- consequences of coronary artery bypass graft report cards. norities are twice as likely to show unstable employment Circulation. 2005;111:1257–1263.

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11. Flattery MP, Baker KM. Evidence for racial disparity in cardiac disparities in health and health care. Public Health Rep. 2003; transplantation survival rates. J Cult Divers. 2004;11:25–30. 118:293–302. 12. Lucas FL, Stukel TA, Morris AM, Siewers AE, Birkmeyer JD. Race 23. Baker DW, Hayes R, Fortier JP. Interpreter use and satisfaction with and surgical mortality in the United States. Ann Surg. 2006;243:281– interpersonal aspects of care for Spanish-speaking patients. Med 286. Care. 1998;36:1461–1470. 13. Underwood W 3rd, Dunn RL, Williams C, et al. Gender and 24. Baker DW, Parker RM, Williams MV, et al. Use and effectiveness of geographic influence on the racial disparity in bladder cancer interpreters in an emergency department. JAMA. 1996;275:783–788. mortality in the US. J Am Coll Surg. 2006;202:284–290. 25. Carrasquillo O, Orav EJ, Brennan TA, et al. Impact of language 14. Baker CC, Oppenheimer L, Stephens B, et al. Epidemiology of barriers on patient satisfaction in an emergency department. J Gen trauma deaths. Am J Surg. 1980;140:144–150. Intern Med. 1999;14:82–87. 15. National Center for Injury Prevention and Control. CDC Injury 26. Erzinger S. Communication between Spanish-speaking patients and Research Agenda. Atlanta, GA: Centers for Diseases Control and their doctors in medical encounters. Cult Med Psychiatry. 1991; Prevention; 2002. 15:91–110. 16. Trunkey DD. Trauma. Accidental and intentional injuries account for 27. Perez-Stable EJ, Napoles-Springer A, Miramontes JM. The effects more years of life lost in the U.S. than cancer and heart disease. of ethnicity and language on medical outcomes of patients with Among the prescribed remedies are improved preventive efforts, hypertension or diabetes. Med Care. 1997;35:1212–1219. speedier surgery and further research. Sci Am. 1983;249:28–35. 28. Seijo R, Gomez H, Freidenberg J. Language as a communication 17. Jager TE, Weiss HB, Coben JH, et al. Traumatic brain injuries barrier in medical care for Hispanic patients. Hispanic J Behav Sci. evaluated in U.S. emergency departments, 1992–1994. Acad Emerg 1991;13:363–376. Med. 2000;7:134–140. 29. Franks P, Fiscella K. Effect of patient socioeconomic status on 18. Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma physician profiles for prevention, disease management, and outcome: an overview of epidemiology, clinical presentations, and diagnostic testing costs. Med Care. 2002;40:717–724. therapeutic considerations. J Trauma. 2006;60(Suppl):S3–S11. 30. Weinick RM, Zuvekas SH, Cohen JW. Racial and ethnic differences 19. Greenwood RJ, Strens LH, Watkin J, et al. A study of acute in access to and use of health care services, 1977 to 1996. Med Care rehabilitation after head injury. Br J Neurosurg. 2004;18:462–466. Res Rev. 2000;57(Suppl 1):36–54. 20. Frankowski RAJ, Whitman S. The Descriptive Epidemiology of 31. Hart T, Whyte J, Polansky M, et al. Community outcomes following Head Trauma in the United States. Bethesda, MD: NINCDS; traumatic brain injury: impact of race and preinjury status. J Head 1985. Trauma Rehabil. 2005;20:158–172. 21. Kraus JF, Fife D, Ramstein K, et al. The relationship of family 32. Kreutzer JS, Marwitz JH, Walker W, et al. Moderating factors in income to the incidence, external causes, and outcomes of serious return to work and job stability after traumatic brain injury. J Head brain injury, San Diego County, California. Am J Public Health. Trauma Rehabil. 2003;18:128–138. 1986;76:1345–1347. 33. Sherer M, Nick TG, Sander AM, et al. Race and productivity 22. Betancourt JR, Green AR, Carrillo JE, et al. Defining cultural outcome after traumatic brain injury: influence of confounding competence: a practical framework for addressing racial/ethnic factors. J Head Trauma Rehabil. 2003;18:408–424.

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Development of a Hospital-Based Trauma Registry in Haiti: An Approach for Improving Injury Surveillance in Developing and Resource-Poor Settings Caleb R. Schultz, MD, Henri R. Ford, MD, FACS, Laura D. Cassidy, PhD, Barbara L. Shultz, RN, Christian Blanc, MD, Leslie W. King-Schultz, MPH, and Henry B. Perry, MD, PhD, MPH, FACS

Background: Trauma-related mor- Results: Retrospective medical record CTR and PTR documenting specific mechanism of injury in 94.6% and 100% ؍ and 2002 (n (43 ؍ bidity and mortality are a growing burden review from 1999 (n in the developing world. However, usable 43) revealed limitations in available data of patients, respectively. The PTR model injury data in resource-poor and developing for trauma surveillance. Specific mecha- was chosen for implementation at the settings is lacking. Trauma registries can nism of injury was documented in 39.3% hospital. improve injury surveillance to enhance and 57.1% of 1999 and 2002 groups, re- Conclusions: Trauma registries in trauma care, outcomes, and prevention. This spectively. Injury date and arrival vital developing settings are plausible tools for article provides, by example from Haiti, an signs were infrequently recorded. Two injury surveillance. Successful trauma reg- approach to developing a hospital-based injury surveillance models were designed istries will be resource- and setting-specific trauma registry in a resource-poor setting. and pilot tested: provider-based (PTR) in design and can potentially be the means and coordinator-based by which trauma care and outcomes are (19 ؍ Methods: An assessment of trauma (pilot n -trauma registries. improved, prevention programs are devel (37 ؍ documentation was performed retrospec- (CTR) (pilot n tively with subsequent development and Analysis of the pilot testing resulted in oped, and capacity-building goals realized. pilot testing of two injury surveillance sys- revisions to operations and the trauma Key Words: Trauma, Injury surveil- tems. The system most promising for registry forms. Both registry models lance, Developing country, Less-developed meeting the needs and capabilities of the showed improved data collection com- country, Trauma registry, Caribbean. institution was implemented. pared with the retrospective study with J Trauma. 2007;63:1143–1154.

he global burden of trauma is alarmingly high with related injuries alone are the second most common cause of injuries accounting for 10% of all deaths and over 15% death in older children and adults.2 Additionally, injury ex- Tof disability-adjusted life years (DALYs).1,2 Road-traffic perienced by working age people in developing countries can injuries rank tenth as a specific cause of global DALYs and have devastating impacts on family and community econo- 7 of the top 30 causes of DALYs are injury related.1 Traffic- mies because of lost wages and productivity.3–9 Future estimates suggest an even greater impact of injury Submitted for publication October 2, 2005. on health systems and economies. The World Health Orga- Accepted for publication July 25, 2007. nization (WHO) and World Bank estimate that by 2020 20% Copyright © 2007 by Lippincott Williams & Wilkins of all DALYs losses will be a result of injuries.1 Although From the Department of Neurosurgery (C.R.S.), Mayo Clinic, Rochester, MN; Department of Surgery (H.R.F.), Children’s Hospital Los Angeles, Keck injuries now account for one in seven healthy life years lost, School of Medicine, University of Southern California, Los Angeles, CA; by 2020 it is estimated that this will increase to one in five, Children’s Hospital of Wisconsin (L.D.C.), Department of Surgery, Division with developing countries being the most impacted.3 Also by of Pediatric Surgery, Medical College of Wisconsin, Milwaukee, WI; Mon- 2020, the burden of injuries globally will equal that of com- roe Carell Jr. Children’s Hospital (B.L.S.), Vanderbilt University, Nashville, TN; formerly Department of Surgery (C.B.), Hopital Albert Schweitzer, municable diseases, and in China, Latin America, and the 7 Deschapelles, Haiti; Mayo Medical School (L.W.K.-S.), Rochester, MN; and Caribbean it will exceed communicable diseases. Future Generations (H.B.P.), Franklin, WV and formerly Hopital Albert In developing countries, injury-related mortality contin- Schweitzer (H.B.P.), Deschapelles, Haiti. ues to increase with little attention devoted to generating Supported in part through the MacArthur International Grant on Global 1,10–12 Change, Sustainability & Justice granted by the Interdisciplinary Center for solutions. Moreover, external funders have failed to the Study of Global Change at the University of Minnesota. recognize the impact of injury on the health and economy of Presented at the World Conference on Injury Prevention and Safety nations when supporting health sector programs or research Promotion, Vienna, Austria. June 2004; and the International Health Medical and development initiatives with injury funding dispropor- Education Consortium (IHMEC) Annual Meeting, Antigua, Guatemala. Feb- tionately low.7,13 ruary 2004. Address for reprints: Caleb R. Schultz, MD, Department of Neurosur- Injury surveillance is one key element in developing gery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; email: geocultural- and resource-specific interventions to enhance [email protected] prevention and treatment of injuries.14,15 In the absence of DOI: 10.1097/TA.0b013e31815688e3 accurate routine medical record data or well-designed injury

Volume 63 • Number 5 1143 The Journal of TRAUMA௡ Injury, Infection, and Critical Care surveillance systems, it is a challenge to understand the prob- testing the injury surveillance models; and (4) initiating im- lems and risk factors for types of trauma, design appropriate plementation of the most promising option meeting the needs interventions to prevent and treat trauma, monitor the effec- and capabilities of the institution. tiveness of interventions, and provide information to policy 10,12,16–28 makers. Needs Assessment Injury surveillance can occur through retrospective or 29 A retrospective medical record review was performed to prospective data collection or through a trauma registry. assess the quality of available data collected on trauma patients. In purely retrospective or prospective studies for trauma, Because most trauma patients were admitted to the surgery hypothesis-specific data are collected for a discrete period. ward, the surgery ward logbook was reviewed for patients dis- As new questions arise data must be collected again. charged with a trauma-related diagnosis during the month of Trauma registry methodology offers a means to collect August in 1999 and 2002, time periods chosen to investigate continuous, standardized data that may not exist through- whether documentation or treatment differences were present as out much of the developing world with the resulting in- a result of surgical leadership changes that occurred over that formation giving the possibility to enhance quality of care, time. The data reviewed included demographics (date of birth, ensure proper resource allocation, and offer evidence- gender, locality of residence, hospital district status); trauma date based capacity building—outcomes especially important 12,27 and time; HAS arrival date; diagnosis; Glasgow Coma Scale in resource-poor settings such as in developing countries. score for head injuries; categorized type of injury (blunt, burn, Such evidence-based capacity building may help bring about penetrating); mechanism of injury; intent of trauma; pre-existing funds for hiring new personnel, implementing community- conditions; whether arrival vital signs were obtained (to include based injury prevention initiatives, new or upgraded operat- blood pressure and minute heart and respiratory rate); whether ing facilities, radiographic machines, or surgical instruments X-ray film, laboratory tests, or ultrasound were ordered; proce- and supplies. Whereas trauma registries in developed coun- dures performed; date of first surgery; length of stay; and dis- tries include hundreds of data points and require several charge status (alive or dead). These variables were identified as full-time staff, registries can be designed to fit the needs and 27 potentially important for inclusion in a trauma registry. In addi- limitations of resource-poor settings. tion, data from the hospital computer database for trauma pa- At Ho´pital Albert Schweitzer in Haiti, concerns about a tients admitted from 1997 to 2003 were analyzed and results perceived increase in trauma incidence, thought to be re- appear in a separate article (Schultz CR, King-Schultz LW, sulting primarily from increases in motor vehicle crashes, Perry HB. Assessing trauma burden in a developing country the burden of trauma care on the hospital, and a desire to hospital: an example from Haiti. Unpublished 2005). improve trauma care led to an initiative to develop an injury surveillance system. The goal of this article is to provide a method for developing a trauma registry that is Development of Trauma Registry Models accessible and generalizable to other developing and re- A trauma registry task force, consisting of the surgery chief, source-poor settings. This article offers our experience in medical director, chief nurse, director general, and the authors of designing a trauma registry in Haiti for potential use in this article was formed to discuss and make decisions by con- other developing settings. sensus on important aspects of developing an injury surveillance system in the form of a trauma registry. Before proceeding with development of potential registry models for use at HAS, several METHODS decisions were addressed by the task force, including (1) defin- This study was conducted at Ho´pital Albert ing the goals of the trauma registry, (2) defining a trauma patient Schweitzer (HAS) in Deschapelles, Haiti. HAS is a 190 for the purposes of the registry, (3) defining the variables to be inpatient and observation and overnight bed facility, serv- collected in the trauma registry, and (4) determining the data ing a rural-living population of 285,000 individuals living collection format. in the Artibonite valley and surrounding mountains in With these preliminary decisions made, the task force Central Haiti. The hospital has surgery, medicine, pediat- addressed several key model-specific aspects of the registry: ric, adult overnight, pediatric overnight, obstetrics, and (1) defining the activation and flow of the trauma patient and nutrition/Kwashiokor wards and an extended-stay, tuber- corresponding registry data collection form through the med- culosis treatment center. Oxygen administration and plain ical system, (2) identifying the person responsible for com- film radiography are available but ventilator assistance out- pleting each portion of the trauma registry data collection side of the operating room and computed tomography scan- form, (3) developing quality assurance and improvement ning are not. The study consisted of four parts: (1) identifying methods, and (4) estimating time and resource demands. the areas in need of improvement with respect to trauma documentation and surveillance; (2) investigating strategies Pilot Testing the Models to alleviate these problems, including the development of a The two trauma registry models developed by the task formal injury surveillance system; (3) developing and pilot force underwent pilot testing to assess functionality, effi-

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Fig. 1. HAS provider-based trauma registry form. ciency, and barriers to implementation. The provider-based registry form and offered feedback on form design and data trauma registry (PTR) model was piloted with surgeons dur- points with daily changes made to the form to reflect physi- ing surgery rounds during a 1-week period in August 2003. cian input. The finalized PTR form is shown in Figure 1. The surgeons completed physician-specific data points on the Nonphysician data points (delineated with a gray back-

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signs, and at least one initial vital sign were infrequently recorded in both years (Table 1).

Development of Trauma Registry Models The task force identified the following goals for an HAS trauma registry: (1) improve performance in caring for trauma patients, (2) provide data for outcomes research, (3) enhance utilization of resources and cost control, (4) aid in designing community health prevention programs, (5) formalize and standardize trauma patient documentation, and (6) offer opportunity for evidenced- based development or capacity building. A trauma patient was defined by a number of variables delineated in Table 2 based on International Classification of Diseases, 9th Revision (ICD-9) injury E-codes.30 Exclusion criteria were determined with the perception that such injuries were not contributing to the trauma burden at HAS and were not currently considered traumatic injuries. The task force designed a new trauma registry-specific form after defining the appropriate variables. The form went through many initial revisions to facilitate accurate and rapid data collection by replacing narratives with check boxes and organizing the flow of data entry from top to bottom to reflect the chronologic flow of an admission history, physical examination, and subsequent care. Based on a careful study of hospital operations and the flow of inpatients through the hospital from arrival to discharge, two trauma registry designs were formulated. The models differ in the personnel primarily responsible for form completion: providers—physicians and nurses— Fig. 1. Continued. in the PTR and a nonclinician registry coordinator in the CTR. ground on the form) were not captured in the PTR pilot. The coordinator-based trauma registry (CTR) model was Provider-Based Trauma Registry pilot tested for 2 weeks in August 2003 by one of the The PTR model is based on input from multiple depart- investigators. The investigator visited surgery, pediatric, ments, with physicians, nurses, ward secretaries, medical records pediatric overnight, and adult overnight wards and fol- personnel, and Monitoring and Evaluation Unit personnel in- lowed trauma patients through until discharge. The CTR volved in the daily functioning of the registry. pilot form (Fig. 2) shows the data collected during the pilot test. Functioning and Flow of the PTR Several patient scenarios were developed to determine RESULTS the flow of a trauma registry data collection form (Fig. 1) Needs Assessment through the hospital (Fig. 3). To avoid requiring front desk Of the 86 patients with diagnosed trauma in August 1999 staff to engage in trauma case identification, the trauma (n ϭ 43) and August 2002 (n ϭ 43), 28 and 21 medical records registry form for the PTR is inserted into every medical were obtained for review, respectively. The remaining medical record. Nursing staff and physicians are responsible for records could not be found in active or inactive record storage completing specific items on the PTR form as designated locations. The types of trauma (burn, blunt, penetrating) were in Figure 3. Further documentation not specified in Figure either specifically recorded, as in burns, or ascertained based on 1 and daily progress would need documentation directly diagnosis and medical record notes. Specific mechanism of into the medical record. injury was known in 39.3% and 57.1% of the August 1999 and The trauma registry form was designed with the fol- 2002 groups, respectively. However, nonspecific mechanism of lowing key sections. Items 1 through 5 provide demo- injuries, such as unspecified fall or traffic-related injuries with- graphic information including utilization data for patients out further description, were documented in 35.7% in August living outside the hospital district. Admission date and 1999 and 19.0% in August 2002. Injury date, full arrival vital time and discharge date and status (items 6, 7, 10, and 11)

1146 November 2007 Trauma Registry Development in Haiti

Fig. 2. HAS coordinator-based trauma registry pilot form.

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Table 1 Comparison of Trauma Documentation for Retrospective Chart Review, CTR, and PTR Pilot Studies at HAS

August August Documentation CTR Pilot 2003 PTR Pilot 2003 1999 2002 Number of patients with diagnosed 43 43 37 19 trauma Number of available medical records 28 21 37 19 Type of trauma documented 27 (96.3) 20 (95.2) 36 (97.3) 19 (100) Specific mechanism of injury 11 (39.3) 12 (57.1) 35 (94.6) 19 (100) documented Injury date documented 5 (17.9) 6 (28.6) 35 (94.6) 19 (100) Arrival vital signs documented 1 (3.6) 4 (19.0) 7 (18.9) NA** At least one arrival vital sign documented 3 (11.1) 11 (52.9) 28 (75.7) NA** Numbers in parentheses are percentages. ** Data were not collected in the PTR pilot because they were recorded by nursing staff.

Table 2 Definition of Trauma Patient for Trauma Registry at HAS

Inclusion Criteria Exclusion Criteria (Ն1 of the Following) 1. ICD-9 diagnosis of E800–999 1. Surgical misadventures (E870–876) 2. Above caused by an acute traumatic event 2. Surgical and medical procedures as the cause of abnormal 3. Ն1 of the following: reaction of patient or later complication, without mention of a. Admission to overnight, surgery, misadventure at the time of the procedure (E878–E879) medicine, or pediatric wards 3. Inhalation and ingestion injuries causing obstruction of respiratory b. Dead on arrival patients tract or suffocation (E911–E912) c. Pregnant patients admitted to the 4. Accidental mechanical suffocation (E913) obstetrics ward for monitoring after a 5. Overexertion and strenuous movements (E927) traumatic event and then discharged 6. Traumatic injury occurring Ͼ14 days prior to arrival at HAS (E929, home E959, E969, E977, E989) 7. Drugs, medicinal, and biologic substances causing adverse effects in therapeutic use (E930–E949) 8. Accidental overdose of drug and wrong drug given or taken in error (E850–E858) 9. Accidents in the technique of administration of drug or biologic substance, such as accidental puncture during injection, or contamination of drug (E870–E876) 10. Cellulitis related to intravenous drug abuse, insect bites, or blisters 11. Patients admitted with a primary medical diagnosis in which the medical diagnosis caused a traumatic event provide information on length of stay (LOS) and outcome. is used as a reference page. The data items that physicians Admitting ward information, item 8, provides information are not responsible for completing (items 1–9 recorded by on human resource needs allocation. Severity of trauma is nurses and items 10–11 collected by ward secretaries) determined through baseline vital signs, mechanism of were delineated by a gray background on the PTR form. trauma, time since trauma, and number and degree of injuries (items 9, and 12–14). Mechanism of injury data PTR Quality Assurance, Maintenance, and Evaluation (item 12) is necessary for prevention. The time elapsed The Monitoring and Evaluation Unit (MEU), a statis- since the trauma and arrival at HAS (item 13) provides tical evaluation office at HAS, maintains the registry. This insight on treatment methods for injuries and ability to consists primarily of quality improvement and assurance access timely care. Description of injuries (item 14) serves measures and training of data collection personnel. Time to document examination of injuries and when compared requirements to complete these tasks may be 2 to 3 hours with diagnostic tools and treatments (items 15–18) provide per 5-day workweek with more time initially for training. information on utilization of resources and treatments for These tasks could be assigned to an existing staff member certain injuries. Injury types and further descriptive items with part-time duties as the registry coordinator. reflect the most prevalent traumatic injuries observed in The registry form serves as a quality improvement tool the trauma patients. A second page with a table for the for documentation of trauma patient information. The reg- Glasgow Coma Scale score and a diagram for burn patients istry coordinator regularly monitors the degree of comple-

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Fig. 3. Flow chart of trauma registry form in provider-based trauma registry for four patient senarios. tion of the registry form and follows up with nurses and patient directly, or from the attending physician; (2) daily physicians who are not documenting properly. Quality follow-up with admitted trauma patients until discharge; assurance checks occur on an unscheduled and unan- and (3) entering data into the trauma registry database. nounced basis with the ward secretary and medical records personnel. Discrepancies between the ward logbook and the trauma registry are an indication of protocol failure on Functioning and Flow of the CTR the part of the ward secretary, responsible for the logbook, Each morning the registry coordinator identifies new or medical records personnel, responsible for trauma reg- trauma patients admitted in the previous 24 hours by visiting istry data entry. Hospital administration or the trauma each ward where patients are typically admitted and begins registry task force determines the frequency of quality completing the registry form shown in its revised, finalized assurance checks, enforcement of documentation guide- version in Figure 4. While at each ward, the registry coordinator lines, and penalties for failure to correctly document. rounds on all trauma patients already in the registry to check In this model, an offsite biostatistician, or, if available, an change in status, including new procedures or treatments, dis- MEU biostatistician analyzes the data and generates reports. charge orders, and discharge functional status, including the ability to walk and feed independently, if applicable. Coordinator-Based Trauma Registry After the patient is discharged, the registry coordinator This registry design utilizes a trained trauma data files the original registry form into the patient medical record collector or coordinator who is not involved in patient and retains a copy for data entry. The copy is filed in a care. The trauma registry coordinator’s responsibilities designated trauma registry file. The duties of the registry include (1) obtaining data on newly admitted trauma pa- coordinator require 10 to 12 hours/week and daily, including tients from documentation in the medical record, from the weekend, coverage.

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Fig. 4. Final coordinator-based registry form.

CTR Quality Assurance, Maintenance, and Evaluation in the patient’s medical record because the CTR relies on It is essential that nurses and physicians involved in such documentation to gather registry information. Over- the care of trauma patients be aware of the registry form time the registry form provides a method for improving and data collection items to ensure proper documentation medical record documentation as the registry coordinator

1150 November 2007 Trauma Registry Development in Haiti

Fig. 4. Continued. provides feedback to nurses and physicians for missing for physicians completing the form to offer feedback on documentation. the ease of completion, layout, and appropriateness of data The direct supervisor of the registry coordinator is re- items. The data items that physicians are not responsible sponsible for quality control and evaluation of the registry for completing were delineated by a gray background. process. Quality control evaluations, conducted similarly to These nonphysician data were not captured in the PTR the PTR, highlight errors made in recording for the trauma pilot, a physician-focused study. The finalized PTR form registry, for which the registry coordinator is responsible, and appears in Figure 1. Overall the physicians thought that the the ward logbook, for which the ward secretary is responsi- final form was easy to complete, requiring only 1 to 2 ble. Medical record and registry form documentation are minutes per patient. Additional documentation, however, compared, to ensure proper transfer of data items. Statistical was needed in the medical records to reflect the complete analysis and report generation for CTR is identical to that physical examination beyond the injury area. Use of the described previously for PTR. registry form increased documentation time overall, but this was acceptable to the physicians given the perceived Pilot-Test Results value of the registry. Pilot-Testing Registry Form for PTR Surgeons participated in a 19-patient pilot test of the Pilot Testing of the CTR registry form developed for the PTR. All the data items on the A total of 37 patients were enrolled and monitored in the form that are physician-specific were completed daily during 2-week pilot of the CTR model. Various methods were used rounds on the surgery ward to capture the largest percentage to identify admitted trauma patients including reviewing ad- of trauma patients (Table 1). This provided the opportunity mission reports and inquiring with charge nurses on various

Volume 63 • Number 5 1151 The Journal of TRAUMA௡ Injury, Infection, and Critical Care wards. In the case of two patients admitted for trauma, inad- recorded by nursing staff) were not collected in the PTR pilot equate data were obtained because of late day admission and as it was directed at physicians, the primary data recorder for next morning discharge. For three patients, functional status the PTR model. It was theorized that, similar to the immedi- at discharge could not be accessed before the patients were ate improvement in physician documentation seen in the PTR discharged. pilot, a rapid improvement in allied health documentation Figure 2 shows the CTR pilot form. Deficits in docu- would also occur. Furthermore, with physicians accessing mentation in the medical record were noted during the pilot. patients and completing the PTR form in real-time they can Specifically, labs and radiographic results were rarely docu- quickly point out any documentation deficits to allied health mented. Radiographic results were obtained by re-reading the workers. The task force also viewed the PTR as more con- films, based on procedures that followed, or by inquiring with ducive to expansion to outpatient trauma. the physician. Procedures and treatments were not always recorded in the medical record, but could be ascertained by DISCUSSION direct observation of the patient. A full set of baseline vital Because of concern about the burden of trauma on hos- signs (blood pressure, pulse and minute respirations recorded pitals in the developing world and the need for improved in the first 12 hours after admission) was recorded for 18.9% trauma care and prevention, this study aimed to provide a patients (Table 1). At least one vital sign was documented in method for developing a hospital-based trauma registry that is 75.7% of patients. Mechanism of injury was infrequently accessible and generalizable to other resource-poor settings. recorded by a physician and so was gathered through patient The effort to improve injury surveillance and trauma care at interviews. HAS began with a needs assessment via retrospective review of Revisions were made to the piloted trauma registry form trauma documentation, which showed unavailability of medical (Fig. 2) with the final CTR form (Fig. 4) being similar in design records and nonstandardized data that infrequently contained and data sets to the PTR form (Fig. 1). The following items variables necessary to accurately assess trauma incidence, type, included in the CTR form capture more epidemiologic infor- and severity. Based on the needs assessment results, the trauma mation for community health policy interventions and more registry task force first outlined the goals for a trauma registry specific outcomes data: date and categorized time (morning, that were aimed at obtaining data for evidence-based improve- afternoon, night) of trauma (items 10–11), geographic location ments in patient care and outcomes, enhanced utilization of of trauma (12a–c), role of alcohol in the injury (14), date and resources, prevention program development, and capacity- time of first procedure or treatment (20–21), and HAS Func- building that would bring about funds for new personnel, tional Status at discharge (24), a simplified version of the initiatives, supplies, and diagnostic machines. The standard- Functional Independence Measure (FIM) score, that evaluates ization of trauma documentation was the final goal of the self-feeding and locomotion (completely independent versus in- registry and directly addressed the deficits in current and past dependent with device versus completely dependent). documentation. Next, the task force developed and piloted two registry models. The results of the pilot testing for both Initiating Trauma Registry Model trauma registry models showed improved injury data collec- The task force compared the data between the retrospec- tion capabilities compared with the retrospective needs as- tive medical record review and the pilot studies of both sessment in nearly all categories. trauma registry models. The decision to move forward with a The PTR model was chosen for implementation at HAS trauma registry was based on the perceived potential and because of a number of factors. Passive injury surveillance, as actual (Table 1) improvement in data collection. Comparing in the PTR model, tends to be more reliable and may require the two trauma registry models, the task force decided to less expenditure of resources compared with active surveil- begin steps to initiate the PTR model at HAS. The various lance (where injury cases and data are sought out, as in the methods that were needed to locate trauma patients in the CTR) as trauma data collection occurs in conjunction with CTR proved more time consuming compared with in the medical or administrative documentation, serving as both PTR, in which the location of trauma patients are easily medical record documentation for clinicians and a data sheet known by physicians who admit or consult on such patients for an injury surveillance system.14,29 As the comparison data and fill out the registry form. The PTR could be more expe- showed, the PTR was the only model able to obtain all ditiously implemented given the requirement for a newly physician-required data for all admitted trauma patients from trained coordinator in the CTR. The charting documentation the onset of the pilot study, showing the immediacy with deficits seen in the CTR pilot among physicians (treatments, which the model could improve injury data collection. Al- radiographs obtained, examination, specified mechanism of though nonphysician data were not collected during the PTR injury) were eliminated during the PTR pilot with complete pilot similar quick improvements in documentation are prob- documentation of all physician-specific data. Nursing docu- able given the way the PTR standardizes nursing and secre- mentation (baseline vital signs) was little improved in the tarial documentation. Recording of nonphysician data such as CTR compared with in the retrospective studies; the nonphy- arrival vitals signs was essentially unchanged in the CTR sician data points (specifically, admission vital signs to be pilot compared with in the retrospective 2002 analysis indi-

1152 November 2007 Trauma Registry Development in Haiti cating that without the data collection standardization that the In conclusion, trauma registries in developing and resource- PTR offers, improvement in documentation would be slower poor settings are a plausible tool for injury surveillance. Suc- in the CTR model. The task force also thought that the PTR cessful trauma registries will be resource and setting specific in could be sooner fully implemented given that all staff essen- design and can potentially be the means by which trauma care tial to its functioning were already available. The registry and outcomes are improved, prevention programs are devel- coordinator in the PTR requires an estimated one-fifth less oped, and capacity-building goals realized. staff time, and accordingly pay, to oversee functioning of the registry, compared with in the CTR, which would require multiple coordinators to cover the 7-day-a-week surveil- REFERENCES lance needed. Finally, the PTR could more feasibly expand 1. Murray CJ, Lopez AD. The Global Burden of Disease: A to include outpatient trauma at the hospital or the many Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. catchment-area clinics and dispensaries, whereas the CTR Cambridge: Harvard University Press; 1996. would need to employ a coordinator at each clinic site, a 2. Krug EG, Sharma GK, Lozano R. The global burden of injuries. heavy human-resource burden. Am J Public Health. 2000;90:523–526. The CTR model may be a preferred design in hospitals 3. Zwi AB, Forjuoh S, Murugusampillay S, Odero W, Watts C. Injuries where (1) trauma documentation is already adequate, (2) in developing countries: policy response needed now. Trans R Soc Trop Med Hyg. 1996;90:593–595. outpatient expansion is not a foreseeable priority, or (3) an 4. Fauveau V, Wojtyniak B, Koenig MA, Chakraborty J, Chowdhury expanded, more numerous data set (which may be too time- AI. Epidemiology and cause of deaths among women in rural consuming for providers to collect and record) is desired for Bangladesh. Int J Epidemiol. 1989;18:139–145. gathering more extensive outcome measures and information 5. Grubb GS, Fortney JA, Saleh S, et al. A comparison of two for potential prevention projects. cause-of-death classification systems for deaths among women of reproductive age in Menoufia, Egypt. Int J Epidemiol. 1988; Although hospital-based trauma registries may help 17:385–391. guide prevention efforts, they are limited in the ability to 6. Nantulya V, Reich M. Equity dimensions of road traffic injuries in capture all trauma within a catchment area and do not low- and middle- income countries. Inj Control Safe Promot. 2003; address the important role of adequate prehospital care for 10:13–20. improving trauma incidence and outcomes.27,31–34 Because 7. Ad Hoc Committee on Health Research Relating to Future Intervention Options. Investing in Health Research and hospitalized trauma poses a greater burden on the hospital Development. Geneva: World Health Organization; 1996:Document system, the most appropriate starting point for HAS injury TDR/Gen/96.1. surveillance was through study of inpatient traumas. Even 8. Nantulya V, Reich M. The neglected epidemic: road traffic injuries with these limitations, hospital-based registries allow for in developing countries. BMJ. 2002;324:1139–1141. identification of injuries for which care is sought, demo- 9. Over M, Ellis R, Huber J, Solon O. The consequences of adult ill- health. In: al Fe, ed. The Health of Adults in the Developing World. graphics of patients seeking care, treatments and proce- Oxford: Oxford University Press; 1992:161–207. dures used to treat trauma, and categories of people at risk 10. Smith GS, Barss P. Unintentional injuries in developing countries: 27 for certain types of injuries. the epidemiology of a neglected problem. Epidemiol Rev. 1991; The HAS hospital system has unique characteristics that 13:228–266. may somewhat limit generalizability to all developing settings. 11. Zwi AB. The public health burden of injury in developing countries: HAS serves a rural population but is located less than 1 km from a critical review of the literature. Trop Dis Bull. 1993;90:R5–R45. 12. London JA, Mock CN, Quansah RE, Abantanga FA, Jurkovich GJ. one of the major highways in Haiti, possibly making average Priorities for improving hospital-based trauma care in an African trauma incidence higher than in rural hospitals not situated city. J Trauma. 2001;51:747–753. closely to a high traffic area. HAS does not have a formal 13. Michaud C, Murray CJ. External assistance to the health sector in emergency department, which, if available in other settings, may developing countries: a detailed analysis, 1972–90. Bull World factor into the design and flow of a trauma registry. As a Health Organ. 1994;72:639–651. 14. Holder YA, Peden M, Krug EG, Lund J, Gururaj G, Kobusingye O. frequent recipient of international volunteers, HAS has academic Injury Surveillance Guidelines. Geneva: World Health Organization; and other health institution partnerships that provide personnel 2001. and technical and analytical resources that may not be available 15. Mock CN, Abantanga F, Cummings P, Koepsell TD. Incidence and to other hospitals in resource-poor settings. The HAS registry outcome of injury in Ghana: a community-based survey. Bull World models also rely on computer databases and advanced Web- Health Organ. 1999;77:955–964. 16. Waxweiler R. Public health, injury control, and emergency medicine. based databases, technologies that some resource-poor settings Acad Emerg Med. 1994;1:204. are not afforded. However, this extensive a system for data 17. Bernstein E, Goldfrank LR, Kellerman AL, et al. A public health analysis is not necessary in all settings. As an aid for enhancing approach to emergency medicine: preparing for the twenty-first statistical analysis of collected data in resource-poor settings the century. Acad Emerg Med. 1994;1:277–286. Centers for Disease Control and Prevention (CDC) developed 18. Allhouse M, Rouse T, Eichelberger M. Childhood injury: a current perspective. Pediatr Emerg Care. 1993;9:159–164. Epi Info, a free easy-to-use computer data analysis program that 19. Committee on Trauma Research. Injury in America: A Continuing may be helpful in resource-poor settings and is available for Public Health Problem. Chapters1&2.Washington, D.C.: National download from their Website (http://www.cdc.gov/epiinfo).35 Academy Press; 1985.

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20. Rahman F, Andersson R, Svanstrom L. Potential of using existing 28. Razzak J, Marsh D, Stansfield S. District hospital based injury data-are injury information for injury surveillance at the local level in they an option in a developing country? Inj Prev. 2002;8:345–346. developing countries: experiences from Bangladesh. Public Health. 29. Britton F, Cales R. Trauma registers: data management. Trauma 2000;114:133–136. Quarterly. 1989;5:25–33. 21. Graitcer PL. The development of state and local injury surveillance 30. World Health Organization. International Classification of Diseases systems. J Safety Res. 1987;18:191–198. and Related Health Problems, Ninth Revision. Geneva: World Health 22. Frerichs RR. Epidemiologic surveillance in developing countries. Organization; 1979. Annu Rev Public Health. 1991;12:257–280. 31. Elechi E, Etawo S. Pilot study of injured patients seen in the University 23. Mohan D, Romer CJ. Accident mortality and morbidity in of Port Harcourt Teaching Hospital, Nigeria. Injury. 1990;21:234–238. developing countries. In: Manciaux M, Romer CJ, eds. Accidents in 32. Nordberg E. Surgical operation in East Africa: a review with Childhood and Adolescence: The Role of Research. Geneva: World conclusions regarding the need for further research. East Afr Med J. Health Organization; 1991. 1990;67:1–28. 24. Malison M. Surveillance in developing countries. In: Halperin W, 33. Arreola-Risa C, Mock C, Lojero-Wheatly L, et al. Low cost Baker E, eds. Public Health Surveillance. New York: Van Nostrand improvements in prehospital trauma care in a Latin American city. Reinhold; 1992. J Trauma. 2000;48:119–124. 25. Berklman R, Stroup D, Buehler J. Public health surveillance. In: 34. Mock C, nii-Amon-Kotei D, Maier R. Low utilization of formal Detels R, Holland W, McEwen J, Omenn G, eds. Oxford Textbook medical services by injured persons in a developing nation: health of Public Health, Vol 2, 3rd edition. Oxford: Oxford University service data underestimate the importance of trauma. J Trauma. Press; 1997. 1997;42:504–511. 26. Berger L, Mohan D. Injury Control: A Global View. New Delhi: 35. Dean A, Dean J, Coulombier D, et al. Epi Info, Version 6.04a. A Oxford University Press; 1996. word-processing, database, and statistics program for public health 27. Kobusingye OC, Lett RR. Hospital-based trauma registries in on IBM-compatible microcomputers. Atlanta, GA: Centers for Uganda. J Trauma. 2000;48:498–502. Disease Control and Prevention; 1996.

1154 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Improved Cerebral Oxygenation After High-Dose Inhaled Aerosolized Prostacyclin Therapy for Acute Lung Injury: A Case Report Michael F. Stiefel, MD, PhD, Kareem A. Zaghloul, MD, PhD, Stephanie Bloom, MSN, Vicente H. Gracias, MD, and Peter D. LeRoux, MD

J Trauma. 2007;63:1155–1158.

raumatic brain injury (TBI) is one of the leading causes cerebral oxygenation in a patient with severe TBI, who was of death among young people in the United States. In the administered high-dose IAP therapy for a pulmonary injury. TTraumatic Coma Data Bank, only 16.4% of patients who suffered severe diffuse injury experienced a good outcome or CASE REPORT moderate disability. This poor outcome is associated, in a This 20-year-old man was involved in a high-speed motor l–4 large part, with secondary cerebral ischemia or infarction. vehicle crash. His Glasgow Coma Scale score at the scene was In addition, several investigators have reported the relation- 5 (Eye: 1, Verbal: 1, Motor: 3) and he was intubated, paralyzed, ship between secondary cerebral insults that further damage and sedated for transport. On arrival at our institution, his Glas- 2,5,6 neural tissue, and poor patient outcome. Many of these gow Coma Scale score was 3. A head computed tomography 7 secondary cerebral insults are avoidable. demonstrated a small right frontal-temporal contusion, without Acute lung injury, pneumonia, atelectasis, and compro- mass effect. Other injuries included multiple facial fractures, a mised pulmonary function are common after severe TBI and mediastinal hematoma, splenic laceration, and fractures of his 8–10 can directly lead to inadequate systemic oxygenation. pelvic ramus, left femur, right tibia, and fibula. He was resus- This hypoxia can cause a secondary cerebral insult and ex- citated according to Advanced Trauma Life Support guidelines 5,11 acerbate outcome. In recent years, inhaled aerosolized and published head injury management guidelines15 and under- prostacyclin (IAP) has been used to treat severe pulmonary went immediate evacuation of the mediastinal hematoma and injury. Prostacyclin is a selective pulmonary vasodilator that exploratory laparotomy for the splenic laceration in the operat- when delivered in the inspiratory gas can redistribute pulmo- ing room. nary blood flow from nonventilated or poorly ventilated lung Bilateral pulmonary contusions were observed in the regions to well-ventilated areas and consequently improve operating room and subsequent chest X-ray film (Fig. 1). systemic oxygenation. Prostacyclin therapy also may play a Postoperatively, the patient was admitted to the Neurotrauma 12 role in the treatment of TBI. Experimental studies suggest Intensive Care Unit. He was cared for according to published 13–15 prostacyclin can decrease infarct size, and reduce corti- recommendations for head injury management.5,15,24 This 16 cal lesion volume after TBI. This beneficial effect may be management focused on maintaining intracranial pressure associated with improved microcirculatory blood flow since (ICP) Ͻ20 mm Hg and cerebral perfusion pressure (CPP) prostacyclin can attenuate platelet and leukocyte adherence.17 Ͼ Ͼ 70 mm Hg. In addition, we aimed at keeping BtO2 25 mm This is important since endogenous prostacyclin production is Hg and S O Ͼ50%.25–27 A propofol infusion was adminis- 18,19 jv 2 decreased after TBI and there is increased platelet tered for sedation. Ventilation was adjusted to maintain pCO 20,21 20,22,23 2 aggregation, and increased leukocyte adherence. approximately 35 mm Hg. In this patient, we describe the effect of prostacyclin on Multimodality Monitoring Submitted for publication May 21, 2004. ICP using an intraparenchymal ICP monitor (Camino, Accepted for publication October 26, 2004. Integra NeuroSciences, Plainsboro, NJ); brain temperature Copyright © 2007 by Lippincott Williams & Wilkins using an intraparenchymal temperature probe (Licox, Integra From the Department of Neurosurgery (M.F.S., K.A.Z., S.B., P.D.L.); NeuroSciences); and local brain tissue oxygen (B O )by and Division of Trauma and Surgical Critical Care (V.H.G.), University of t 2 Pennsylvania, Philadelphia, Pennsylvania. intraparenchymal Clark-type electrode (LICOX, Integra Neu- Address for reprints: Peter D. LeRoux, MD, Department of Neurosur- roSciences) were continuously monitored. CPP was calcu- gery, University of Pennsylvania, 330 S. 9th Street, Philadelphia, PA 19107; lated from the measured parameters (CPP ϭ MAP – ICP). email: [email protected]. The ICP, brain temperature, and BtO2 probes were inserted DOI: 10.1097/TA.0b013e31815965e3 into frontal white matter through a triple lumen introducer/

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ables were continuously recorded using a Hewlett Packard Component Monitoring System (M1O46-9090C, Hewlett Packard, Andover, MA). In addition, physiologic variables were recorded every 15 minutes on the intensive care unit

flow sheet. His initial ICP and BtO2 during the first 24 hours were 16 Ϯ 4 mm Hg and 17.1 Ϯ 2.2 mm Hg (mean Ϯ SD), Ϯ respectively (Fig. 2). The initial SjvO2 values were 71% 13%.

Hospital Course and IAP Therapy ICP remained stable until day 3 when it became to increase. This ICP increase was associated with reduced CPP (Fig. 2). The patient was refractory to first-tier medical management for raised ICP including sedation, mannitol, and cerebrospinal fluid drainage.5,24 Consequently pentobarbital was administered to burst suppression to help control ICP. His pulmonary function was severely compromised because

Fig. 1. Portable chest x-ray obtained on hospital day 3, before of his pulmonary contusions, and he required increasing FIO2 inhaled aerosolized prostacyclin therapy was started. to sustain adequate oxygenation (Fig. 2). IAP therapy was titrated to help pulmonary function. Epoprostenol was recon- bolt system (Integra NeuroSciences). Jugular venous oxygen stituted in a standard 30,000 ng/mL concentration and was saturation was monitored using a retrograde jugular bulb delivered based on an ng ⅐ kgϪ1 ⅐ minϪ1 dose. In this case catheter. Other physiologic variables including (1) heart rate, report, we used an initial dose of 50 ng ⅐ kgϪ1 ⅐ minϪ1(Fig. 2). (2) 12 lead electrocardiogram, (3) mean arterial blood pres- This however, had little effect on pulmonary oxygenation and sure by radial artery catheter, (4) arterial oxygen saturation so IAP was titrated to 150 ng ⅐ kgϪ1 ⅐ minϪ1 48 hours later

(SaO2) by pulse oximetry, (5) end-tidal carbon dioxide (Fig. 2). This improved the patient’s pulmonary function and (EtCO2) also were continuously recorded. Physiologic vari- allowed for a reduction in FIO2.

Fig. 2. Line graphs illustrating daily Brain tissue oxygen (BtO2), Cerebral Perfusion Pressure (CPP), Intracranial Pressure (ICP), and Ϯ Fraction of inspired oxygen (FiO2) during the patients initial 12 days in the intensive care unit. Data are expressed as the daily mean SD.

1156 November 2007 Cerebral Oxygenation After Prostacyclin Therapy

During prostacyclin therapy, we continuously measured proved, even though FIO2 was reduced. We observed a slight BtO2 and jugular venous (SjvO2) oxygenation pressure. At the increase in SjvO2 when IAP was first started suggesting im- onset of IAP, BtO2 was not significantly different from initial proved oxygen delivery, decreased metabolic demand or recordings. However, once the IAP dose was increased and both. However, the jugular bulb catheter was removed one pulmonary function improved BtO2 also increased. This in- day later because of malfunction. This prevented us from crease was not associated with a change in CPP (Fig. 2). His measuring jugular bulb saturation for the duration of IAP.

BtO2 showed steady improvement during the ensuing days There is evidence suggesting an association between 1,2 and the FIO2 was further reduced and on day 10 IAP de- focal cerebral ischemia and neural injury after TBI. This creased to 50 ng ⅐ kgϪ1 ⅐ minϪ1. On day 12 IAP was stopped. may be ameliorated by prostacyclin. For example, in a mi-

BtO2 was between 30 mm Hg and 40 mm Hg and FIO2 crodialysis study, low-dose prostacyclin was shown to reduce between 0.6 and 0.7. Shortly after his IAP was stopped, his focal lactate concentration in patients suffering from severe ICP again increased during a 24-hour period. There was no TBI.12 In normal aerobic metabolism, pyruvate is decarboxy- associated change in pulmonary function. Follow-up head lated to acetyl-CoA and enters the citric acid cycle.39 Under computed tomography scan demonstrated evolution of his hypoxic conditions, however, lactate levels increase relative contusion and cerebral edema. He required a decompressive to pyruvate. In TBI patients administered low-dose prostacy- hemicraniectomy to control his ICP. The patient ultimately clin, these high lactate concentrations return to normal.12 In experienced an outcome with moderate disability alone. these same patients, prostacyclin also caused a simultaneous

increase in SjvO2, suggesting that this therapy was directly DISCUSSION responsible for improved oxygenation. In experimental stud- In this case report, we describe the effects of high-dose ies, prostacyclin therapy can reduce cortical lesion volume in IAP therapy on cerebral oxygenation in a patient with severe rats after TBI,16 suggesting that it may help preserve neuronal head injury. The cerebral metabolic effects of prostacyclin function. This effect may be through improved brain oxygen are only beginning to be elucidated; to date there is limited that can result from a direct effect on brain function or literature describing low dose, but not high-dose IAP, after indirectly through improved pulmonary function as in this TBI in humans. Prostacyclin use in multisystem trauma pa- case report. tients has drawn increasing recent attention because it can Other case reports have demonstrated that low-dose improve pulmonary function. In addition, it has possible prostacyclin can restore BtO2 without causing adverse protective effects on the injured brain.12,16 After trauma, reactions. For example, no increase in ICP was acute lung injury and pulmonary hypertension, among other observed.12,16 However, the dosage used in our patient factors, may cause decreased lung compliance28 and, there- (50–150 ng ⅐ kgϪ1 ⅐ minϪ1) was significantly higher than fore, decreased systemic oxygenation. Although there is some the dosages used in these other reports (0.5–1.0 debate regarding the therapeutic benefits of prostacyclin29 ng ⅐ kgϪ1 ⅐ minϪ1). We observed a slight increase in ICP in and debate about intravenous or aerosolized prostacyclins,30 our patient when prostacyclin therapy was started although recent studies have demonstrated that both intravenous and CPP was not adversely affected. After IAP termination, the aerosolized prostacyclin may be important in reducing pul- patient described in this report experienced progression of his monary vascular resistance31,32 and play a therapeutic role in contusion and increased ICP that subsequently required a managing pulmonary hypertension.28,33–35 decompressive hemicraniectomy. This may have been a re- Recently, continuous brain tissue oxygen monitoring has sult of the natural progression of TBI. Further studies will become available in the United States. Several converging need to identify the relationship between higher doses of lines of evidence suggest that this may be an ideal monitor to prostacyclin and ICP and intracranial hemorrhage. Although complement ICP monitors as the brain is highly dependant on we cannot conclude that the prostacyclin administration was a constant supply of oxygen and glucose to maintain normal responsible for this patient’s outcome, we did observe an neuron and astrocyte homeostasis. The brain oxygen monitor improvement in BtO2 with prostacyclin therapy. Further stud- used in this case report (Licox) provides a measure of the ies, however, are necessary before any conclusions can be adequacy of cerebral blood flow, a measure that is not always drawn about prostacyclin therapy and its role in the treatment provided by ICP or CPP monitoring.26,36,37 Several clinical of TBI. series have demonstrated a relationship between poor outcomes and the number, duration, and intensity of cerebral ACKNOWLEDGMENTS 26,38 hypoxia episodes. The information provided by BtO2 We acknowledge the help of Eileen Maloney-Wilensky, MSN, and M. monitoring can help monitor the effects of ICP treatment or Sean Grady, MD, in helping to establish multimodality monitoring in Neu- other surgical and medical interventions. To that end, we rocritical Care at the University of Pennsylvania. administered prostacyclin therapy to a patient with severe pulmonary- and brain injury and directly measured BtO2.We REFERENCES found that after an extended course of prostacyclin therapy, 1. Bouma GJ, Muizelaar JP, Stringer WA, Choi SC, Fatouros P, Young brain tissue oxygen improved as pulmonary function im- HF. Ultra-early evaluation of regional cerebral blood flow in

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severely head injured patients using xenon-enhanced computerized 21. Maeda T, Katayama Y, Kawamata T, Aoyama N, Mori T. tomography. 1992;77:360–368. Hemodynamic depression and microthrombosis in the peripheral 2. Bullock R, Sakas D, Patterson J, et al. Early post-traumatic cerebral areas of cortical contusion in the rat: role of platelet activating blood flow mapping: correlation with structural damage after focal factor. Acta Neurochir. 1997;70:102–105. injury. Acta Neurochir. 1992;55:14–17. 22. Holmin S, Soderlund J, Biberfeld P, Mathiesen T. Intracerebral 3. Graham DI, Ford I, Adams JH, et al. Ischaemic brain damage is still inflammation after human brain contusion. Neurosurgery. 1998; common in fatal nonmissile head injury. J Neurol Neurosurg 42:291–298. Psychiatr. 1989;52:346–350. 23. Whalen MJ, Carlos TM, Kochanek PM, et al. Neutrophils do not 4. Shima K, Umezawa H, Chigasaki R, Okuyama S, Araki R. Stable mediate blood-brain barrier permeability early after controlled prostacyclin improves postischaemic microcirculatory changes in cortical impact in rats. J Neurotrauma. 1999;16:583–594. hypertensive rats. Acta Neurochir. 1995;137:89–95. 24. Robertson C. Critical care management of traumatic brain injury. In: 5. Chestnut RM. Medical management of intracranial pressure. In: Winn HR, ed. Youmans Neurological Surgery. 5th ed. Philadelphia: Cooper PR, Golfinos JG, eds. Head Injury. 4th ed. New York, NY: Saunders; 2004:5103–5144. McGraw-Hill; 2000:229–263. 25. Hemphill JC III, Knudson MM, Derugin N, Morabito D, Manley 6. Miller JD. Head injury and brain ischemia—implications for therapy. GT. Carbon dioxide reactivity and pressure autoregulation of brain Br J Anaesth. 1985;57:120–130. tissue oxygen. Neurosurgery. 2001;48:377–383. 7. Schenk P, Petkov V, Madl C, et al. Aerosolized iloprost therapy 26. van Santbrink E, vd Brink WA, Steyerberg EW, Carmona Suazo JA, could not replace long-term IV epoprostenol (prostacyclin) Avezaat CJ, Maas AI. Brain tissue oxygen response in severe administration in severe pulmonary hypertension. Chest. 2001; traumatic brain injury. Acta Neurochir. 2003;145:429–438. 119:296–300. 27. van den Brink WA, van Santbrink H, Steyerberg EW, et al. Brain 8. Bratton SL, Davis RL. Acute lung injury in isolated traumatic brain oxygen tension in severe head injury. Neurosurgery. 2000;46:868– injury. Neurosurgery. 1997;40:707–712. 878. 9. Holland MC, Mackersie RC, Morabito D, et al. The development of 28. Jeffery TK, Wanstall JC. Pulmonary vascular remodeling: a target acute lung injury is associated with worse neurologic outcome in for therapeutic intervention in pulmonary hypertension. Pharmacol patients with severe traumatic brain injury. J Trauma. 2003;55:106– Ther. 2001;92:1–20. 111. 29. Schroder ML, Muize1aar JP, Bullock MR, Salvant JB, Povlishock 10. Mascia L, Andrews PJ. Acute lung injury in head trauma patients. JT. Focal ischemia due to traumatic contusions documented by Intensive Care Med. 1998;24:1115–1116. stable xenon-CT and ultrastructural studies. J Neurosurg. 1995; 11. Jeremitsky E, Omert L, Dunham M, Protetch J, Rodriguez A. 82:966–971. Harbingers of poor outcome the day after severe brain injury: 30. Schermuly RT, Krupnik E, Tenor H, et al. Coaerosolization of hypothermia, hypoxia, and hypoperfusion. J Trauma. 2003;54:312– phosphodiesterase inhibitors markedly enhances the pulmonary 319. vasodilatory response to inhaled iloprost in experimental pulmonary 12. Grande PO, Moller AD, Nordstrom, CH, Ungerstedt U. Low-dose hypertension. Maintenance of lung selectivity. Am J Respir Crit prostacyclin in treatment of severe brain trauma evaluated with Care Med. 2001;164:1694–7000. microdialysis and jugular bulb oxygen measurements. Acta 31. Blumberg FC, Riegger GA, Pfeifer M. Hemodynamic effect of Anestesiol Scand. 2000;44:886–894. aerosolized iloprost in pulmonary hypertension at rest and during 13. Dogan A, Temiz C, Turker RK, Egemen, N, Baskaya MK. Effect of exercise. Chest. 2001;121:1566–1571. the prcstacyclin analogue, iloprost, on infarct size after permanent 32. Castelain V, Chemla D, Humbert M, et al. Pulmonary artery focal cerebral ischemia. Gen Pharmacol. 1996;27:1163–1166. pressure-flow relations after prostacyclin in primary hypertension. 14. Siesjo BK. Brain Energy Metabolism. New York: John Wiley & Am J Respir Crit Care Med. 2001;165:338–340. Sons; 1978. 33. Galie N, Manes A, Branzi A. Medical therapy for pulmonary 15. The Brain Trauma Foundation. The American Association of hypertension. The prostacyclins. Clin Chest Med. 2001;22:529–537. Neurological Surgeons. The Joint Section on Neurotrauma and 34. Hache M, Denault AY, Be´lisle S, et al. Inhaled prostacyclin (PGI2) Critical Care. Critical pathway for the treatment of established is an effective addition to the treatment of pulmonary hypertension intracranial hypertension. J Neurotrauma. 2000;17:537–538. and hypoxia in the operating room and intensive care unit. Can J 16. Bentzer P, Mattiasson G, McIntosh TK, Wieloch T, Grande PO. Anaesth. 2001;48:924–929. Infusion of prostacyclin following experimental brain injury in the 35. Max M, Rossaint R. Inhaled prostacyc1inin the treatment of rat reduces cortical lesion volume. J Neurotrauma. 2001;18:275–285. pulmonary hypertension. Eur J Ped. 1999;158(suppl 1): S23–S26. 17. Orfeo T, Doherty JM, Adey G, Penar PL, Shatos MA. Sublethal 36. Gopinath SP, Robertson CS, Contant CF, et al. Jugular venous percussion trauma in vitro causes a persisting derangement in the desaturation and outcome after head injury. J Neurol Neurosurg nonthrombogenic properties of brain endothelial cells. J Trauma. Psychiatr. 1992;57:717–723. 1994;37:347–357. 37. Le Roux P, Lam AM, Newell DW, Grady MS, Winn HR. Cerebral 18. AI-Turki A, Armstead WM. Altered release of prostaglandins by arteriovenous difference of oxygen: a predictor of cerebral infarction opioids contributes to impaired cerebral hemodynamics following and outcome in severe head injury. J Neurosurg. 1997;87:1–8. brain injury. Crit Care Med. 1998;26:917–925. 38. Dings J, Meixensberger J, Jager A, Roosen K. Clinical experience 19. Annstead WM. Brain injury impairs prostaglandin with 118 brain tissue oxygen partial pressure catheter probes. cerebrovasodilation. J Neurotrauma. 1998;15:721–729. Neurosurgery. 1998;43:1082–1095. 20. Dietrich WD, Alonso O, Busto R, et al. Posttraumatic cerebral 39. Tanaka K, Gotoh F, Fukuuchi Y, et al. Stable prostacyclin analogue ischemia after fluid percussion brain injury: an autoradiographic and preventing microcirculatory derangement in experimental cerebral histopathological study in rats. Neurosurgery. 1998;43:585–593. ischemia in cats. 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1158 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Surgical Stabilization of a Rib Fracture using an Angle Stable Plate Roel Beelen, MD, Jan Rumbaut, MD, and Raphae¨l De Geest, MD

J Trauma. 2007;63:1159–1160.

ixation of a rib fracture is a rarely performed procedure. centered over the long axis of the rib and in contact with the The most common indications are flail chest with failure rib over its entire length. Six holes were drilled and the plate Fto wean, acute pain with instability, painful nonunion, was fixated with four self-tapping 3.5-mm bicortical screws and chest wall defects.1–2 Various techniques for surgical to compress the fracture. Then we used two self-tapping stabilization are described including fixator plates, intramed- 3.5-mm locking head screws for superior fixation of the LCP ullary wires or nails, struts, and even bioabsorbable plates.3–5 on the rib. Screws were inserted as described in the LCP Recently, we performed an internal fixation of a painful application notes.6 The procedure ended by closing all layers nonunion by using an angle stable plate. including the split muscle over the plate.

CASE REPORT RESULTS This technique was very successful; at discharge, pain level One year ago, a 67-year-old woman underwent an exclu- was 4 on a scale of 10. After 4 weeks, pain level was 0 and plain sion replacement of a thoracoabdominal aneurysm by a left radiographs showed already diffuse bone healing with callus. sided thoracophrenolaparotomy. Since the immediate postoper- After 2 months, the fracture was completely healed (Fig. 1). ative phase, she mentioned severe pain over the lower left thoracic cage, especially rib 8. Pain level was assessed using a DISCUSSION visual pain scale of 0 to 10. Pain level at discharge was 9. At 3 In our opinion, the described technique is superior to months, the pain level was still 7. After 1 year, the pain level was other known techniques for surgical fixation of a rib fracture. still 6 and she mentioned a “clacking” feeling during inspiration. Because there are no cerclage wires or pins used, the neuro- At that moment, we performed a plain chest and thoracic cage vascular bundle is not jeopardized and the risk for residual plain radiograph that revealed a pseudarthrosis of the left eighth intercostal pain is very low. Surgical stabilization using an rib. Computed tomographic scan showed a clear image of the angle stable plate is a good combination to compress the nonunion and displacement. The conclusion was that without a fracture and to obtain a very solid fixation on the rib by using surgical stabilization the pain would last. the locking head screws. Another advantage of this technique We performed a limited left thoracic muscle-splitting incision located over the fracture and found a pseudarthrosis of the eighth rib. Thoracic cavity or pleura were not opened. Manipulation showed an extremely unstable nonunion. The pseudarthrosis was resected. A curette was used to clean the fracture side. After this maneuver, successful reduction without gap was achieved and the fracture was fixated with a reduction forceps. The length of the plate was determined by allowing for at least three cortical screws on both sides of the fracture. If necessary, plate-contouring is obtained by using the bending instruments. For this case we choose as angle stable plate: a six-hole Locking Compression Plate (LCP; LCP system, Synthes/Mathys, Switzerland). The plate was

Submitted for publication December 3, 2004. Accepted for publication April 20, 2005. Copyright © 2007 by Lippincott Williams & Wilkins From the Department of Surgery, OLV Hospital, Oost-Vlaanderen, Belgium. Address for reprints: Roel Beelen, MD, Department of Cardio-vascular and Thoracic Surgery, OLV Hospital, Moorselbaan 164, 9300 Aalst, Oost- Vlaanderen, Belgium; email: [email protected]. Fig. 1. Postoperative plain chest radiograph showing the angle DOI: 10.1097/01.ta.0000222536.91745.b4 stable plate.

Volume 63 • Number 5 1159 The Journal of TRAUMA௡ Injury, Infection, and Critical Care is that it is not always necessary to open the thoracic pleura 2. Cacchione RN, Richardson JD, Seligson D. Painful non-union of to perform the plate and screw osteosynthesis like we dem- multiple rib fractures managed by operative stabilization. J Trauma. onstrated in this case report. To define the definitive role and 2000;48:319–321. 3. Quell M, Vecsei V. Surgical stabilization of thoracic wall fractures. possibilities of angle stable plates in the surgical stabilization Unfallchirurg. 1991;94:129–133. of rib fractures, further studies need to be performed. 4. Mayberry JC, Terhes JT, Ellis TJ, Wanek S, Mullins RJ. Absorbable plates for rib fracture repair: preliminary experience. J Trauma. 2003;55:835–839. REFERENCES 5. Tanaka H, Yukioka T, Yamaguti Y, et al. Surgical stabilization of 1. Voggenreiter G, Neudeck F, Aufmkolk M, Obertacke U, Schmit- internal pneumatic stabilization? A prospective randomized study of Neuerburg KP. Operative chest wall stabilization in flail chest: management of severe flail chest patients. J Trauma. 2002;52:727–732. outcomes of patients with or without pulmonary contusion. JAm 6. Locking Compression Plate Application notes. Synthes, Mathys Coll Surg. 1998;187:130–138. Medical Ltd, Bettlach, Switzerland.

1160 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Colorectal and Vaginal Injuries in Personal Watercraft Passengers Sashil Singh Kapur, BA, and Lonnie Warren Frei, MD, FACS, FCCM

J Trauma. 2007;63:1161–1164.

ersonal watercraft (PWC) usage has grown in the past tone. She was discharged home after the colostomy began 15 years. The increase in activity during this time has functioning. She subsequently underwent colostomy closure Pbeen accompanied by an increase in injuries. A partic- and is continent of both stool and flatus. ular group of PWC-related injuries, rectal and vaginal injuries, are being recognized with increasing frequency. We CASE 2 report two cases of female passengers sustaining perineal A 19-year-old female passenger was thrown off the back (rectal and vaginal) injuries after falling off the back of their of her PWC. She immediately experienced severe perianal vehicles, and a review of the literature of these injuries. and diffuse abdominal pain. She was taken to a local community hospital where an abdominal and pelvic computed CASE 1 tomography scan showed free air and fluid in the peritoneal A 15-year-old female passenger was thrown off the back cavity. She was transferred to a trauma center. The patient of a PWC as it accelerated. She landed on her back with her was mildly anxious and in moderate distress. She had mild legs thrown up in the air. She experienced perineal discom- dyspnea, severe suprapubic and rectal pain, and diffuse ab- fort, but was able to swim over to the dock. She was noted by dominal pain with rebound tenderness. Her vital signs were: her family to have bloody drainage on her legs as she climbed blood pressure, 110/52; heart rate, 88 bpm; respiratory rate,

onto the dock. She was brought to an emergency room, where 20; temperature, 97.9°C; SaO2, 97% on room air. The rectal her main complaint was perineal discomfort and numbness. examination revealed a 3-cm laceration of the posterior rectal She was given antibiotics. Rectal examination revealed a wall and a hematoma. She was given intravenous antibiotics patulous sphincter and obliteration of the anorectal junction. and was taken to the operating room for examination under A deep laceration in her perineum extended up to the vaginal anesthesia and emergent exploratory laparotomy. fourchette. In the operating room, two rectal lacerations were iden- She was taken to the operating room, where vaginal tified, one posterior (Fig. 1) and the other posterolateral. The examination revealed no internal gynecologic injuries. The larger laceration interrupted the external anal sphincter. Care- perineal laceration extended deep into the pelvic soft tissues; ful examination found no lacerations communicating with the the anterior wall of the rectum was easily identified in the vagina. Laparotomy revealed free air, with murky fluid in the depths of the wound. The anoderm was completely dissected pelvic cul-de-sac. After careful examination, a rectosigmoid off the underlying muscular layers and had retracted up into perforation was found (Fig. 2). An end-colostomy was cre- the distal colon. Rigid sigmoidoscopy could be performed ated. Antibiotics were continued postoperatively. The patient and, except for some mild ecchymotic areas of the rectal wall, was discharged on the sixth postoperative day with subse- was normal. The anoderm and the rectum were reapproxi- quent colostomy closure planned. mated after the sphincter mechanism was repaired. The soft tissues were drained. Because of concerns about continence, DISCUSSION a sigmoid colostomy was performed. Within 24 hours of There were a total of 1,070 PWC-related injuries reported surgery, she noted some mild increase in sensation in the in the literature from 1985–2000 (table 1). Most studies perineum and rectal examination showed slight sphincter showed that the most common injuries from PWC accidents were superficial blunt trauma (lacerations, contusions, sprains, Submitted for publication December 2, 2004. etc.).1–8 Fractures were the second most common injury, fol- Accepted for publication April 7, 2005. lowed by head (brain) injuries and internal injuries (splenic Copyright © 2007 by Lippincott Williams & Wilkins From the Department of Surgery, Saint Louis University, St. Louis, lacerations, liver lacerations, etc.). There was some variation in 9,10 Missouri. the incidence of injuries among the studies, however. Not Address for reprints: Lonnie W. Frei, MD, Department of Surgery, including the case reports, there was only one reported vaginal 3635 Vista at Grand, St. Louis, MO 63110; email: [email protected]. injury and one reported rectal injury, an incidence of 0.09% DOI: 10.1097/01.ta.0000222533.97505.4e each. In addition to the above referenced reports of injuries, six

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Most of these involved a PWC colliding with another PWC, a stationary object, or a swimmer. The mean age of victims of PWC injuries was in the mid-20s. Males were involved in PWC-related injuries more than twice as often as females. A personal watercraft is defined as a vessel that uses an inboard motor powering a water jet pump as its primary source of motive power, is less than 16 feet in length, and is designed to be operated by a person sitting, standing, or kneeling on the vessel. They are powered by two- or four-stroke engines (the latter being the same type of engine used in cars) with up to 185 Fig. 1. Posterior laceration through anal verge. horsepower.14 Sales of PWC (s) reached an all-time high in the mid-1990s. Units sold have been declining steadily since that time.15 Despite the diminishing sales figures, the number of PWCs owned in the United States has increased annually.16 From 1990 to 1995, there was an estimated fourfold increase in the number of PWC- related injuries, with a threefold increase in the number of PWCs in operation.4 Increased popularity in PWC during this time and increased usage led to a higher frequency of injuries. Rectal and vaginal injuries have been uncommonly reported in the literature, at 0.09%. Multiple authors suggest the underreporting of PWC injuries.2–5,17 Case reports on rectal injuries have been increasing recently, including this report which presents two cases that occurred over a 2-year period. The seriousness of these injuries mandates a high degree of clinical suspicion to diagnose and appropriately treat them. Rectal and vaginal injuries related to PWCs are very Fig. 2. Full-thickness perforation of rectosigmoid in pelvis. serious injuries that can be potentially life-threatening. The mechanism of this type of injury is due to a high-pressure jet case reports of PWC-related vaginal (three) or rectal (three) which can achieve pressures exceeding 800 PSI, approaching injuries were found in the literature (table 2).11–13 the force of industrial pressure washers.18 If a driver or Fatalities were uncommon among the population of passenger of a PWC falls off the rear of the vehicle in a PWC-related injuries, occurring at a rate of 2.0% (21/1,070). supine position with their legs splayed while the throttle is

Table 1 Literature Review of Personal Watercraft–Related Injuries

Injuries Total Mean Male: Deaths Superficial Closed Study Year Injuries Fractures Internal Rectal Vaginal Age Female Blunt Head Vernberg et al.1 9/1985–8/1988 6 2 4 2 0 0 15.7 Hamman et al.2 1989–1991 94 0 31 17 10 1 0 0 65:21 Francis and 6/1991–10/1992 37 0 23 10 4 0 0 20.7 23:14 Vize3 Branche et al.4 1/1990–12/1995 624 * 50% 12% 0 0 25 442:182 Jeffery et al.10 1991 6 0 1 4 2 2 0 0 30 Swinburn11 1992–1996 6 1 1 4 2 0 0 31 Shatz et al.8 9/1991–6/1996 37 12 6 15 6 3 0 0 24 27:10 White and 1/1993–12/1997 68 0 70% 28% 13% 8% 0 0 26 45:23 Cheatham5 Jones6† 1994–1997 106 5 15 14 4 0 0 24 79:27 Haan et al.9‡ 8/1996–1/2001 24 0 0 1 30 Kim et al.7 1984–1997 62 1 51 32 8 9 1 0 23 41:21 Total 1070 21 1 1 722:298 Blank fields indicate values not assessed in respective study. Multiple injuries to a single patient are common. * Study did not include fatalities; trauma. † 53% of injuries in study were unspecified. ‡ Types of injuries not specified.

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Table 2 Case Reports of Personal Watercraft–Related Rectal and Vaginal Injuries

Passenger Author Year Age/Sex Injuries Treatment or Driver Wein et al.12 1990 29/F Passenger 5-cm midline perineal tear, 10-cm tear Suturing of broad ligament, suturing posterior vaginal fornix extending in layers of the vagina and into the base of the left broad peritoneum ligament, 5-cm defect in the peritoneum of the pouch of Douglas Haefner et al.13 1991 17/F Passenger 4-cm laceration right vaginal fornix Right hypogastric artery ligation extending into broad ligament, retroperitoneal hematoma Muller14 1993 22/F Passenger 7-cm right vaginal laceration, 4- to Ligation of arteries, suturing of 5-cm left vaginal laceration, bilateral lacerations, placement of Penrose pudendal artery lacerations, right drain vaginal artery laceration Parsons et al.15 1999 30/F Passenger 4-cm laceration posterior rectum Loop sigmoid colostomy with 12-cm from the anal verge transanal drainage of presacral space Philpott et al.16 1999 15/F Passenger Peritoneal fecal contamination, 8-cm Proximal diverting colostomy, 16-L laceration of anterior rectum, 2-cm irrigation, Betadine irrigation mesenteric hematoma Descottes et al.17 2003 16/M Passenger 5-cm laceration anterior sigmoid None, death from multisystem colon, dissection up rectal wall, failure distal perforation of anterior rectal mucosa still activated, their perineum is exposed to the effects of know how to react to dangerous situations such as a near hydrostatic injury. The energy that these jets create is more collisions, high wakes, and choppy weather. Many states did than enough to create mucosal injuries and full-thickness not have requirements for written tests, hours logged, or even perforations into the peritoneal cavity. licensure when many of the articles reviewed were written. The reduced potential for rectal and vaginal injuries to Therefore, the primary mode of prevention should be educa- produce systemic effects makes proper diagnosis critical. Pa- tion of the consumer, spearheaded by manufacturers, organi- tients with such injuries may present with only vague abdominal zations such as the Personal Watercraft Industry Association, pain. Even with a more obvious presentation of abdominal pain and state regulatory agencies. and rectal bleeding, a lesion can be fatally missed at emergency Since the mid to late 1990s, many states have enacted 19 laparotomy. Therefore, these types of injuries necessitate a legislation to improve PWC safety. Many states currently re- high degree of clinical suspicion. quire some kind of testing and documentation to legally operate The initial examination should include a thorough rectal, a PWC; minimum age requirements have also been added. perineal, and vaginal examination. If the patient is stable There are multiple online exams available for consumers which enough, an abdominal and pelvic computed tomography scan are accepted by many states.21–23 may be indicative of signs of perforation if peritoneal signs Other types of measures are needed to prevent rectal are absent. Intravenous antibiotics should be started. If the and vaginal injuries. These injuries appear to occur to patient’s clinical picture and examination warrant surgery, a passengers rather than drivers.24 Passengers may be more more thorough examination under anesthesia must be performed. This includes rigid proctoscopy and pelvic examina- susceptible to these injuries because of a lack of a handle- tion with careful inspection for communication of lacerations bar for maintaining stability during a ride. Passengers may to the vagina in females. An open laparotomy is recom- not be paying attention to the path of their vehicle and may mended to enable a full inspection of the abdomen and distal not be ready to brace themselves for a sudden jolt, causing colon in appropriate cases. Surgical treatment may include a loss of balance. Most importantly, passengers do not standard colonic fecal diversion techniques. A combined ap- have an auto-shutoff switch on most PWCs. Drivers will proach between gynecology and general surgery is advocated automatically shut off the throttle if they fall off their when diagnosing and treating these types of injuries in vehicle. When passengers fall off, the throttle can still females. operate, allowing the jet to continue, potentially leading to To minimize rectal and vaginal as well as other PWC- injury. Also, in none of the cases was there a report of the related injuries, prevention is key. The majority of PWC patient wearing a neoprene suit (“wet suit”) or any other accidents and injuries are attributable to inexperience, reck- type of protective clothing. These suits are essential in lessness, and excessive speed.1–3,5–8,9,20 Many riders do not directly protecting soft tissue from hydrostatic injury.

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CONCLUSION 10. Shatz DV, Kirton OC, McKenney MG, et al. Personal watercraft In conclusion, rectal and vaginal injuries may not be as crash injuries: an emerging problem. J Trauma. 1998;44:198–201. 11. Wein P, Thompson DJ. Vaginal perforation due to a jet-ski accident. rare as previously reported. Appropriate medical interven- AustNZJObstet Gynaec. 1990;30:384–385. tions will prevent further morbidity and mortality when these 12. Muller RJ. Jet ski injury: a case report. J La State Med Soc. 1993; cases present, especially with the female PWC passenger. 145:27–28. Preventive interventions include education, the standardiza- 13. Descottes B, Lachachi F, Moumouni I, Durand-Fontanier S, Geballa tion of auto-shutoffs for passengers or restricting passengers, R. Rectal injury caused by personal watercraft accident: report of a Dis Colon Rectum. and wearing protective gear such as wet suits when riding case. 2003;46:971–973. 14. Personal Watercraft Industry Association. Available at http:// PWCs. www.pwia.org/faqs/pw-qa.html. Accessed February 10, 2004. 15. National Marine Manufacturers’ Association. Available at http:// REFERENCES www.nmma.org/facts/boatingstats/2002/files/unitsales.asp. Accessed 1. Vernberg D, Fine EG, Jagger J. Personal watercraft injuries. JAMA. February 10, 2004. 1989;261:1883. 16. National Marine Manufacturers’ Association. Available at http:// 2. Hamman BL, Miller FB, Fallat ME, Richardson JD. Injuries www.nmma.org/facts/boatingstats/2002/files/populationestimates.asp. resulting from motorized personal watercraft. J Pediatr Surg. 1993; Accessed February 10, 2004. 28:920–922. 17. Swinburn EEL. Serious injuries in jet-skiers. Med J Aust. 1996; 3. Francis RA, Vize R. Personal watercraft injuries: experience at a 165:606–609. community hospital. Mo Med. 1994;91:241–243. 18. Philpott JM, Ng PC, Wixon CL, et al. Rectal blowout by personal 4. Branche CM, Conn JM, Annest JL. Personal watercraft-related watercraft water jet: case report and review of literature. J Trauma. injuries. A growing public health concern. JAMA. 1997;278: 1999;47:385–388. 663–665. 19. Parsons DP, Kahn HA, Isler JT, Billingham RP. Rectal injury 5. White MW, Cheatham ML. The underestimated impact of personal caused by a personal watercraft accident: report of a case. Dis Colon watercraft injuries. Am Surg. 1999;65:865–869. Rectum. 1999;42:959–960. 6. Jones CS. Epidemiology of personal watercraft-related injury on 20. Jones CS. Personal watercraft-related injuries in Arkansas: Arkansas waterways, 1994–1997: identifying priorities for 1994–1996. J Ark Med Soc. 1997;94:111–112. prevention. Accid Anal Prev. 2000;32:373–376. 21. Boat US Foundation. Available at https://www.boatus.com/ 7. Kim CW, Smith JM, Lee A, et al. Personal waterfraft injuries: 62 foundation/. Accessed March 17, 2004. patients admitted to the San Diego County trauma services. J Orthop 22. PWC Safely School. Available at http://www.pwcsafetyschool.com/. Trauma. 2003;17:571–573. Accessed March 17, 2004. 8. Jeffery RS, Caiach S. Waterbike injuries. Br J Sports Med. 1991; 23. Offical Boater Safety and Education. Available at http://www.boat-ed. 25:232–234. com/index.htm. Accessed March 17, 2004. 9. Haan JM, Kramer ME, Scalea TM. Pattern of injury from personal 24. Haefner HK, Andersen HF, Johnson MP. Vaginal laceration watercraft. Am Surg. 2002;68:624–627. following a jet-ski accident. Obstet Gynecol. 1991;78:986–988.

1164 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Laparoscopy and the Management of Blunt Bladder Trauma Jonathan L. Wright, MD, and James R. Porter, MD

J Trauma. 2007;63:1165–1166.

he role of laparoscopy in the diagnosis and management with catheter drainage and a follow-up cystogram at 2-weeks of abdominal trauma in select hemodynamically stable showed no evidence of a leak. Tpatients is slowly evolving,1–3 but there are few reports of its use in genitourinary trauma. We report two cases in which exploratory laparotomy were avoided by performing DISCUSSION diagnostic and therapeutic laparoscopy. Traditional evaluation of the abdomen in trauma has included the DPL, ultrasound and/or CT scan. Despite the high CASE PRESENTATION AND MANAGEMENT sensitivity and specificity of these tests, the rate of negative laparotomy approaches 20% in some series. Additionally, the CASE 1 complication rate associated with exploratory laparotomy can A 38-year-old man’s pant leg became caught in a chain reach 40% with a mortality rate of up to 5%.4 As a result, some drive, while working at a sawmill, pulling him into the machine. centers are including diagnostic laparoscopy in the evaluation of He sustained lower extremity and pelvic fractures. In the emer- abdominal trauma and the use of therapeutic laparoscopy when gency room, he had gross hematuria and a computerized tomog- feasible. raphy (CT) cystogram demonstrated an intraperitoneal bladder Trauma victims undergoing laparoscopic procedures re- rupture (Fig. 1). He was hemodynamically stable and his diag- quire special consideration. The patient must be hemodynam- nostic peritoneal lavage (DPL) was negative. Therapeutic lapa- ically stable and well resuscitated to counter the decrease in roscopy was performed through three ports. A 5-cm bladder venous return induced by the pneumoperitoneum. The pneu- dome rupture was repaired intracorporeally with a running 2.0 moperitoneum will also decrease renal blood flow resulting in Dexon. A cystogram on postoperative day 7 showed no leakage oliguria and fluids should be managed accordingly. (Fig. 2). At 6-month follow-up, he had no lower urinary tract Diaphragmatic injury must be ruled out, and over- symptoms. inflated bowel caused by aggressive bag ventilation should be considered a relative contraindication to laparoscopy because CASE 2 of the risk of inadvertent bowl injury. Finally, patients with A 30-year-old woman was a restrained driver in a high- head injuries and risk of intracranial hemorrhage should not speed motor vehicle collision. In the emergency room she be placed in the Trendelenberg position as this may increase was intubated and found to have a severe pelvic fracture and intracranial pressures. gross hematuria. A CT cystogram demonstrated a large ex- Technical limitations of laparoscopy in the trauma patient traperitoneal bladder rupture not involving the bladder neck depend on associated injuries. Laparoscopic port site placement and a possible intraperitoneal bladder rupture with contrast must be adjusted as necessary especially in patients with com- near the right colon. She was hemodynamically stable and her plex pelvic fractures and risk for pelvic hematoma and in pa- DPL was negative. Diagnostic laparoscopy was performed tients with bowel distension. We recommend using the Hasson with a 10-mm umbilical port and a second 5-mm port. The technique with the initial trocar in the midline just above the bladder dome was intact with no evidence of intraperitoneal umbilicus. This approach will avoid bowel injury as well as a rupture. Her extraperitoneal bladder rupture was managed pelvic hematoma, and if exploratory laparotomy is necessary, the trocar site can be converted to a midline laparotomy incision. In case number 1, intraperitoneal bladder rupture usually Submitted for publication November 3, 2004. warrants exploratory laparotomy and repair of the bladder rup- Accepted for publication February 2, 2005. ture. However, with no other evidence of intra-abdominal injury Copyright © 2007 by Lippincott Williams & Wilkins on CT scan, and the ability to suture the bladder injury laparo- From the Department of Urology, University of Washington, Seattle, WA. Address for reprints: Jonathan L. Wright, MD, MS, Department of scopically, the bladder was repaired while avoiding laparotomy. Urology, University of Washington Medical Center, Health Sciences Building, In case number 2, there was suspicion of intraperitoneal injury 1959 NE Pacific, BB-1115, Box 356510, Seattle, WA 98195; email: jlwright@ given the CT finding of contrast near the right colon. In addition, u.washington.edu. intraperitoneal bladder ruptures can be missed on CT cystogra- DOI: 10.1097/01.ta.0000235240.37380.e5 phy especially in the setting of a very large extraperitoneal

Volume 63 • Number 5 1165 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

plished with diagnostic laparoscopy. We chose not to repair the extraperitoneal injury because it was extraperitoneal and not associated with the bladder neck. However, as in open bladder repair, extraperitoneal injuries can be sutured laparoscopically as long as an ample cystotomy incision is made to provide exposure. These cases illustrate the application of laparoscopy to bladder trauma for both diagnostic and therapeutic purposes. Parra described the first nonlaparoscopic induced bladder injury repaired by laparoscopy after an endoscopic perforation.6 To our knowledge, there is only one other case of laparoscopic repair of traumatic bladder injury.7 Limitations of laparoscopy, specifically for bladder injuries, include lack of familiarity with this procedure and incomplete ability to evaluate the entire bladder. In particular, lacerations of the posterior bladder wall and blad- Fig. 1. Preoperative computed tomography cystogram with intra- der neck may be difficult to identify unless a transvesical ap- peritoneal bladder rupture in patient 1. proach is used. Although most extraperitoneal injuries can be managed with catheter drainage alone, involvement of the bladder neck requires prompt repair to reduce the risk of inconti- nence. Finally, we found laparoscopy performed on patients with pelvic trauma to be straightforward and the pelvic hematoma did not present a problem. Although isolated bladder injuries are rare, when patients present with a pelvic fracture, likely bladder injury and the absence of other intra-abdominal injuries requiring laparotomy, diagnostic laparoscopy should be considered with therapeutic laparoscopy performed when feasible.

REFERENCES 1. Chelly MR, Major K, Spivak J, et al. The value of laparoscopy in management of abdominal trauma. Am Surg. 2003;69(11):957. 2. Miles EJ, Dunn E, Howard D, Mangram A. The role of laparoscopy in penetrating abdominal trauma. JSLS. 2004;8(4):304. 3. Zantut LF, Ivatury RR, Smith RS, et al: Daignostic and therapeutic laparoscopy for penetrating abdominal trauma: a multicenter experience. J Trauma. 1997;42(5):825. 4. Choi YB, Lim KS. Therapeutic laparoscopy for abdominal trauma. Fig. 2. Postoperative cystogram in patient 1 at 7 days with no Surg Endosc. 2003;17:421. evidence of leakage. 5. Deck AJ, Shaves S, Talner L, Porter JR. Computerized tomography cystography for the diagnosis of traumatic bladder rupture. J Urol. injury.5 Regarding head injured patients or those intubated (as 2000;164(1):43. this patient was), serial exams are not reliable to evaluate ab- 6. Parra RO. Laparoscopic repair of intraperitoneal bladder perforation. J Urol. 1994;151(4):1003. dominal pathological findings. Given her severity of injury 7. Cottam D, Gorecki PJ, Curvelo M, et al. Laparoscopic repair of mechanism and the presence of an extraperitoneal bladder rup- traumatic perforation of the urinary bladder. Surg Endosc. 2001; ture, evaluation of her abdomen was warranted and accom- 15(12):1489.

1166 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Perforated Meckel’s Diverticulum in a Child After Blunt Abdominal Trauma Kennith H. Sartorelli, MD, Christopher Healey, MD, and Anthony Deross, MD

J Trauma. 2007;63:1167–1168.

eckel’s diverticulum (MD) in children is most com- DISCUSSION monly encountered as an asymptomatic finding dur- MD is the most common congenital anomaly of the Ming abdominal exploration or as a source of painless gastrointestinal (GI) tract with an incidence of approximately gastrointestinal bleeding.1–3 In children perforation of an MD 2% in the general population, and represents failure of the has been reported from ulceration related to ectopic gastric omphalomesenteric duct to fully regress.1–3 The omphalomes- mucosa in the diverticulum and from injury secondary to enteric duct is the connection from the yolk sac to the gut ingested foreign bodies, but never as a consequence of blunt of the developing fetus, and is supposed to involute after abdominal trauma.1–3 the establishment of the placenta. A variety of pathologic conditions have been described to occur with MD including bleeding (most common presentation in childhood), CASE REPORT bowel obstruction (most common presentation in adult- A previously healthy 6 year-old boy was injured when hood), inflammation, intussusception, and perforation from ul- 1–3 he struck his abdomen on a handlebar during a bicycle ceration and foreign bodies. crash. He had the immediate onset of abdominal pain and Blunt small bowel injuries account for approximately 1 4–7 had several episodes of emesis that prompted his mother to to 7% of intra-abdominal injuries in children. Injuries to bring him to local community hospital. The child was the jejunum are most common followed in decreasing fre- noted to be hemodynamically stable, but on physical ex- quency by injuries to the ileum, duodenum, colon, and stom- 4 amination was found to have signs of peritonitis (rigid ach injuries. Blunt small bowel injuries may be very difficult 4–6 abdomen with rebound tenderness). A plain radiograph of to diagnose and often present on a delayed basis. Com- puted tomography (CT) scans with or without oral contrast the abdomen showed pneumoperitoneum (Fig. 1). The 8 child was given intravenous fluids and antibiotics and was are notoriously poor at demonstrating small bowel injuries. transferred to the pediatric surgery service at the Univer- In the setting of blunt abdominal trauma a physical exami- sity of Vermont for management of a presumed hollow nation that reveals peritonitis should prompt immediate viscus injury. At exploration a moderate volume of enteric surgical consultation and exploration without extensive abdominal imaging.4–7 contents was found coming from the tip of a perforated The mechanism of MD perforation in the child described MD (Fig. 2). An area of bleeding was encountered in the in this report appears to be from the bicycle handlebar being small bowel mesentery where the tip of the MD had been a vector for transmitting energy through the abdominal wall torn from a point of fixation to the mesentery. No other and tearing the tip of the Meckel’s from a point of fixation to hollow viscus or solid organ injuries were identified. The the small bowel mesentery. In a 12-year review of pediatric MD was resected by stapling transversely across its base. blunt GI tract perforations Canty noted that children were The child recovered uneventfully and has done well on more likely to have a mechanism of injury that involved a follow up. point of discrete energy transfer to the abdomen than were adults.4 He found that in children with GI tract perforations that seatbelts (19%), child abuse (19%), and handlebars Submitted for publication November 30, 2004. (13%) were the most common identifiable agents of energy Accepted for publication January 19, 2005. transfer.4 Copyright © 2007 by Lippincott Williams & Wilkins Given the low incidence of both MD and blunt small From the Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont. bowel injuries it is not surprising that reports of MD perfo- Address for reprints: Kennith H. Sartorelli, MD, Department of Surgery, ration from blunt trauma are exceedingly rare. Our review of 309 Fletcher House, FAHC, 111 Colchester Avenue, Burlington, Vermont, the literature found only two previously published cases.9,10 05401; email: [email protected]. Lucas in 1972 described a 21-year-old man who presented DOI: 10.1097/01.ta.0000223940.42486.c8 with abdominal rigidity and hypotension after a motor vehicle

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crash. At exploration he was found to have perforated MD and hemorrhage from a tear in the mesentery of the diverticulum.9 Chalenko in 1990 reported on a 41-year-old man with a perforated MD and adjacent ileum from a blow to the abdomen. Both of the patients recovered fully after resection of the perforated MD.10 The case described here is the first report of perforation of a MD from blunt trauma in a child. This report describes the first known case of a perforated MD from blunt trauma in a child. The presentation of a perforated MD is the same as for a perforation in any other area of the small bowel, and should be treated with prompt operative resection.

REFERENCES 1. Firor HV. The many faces of Meckel’s diverticulum. South Med J. Fig. 1. Abdominal radiograph showing free air under both diaphragms. 1980;73:1507–1511. 2. Jelenec F, Strilic M, Gvardijancic D. Meckel’s diverticulum with intraabdominal hemorrhage. J Ped Surg. 2002;37:E18. 3. Yahchouchy EK. Marano AF, Etienne JC, et al. Meckel’s diverticulum. J Am Coll Surg. 2001;192:658–662. 4. Canty TG Sr, Canty TG Jr, Brown C. Injuries to the gastrointestinal tract from blunt trauma in children. A 12 year experience at a designated pediatric trauma center. J Trauma. 1999;46:234–240. 5. Bensard DD, Beaver BL, Besner GE, et al. Small bowel injury in children after blunt abdominal trauma: is diagnostic delay important? J Trauma. 1996;41:476–483. 6. Holland AJA, Cass DT, Glasson MJ, et al. Small bowel injuries in children. J Paediatr Child Health. 2000;36:265–269. 7. Kovacs GZ, Davies MRQ, Saunders W, et al. Hollow viscus rupture due to blunt trauma. Surg Gynecol Obstet. 1986;163:335–338. 8. Shankar KR, Lloyd Da, Kitteringham L, et al. Oral contrast with computed tompography in the evaluation of blunt abdominal trauma in children. Br J Surg. 1999;86:1073–1077. 9. Park H, Lucas CE. Perforated Meckel’s diverticulum following blunt abdominal trauma. J Trauma. 1970;10:706–707. 10. Chalenko VV, Medvedev AN. Blunt abdominal trauma with injury Fig. 2. MD with perforation adjacent to the tip of the diverticulum. of a Meckel’s diverticulum. Klin Khir. 1990;4:62–63.

1168 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Extensor Pollicis Longus Rupture After Fixation of Radius and Ulna Fracture With Titanium Elastic Nail (TEN) in a Child: A Case Report Tomar Kravel, Neer Sher-Lurie, PhD, and Abraham Ganel, PhD

J Trauma. 2007;63:1169–1170.

ractures of the midshaft radius and ulna in children are CASE REPORT among the most common fractures that orthopedic sur- An 11-year-old boy sustained an isolated injury to the Fgeons have to deal with.1 The main goal of treatment is left forearm after a fall during a football game. The patient to achieve and maintain an acceptable reduction. However, had diaphyseal open (Gustilo and Anderson7 grade 1) fracture some forearm fractures are very unstable and can displace with complete displacement of both radius and ulna. There resulting in increased radio-ulnar angulation, rotational mal- was no neurovascular damage. alignment, and permanent impairment of the normal range of The patient underwent surgery on the day of admission. motion. It is accepted that the initial treatment for most The wound was debrided and the fracture underwent closed children with diaphyseal forearm fractures should be a closed reduction and internal fixation with elastic intramedullary reduction and cast immobilization. Surgical intervention is nails (Titanium Elastic Nail [TEN] Synthes, Oberdorf, Swit- required if closed treatment fails. zerland). The radius was stabilized first. This was performed Surgical fixation of these fractures in children can be in a retrograde fashion via an entry point over Listers tubercle achieved by plating. Plating requires an extensive exposure proximal to the distal radial physis, in the mid-lateral plane. and soft tissue stripping at the fracture site, this leaves ex- A blunt dissection was made to protect and displace the tensive scars. In addition, after hardware removal, there is an extensor tendons out of the way, and an oblique, 2.5-mm drill increased risk for refracture. hole was made to serve as an entry point. The nail was Since the 1980s, flexible intramedullary nailing has be- inserted under fluoroscopy and after measuring the desired come the preferred method for surgical fixation of forearm length, the nail was retracted, trimmed using the cutting pliers fractures in children in our institute.2 Lascombes et al.3 defor TEN and readvanced leaving about 5 mm of the nail protruding out of the bone. scribed elastic intramedullary nailing for forearm shaft frac- The ulnar nail was inserted antegrade via an entry point tures in children. They advocated closed reduction and distal to the olecranon physis, on the radial border of the ulna intramedullary fixation with specially made steel or titanium to avoid damage to the ulnar nerve as well as to prevent nails. Numerous authors have reported success using similar damage to the physis. The nail was inserted under image techniques.4–6 The advantages of this method include small intensifier control with a combination of hand pressure and incisions, shorter operating time, and good functional out- taps by a hammer. Both the radial and ulnar nails were buried come. As with any surgical procedure, intramedullary nailing under the skin. An above-elbow cast was applied. of forearm fractures is not free of potential complications. We The patient was admitted to the hospital for 3 days for report here an uncommon complication in a child, alerting us compartment monitoring, neurovascular observation, and in- to a possible problem of this technique. travenous antibiotic therapy. Stitches were removed after 2 weeks in the outpatient clinic. The cast was removed 6 weeks postoperatively. At the 12-week follow-up visit, radiographic evaluation Submitted for publication May 18, 2004. revealed solid union with good alignment of both bones. The Accepted for publication March 31, 2005. patient was pain-free and had a full range of motion at the Copyright © 2007 by Lippincott Williams & Wilkins elbow and wrist. However, there was no active extension of From the Department of Orthopedics Surgery, Pediatric Unit, Chaim the thumb at the interphalangeal joint implying of extensor Sheba Medical Center, Tel-Hashomer, affiliated with Sackler School of Medicine, Tel-Aviv university, Ramat Aviv, Israel. pollicis longus tendon rupture, which was verified at surgery. Address for reprints: Abraham Ganel, E-mail: Abraham.Ganel@sheba. Transfer of the extensor indicis proprius tendon to the stump health.gov.il. of extensor pollicis longus was combined with removal of the DOI: 10.1097/TA.0b013e31802e3fd9 intramedullary nails (25 weeks posttrauma). At follow-up (30

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radius because of the proximity of the extensor tendons in the dorsal aspect of the wrist. REFERENCES 1. Price CT. Injuries to the shafts of the radius and ulna. Volume 3, 4th Ed. In: Rockwood CA Jr, Wilkins KE, Beaty JH, eds. Fractures in Children. Philadelphia: Lippincott Williams & Wilkins; 1996:515– 543. 2. Amit Y, Chechik A, Blankstein A, Horoszowski H. Closing intramedullary nailing for the treatment of diaphyseal forearm fractures in adolescence: a preliminary report. J Pediatr Orthop. 1985;5:143–146. 3. Lascombes P, Prevot J, Ligier JN, Metazeau JP. Elastic stable intramedullary nailing in forearm shaft fractures in children: 85 cases. J Pediatr Orthop. 1990;10:167–171. 4. Rang M. Radius and Ulna. Children’s Fractures. Ed 2. Toronto: JB Lippincott Company; 1983;197–220. 5. Mantout JP, Metaizeau JP, Ligier JN, Prevot J. Embrochage centro- Fig. 1. Cutting the TEN leaves a sharp, irregular edge (above), in medullaire des fractures des deux os de l’avant-bras chez l’enfent. comparison to the intact, smooth edge (below). Technique. Indications. Ann Med Nancy. 1984;23:149–151. 6. Verstreken L, Delronge G, Lamoureaux J. Shaft forearm fractures weeks after the last surgery), the patient had an excellent in children: Intramedullary nailing with immediate motion: a clinical result. preliminary report. J Pediatr Orthop. 1988;8:450–453. 7. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: DISCUSSION retrospective and prospective analysis. J Bone Jt Surg. 1976; Surgical treatment of forearm midshaft fractures in chil- 58A:453–458. dren should be reserved for patients with irreducible fractures 8. Jones K, Weiner D. The management of forearm fractures in or those who fail an attempt of closed treatment. In our children: a plea for conservatism. J Ped Orthop. 1999;19:811–815. 9. Wilkins K. Operative management of children’s fractures: is it a sign opinion, surgical stabilization is also recommended in the of impetuousness or do the children really benefit? J Ped Orthop. presence of an open fracture. However, the treatment of 1998;18:1–3. choice in the majority of diaphyseal forearm fractures in 10. Yung SH, Lam CY, Choi KY, Ng KW, Maffulli N, Cheng JC. children should be by closed fracture reduction and cast Percutaneous intramedullary Kirschner wiring for displaced immobilization.8,9 diaphyseal forearm fractures in children. J Bone Joint Surg. 1998; 80:91–94. For more than 20 years in our institution, intramedullary 11. Shoemaker SD, Comstock CP, Mubarak SJ, Wenger DR, Chambers fixation had became the preferred method of stabilization in HG. Intramedullary Kirschner wire fixation of open or unstable children with diaphyseal forearm fractures.2 The use of forearm fractures in children. J Pediatr Orthop. 1999;19:329–337. K-wires,10,11 Steinman pins,12 reamed square nails,13 and 12. Pugh DM, Galpin RD, Carey TP. Intramedullary Steinmann pin elastic intramedullary nails3,14 have been reported by others fixation of forearm fractures in children: long-term results. Clin Orthop. 2000;376:39–48. with acceptable results. The advantages of the intramedullary 13. Luhmann SJ, Gordon JE, Schoenecker PL. Intramedullary fixation of fixation method include shorter operating time, minimal unstable both-bone forearm fractures in children. J Pediatr Orthop. scars, and minimal soft tissue dissection. Implant removal is 1998;18:451–456. also easier and is seldom associated with refractures.15 14. Waseem M, Paton RW. Percutaneous intramedullary elastic wiring Our patient ruptured his extensor pollicis longus (EPL) of displaced diaphyseal forearm fractures in children: a modified technique. Injury. 1999;20:21–24. tendon more than 6 weeks post-TEN insertion because until 15. Hidaka S, Gustilo RB. Refracture of bones of the forearm after plate that time he was immobilized in a plaster cast. The tendon removal. J Bone Joint Surg. 1984;66:1241–1243. rupture occurred most probably secondary to irritation from 16. Kay R, Khounganian G, Stevanovic M. Late extensor pollicis longus the trimmed sharp edge of the radial nail (Fig. 1). Kay et al.16 rupture following displaced distal radius and ulna fractures in a reported delayed EPL rupture after surgical fixation of frac- child. J Orthop Trauma. 2004;18:53–56. 17. Bonatz E, Kramer TD, Masear VR. Rupture of the extensor pollicis ture of the distal radius in a child using percutaneous pinning. longus tendon. Am J Orthop. 1996;25:118–122. Delayed rupture of the EPL tendon has been described also 18. Simpson RG. Delayed rupture of extensor pollicis longus tendon after minimally displaced fractures of the distal radius in following closed injury. Hand. 1977;9:160–161. adults and children.17,18 Mechanical and vascular causes have 19. Chistophe K. Rupture of the extensor pollicis longus tendon been suggested as reasons for this rare complication.19,20 following Colle’s fracture. J Bone Joint Surg Am. 1953;35A:1003– 1005. Our case highlights the potential damage for EPL tendon 20. Engkvist O, Lundborg G. Rupture of the extensor pollicis longus rupture after TEN insertion. Care must be exercised to avoid tendon after fracture of the lower end of the radius—a clinical and leaving sharp edges when trimming the nail inserted to the microangiographic study. Hand. 1979;11:76–86.

1170 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Damage Caused by a Kirschner Wire Tammo S. de Vries Reilingh, MD, Michel F. P. van der Jagt, MD, William A. H. van der Stappen, MD, and Wout B. Barendregt, MD, PhD

J Trauma. 2007;63:1171–1172.

n this case report we discuss a 66-year-old woman who For example, percutaneous K-wires are used in distal radial was treated in 2003 for a nonunionized lateral clavicle fractures or in loop tension band osteosynthesis, as well as in Ifracture with loop tension band osteosynthesis. This was distraction-type fractures (transverse patella, olecranon). This done by performing an iron loop tension band osteosynthesis technique provides stability to and compression of the frac- with 2.0-mm Kirschner wire (K-wire) in an uncomplicated ture. It is a common technique for fractures in which there is procedure. too little room to fixate a plate and screws on one side of the Ten months later, the patient presented to the emergency fractured bone. The loop tension band osteosynthesis can department with severe respiratory distress. On physical ex- resist high axial strain and stabilizes the forces in articular amination, this patient had a respiratory rate of 20 to 30 fractures. The loop tension band technique uses two parallel breaths/min, with a blood pressure of 140/80 mm Hg, satu- K-wires positioned in axial direction through both parts of the ration of 96% (5 L O2), and decreased breath sounds on the fracture and penetrating both cortices. A “figure eight” is left hemi thorax. positioned through the bone at the top of the K-wire and On further investigation, an electrocardiogram showed through the bowed proximal end of the K-wire. signs of ischemia and chest X-ray showed a pneumothorax, Migration of a K-wire into the thorax is a rare phenom- with a broken K-wire positioned in the left diaphragmatical enon, but can cause serious complications. Only a few cases sinus. A broken K-wire and remains of a second K-wire in the have been reported. In 1943, Mazet reported about a K-wire left clavicle were noticed (Figs. 1 and 2). Further blood placed in the shoulder that had migrated to the lung.1 A investigations showed raised troponine-T and creatine phos- PubMed search found two case reports in which tension band ␮ phokinase levels (1.6 g/L and 367 U/L, respectively), indi- osteosynthesis used for a clavicle fracture resulted in a mi- cating an acute coronary syndrome. grating K-wire.2,3 Leppilahti reported a K-wire that migrated It was concluded that the patient had a persistent non- into the neck, between the trachea and the cervical vertebrae, union of a lateral clavicle fracture after loop tension band only 1 week after it was placed.2 Wirth reported a broken osteosynthesis. A broken K-wire had migrated into the left K-wire that had migrated into the right heart.3 Ullmer re- lung, causing a left pneumothorax and secondary acute cor- ported a migrating K-wire causing a pneumothorax after loop onary syndrome caused by the respiratory distress. tension band osteosynthesis of a subcapital fracture of the The pneumothorax was successfully treated with chest humerus.4 tube decompression in the acute phase. Because of the recent There are a few case reports about singly placed K-wires acute coronary syndrome and the estimated risk for periop- in the shoulder that migrated. Years after a K-wire was erative cardiac complications, the thoracoscopic removal of positioned for a fracture of the clavicle, it migrated between the K-wire was postponed for 3 months. The remaining the thyroid and trachea; in another patient, a migrating K- K-wires in the clavicle were removed at the same time. wire caused a Brown-Sequard syndrome by penetrating the DISCUSSION myelum.5,6 A K-wire positioned for a sternoclavicular luxa- A migrating K-wire can cause serious complications. tion was found in the mediastinum within 1 month after 2 K-wires are commonly used for the treatment of fractures. insertion. In all of the previous cases, the K-wire migrated after it Submitted for publication May 23, 2005. was positioned in the shoulder region. The K-wire had not Accepted for publication August 16, 2005. been bowed after positioning. It is likely that a straight K-wire in Copyright © 2007 by Lippincott Williams & Wilkins the shoulder region can easily lead to migration, probably be- From the Department of Surgery, Canisius-Wilhelmina Hospital, cause it is positioned in a very dynamic part of the body. Nijmegen, Netherlands (T.S.dvR., M.F.D.vdJ., W.A.H.vdS., W.B.B.). Address for reprints: T. S. de Vries Reilingh, MD, Department of Surgery, Osteosynthesis material for fractures of the clavicle can Canisius Wilhelmina Hospital, P.O. box 9015, 6500 GS Nijmegen, The break as a result of the relatively high forces that are applied Netherlands; email: [email protected]. to it, especially in recurrent nonunion fractures. Alternatives DOI: 10.1097/01.ta.0000196678.71801.31 for osteosynthesis in lateral fractures of the clavicle and

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Fig. 3. Loop tension band osteosynthesis in which the two K-wires are positioned through both opposing cortices of the bone. Both sides of the K-wires are bowed after the tension band is placed.

The two parallel K-wires must be positioned through both opposing cortices of the bone. The K-wires must be curved or bowed on both sides after the loop tension band is positioned (Fig. 3). This does not decrease the chances of breaking of the K-wire; therefore, the K-wires have to be removed as soon as consolidation has been achieved. CONCLUSION The use of K-wires in fracture management can give rise Fig. 1. Chest X-ray showing a left pneumothorax with a broken to breaking and migrating of the K-wire even after the frac- K-wire in the left diaphragmatical sinus. ture has healed. A K-wire used for the management of fractures of the clavicle could lead to serious complications. If conservative treatment for this fracture fails or an operation is indicated, the modified loop tension band osteosynthesis with bowed K-wires should be performed. All material should be removed after consolidation of the fracture.

REFERENCES 1. Mazet RJ. Migration of a Kirschner wire from the shoulder region into the lung. J Bone Joint Surg. 1943;25:477. 2. Leppilahti J, Jalovaara P. Migration of Kirschner wires following fixation of the clavicle-a report of 2 cases. Acta Orthop Scand. 1999; 70:517–519. 3. Wirth MA, Lakoski SG, Rockwood CA Jr. Migration of broken cerclage wire from the shoulder girdle into the heart: a case report. Fig. 2. Loop tension band osteosynthesis for a fracture of the J Shoulder Elbow Surg. 2000;9:543–544. lateral clavicle showing broken K-wires. Fracture is still not 4. Ullmer E, Bolliger CT, Soler M. Pneumothorax or the end of a consolidated. wire’s journey. Respiration. 1998;65:151. 5. Foster GT, Chetty KG, Mahutte K, Kim JB, Sasse SA. Hemoptysis luxations of the acromioclavicular joint are few. If using due to migration of a fractured Kirschner wire. Chest. 2001;119: 1285–1286. osteosynthesis in a nonunion clavicle fracture because of 6. Loncan LI, Sempere DF, Ajuria JE. Brown-Sequard syndrome persisting pain, for example, the advice is to adjust the ten- caused by a Kirschner wire as a complication of clavicular sion band osteosynthesis in the following way. osteosynthesis. Spinal Cord. 1998;36:797–799.

1172 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Intrapelvic Penetration of the Dynamic Hip Screw During Removal: Lesson Learnt—Always Use a Coupling Screw Rahij Anwar, MS, MSc, MRCS, Venkat Boorgula, MRCS and James E. Nicholl, FRCSOrth

J Trauma. 2007;63:E105–E106.

enetration of the hip joint may occur after dynamic hip found to be quite large but the outer end of the screw could screw fixation. The screw can cut out in the osteopo- not be felt. Multiple attempts to grab the screw were un- Protic bone and occasionally will perforate the acetabu- successful. The search for the screw was abandoned because lum and migrate into the pelvis. We report an unusual case of of the deteriorating general condition of the patient during intrapelvic penetration of the dynamic hip screw during sur- surgery. gery for its removal, and give advice on how to prevent this Re-exploration by a more senior surgeon 48 hours later potentially catastrophic complication. and under image intensifier control showed penetration of the dynamic hip screw into the pelvis (Fig. 3), with its outer half Case Report still inside the head of femur. The central core of the head of A 61-year-old man presented with a deformed left leg. femur was nibbled out to gain access to the outer end of the There was no definite history of a fall, but the patient was screw. The screw was successfully extracted and was fol- dependent on a wheelchair because of multiple sclerosis. lowed by the excision of the remaining part of the femoral There was shortening of the lower extremity and abnormal head (Girdlestone’s procedure). No intrapelvic complications motion of the hip on the affected side. Radiographs of the hip occurred. The wound responded well to treatment with a vac- revealed a comminuted intertrochanteric fracture associated uum pump, regular dressings, and antibiotics. Unfortunately, the with severe osteoporosis. patient died a few months later from unrelated causes. The fracture was treated with a dynamic hip screw, 6-hole side plate (Synthes, Switzerland), and a trochanetric support plate. Comminution of the fracture and the fragility DISCUSSION of the bone made fixation difficult and prolonged the opera- Multiple sclerosis is associated with severe osteope- tive time. However, satisfactory fracture fixation (Fig. 1) was nia, mainly because of immobility. Special care is required achieved without the use of a compression screw. There was in handling such patients, especially during transfers. The significant intra- and postoperative hemorrhaging, and a fragile bones in these patients may fracture with minimal blood transfusion was required. trauma. Fracture fixation is difficult in such bones because Five days after surgery, the patient fell out of his bed on the of a greater degree of comminution; poor purchase of ward. His wound became infected and dehisced, and subsequent hardware used for fixation in osteoporotic bone, which X-rays of the hip (Fig. 2) revealed a failure of the fixation with increases the risk of further fractures; and future failure of penetration of the dynamic hip screw into the joint. Comminu- fixation. In our case, the fall during the postoperative tion of the fracture, poor bone quality, and the fall itself may period, in addition to the reasons mentioned above, may have contributed to the implant failure. also have contributed to the displacement of the fracture The hip was explored with the intent of removing the and hardware. hardware and debriding the infected wound. The screws hold- The screw can penetrate into the joint for various rea- ing the trochanteric and barrel plate were loose and were sons.1,2 Loss of contact between the dynamic hip screw and easily removed. The entry of the dynamic hip screw was the barrel plate is commonly referred to as “disengagement”, and it is thought to be the major cause3–6 of the sliding-screw Submitted for publication November 5, 2004. plate failure. Accepted for publication September 1, 2005. In our patient, we think the screw was pushed through From the Department of Trauma and Orthopaedics, Kent and Sussex the floor of the acetabulum into the pelvis when blind at- Hospital (R.A., V.B., J.E.N.), Tunbridge Wells, Kent, England, United Kingdom. tempts were made to grab the end of the screw. The intrapel- Copyright © 2007 by Lippincott Williams & Wilkins vic penetration of the screw during surgery for its removal Address for reprints: Rahij Anwar, MS, MSc, MRCS, 2 Lordswood could have possibly been avoided if a coupling (compression) Close, Bexleyheath, Greater London DA6 8LB; email: [email protected]. screw was used. It could have been applied before removing DOI: 10.1097/01.ta.0000196929.07639.7a the screws from the side plate. The barrel plate should have

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Fig. 3. Penetration of the dynamic hip screw into the pelvis during removal.

screw. This would have provided some tension at the screw- barrel interface. A coupling screw makes the dynamic hip screw construct more stable and secure, thereby making the removal easier. The coupling screw should be tightened to the sliding Fig. 1. A comminuted intertrochanteric fracture fixed with a dy- screw while the barrel plate is still in contact with the bone namic hip screw and a trochanteric support plate. and sliding device. After ensuring that the coupling is secure the barrel plate can be safely pulled out. The chance of losing been securely held at an angle after removal of the screws the dynamic hip screw with this technique is minimal and any from the plate while it was still engaged with the dynamic hip medial migration can easily be avoided because of the presence of the coupling screw. Rao and Pringle2 reported a similar complication. How- ever, they discontinued the exploration of the intrapelvic screw because they thought it was retroperitoneal, deep to the iliacus muscle, and unlikely to cause any future pelvic problems. The removal of a dynamic hip screw should be performed very cautiously. A coupling screw provides better control over the sliding screw. We recommend the routine use of a compression screw in any hip surgery involving the dynamic hip screw, whether it is initial fixation or later removal. REFERENCES 1. Kyle RF, Wright TM, Burstein AH. Biomechanical analysis of the sliding characteristics of compression hip screws. J Bone Joint Surg. 1980;62:1308–1314. 2. Rao SB, Pringle RG. Intrapelvic penetration of a sliding screw: a rare complication. Injury. 1992;23:56–57. 3. Brodell JD, Leve AR. Disengagement and intrapelvic protrusion of the screw from a sliding screw-plate device. J Bone Joint Surg. 1983;65:697–701. 4. Cameron HU, Graham JD. Retention of the compression screw in sliding screw plate devices. Clin Orthop. 1980;146:219–221. 5. Dunn EJ, Skinner SR. Disengagement of a sliding screw plate. Case report. J Bone Joint Surg. 1976;58:1027–1028. 6. Jacobs RR, McClain O, Armstrong HJ. Internal fixation of Fig. 2. Loss of fixation with penetration of the dynamic hip screw intertrochanteric hip fractures: a clinical and biomechanical study. into the joint. Clin Orthop. 1980;146:62–70.

E106 November 2007 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Hybrid Procedures Combining Open and Endovascular Surgical Techniques for the Management of Subclavian Artery Injuries Christos D. Karkos, FRCSEd, PhD, Richard Mair, MB, ChB, George Markose, FRCR, Guy Fishwick, FRCR, Nicholas J. M. London, MD, FRCS, and A. Ross Naylor, MD, FRCS

J Trauma. 2007;63:E107–E110.

ubclavian vascular injuries are notorious for their dif- was transferred directly to the operating theater with the ficult surgical exposure. Proximal and distal control of guidewire in place. An occlusion balloon (Cook, William Sthe vessel may require a combination of supraclavicular Cook Europe, Denmark) was introduced and inflated at the or infraclavicular incision, clavicular transection, median origin of the left subclavian artery and a supraclavicular sternotomy, or thoracotomy. Such an extensive dissection is incision was made revealing a large hematoma. The in- associated with significant morbidity, whereas delay or loss fected thrombus was evacuated, but there was still consid- of control can result in rapid exsanguination and death. In this erable back bleeding that was controlled digitally. The PTFE context, endovascular maneuvers may offer an appealing graft was removed and the disrupted proximal subclavian alternative approach to these technically challenging injuries. artery was oversewn. Upon deflation of the occlusion balloon We describe the management of two complex traumatic false there was no further bleeding. The upper limb remained aneurysms of the proximal subclavian artery using a combi- viable obviating the need for revascularization. The wound nation of open and endovascular techniques. was packed and left open to heal via secondary intention. He made a slow but steady recovery. Ten days later he was CASE REPORT transferred back to his local hospital to the care of the ortho- Case 1 pedic and plastic surgeons. He has a viable but useless upper A 21-year-old man was admitted to a neighboring hospital limb. after being hit by a lorry. Among other injuries, he sustained a fracture of the left scapula, avulsion injury of the brachial Case 2 plexus, and laceration to the subclavian artery. He underwent A 51-year-old woman was referred to us with an urgent repair necessitating a vein bypass graft from the sub- expanding false aneurysm at the right supraclavicular fossa clavian to brachial artery. Because of problems at the prox- after an attempt to insert a long-term chemotherapy cath- imal anastomosis, the first few centimeters of the vein graft eter into the subclavian vein. Ultrasonography had re- were replaced with a 5-cm length of 6-mm PTFE. Four weeks vealed a large false aneurysm arising from the confluence later, he developed a rapidly expanding mycotic false aneu- of the vertebral and subclavian arteries. She underwent rysm arising from the anastomosis between the PTFE and selective arteriography that confirmed the ultrasonographic find- vein grafts. Blood cultures yielded Pseudomonas species and ings (Fig. 2A, B). Two attempts at percutaneous ultrasound- later MRSA. He was referred to our vascular unit for further guided thrombin injection and coil delivery after balloon management. Urgent angiogram, performed via the right fem- tamponade of the origins of the subclavian and vertebral oral approach, showed complete disruption of the anastomo- arteries failed to thrombose the false aneurysm (Fig. 2C, D). sis between the PTFE and vein grafts (Fig. 1). The patient It was decided to proceed to a combined open and endovascular repair of the aneurysm with transposition of the verte- Submitted for publication November 8, 2004. bral into the common carotid artery followed by implantation Accepted for publication May 9, 2005. of a stent-graft. She was taken to the operating theater 48 Copyright © 2007 by Lippincott Williams & Wilkins hours later. From the Department of Vascular and Endovascular Surgery (C.D.K., The operation was performed under general anesthesia. R.M., N.J.M.L., A.R.N.) and the Department of Radiology (G.M., G.F.), Leicester Royal Infirmary, Leicester, United Kingdom. Via a right groin puncture, a guidewire was positioned in the Address for reprints: Christos D. Karkos, Department of Vascular & subclavian artery. An oblique presternomastoid incision was Endovascular Surgery, Leicester Royal Infirmary, Leicester LE1 5WW, UK; made to access the common carotid and vertebral arteries. email: [email protected]. However, the dissection was extremely difficult because of DOI: 10.1097/01.ta.0000223943.61967.73 the extensive hematoma. This was unavoidably entered and

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over the stent-graft achieving a tamponade effect. The wound was tightly packed and she was transferred to the Intensive Care Unit where she was ventilated. A second look was performed 24 hours later when no further bleeding was found and the wound was closed. Postoperatively, she was noted to have visuo-spatial neglect and inattention and computed tomography scan showed a small right middle cerebral artery infarct. However, she quickly improved and made an otherwise uneventful recovery with no residual neurologic deficits.

DISCUSSION Subclavian artery trauma can be extremely challenging to tackle operatively and can provoke life-threatening hemorrhage. Fortunately, such injuries are uncommon, representing only 5% of all arterial injuries.1 Even in the elective setting, surgical exposure and control may well require sternotomy, thoracotomy, or clavicular transection.1 In the presence of multiple traumatic injuries and medical co-morbid conditions, this major dissection contributes significantly to the high morbidity and mortality seen with these lesions. As a result, endovascular therapy seems to be ideal for such injuries. Stent-grafting is minimally invasive, can be performed under local anesthesia, and is associated with shorter operative time, reduced blood loss and shorter hospital stay.2–6 When stent-graft placement is not feasible, combining endovascular procedures with classical surgery may reduce the risks of massive and difficult open surgery. We decided against stent-grafting in the first patient because of the severe infection and the presence of a mycotic aneurysm. Eradication of the sepsis could have been achieved only by complete removal of the prosthetic graft. We opted Fig. 1. (A, B) Angiogram showing a large mycotic false aneurysm for ligation alone without revascularization, as ischemia is in the left supraclavicular fossa. usually well tolerated because of the extensive collateral circulation. Furthermore, avulsion injury of the brachial plexus heavy bleeding was encountered. An occlusion balloon, in- results in devastating functional disability of the upper limb and persistent causalgia. This may lead to repeated hospital- troduced over the guidewire, was inflated across the false ization and even subsequent elective amputation regardless of aneurysm to control the bleeding. The hematoma was evac- patent arterial repair. uated, but there was some residual bleeding from deep within In the second patient, an ultrasound-guided percutaneous the aneurysm cavity that was controlled digitally. Subse- approach was attempted first to deliver thrombin and coils quently, it became apparent that the vertebral artery had in within the aneurysm sac and pulsatile flow had been arrested fact thrombosed approximately 2 cm distal to its origin, by two balloons inflated in the subclavian and vertebral perhaps because of secondary compression by the false aneu- arteries, respectively. In retrospect, given the extent of the ϫ rysm. A 10-mm 5-cm Wallgraft (Boston Scientific, Natick, arterial disruption, this was unlikely to succeed. We decided Mass.) was then deployed across the false aneurysm but did not to proceed with stent-grafting, but opted to preserve the vertebral gain complete control of the bleeding. A check angiogram artery by transposing this into the common carotid artery. How- showed that there was still flow within the false aneurysm. The ever, this was not performed as the vertebral artery, which was balloon was re-inflated in the subclavian artery and a second patent the day before on a preoperative duplex scan, was found Wallgraft was deployed within the first one starting immediately to be occluded intra-operatively. An alternative approach would beyond the origin of the right common carotid artery (Fig. 3). have been to embolize the vertebral and other arterial branches Unfortunately, this still failed to fully control the bleeding from with coils followed by stent-grafting of the proximal subclavian the deep tissues because of the extensive tissue disruption, and artery under local anesthesia. DuToit et al. performed coil em- the back bleeding from torn arterial branches of the thyrocervical bolization of the vertebral artery before stent-grafting in four trunk. These were ligated and the disrupted tissues were closed patients with no neurologic complications.2

E108 November 2007 Management of Subclavian Artery Injuries

Fig. 2. (A–D) Arch angiogram (A) and selective views (B) demonstrating a false aneurysm of the proximal right subclavian artery. Percutaneous ultrasound-guided thrombin (C) and coil (D) delivery and pulsatile flow within the aneurysm sac had been arrested by inflating angioplasty balloons in the origins of the subclavian and vertebral arteries.

A technique often employed by vascular and trauma lesion. To our knowledge, there is only one similar report surgeons is the use of Fogarty catheters with a three-way tap published in the literature in a patient with a large supracla- to obtain proximal and distal control, allowing for further vicular false aneurysm and a fistula between the subclavian dissection and, then, direct surgical control of the vessels. artery and the internal jugular vein.10 Proximal bleeding con- However, neither of our patients was suitable for such a trol was obtained by a balloon catheter and this allowed the maneuver. Both arterial lesions were located in a relatively direct surgical repair of the fistula avoiding the transthoracic inaccessible point and the tissues and anatomic planes were approach. In such complex lesions, a percutaneous balloon distorted because of the presence of extensive hematoma catheter introduced at a remote site is a helpful tool for the and/or infection. Therefore, Fogarty catheter balloon occlu- surgeon. sion through the wound without prior proximal control would It should be stressed that proximal only balloon occlu- have been extremely difficult and unlikely to result in early sion will not result in an entirely bloodless field during control of the bleeding. exploration of the injured arterial segment. Significant bleed- The principle of endovascular balloon occlusion to gain ing may still occur resulting in back bleeding from the axil- proximal arterial control is not new and has been reported in lary artery and the numerous sizable side branches of the several clinical circumstances, primarily trauma.7 Intra-aortic subclavian artery that might be involved in the injury. To balloon tamponade has been used to arrest bleeding from pen- minimize back-bleeding from the axillary artery, distal con- etrating or blunt abdominal trauma, ruptured abdominal aortic or trol can be achieved through the wound by a Fogarty balloon iliac aneurysms, and gastrointestinal bleeding from a peptic with a three-way tap, or a second balloon occlusion catheter ulcer or an aorto-enteric fistula.7–9 The use of catheter-directed threaded in retrograde fashion via a brachial approach and techniques in patients with proximal subclavian artery inju- inflated distal to the arterial lesion. Side-branch involvement ries has been employed to avoid the obvious disadvantages of may be another source of significant bleeding during the a major second incision (thoracotomy or sternotomy) in crit- direct approach of the artery as well as the cause of endoleak ically ill patients and allow direct approach to the arterial during stent-grafting. Side-branches resulted in excessive

Volume 63 • Number 5 E109 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

blood loss in both our patients and in a persistent endoleak in the second one. Direct suturing and ligation was required to control this. The potential occurrence of thromboembolism during or after stent deployment or manipulations, especially in the carotid artery, is also a cause of concern. This was seen in our second patient, but, fortunately, did not result in a disabling stroke and the symptoms quickly improved. Meticulous technique and extra care is, therefore, required during guidewire and catheter manipulation. In summary, when faced with a complex thoracic outlet arterial injury unsuitable for stent-grafting, we found the combination of endovascular procedures with classical surgery to be quite rewarding. This approach offers an alternative less invasive solution in patients who would otherwise require sternotomy or thoracotomy for proximal control.

REFERENCES 1. Hyre CE, Cikrit DF, Lalka SG, Sawchuk AP, Dalsing MC. Aggressive management of vascular injuries of the thoracic outlet. J Vasc Surg. 1998;27:880–885. 2. Du Toit DF, Strauss DC, Blaszczyk M, De Villiers R, Warren BL. Endovascular treatment of penetrating thoracic outlet arterial injuries. Eur J Vasc Endovasc Surg. 2000;19:489–495. 3. May J, White G, Waugh R, Weiyun YU, Harris JE. Transluminal placement of a prosthetic graft-stent device for treatment of subclavian artery aneurysm. J Vasc Surg. 1993;18:1056–1059. 4. Patel AV, Marin ML, Veith FJ, Kerr A, Sanchez LA. Endovascular graft repair of penetrating subclavian artery injuries. J Endovasc Surg. 1996;3:382–388. 5. Babatasi G, Massetti M, Le Page O, Theron J, Khayat A. Endovascular treatment of a traumatic subclavian artery aneurysm. J Trauma. 1998;44:545–547. 6. Xenos ES, Freeman M, Stevens S, Cassada D, Pacanowski J, Goldman M. Covered stents for injuries of subclavian and axillary arteries. J Vasc Surg. 2003;38:451–454. 7. Sobeh MS, Westacott S, Blakeney C, Ham RJ. Balloon angioplasty catheters for endovascular tamponade after vascular trauma. Injury. 1993;24:355–356. 8. Loftus IM, Thompson MM, Fishwick G, et al. Technique for rapid control of bleeding from an aortoenteric fistula. Br J Surg. 1997; 84:1114. 9. Karkos CD, Bruce IA, Lambert ME. Use of the intra-aortic balloon pump to arrest gastrointestinal bleeding. Ann Emerg Med. 2001; 38:328–331. 10. Nemes A, Pinter L, Huttl K, Biro G, Acsady G. Proximal bleeding Fig. 3. (A, B) Intra-operative digital subtraction angiogram show- control obtained by a balloon catheter in the surgical repair of a left ing the Wallgraft deployment in the proximal subclavian artery. supraclavicular traumatic arteriovenous fistula. J Vasc Surg. 1997; There is some residual bleeding and late filling of the aneurysm sac. 25:587–590.

E110 November 2007 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

Low-Molecular-Weight Heparin for Prevention of Thrombosis: Inverted Role Zoe H. Dailiana, MD, Konstantinos N. Malizos, MD, Sokratis Varitimidis, MD, Michael Hantes, MD, George Basdekis, MD, and Nikolaos Rigopoulos, MD

Background: Heparin induced throm- days (4–7) and had signs of arterial occlu- platelet decrease, heparin administration bosis (HIT) after low-molecular-weight sions on the 9th and 10th postoperative should be ceased after emergency testing (LMWH) administration for thrombosis days. The patient with the initially success- for heparin induced antibodies. When HIT prevention is a limb and life threatening ful forearm replantation was finally ampu- syndrome is confirmed to have occurred, condition. tated below the elbow, whereas the lower heparin/LMWH must be replaced with Methods: Two previously healthy in- extremity of the patient with total knee ar- thrombin-specific inhibitors. dividuals, with nonviable forearm ampu- throplasty and contralateral femoral artery Key Words: Heparin-induced throm- tation and knee osteoarthritis, suffered occlusion was salvaged with foot fingers am- bocytopenia/thrombosis, LMWH, White- from multiple arterial thromboses (>2 putation only. clot syndrome, Orthopedics, Trauma. sites each) after postoperative administra- Conclusions: Early recognition of the tion of LMWH. syndrome by monitoring daily platelet counts Results: Both patients suffered from during heparin therapy is essential. In case thrombocytopenia on the first postoperative of postheparin (LMWH or unfractionated) J Trauma. 2007;63:E111–E115.

eparin, unfractionated or low-molecular-weight (LMWH) thrombosis in patients with HIT to 20%, of mortality to 30% has been used traditionally for the prevention of throm- and of permanent morbidity to 20 to 30%.15 Hbosis in reconstructive orthopedic and microsurgical In contrast to the old belief that the formation of anti- procedures.1–4 However, there are cases where heparin causes bodies is associated to the use of unfractionated heparin only thrombocytopenia and thrombosis, arterial, or venous. Although and not to the use of LMWH, which led to inappropriate use the syndrome has been recognized since the 1980s5–10 and de- of LMWH for HIT treatment,16 it has been found that there is scribed as heparin induced thrombocytopenia/thrombosis (HIT) or extensive cross-reactivity between the two types of heparin.13 White Clot Syndrome, it is not well known and leads to limb and LMWH has proved to cause HIT, however, in lower rates life threatening thrombosis.9,11–13 than unfractionated heparin. The difference between the rates HIT is related to the formation of antibodies against a of anti-PF4/heparin antibody formation for LMWH and un- complex of heparin (unfractionated or LMWH) and a platelet fractionated heparin varies in different studies. The rates lie factor (PF4). This immune reaction may lead to severe throm- between 1% and 8% for LMWH and between 5% and 17% bocytopenia and in some cases to thrombosis. An iceberg for unfractionated.13–14,17 Thus, HIT is associated with the phenomenon had been described, where only a small percent- use of both types of heparin (unfractionated and LMWH), age (1%) of the patients that form anti-PF4/heparin antibodies however, the syndrome is less likely to occur with LMWH causing HIT will develop thrombocytopenia and thrombosis. than with unfractionated heparin.13 Orthopedic procedures are associated with a high percentage The experience from patients who underwent this cata- of antibody formation (10–15%), and a relatively low per- strophic syndrome will be presented along with contemporary centage (3–5%) of thrombocytopenia with or without throm- methods of prevention and treatment, to elucidate this under- botic complications.14 Other studies raise the percentage of recognized and relatively common complication of LMWH use.

Submitted for publication November 14, 2004. Accepted for publication May 20, 2005. Copyright © 2007 by Lippincott Williams & Wilkins MATERIALS AND METHODS From the Department of Orthopaedic Surgery, School of Health Sci- Two patients suffered from multiple arterial thromboses ences, University of Thessalia, 22 Papakiriazi St, Larissa 41222, Greece. after postoperative administration of LMWH in a period of 5 The paper was previously presented in whole or in part in the following months. Both patients were retrospectively included in this meeting: 9th Congress of the International Federation of Societies for Sur- gery of the Hand, Budapest, Hungary, June 13–17, 2004. study, were informed that their cases would be reported in the Address for reprints: Zoe H. Dailiana, MD, School of Health Sciences, scientific world and have a minimum follow-up of 2 years University of Thessalia, 22 Papakiriazi St., Larissa 41222, Greece; email: (25–30 months). A 48-year-old male patient with incomplete [email protected] nonviable amputation of the left forearm, received LMWH DOI: 10.1097/01.ta.0000233909.88264.43 after a successful forearm replantation, whereas a 72-year-old

Volume 63 • Number 5 E111 The Journal of TRAUMA௡ Injury, Infection, and Critical Care female patient received LMWH after a total knee arthro- mobile), the administration of LMWH was discontinued im- plasty. Both patients had no history of previous illness, mediately. The lower extremity was successfully revascular- thrombosis, or prethrombotic conditions. ized after removal of the thrombus with a Fogarty catheter The patient with nonviable amputation of the left fore- and fasciotomy, however, another occlusion occurred at the arm had both radial and ulnar arteries bridged with a vein level of the ipsilateral popliteal artery 2 days later, that graft from the right saphenous vein. He received LMWH so necessitated another vascular procedure. that thrombosis of anastomoses would be prevented. Recov- ery was uneventful and dressing changes the 4th and 8th RESULTS postoperative day confirmed the viability of all structures and Both patients presented thrombocytopenia (Ͼ40% re- the necessity for a split thickness skin graft on the palmar duction of the preoperative and pre-LMWH administration aspect of the forearm. However, in the evenings of the 8th, levels), which started on the first postoperative days (4th and 9th, and 10th postoperative days the patient experienced 7th, respectively). Platelets revealed a drop from 209 ϫ 109/L acute pain in the left forearm and hand without changes of to 99 ϫ 109/L and from 278 ϫ 109/L to 20 ϫ 109/L for the vascularity. Each episode lasted 2 to 3 hours and the pain was first and second patient, respectively (Table 1). relieved by administration of opioids. In the last episode (late Both patients had signs of arterial occlusion on the 9th and evening of the 10th postoperative day) acute pain was expe- 10th postoperative days. Administration of LMWH was discon- rienced again, followed by signs of ischemia. The patient was tinued after confirmation of arterial occlusions and the patients transferred to the operating room where examination of the were treated subsequently by vascular surgeons (Table 1). grafted arteries revealed complete occlusion of both arteries Anti-PF4/heparin antibodies were detected in the second with white clots,5,9,18 which occupied the grafts and extended patient. As for the first patient, for whom the test was per- beyond the anastomoses. A Fogarty catheter revealed thrombi formed with delay (4 months after the complication), the extending to the middle third of the brachial artery. A re- results were negative. Hematologic tests to reveal predispo- grafting of ulnar and radial arteries with a vein graft from the sition to thrombosis were also made and were negative for saphenous of the left lower extremity was attempted. The both patients. results were negative because of immediate formation of The patient with the initially successful forearm replan- thrombi. Intravenous administration of unfractionated hepa- tation was finally amputated below the elbow because of rin was started in the operating room and continued postop- brachial artery thrombosis. The thromboses of lower extrem- eratively (30,000 IU/date), replacing the LMWH. On the 12th ities (left common iliac and right popliteal artery), the ex- postoperative day (1st postrevision day) the patient had a tended thrombosis of the upper extremity (left subclavian painful and pale left lower extremity. The hypothesis that artery), and the left atrium appendage thrombosis were suc- arterial occlusion might have occurred was confirmed by cessfully treated with or without surgical intervention. The computed tomography angiography, which revealed occlu- lower extremity of the patient with total knee arthroplasty and sion of the left common iliac artery. HIT was suspected, secondary occlusion of the contralateral femoral and popliteal which led the treating orthopedic surgeons to discontinue arteries was salvaged with secondary amputation of foot heparin administration and to transfer the patient to a vascular fingers only (Table 1).19 At the latest follow-up (30 and 25 surgery center. The clot was removed and the left lower months, respectively) both patients were alive and able to extremity was successfully revascularized, whereas the left move without support and had resumed their daily activities. upper extremity was amputated at the level of the upper forearm. On the 18th postoperative day, an occlusion of the DISCUSSION right popliteal artery necessitated another procedure for revas- Thrombocytopenia can develop after the use of heparin cularization of the right lower extremity. Finally, on the 25th either early in the first postoperative days (2nd through 4th), postoperative day, after detection of thrombosis of the left sub- or later after the 5th day. In general, two distinct types of HIT clavian artery and of the left atrium appendage (the later was not have been described: (1) the clinically benign type I, which is present at the two-dimensional doppler examination performed characterized by early mild thrombocytopenia and affects one on the 12th postoperative day), the patient was placed in anti- fourth of the patients who have received heparin, and (2) the platelet agents. Surgical treatment was not required for the last relatively uncommon but severe type HIT II, which affects 1 two thrombotic episodes. to 5% of patients. In type II HIT, severe thrombocytopenia The 72-year-old previously healthy female patient, who (platelet count below 150 ϫ 109/L and/or 50% decrease from underwent a total knee arthroplasty of the right knee and the permanent platelet count) is associated with limb and life received LMWH postoperatively, had an uneventful recovery threatening thrombosis. The syndrome is immuno-mediated and was able to move after the 2nd postoperative day. How- and usually develops within a period of 5 to 14 days after the ever, on the 9th postoperative day, she developed an occlu- initiation of heparin therapy. In the present study, both pa- sion of the femoral artery of the contralateral lower extremity. tients developed thrombocytopenia and the symptoms of ar- As she was the second patient in a 5-month period with terial occlusion within the aforementioned periods, i.e. on the inexplicable arterial thrombosis (although under LMWH and 4th and 7th postoperative/post-LMWH administration days

E112 November 2007 LMWH for Prevention of Thrombosis

Table 1 Clinical and Laboratory Findings of Patients With HIT

Patient 1 Patient 2 Procedure Forearm replantation L Total knee arthroplasty R Plt pre-op 209 278 Plt 1st post-op day 155 209 Plt 4th post-op day 100 220 Plt 7th post-op day 108 89 Plt day of occlusion (10th & 9th 99 25 post-op day) Plt 11th post-op day 108 20 Occlusion site 1 Brachial, radial, ulnar arteries L Femoral artery L Procedure 1 Revision of anastomoses and thrombectomy Thrombectomy and fasciotomy (unsuccessful) Date 1 10th post-op 9th post-op Occlusion site 2 Common iliac artery L Popliteal artery L Procedure 2 Thrombectomy Thrombectomy Date 2 12th post-op 11th post-op Occlusion site 3 Popliteal artery R — Procedure 3 Thrombectomy — Date 3 18th post-op — Other occlusions Subclavian artery L and L atrium appendage — Follow-up 30 mo 25 mo Current condition Upper forearm amputation L Foot fingers amputation L independently mobile independently mobile Plt, platelet counts expressed x109/L; L, left; R, right; Pre-op, preoperative; Post-op, postoperative and post-LMWH administration day; mo, months.

(thrombocytopenia), and on the 9th and 10th days (arterial reaction.15,18 Finally, patients with clinical symptoms of HIT occlusion).9,11–14,18,20,21 and absence of antibodies to PF4/heparin have been reported: The pathophysiology of the syndrome has been elucidated other antigens (chemokines interleukin-8 and neutrophil- during the past decade. Antibodies, usually of IgG class, develop activating peptide-2) have been incriminated in such cases.25–27 against the complex of heparin that binds to the PF4. These Although the above reports may explain the negative labora- immune complexes of IgG and PF4/heparin (anti-PF4/heparin tory findings (absence of anti-PF4/heparin antibodies) about antibodies) promote platelet activation and aggregation, excess the first patient who had all the clinical symptoms of HIT thrombin generation and activation of microvascular endothelial along with thrombocytopenia, the elapsed period of 4 months cells. Enhanced thrombin generation in combination with the between the outgrowth of the syndrome and the realization of activation of platelets and endothelial cells can explain the the test should be also considered as a negative factor for thromboembolic incidents.11,12,14,18,22,23 A genetic predisposi- detection of antibodies. tion to HIT has recently been found.18,24 The diagnostic criteria of HIT include a normal platelet Although HIT is clinically diagnosed,11 laboratory con- count before heparin treatment, thrombocytopenia after initi- firmation of the syndrome is urgently required to help decide ation of heparin that cannot be attributed to other causes whether heparin (unfractionated or LMWH) treatment should (sepsis, bypass surgery)12 and detection of anti-PF4/heparin continue or not. Laboratory tests for detection of heparin- antibodies.18 Both patients in the present study developed induced antibodies are of two types: (1) functional assays and thrombocytopenia on the 4th and 7th days after administra- (2) immuno-assays. The functional assays measure heparin- tion of heparin and thrombosis on the 10th and 9th days, dependent platelet activation by the HIT antibody in vitro. respectively. It has been reported that after orthopedic surgi- They include the platelet aggregation test, the C-serotonin cal procedures most patients show a transient decrease in the release assay and the heparin-induced platelet-activation as- platelet count followed by an increase above the preoperative say. Enzyme immunoassays measure IgG, IgA, or IgM that count.13 This was partially true for the first patient, who bind to PF4/heparin complexes absorbed onto the walls of developed a steady decrease in the platelet count from the microtiter plates.12,14,18,25 Although there are different opin- first postoperative and post-LMWH administration days that ions on which method, functional or immunoassay, offers the became marked on the 4th day. The second patient, on the greatest sensitivity and specificity,14,18 it seems that neither other hand, developed an acute thrombocytopenia on the 7th of the two methods is 100% sensitive and that the two types day (Table 1). of assays complement each other.18 The presence of heparin Both patients developed arterial thrombosis (brachial, com- is not necessary for HIT antibodies to cause platelet activa- mon iliac, popliteal, subclavian arteries and femoral, popliteal tion; other polysulfated saccharides may also lead to the same arteries, respectively). Although HIT was traditionally associ-

Volume 63 • Number 5 E113 The Journal of TRAUMA௡ Injury, Infection, and Critical Care ated with arterial thrombosis,28,29 it seems that venous thrombi REFERENCES 12,14 predominate over arterial in a ratio of 4 to 1. Possible 1. Gillespie W, Murray D, Gregg PJ, et al. Risks and benefits of explanations for this discrepancy are (1) the venous thromboses profhylaxis against venous thromboembolism in orthopaedic surgery. pass undetected or (2) the concomitant thrombocytopenia is not J Bone Joint Surg Br. 2000;82B:475–479. evaluated (because of relative unawareness of the syndrome) 2. Soucacos PN, Beris AE, Malizos K, et al. Treatment of avascular whereas the venous thromboses are misinterpreted and attributed necrosis of the femoral head with vascularized fibular transplant. Clin Orthop. 2001;386:120–130. to the decreased mobility of the postoperative period. Thus, only 3. Nurmohamed MT, Rosendaal FR, Buller HR, et al. Low-molecular- the subsequent arterial thromboses could lead the treating phy- weight heparin versus standard heparin in general and orthopaedic sicians to relate the thrombotic complications to HIT. surgery: a meta-analysis. Lancet. 1992;340:152–156. Early recognition of the syndrome by monitoring daily 4. Colwell CW Jr. Low molecular weight heparin prophylaxis in total platelet counts during heparin therapy is the first and most knee arthroplasty: the answer. Clin Orthop. 2001;392:245–248. essential measure for HIT treatment.20 In case of thrombo- 5. Towne JB, Bernhard VM, Hussey C, et al. White clot syndrome. Peripheral vascular complications of heparin therapy. Arch Surg. cytopenia occurrence, heparin administration must be discon- 1979;114:372–377. tinued and a test to detect anti-PF4/heparin antibodies should 6. Bottiger LE. Heparin-induced thrombocytopenia. Acta Med Scand. be made. If a diagnosis of HIT is confirmed the patient should 1985;218:257–259. be informed about and advised on how to avoid heparin in the 7. Battey PM, Salam AA. Venous gangrene associated with heparin- future whereas the treating physicians and nursing stuff must induced thrombocytopenia. Surgery. 1985;97:618–620. 8. Kelton JG. Heparin-induced thrombocytopenia. Haemostasis. 1986; be cautious to avoid all kinds of heparin, even solutions for 14 16:173–186. flushing of catheters. 9. Baldwin DR. Heparin-induced thrombocytopenia. J Intraven Nurs. Because of a very high rate of thrombotic progression that has 1989;12:378–382. been demonstrated in patients with HIT, alternate antithrombotic 10. Chong BH, Berndt MC. Heparin-induced thrombocytopenia. Blut. therapy should be administered after discontinuation of heparin 1989;58:53–57. or LMWH treatment.14,30 Several agents have been proposed 11. Deitcher SR, Carman TL. Heparin-induced thrombocytopenia: natural history, diagnosis, and management. Vasc Med. 2001;6:113– and used including danaparoid (Orgaran), a low-molecular 119. 12,20 weight heparinoid without high cross-reactivity ; thrombin- 12. Alving BM, Krishnamurti C. Recognition and management of 11,12,14 specific inhibitors (argatroban, hirudin, lepirudin) ;or heparin-induced thrombocytopenia (HIT) and thrombosis. Semin other agents such as warfarin, that have shown some efficacy. Thromb Hemost. 1997;23:569–574. However, it has been shown that in patients with HIT, heparin 13. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced should not be substituted with warfarin in the acute phase of the thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332:1330– syndrome but rather be gradually introduced after resolution of 1335. 12,14,20 31 the syndrome. Finally, pentasaccharides, the newer syn- 14. Kelton JG. Heparin-induced thrombocytopenia: an overview. Blood thetic compounds acting through specific inhibition of factor Xa, Rev. 2002;16:77–80. which reportedly lack cross-reactivity with antibodies developed 15. Greinacher A. Antigen generation in heparin-associated in HIT,32 have not been evaluated yet for treatment of HIT. thrombocytopenia: the nonimmunologic and the immunologic type Thrombin-specific inhibition is currently considered as the treat- are closely linked in their pathogenesis. Thromb Haemostas. 1995; 21:106–116. ment of choice for patients with HIT. Among the different direct 16. Reuter HD. Low-molecular weight heparin in the therapy of heparin- thrombin inhibitors, argatroban (hepatically cleared) and hirudin induced thrombocytopenia. Med Klin. 1987;82:115–118. (excreted renally) are the approved drugs for the treatment of 17. Amiral J. Diagnostic tests in heparin-induced thrombocytopenia. HIT in the United States.14 Platelets. 1997;8:68–72. Although LMWH-induced HIT is not unusual, very few 18. Chong BH, Eisbacher M. Pathophysiology and laboratory testing of heparin-induced thrombocytopenia. Semin Hematol. 1998;35(Suppl incidents have been reported in the orthopedic literature,19,33–36 5):3–8. which reveals relative unawareness of the syndrome. For the 19. Lam F, Hussain S, Li P. Limb loss following the use of heparin. A orthopedic and traumatology community who use heparin and lesson to be remembered. J Bone Joint Surg Br. 2002;84:588–589. LMWH for prevention of thrombosis, the index of suspicion 20. Benton RE, Gersh BJ. Cardiology for the primary care provider: must remain high.37 In case of platelet decrease the first postheparin-induced thrombocytopenia. South Med J. 1998;91:133–137. heparin (or LMWH) administration days (4th through 14th), 21. Fabris F, Luzzatto G, Stefani PM, et al. Heparin-induced thrombocytopenia. Haematologica. 2000;85:72–81. temporary cease of administration of heparin must be followed 22. Blank M, Shoenfeld Y, Tavor S, et al. Anti-platelet factor 4/heparin by emergency testing for heparin induced antibodies and in antibodies from patients with heparin-induced thrombocytopenia confirmed HIT syndrome heparin/LMWH must be replaced provoke direct activation of microvascular endothelial cells. Int with other agents (thrombin-specific inhibitors). Immunol. 2002;14:121–129. 23. Mikhailidis DP, Jagroop IA, Ganotakis ES. Pathophysiology of heparin-induced thrombocytopenia (HIT). Platelets. 1997;8:66–68. 24. Gruel Y, Pouplard C, Lasne D, et al. The homozygous ACKNOWLEDGMENTS FcgammaRIIIa-158V genotype is a risk factor for heparin-induced We thank Eugenia Pappa, MD, for the scientific assistance in the thrombocytopenia in patients with antibodies to heparin/platelet diagnosis of the White Clot Syndrome. factor 4 complexes. Blood.2004;104:2791–2793.

E114 November 2007 LMWH for Prevention of Thrombosis

25. Greinacher A, Amiral J, Dummel V, et al. Laboratory diagnosis of 32. Elalamy I, Lecrubier C, Potevin F, et al. Absence of in vitro cross- heparin-associated thrombocytopenia and comparison of platelet reaction of pentasaccharide with plasma heparin dependent factor of aggregation test, heparin-induced platelet activation test and platelet twenty-five patients with heparin associated thrombocytopenia. factor 4/heparin enzyme linked immunosorbent assay. Transfusion. Thromb Haemost. 1995;74:1384–1395. 1994;34:381–385. 33. Planes A, Samama MM, Lensing AW, et al. Prevention of deep vein 26. Amiral J, Marfaing-Koka A, Wolf M, et al. Presence of thrombosis after hip replacement-comparison between two low- autoantibodies to interleukin-8 or neutral activating peptide-2 in molecular heparins, tinzaparin and enoxaparin. Thromb Haemost. patients with heparin-associated thrombocytopenia. Blood. 1996; 1999;81:22–25. 88:410–416. 34. Elalamy I, Potevin F, Lecrubier C, et al. A fatal low-molecular- 27. Amiral J. Antigens involved in heparin-induced thrombocytopenia. weight heparin associated thrombocytopenia after hip surgery: Semin Hematol. 1999;36(Suppl):7–11. possible usefulness of PF4-heparin Elisa test. Blood Coagul and 28. Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Prog Fibrinolysis. 1996;7:665–671. Hemost Thromb. 1991;10:1–34. 35. Marx A, Huhle G, Hoffmann U, et al. Heparin-induced 29. Shuster TA, Silliman WR, Coats RD, et al. Heparin-induced thrombocytopenia: twenty-nine years later. J Vasc Surg. 2003; thrombocytopenia after elective hip joint replacement with 38:1316–1322. postoperative prevention of thromboembolism with low-molecular- 30. Jeske WP, Walenga JM. Antithrombotic drugs for the treatment of weight heparin. Z Orthop Ihre Grenzgeb. 1999;137:536–539. heparin-induced thrombocytopenia. Methods Mol Med. 2004;93: 36. Koninger J, Greinacher A, Muller-Beissenhirtz W, et al. Heparin- 61–82. associated thrombocytopenia caused by low-molecular-weight 31. Turpie AGG, Bauer KA, Eriksson BI, et al. Postoperative heparin. Unfallchirurg. 1995;98:49–51. fondaparinux versus postoperative enoxaparin for prevention of 37. Baird RA, Convery FR. Arterial thromboembolism in patients venous thromboembolism after elective hip-replacement surgery: receiving systemic heparin therapy. J Bone Joint Surg Am. 1977; a randomised double-blind trial. Lancet. 2002;359:1721–1726. 59:1061–1064.

Volume 63 • Number 5 E115 ௡ Case Report The Journal of TRAUMA Injury, Infection, and Critical Care

Peri-Operative Considerations During Biliary Exploration and Reconstruction: Report of Delayed Biliary Obstruction by a Bullet William Elliott Stansfield, MDCM, and Kenneth A. Andreoni, MD

J Trauma. 2007;63:E116–E118.

e present an unusual case of jaundice secondary to as suggested by angiography, and the gall bladder overlay the obstruction of the common hepatic duct by a bullet. artery and the common hepatic duct. Cholecystectomy was WWe use this case to demonstrate the variety of diag- performed to optimize safe exposure. Further dissection ver- nostic and therapeutic techniques that can be brought to bear ified that the bullet was indeed lodged within the duct. The on the larger problem of biliary obstruction. duct was dilated to approximately 1.5 cm external diameter. A longitudinal choledochotomy was made over the bullet. A CASE REPORT slight T shape was added to the inferior aspect of the incision A 17-year-old man received a gunshot wound to his right to accommodate the large size of the missile (Fig. 2). The posterior chest. The bullet passed first through the seat back bullet was grasped and removed. Examination of the duct in an automobile, then into his chest, traversed his diaphragm revealed healthy epithelium and well vascularized edges, and lodged in his liver. The patient was successfully managed with the PTBD along the posterior aspect of the duct lumen. nonoperatively, with a chest tube for the treatment of his The duct was then closed primarily with interrupted 6-0 PDS pneumothorax. suture. Intra-operative cholangiography performed through After 16 months he acutely developed jaundice, pruritis, the PTBD demonstrated both the patency and security of the and bilirubinuria. His gallbladder was interrogated with right closure (Fig. 3). A Jackson-Pratt drain was placed near the upper-quadrant ultrasound and found to be normal. Referral anastomosis to assist with postoperative monitoring of poten- to a gastroenterologist resulted in endoscopic retrograde tial bile leak. cholangiography (ERC), showing complete obstruction of the Postoperative labs showed a decreased bilirubin at 3.1 common hepatic duct. Passage of a wire was unsuccessful, mg/dL, and an elevated lipase of 5568 U/L. The white blood and the patient was referred for surgical decompression. His cell count was mildly elevated at 12.0 ϫ 109th cells/L, but fell last bilirubin before intervention was 5.4 mg/dL, and his to normal the following day. The elevated lipase was attrib- lipase mildly elevated at 303 U/L. Before surgery, percuta- uted to repeated intervention and cholangiography. On the neous transhepatic cholangiography (PTC), and angiography third postoperative day the patient’s lipase had appropriately were performed by interventional radiology. At that time an fallen to 900 U/L, and his anastomosis was re-studied with 8-French all-purpose percutaneous transhepatic biliary drain cholangiography. Slight narrowing of the common hepatic (PTBD) was successfully placed (Fig. 1). Angiography re- duct was consistent with postoperative edema, and the all- vealed the proximity of the bullet and CBD to the right purpose drain was exchanged for an 8-French internal/exter- hepatic artery. Of note, the patient had a replaced left hepatic nal biliary drain. Over the next several days the patient’s artery with its origin from the left gastric artery. lipase climbed steadily, and on the 7th postoperative day the At operation, the bullet was found to obstruct the com- patient was again restudied out of concern for bile leak or mon hepatic duct in the area 1 cm superior to the cystic duct. obstruction of the pancreatic duct. Note that the patient’s The right hepatic artery was partially displaced by the bullet, operatively placed drain had only minimal, nonbilious output. The cholangiogram showed some irregularity at the site of Submitted for publication November 14, 2004. common duct repair but had brisk flow of contrast across this Accepted for publication July 28, 2005. area. There was some concern that the PTBD may have been Copyright © 2007 by Lippincott Williams & Wilkins partially obstructing the pancreatic duct. Therefore, the fol- From the Department of Surgery, University of North Carolina Hos- lowing day, the internal/external biliary drain was exchanged pitals, Chapel Hill, North Carolina. Address for reprints: Kenneth A. Andreoni, MD 4023 Burnett- back to a standard 8-French all-purpose drain, the tip of Womack Bldg. Department of Surgery, UNC School of Medicine Chapel, which was pulled back to just below the stump of the cystic Hill NC 27519-7211; email: [email protected]. duct. An abdominal computed tomography scan the same day DOI: 10.1097/01.ta.0000196680.85576.8b showed no evidence of pancreatitis and the patient’s lipase

E116 November 2007 Delayed Biliary Obstruction

Fig. 3. Intra-operative cholangiography demonstrating a secure Fig. 1. Preoperative transhepatic cholangiography showing a wire anastomosis and grossly normal biliary anatomy. passing through the obstructed common hepatic duct. placed, with its tip running from the right hepatic duct to the eventually trended down. The patient’s diet was resumed with- left hepatic duct. This drain was left to internal drainage, and out difficulty, and he was discharged to home with follow-up repeat study was performed in one week. The repeat study, 3 weeks later. approximately 1 month postoperative, showed no evidence of Cholangiography at this time showed persistent mild stenosis in the common hepatic duct. The drainage catheter narrowing of the proximal common hepatic duct, but again was then removed without complication. Laboratory studies with excellent flow of contrast. Another drain was then at that time showed a Bilirubin of 1.2 mg/dL and lipase of 486 U/L, near normal. Follow-up visit one week later revealed the patient to be in good health with a Bilirubin of 0.8 mg/dL.

DISCUSSION Biliary ductal obstruction is a relatively common problem faced by surgeons. Most cases derive from choledocholithiasis, and most cases resolve spontaneously. For those that do not resolve, the normal decision algorithm at our institution involves laparoscopic cholecystectomy with either preoperative or postoperative ERC with papillotomy.1 Occasionally, alternate diagnostic and therapeutic measures are necessary. This unique case serves to highlight some of those techniques, and models how those techniques may be integrated to achieve a successful patient outcome. In the initial evaluation of this patient, ERC clearly confirmed common hepatic duct obstruction by the bullet. The size and nature of the lesion precluded endoscopic treatment, and the inability to pass a wire likewise prevented stenting for palliation of obstructive symptoms. Before operation, we elected to perform PTC for imaging of the proximal Fig. 2. Intra-operative photograph showing the exposed bullet biliary tree. This was highly useful in this case, confirming after choledochotomy, as well as the prominent right hepatic artery the integrity of the proximal bile duct system. Visceral an- crossing anteriorly and inferiorly. giography performed in the same setting provided additional

Volume 63 • Number 5 E117 The Journal of TRAUMA௡ Injury, Infection, and Critical Care anatomic information. Specifically, it demonstrated the pres- postoperatively. The only notable complication was a tran- ence of a replaced left hepatic artery and a lateral right sient hyperamylasemia, which occurs in approximately 25% hepatic artery in close proximity to the obstructed hepatic of percutaneous cholangiograms.7 Several manipulations of the duct. At the conclusion of the diagnostic phase, a guidewire PTBD were performed, but none appeared to have a significant and PTBD were successfully placed across the lesion. It is effect on the patient’s pancreatic enzyme levels. In time, both likely that the approach angle and the variety of guidewires liver function tests and pancreatic enzymes normalized. available were more favorable in this setting than in ERC. The operative procedure was straightforward. Cholecys- CONCLUSION tectomy was deemed necessary to safely optimize exposure There are a growing number of nonoperative techniques for the remainder of the procedure. After visualizing the involved in the successful evaluation and treatment of com- portal hilum, the bulging common hepatic duct was readily plex hepato-biliary obstructive disease. As surgeons, we can identified. Traditional longitudinal choledochotomy was per- best make recommendations to patients by understanding the formed along the length of the bullet to preserve the vascular variety of techniques available and the nature of the infor- supply of the CHD at the 3 and 9 o’clock positions.2 The size mation they provide. We stress that the decision making of the bullet ultimately required us to T off the incision to process is significantly different for trauma and acutely ill safely remove the bullet. patients as compared with others with chronic disease. Lastly, The decision to close the CHD primarily was carefully it is only with full and active participation in a concerted considered both preoperatively and intra-operatively. A re- multidisciplinary effort that we can continue to devise cre- cent literature review of biliary obstruction secondary to ative solutions to complex hepato-biliary problems, and in so ballistic trauma indicates that these injuries have been prin- doing ensure the highest level of care. cipally treated with choledochojejunostomy.3,4 When used in the treatment of biliary stricture, this reconstructive technique REFERENCES is reported to have a morbidity of 20 to 30% and a surgical 1. NIH state-of-the-science statement on endoscopic retrograde success rate of approximately 90% if performed by biliary cholangiopancreatography (ERCP) for diagnosis and therapy. NIH 5 Consens State Sci Statements. Jan 14–16 2002;19:1–26. surgeons at tertiary referral centers. Choledochotomy with 2. Cameron JL. Current Surgical Therapy, 7th ed. St. Louis, MO: primary closure for choledocholithiasis, by contrast, is re- Mosby; 2001. ported to have a morbidity less than 10% and a near 100% 3. Mitchell R, Kerr R, Barton J, Schmidt A. Biliary obstruction success rate.6 This patient’s CHD appeared to have a healthy secondary to shrapnel. Am J Gastroenterol. 1991;86:1531–1534. epithelium, the vascular supply appeared intact, there was no 4. Maheshwari M, Chawla A, Dalvi A, Thapar P, Raut A. Bullet in the common hepatic duct: a cause of obstructive jaundice. Clin Radiol. evidence of stenosis, and a decompressive stent was already 2003;58:334–335. in place. Given these factors, we elected to perform primary 5. Lillemoe KD, Melton GB, Cameron JL, et al. Postoperative bile duct duct closure over the stent, and to save choledochojejunos- strictures: management and outcome in the 1990s. Ann Surg. Sep tomy as a fall-back alternative. 2000;232:430–441. In the postoperative period, the two greatest concerns 6. Waage A, Stromberg C, Leijonmarck CE, Arvidsson D. Long-term results from laparoscopic common bile duct exploration. Surg were bile leak and biliary duct stenosis. Repeat cholangiog- Endosc. 2003;17:1181–1185. raphy using the PTBD allowed us to demonstrate the contin- 7. Yee AC, Ho CS. Percutaneous transhepatic biliary drainage: a ued integrity and patency of the duct closure in the weeks review. Crit Rev Diagn Imaging. 1990;30:247–279.

E118 November 2007 ௡ Review Article The Journal of TRAUMA Injury, Infection, and Critical Care

Esophageal Perforations: New Perspectives and Treatment Paradigms James T. Wu, MD, Kenneth L. Mattox, MD, and Matthew J. Wall Jr, MD

Despite significant advances in mod- ever, less invasive approaches to esophageal attempt to summarize the pathogenesis ern surgery and intensive care medicine, perforation continue to evolve. As the inci- and diagnostic evaluation of esophageal esophageal perforation continues to present dence of esophageal perforation increases injuries, and highlight the evolving thera- a diagnostic and therapeutic challenge. Con- with the advancement of invasive endo- peutic options for the management of troversies over the diagnosis and manage- scopic procedures, early recognition of esophageal perforation. ment of esophageal perforation remain, and clinical features and implementation of Key Words: Esophageal trauma, debate still exists over the optimal therapeu- effective treatment are essential for a fa- Esophageal perforation, Minimally inva- tic approach. Surgical therapy has been the vorable clinical outcome with minimal sive thoracoscopic surgery, Esophageal traditional and preferred treatment; how- morbidity and mortality. This review will stenting, Esophageal endoclipping. J Trauma. 2007;63:1173–1184.

PATHOPHYSIOLOGY injuries to the esophagus occurred in 4% of patients, and the External Trauma overall mortality rate was 19%.5 enetrating esophageal trauma occurs mainly in the cer- Esophageal perforation from external blunt trauma is an vical esophagus, and morbidity is usually associated exceedingly rare event. The most common cause is related to 6–9 Pwith vascular, tracheal, and spinal cord injuries.1,2 high-speed motor vehicle crashes. Beal et al. examined 96 Hirshberg et al. evaluated 34 patients with transcervical gun- reported cases of blunt esophageal trauma, and found that the shot wounds, and found 2 patients (6%) with esophageal site of perforation occurred in the cervical and upper thoracic 10 injuries.1 Similarly, Demetriades et al. examined 97 patients esophagus in 82% of patients. The clinical outcome of these with transcervical gunshot wounds, and reported injury to the patients is influenced by the delay in diagnosis, complications aerodigestive tract in 6% of patients.2 Sheely et al. docu- from the esophageal perforation, and associated injuries. Be- mented a 22-year experience in over 700 patients with pen- cause the signs and symptoms of early esophageal perforation etrating neck trauma, and found 39 patients (5.5%) with are subtle, accurate and prompt diagnosis can be challenging cervical esophageal injury.3 Of these patients, there were 55 in patients presenting with multiple blunt injuries. Therefore, associated injuries, with trachea being the most often injured a high index of suspicion is required when treating patients structure (Table 1). In contrast, the thoracic esophagus is less sustaining high-energy trauma to the neck or torso. vulnerable to external trauma because of its central anatomic location and small compact size. Cornwell et al. reported that Spontaneous Esophageal Rupture (Boerhaave’s intrathoracic esophageal injuries occurred in 0.7% of 1,961 Syndrome) 4 patients with gunshot wounds to the chest. A retrospective In 1724, Dr. Hermann Boerhaave described a case of multi-institutional study during a 10.5-year period involving spontaneous esophageal rupture in the autopsy of Baron von 405 patients with known penetrating esophageal injuries Wassenaer, Grand Admiral of the Dutch Fleet. Boerhaave’s showed that the predominant mechanism of injury was gun- patient was a previously robust admiral, who developed a shot or shotgun wounds in 78.8% of patients and stab wounds sudden excruciating chest pain while straining to vomit after 5 in 18.5% of patients. Cervical esophageal injuries were most indulging himself with food and wine. The details of Boer- common (57%), and thoracic and abdominal esophageal in- haave’s findings have been recorded in the report of Derbes juries occurred in 30% and 17%, respectively. Combined published in 1955.11 The incidence of Boerhaave’s syndrome is relatively rare, although likely an underreported phenom- Submitted for publication December 27, 2006. enon, with 300 cases reported in the literature worldwide.12 Accepted for publication March 13, 2007. Boerhaave’s syndrome is thought to arise from a rapid in- Copyright © 2007 by Lippincott Williams & Wilkins crease in intraluminal esophageal pressure through a patent From the Division of Cardiothoracic Surgery, Baylor College of Med- icine, Houston, Texas; and Trauma/Emergency Surgery Service, Ben Taub lower esophageal sphincter during vomiting. This sudden General Hospital (J.T.W., K.L.M., M.J.W.), Houston, Texas. increase of intraluminal pressure is the result of failure of Address for reprints: James T. Wu, MD, 350 Parnassus Ave., Ste. 150, relaxation of the cricopharyngeal muscle. As such, transmural San Francisco, CA 94143-150; email: [email protected]. rupture of the esophageal wall occurs, commonly in the left DOI: 10.1097/TA.0b013e31805c0dd4 posterolateral wall of the lower third esophagus located 2 cm

Volume 63 • Number 5 1173 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

instrumentation as the most common cause of esophageal Table 1 Associated Injuries in Penetrating Cervical perforation, accounting for 59% of patients in recent series.18 Esophageal Trauma Esophageal perforation during upper endoscopy is estimated Associated Injuries Number to occur at a frequency of 0.03%, compared with 0.11% 19,20 Trachea 20 during rigid endoscopy. The more common sites of iat- Spinal cord 6 rogenic esophageal perforation are at the normal anatomic Thyroid 7 narrowings of the esophagus. Perforation most often occurs Thyroid cartilage 5 Jugular vein 4 in the hypopharynx or cervical esophagus secondary to ex- Recurrent laryngeal nerve 4 ertion of force in attempting to pass the endoscope through 21 Common carotid artery 3 the cricopharynx. The risk of esophageal injury also increases Cricoid cartilage 3 when therapeutic manipulations are undertaking during endo- Lung 2 scopic intervention. Perforation of the distal esophagus is most Larynx 1 Total 55 frequently related to esophageal dilation performed for esophageal strictures or achalasia. The incidence of distal esophageal Reproduced with permission from Sheely CH, Mattox KL, Beall rupture after pneumatic dilation for achalasia ranges from 2% to AC, et al. Penetrating wounds of the cervical esophagus. Am J Surg. 22 1975;130:707–711. 6%. Such a complication is often associated with previous pneumatic dilation or the use of high inflation pressures.23 Endoscopic sclerotherapy for esophageal varices leads to to 3 cm proximal to the gastroesophageal junction. This area esophageal perforation in 1% to 3% of patients.24 Salo et al. is structurally and inherently weakened as the longitudinal reported esophageal perforation and mediastinal gas gan- muscle fibers taper out before passing onto the stomach wall. grene after sclerotherapy of bleeding from a Mallory-Weiss laceration.25 The local necroinflammatory reaction after scle- Foreign Body rosant injection contributes to the transmural necrosis of Barber et al. described a variety of objects and materials esophageal wall.26,27 Avoidance of perforation may be that were inappropriately ingested, especially by children and achieved by attempting to control the depth, volume, and individuals with psychiatric disorders.13 The common offend- concentration of injection to prevent extensive and prolonged ers are chicken or fish bones, partial dentures, plastic eating ischemia to the surrounding tissue.28 utensils, and metal safety pins. Objects less than 2 cm in size Perforation of the esophagus can result from a variety of may traverse the normal adult esophagus without problems.14 other forms of endoscopic instrumentation. Iatrogenic esopha- Once in the stomach, most objects can pass through the rest geal perforation during transesophageal echocardiography has of the gastrointestinal tract. About 80% to 90% of ingested been well documented with an incidence of 0.18%.29–31 Rarely, foreign bodies pass the gastrointestinal tract spontaneously.15 rupture of distal esophagus may occur with improper placement Of those that mandate intervention, less than 1% need open and inflation of the gastric balloon of a Sengstaken-Blakmore surgery, whereas the remainder can be removed by endo- tube to control bleeding esophageal varices.27,32 Other forms of scopic manipulation.15 Lam et al. retrospectively reviewed esophageal intubation associated with perforation include naso- 5,848 patients with foreign body ingestion, and found 8 gastric tube placement,33 endotracheal tubes,34,35 endoscopic patients (0.001%) with esophageal perforation secondary to retrograde cholangiopancreatography,36 and endoscopic ultra- bone impaction in the cervical esophagus; 3 patients pre- sound-guided interventions.37,38 sented with clinical evidence of esophageal injury at the time Esophageal injuries during surgical procedures in of presentation, and 5 patients were diagnosed with iatrogenic close proximity to or directly involving the esophagus perforation during esophagoscopy.16 occur infrequently. Operative procedures associated with In some instances, sharp or jagged foreign bodies lacer- esophageal injuries include fundoplication, vagotomy, hi- ate the wall partially or completely. Most commonly, such atal hernia repair, lung transplantation, pneumonectomy, laceration or perforation occurs in the normal anatomic nar- thyroid resection, tracheostomy, thoracic aneurysm repair, rowings of the esophagus. These narrowing points typically esophageal leiomyoma enucleation, mediastinoscopy, and occur at the cricopharyngeal muscle of the upper esophageal cervical spine surgery.39–47 When injury to the esophagus sphincter, level of aortic arch, left mainstem bronchus, and is recognized intraoperatively, direct primary repair is al- lower esophageal sphincter. Up to 5% of patients may present most always successful with minimal morbidity. with acute airway obstruction when the foreign body is impacted near the upper esophageal sphincter, causing compres- Chemical-Induced Esophageal Perforations sion of the trachea.17 Most of the chemical-induced esophageal injuries occur from accidental ingestion of caustic agents by young chil- Iatrogenic Esophageal Perforation dren, usually under 5 years of age. Occasionally, adults may The diagnostic and therapeutic contributions of endo- ingest these agents in an attempted suicide. The severity and scopic procedures during the last two decades have made site of caustic esophageal injury depend not only on the

1174 November 2007 Contemporary Treatment of Esophageal Perforations nature, amount, and concentration of substance ingested, but border. Subcutaneous emphysema after thoracic esophageal also on the duration of mucosal contact.48,49 Because of a rela- perforation is detected by palpation in 30% of patients, tive delay in transit time, the anatomic narrowings of the esoph- whereas emphysematous crepitus in the neck after cervical agus are most susceptible to caustic burns. Spitz and Lakhoo esophageal perforation is detected by palpation in 60% of reported that caustic injury results in a hypotensive lower esoph- patients.59 Interestingly, subcutaneous emphysema, chest ageal sphincter with constant reflux, leading to a prolonged pain, and vomiting constitute the Mackler’s triad, a patho- exposure of the distal esophagus to ingested substances.50 The gnomonic sign for spontaneous esophageal rupture observed greater period of contact in the lower esophagus reflects the in less than half of the cases. more extensive injury occurring in this area. With cervical esophageal perforation, neck ache and stiff- Although alkaline and acid ingestion are the most com- ness are common clinical findings, but pain is typically less mon chemicals implicated in caustic burns, there are several severe. Soilage of oropharyngeal flora through the retroesopha- important fundamental differences between alkali and acid geal space is limited because of esophageal attachment to the injury.51,52 Alkali ingestion causes more esophageal than prevertebral fascia.60 In thoracic esophageal perforation, retro- gastric injury, but the converse is true for acid ingestion. sternal or chest pain lateralizing to the side of perforation is Alkali causes liquefactive necrosis, causing a deep burn, common. The initial contamination of the visceral mediastinum whereas acid produces coagulative necrosis, forming an es- is followed by subsequent perforation of the mediastinal pleura. char that limits tissue penetration.53 Alkali ingestion induces The left pleural space is usually involved with distal esophageal in pylorospasm with regurgitation of the caustic agent into the perforation, whereas the right pleural space is commonly esophagus, followed by cricopharyngeal muscle spasm and violated with proximal esophageal perforation. The influx of propulsion back into the stomach, aggravating both the gastric contents into the mediastinum initiates an intense esophageal and gastric burns.54 On the other hand, acid passes inflammatory response and cytokine activation, resulting in through the esophagus more quickly than alkalis. In the stomach, mediastinitis accompanied with fluid sequestration, hypoten- acid also triggers immediate pylorospasm, pooling the acid in sion, and sepsis.61With intra-abdominal esophageal perfora- the distal antrum and producing severe gastritis that may tion, dull epigastric pain radiating to the back may occur if progress within 24 hours to 48 hours to full-thickness necrosis the perforation is posterior and communicates with the lesser and perforation. sac. More commonly, sharp, unrelenting, epigastric pain is Caustic injury to the esophagus has been divided into often associated with anterior perforation with subsequent three phases.50,51 The initial phase is characterized by inflam- widespread peritoneal contamination. The early onset of sys- mation, edema, and necrosis during the initial few days after temic signs such as tachycardia, tachypnea, and fever are the injury. This is followed by sloughing of esophageal debris usual clinical features. Rapid deterioration with signs of sys- with mucosal ulceration, accompanied by the development of temic inflammatory response such as leukocytosis, sepsis, and granulation tissue and collagen deposition, and subsequent shock develop within hours of presentation. re-epithelization lasting about 3 weeks to 4 weeks. During this second phase, the esophageal wall is weakest and prone DIAGNOSIS OF ESOPHAGEAL PERFORATION to perforation. In the third phase, cicatrisation and stricture Radiographic studies are invaluable in establishing the formation may progress for many weeks as the destroyed diagnosis of esophageal perforation. If cervical esophageal esophageal submucosa and muscularis are replaced with scar perforation is suspected, a lateral neck X-ray may demon- tissue. strate air in the prevertebral facial planes before it is detectable by chest radiograph.40 In thoracic or intra-abdominal CLINICAL PRESENTATION esophageal perforation, posterior and lateral chest radio- The signs and symptoms of early esophageal injury can graphs, and upright abdominal series should be obtained. be vague and nonspecific. Therefore, a high index of suspi- Chest radiograph is suggestive in 90% of patients with esoph- cion is critical to avoid delays in establishing an accurate ageal perforation, but may be normal immediately after the diagnosis. The clinical presentation depends on the cause, injury.62 Han et al. reported that radiographic evidence of location of the injury, size of the perforation, degree of mediastinal emphysema requires at least 1 hour after the contamination, length of time elapsed after injury, and pres- initial injury to become discernable, whereas pleural effusion ence of associated injury.55 Nesbitt and Sawyers reviewed and mediastinal widening may take several hours to evolve.62 esophageal injuries from all causes during a 50-year period, Panzini et al. documented that 75% of patients manifested and found pain to be the most common symptom (71%), abnormal radiographic findings on chest radiograph within 12 followed by fever (51%), dyspnea (24%), and crepitus hours of instrumental esophageal perforation, and pneumo- (22%).56 Other investigators have also reported similar mediastinum was the most common radiographic finding.63 trends.57,58 Dissection of air along the subcutaneous planes or An interesting roentgen finding, the “V sign”, associated with into the mediastinum is a hallmark of esophageal perforation. spontaneous esophageal rupture has been described.64 It re- Occasionally, a systolic crunching sound, the “Hammon’s flects localized mediastinal emphysema in the left lower sign”, can be heard over the cardiac apex and left sternal mediastinum along the aorta and above the left diaphragm,

Volume 63 • Number 5 1175 The Journal of TRAUMA௡ Injury, Infection, and Critical Care forming the characteristic “V sign”. Aside from mediastinal Table 2 Management of Esophageal Perforation emphysema, other suspicious radiographic findings include mediastinal air-fluid level, hydropneumothorax, mediastinal Drainage only widening, and pleural effusions.63 Pleural effusions are lo- Esophagectomy cated on the right if the perforation is in the midesophagus, Immediate reconstruction Delayed reconstruction whereas left-sided pleural effusions are commonly associated Exclusion and diversion with distal esophageal perforation. Minimally invasive repairs Esophageal perforation may also be identified by pleural Esophageal stenting fluid analysis. Diagnostic pleural fluid findings are food par- Endoclip application ticles, a pH of less than 6.0, or the presence of an elevated Video-assisted thoracoscopic surgery 40 Nonoperative treatment amylase level. Primary closure Contrast esophagography is the study of choice for Primary closure with buttressing of repair suspected esophageal perforation, but has an overall false- Pleural flap negative rate of 10%.65 Traditionally, water-soluble contrast Pericardial fat pad agents, such as gastrograffin (meglumine sodium), have been Diaphragmatic pedicle graft Omentum onlay graft recommended over barium sulfate as the contrast of choice. Rhomboid muscle There is a concern that extravasation of barium sulfate into Latissimus dorsi muscle the mediastinum can lead to an intense inflammatory re- Intercostal muscle sponse, resulting in fibrosing mediastinitis.66–68 In addition, T-tube drainage the long-term presence of barium in the mediastinum makes interpretation of future mediastinal imaging difficult, whereas gastrograffin is rapidly absorbed.69 However, gastrograffin, if fold and the potential to convert a small mucosal or submu- aspirated, can induce a severe necrotizing pneumonitis and cosal tear into a large perforation during air insufflation argue pulmonary edema because of its inherent hypertonicity.70 against the use of esophagoscopy in the diagnosis of esoph- 77 Also gastrograffin extravasates in only 50% of cervical and ageal injuries. 80% of thoracic esophageal perforations.70 As the higher density and better mucosal adherence of barium allow the MANAGEMENT OF ESOPHAGEAL PERFORATION detection of smaller esophageal perforation,71 it will detect The fundamental principles of management in esopha- 60% of cervical and 90% of surgically confirmed intratho- geal perforation include elimination of septic focus, provision racic esophageal perforations.59,72 Our preference is to obtain of adequate drainage, augmentation of host defenses by an- a barium study as the initial test as any extravasation will tibiotics, and maintenance of adequate nutrition.78 Therapeu- likely lead to surgical intervention. Local inflammation and tic interventions aimed to achieve these goals vary with the edema of the injured esophagus may preclude a positive cause, location, and severity of the perforation, as well as the barium study. Therefore, if the clinical suspicion remains time interval between perforation and intervention (Table 2). high, serial repetition of barium studies beginning several The overall health status and physiologic reserve of the pa- hours after the first attempt is warranted. tient, extent of associated injuries, and underlying esophageal Chest computed tomography (CT) is an indispensable pathologic findings are also the critical determinants of suc- adjunct in diagnosing esophageal perforation. In the settings cessful therapy. of a negative esophagram with a high clinical suspicion, critically ill patients unable to undergo esophagography, or Surgical Therapy atypical symptoms of esophageal injury at presentation, tho- Surgical intervention includes primary closure with or racic CT imaging is useful to confirm the diagnosis. Typical CT without autogenous tissue reinforcement, esophageal resec- findings include mediastinal or extraluminal air, esophageal tion, exclusion and diversion, esophageal T-tube, and drain- thickening, pneumomediastinum, esophagopleural fistula, pleu- age alone (Fig. 1). Cervical esophageal perforation can be ral effusions, abscess cavities adjacent to the esophagus, and treated by drainage alone.79 Drainage alone is less successful communication of an air-filled esophagus with an adjacent me- with thoracic or abdominal perforation because containment diastinal air-fluid collection.73–75 Of these, extraluminal air is the of contamination is difficult. Intrathoracic esophageal disrup- most common CT finding associated with esophageal perforation requires aggressive mediastinal and pleural drainage. tion, occurring in 92% of cases.74 The parietal pleura is opened along the entire length of the Although esophagoscopy is not recommended as the esophagus, and both the mediastinum and pleural space are primary diagnostic study of choice, it is useful in providing a debrided, irrigated, and drained by thoracostomy. direct visualization of the perforation. Horwitz et al. showed The surgical technique for perforation of the cervical that flexible esophagoscopy had a sensitivity of 100% and a esophagus involves a cervical incision along the anterior specificity of 83% in the evaluation of penetrating esophageal border of left sternocleidomastoid from the level of the cri- injury.76 However, a missed perforation hidden in a mucosal coid cartilage to the sternal notch. The sternocleidomastoid

1176 November 2007 Contemporary Treatment of Esophageal Perforations

Signs & Symptoms of Esophageal Perforation

Chest X-Ray, Chest Computed Tomography & Contrast Esophagography

Contained Free Perforation or Contained Perforation Perforation with Systemic Symptoms

See Figure 4

Cervical Thoracic Abdominal

Assessment of Injury Drainage

Megaesophagus, Stable Malignancy or Multiple Unstable Undilatable Strictures

Exclusion and Diversion Primary Closure with Esophagectomy T-Tube Drainage with Cervical Esophagostomy, or without Autogenous Tissue Gastrostomy & Jejunostomy

Immediate Delayed Delayed Reconstruction Reconstruction Reconstruction

Fig. 1. Algorithm for surgical therapy of esophageal perforation. and carotid sheath are retracted laterally, and the trachea and full exposure of the mucosal defect after longitudinal esoph- thyroid are displaced medially to expose the esophagus (Fig. agomyotomy, and approximation of mucosal and submucosal 2). Blunt, finger-dissection technique is used to gain access to edges over a 40F to 46F bougie in a tension-free closure. the prevertebral space, taking care to avoid injury to the Muscular layer is then reapproximated using a running or recurrent larygneal nerve in the tracheoesophageal groove. interrupted absorbable suture technique.80 A variety of vas- Alternatively, the prevertebral space can be approached be- cularized autogenous tissues, including pleural flap, dia- hind the carotid sheath (Fig. 3). Access to perforation in the phragmatic pedicle graft, omentum onlay graft, rhomboid and middle third of the esophagus is through a right thoracotomy latissimus dorsi muscles, intercostals muscles, and pericardial in the fifth or sixth intercostal space, and perforation in the fat pad have been used to buttress the primary repair.81–85 lower third is best approached through a left thoracotomy in Our preference is to buttress the esophageal repair with a the sixth or seventh intercostal space. Perforation at the pedicled intercostal muscle flap, developed during the initial esophagogastric junction can be accessed by either a left chest incision. Although reinforcement with vascularized tis- thoracotomy or upper midline laparotomy. sue may decrease fistula formation and mortality,85 postop- Primary repair is the preferred surgical treatment of erative esophageal leaks after reinforced primary repair can choice in thoracic or abdominal esophageal perforation. Suc- be as high as 83% in patients presenting after 24 hours of cessful outcome requires the debridement of necrotic tissue, perforation.86

Volume 63 • Number 5 1177 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

correction at the time of primary repair constitute an indication for esophagectomy. If primary repair is not possible at the time of surgery because of severe mediastinitis or underlying esophageal pathologic findings, surgical options include esophageal resection with immediate or delayed reconstruction, or exclusion and diversion. Esophagectomy should be considered as the procedure of choice for perforations associated with megaesophagus, carcinoma, caustic ingestion, or severe undilatable reflux strictures.54 Segmental resection as a therapy for esophageal perforation is undertaken as a prelude to either immediate or delayed reconstruction using transposed stomach or colon.89 The decision to restore gastrointestinal continuity in a single stage must be made on an individual basis. If the underlying pathologic process is a localized resectable cancer, or an undilatable or malignant stricture, resection with immediate reconstruction is indicated.90 However, perforation caused by caustic ingestion requires segmental resection, cervical esophagostomy, and placement of jejunostomy. Sev- Fig. 2. Exposure of the cervical esophagus. eral investigators have also recommended cervical esophagogastric anastomosis during the primary operation in selected patients with intrathoracic perforation to restore gastrointestinal integrity.89,91 With this approach, the esophagogastric anastomosis is performed outside the soiled mediastinal field, and postoperative anastomotic leak can be managed by cervical drainage. Exclusion and diversion techniques have been employed in patients with extensive mediastinal contamination, grossly devitalized esophagus, or hemodynamic instability unable to tolerate definitive repair or resection.92,93 Traditional techniques include cervical esophagostomy, gastrostomy, jejunostomy, mediastinal or pleural drainage, and exclusion of the perforated esophageal segment to prevent further contamination. This approach has evolved to one that preserves esophageal continuity by the placement of either a staple line or removable ligature distally in conjunction with cervical esophagostomy.94 Nonetheless, the ongoing septic focus, need for a second operation to restore gastrointestinal continuity, and difficulties with subsequent esophageal reconstruction have all limited the technical application of this Fig. 3. Surgical approaches to the cervical esophagus. approach.79,85 Of paramount significance is the elimination of distal In patients with esophageal injuries that cannot be re- obstruction distal to the site of primary repair commonly seen paired at the time of surgery or hemodynamic instability in strictures and achalasia. Moghissi and Pender reported that unable to tolerate definitive repair, management with an 79 primary repair without treatment of distal obstruction resulted esophageal T-tube has been advocated. The T-tube creates in a mortality of 100%, whereas treatment of both perforation a controlled esophagocutaneous fistula, allowing drainage of and distal obstruction reduced the mortality to 29%.87 There- the esophagus and time for surrounding tissues to heal. Al- fore, intraoperative dilation should be attempted for distal though continued leakage can progress to sepsis and chronic strictures, and esophagomyotomy opposite the site of perfo- fistula formation,59,79,85,95 several investigators have reported ration should be accomplished for achalasia after primary successful clinical outcome with the use of esophageal repair of perforation.88 When perforation occurs in the pres- T-tube.79,95 In our experience, the placement of a large T-tube ence of severe gastroesophageal reflux, an antireflux proce- has become one of the most versatile techniques for the dure can be considered and used to bolster the esophageal complicated esophageal perforation, avoiding the suboptimal repair. Multiple sites of distal obstruction not amendable to results associated with ligation or exclusion.

1178 November 2007 Contemporary Treatment of Esophageal Perforations

Signs & Symptoms of Esophageal Perforation

Chest X-Ray, Chest Computed Tomography & Contrast Esophagography

Contained Perforation with Minimum Systemic Signs

Megaesophagus, Malignancy,or Multiple Undilatable Strictures

Surgical Therapy (See Figure 1)

Failure of Treatment Nonoperative Treatment with NPO, Antibiotics & Parenteral Nutrition

7-10 days

Contrast Esophagram

Uncontained Healed Contained Perforation Perforation Perforation

Surgical Therapy Resume (See Figure 1) Oral Intake

Fig. 4. Algorithm for nonoperative treatment of esophageal perforation. NPO, nil per os.

Brinster et al. reviewed published case series from Nonoperative Treatment 1990 to 2003, and found that the overall mortality associ- Nonoperative approach for esophageal perforation is ac- ated with esophageal perforation in 726 patients was ceptable in selected patients with well-contained perforation 18%.18 Surgical primary repair, with or without reinforce- and minimal mediastinal soilage, and includes maintenance ment, is the most successful therapeutic modality with an of oral hygiene, cessation of oral intake, broad-spectrum averaged mortality of 12%. This is followed by esopha- antibiotics, and parenteral nutritional support (Fig. 4). Medi- gectomy with a mortality of 17%. In contrast, other sur- astinal or pleural fluid collections are drained with chest gical therapies are associated with a higher mortality rate. tubes. This therapeutic modality has been successful in treat- A mortality of 24% was observed with the various exclu- ing cervical tears after instrumentation, well-circumscribed sion and diversion procedures, and drainage alone was intramural dissections after pneumatic dilatation, small post- associated with a mortality of 37%.18 operative anastomotic leak, chronic perforation with minimal

Volume 63 • Number 5 1179 The Journal of TRAUMA௡ Injury, Infection, and Critical Care

A B

Esophageal Perforation Associated Esophageal Perforation Associated with with Instrumentation, Boerhaave’s Syndrome, Instrumentation or Boerhaave’s Syndrome Postoperative Leak or Foreign Body Ingestion

Video-Assisted Esophageal Stenting Thoracoscopic Surgery or Endoclip Application

< 1cm Perforation and Minimum > 1cm Perforation or Extensive Mediastinal Contamination Mediastinal Contamination <12 Hour Perforation >12 Hour Perforation

Primary Closure with T-Tube Drainage with Contrast Irrigation, Irrigation & Drainage Irrigation & Drainage Esophagram Drainage & Antibiotics

Fig. 5. Algorithm for management of esophageal perforation with video-assisted thoracoscopic surgery (A) and endoscopic stenting and clipping (B). clinical symptoms, and intramural tears secondary to varix contamination can be a safe and effective option. These sclerosis when the periesophageal fibrosis prevents the de- patients, however, require diligent clinical assessment with a velopment of mediastinitis.96,97 high index of suspicion for failures of nonoperative therapy. Cameron et al. proposed criteria for nonoperative man- Failure to improve or deterioration in the clinical status dur- agement: disruption contained in the mediastinum or between ing surveillance requires prompt surgical intervention. the mediastinum and visceral lung pleura, drainage of the cavity back into the esophagus, and minimal signs of clinical Minimally Invasive Techniques sepsis.98 Altorjay et al. extended these criteria, including the Video-Assisted Thoracoscopic Surgery detection of early perforation, or a well-circumscribed late Minimally invasive thoracoscopic surgery offers a mag- perforation, findings of esophageal tissue defect not neoplas- nified view of the entire thoracic cavity and excellent access tic, not in the abdominal cavity, and not accompanied by to all mediastinal compartments. The use of this technique in simultaneous obstructive esophageal disease, and availability the setting of esophageal injury has been largely limited to of imaging modalities and thoracic surgical expertise.97 Even instrumental or spontaneous esophageal perforation99–101 with strict adherence to these criteria for nonoperative treat- (Fig. 5). In addition, Chung and Ritchie emphasized that ment, up to 20% of patients managed nonoperatively develop minimally invasive surgery is preferred in patients who are multiple complications within 24 hours and required surgical too ill to tolerate radical surgical debridement and drainage; intervention.97 it is less invasive and provides an expeditious life-saving Brinster et al. retrospectively reviewed the clinical out- alternative with good clinical outcome.102 Nguyen et al. pro- come from case series in 154 patients managed with nonop- posed the fundamental goals in thoracoscopic surgery: iden- erative treatment, and reported an averaged mortality of 18%; tification of esophageal perforation, debridement of necrotic the average mortality in 322 patients treated with primary debris, control of leak, and wide drainage of mediastinum.99 repair was 12%.18 Nonoperative treatment of selected pa- The usual thoracoscopic approach employs three or four tients with contained esophageal perforation and minimal trocars positioned conventionally through the right chest. A

1180 November 2007 Contemporary Treatment of Esophageal Perforations left video-assisted thoracoscopic surgery or transabdominal capable of expansion at body temperature to conform to the approach can be used in distal esophageal perforation, or esophageal wall. The central covering of the stent seals the when the leak is demonstrated to extend into the left perforation, and the uncovered metal ends allow integration chest.100,101 Intraoperative endoscopy is an invaluable ad- into the esophageal wall. junct in identifying the site of perforation. The suspected Fisher et al. examined 15 consecutive patients with region can be submerged under irrigation during endoscopic spontaneous or iatrogenic esophageal perforation treated insufflation to precisely localize the site of perforation. Once with self-expandable metal stents.123 All patients were identified, the devitalized margins of the perforation are de- eventually discharged to home except for one patient died brided. If the defect is Ͻ1 cm surrounded by viable tissue, a of aspiration pneumonia after 6 days of stent insertion. The primary closure can be performed with interrupted sutures. In stents were extracted after an average of 4 weeks, and the case of a larger perforation surrounded by inflamed tissue, the perforations were well healed and remained sealed. The wide drainage is advocated with the placement of a T-tube to authors emphasized that stent insertion should be performed control the soilage. Although minimally invasive thoraco- expeditiously once the diagnosis is established to reduce the scopic surgery for esophageal injury has become the pre- extent of mediastinal contamination. Thoracoscopic irrigation ferred approach in many institutions, its role in the diagnosis and drainage, and antibiotic administration should be insti- and management of esophageal perforation requires further tuted if the stent is not inserted within the first 12 hours of clinical investigation. As more experience is acquired in perforation (Fig. 5). video-assisted esophageal surgery, minimally invasive ap- Endoscopic clipping has been historically used for the proach to esophageal perforation will continue to emerge as control of gastrointestinal bleeding.124 In 1995, Wewalka et an evolving technique for managing a challenging and po- al. described the treatment of esophageal perforation with tentially life-threatening problem. endoscopic clipping after pneumatic dilation for achalasia.125 Since then, successful endoscopic closure of esophageal per- Endoscopic Stenting and Clipping foration with metallic clips has been reported for perforations In 1959, Celestin described the palliation of esophageal associated with instrumentation, foreign body ingestion, and malignancy with a plastic endoprosthesis introduced at Boerhaave’s syndrome126–129 (Fig. 5). This mode of treat- laparotomy.103 In the 1970s, Atkinson and Ferguson sug- ment is suitable only for selected patients with small (Ͻ1.5 gested that endoscopic placement of plastic prosthesis (Celes- cm) clean perforation, and minimal symptoms of infection. tin tube) for inoperable esophagogastric neoplasms provided Although the length of time between the occurrence and the a simple and relative safe alternative of relieving dysphagia diagnosis of perforation is an important prognostic factor, and improving nutrition.104 The last three decades have wit- recent reports advocated clipping of mature perforation in nessed a tremendous growth in the indications for endolumi- special circumstances.130,131 Raymer et al. applied endo- nal prosthesis, including anastomotic tumor recurrence after scopic metallic clips to close mature perforations associated surgery, primary or secondary tumors within the mediastinum with fistulae after controlling mediastinal drainage.130 Simi- causing extrinsic esophageal compression, tracheoesophageal larly, Abe et al. described a case of delayed esophageal fistula, and benign esophageal strictures.105–107 Successful perforation with mediastinitis from foreign body ingestion; management of early esophageal perforation with endolumi- endoscopic nasomediastinal drainage followed by metallic nal stenting has also been described in the settings of endo- endoclip closure of perforation was performed in a patient scopic instrumentation, postoperative repair, foreign body whom refused surgical intervention.131 Six days after en- ingestion, and Boerhaave’s syndrome.108–122 The insertion of doclip application, esophagography demonstrated no further an endoscopic prosthesis may provide as an effective thera- leakage, and the patient was eventually discharge to home. peutic maneuver, or temporary relief of symptoms to allow a more definitive treatment at a later date. The management of CONCLUSION these patients should be individualized and through a multi- Esophageal perforation is a critical and potentially life- disciplinary team approach. Endoscopist, thoracic surgeon, threatening event with considerable morbidity and mortality. and radiologist should interact in a coordinated effort in the The management of esophageal perforation, although contro- planning of therapeutic decisions and participating in the versial, requires a thoughtful and individualized approach. clinical evaluation of treatment outcome. When the diagnosis is made early, an unconfined esophageal Endoluminal stents are made from Nitinol (titanium- leak is a surgical emergency, and surgery therapy is still nickel alloy) or stainless steel compressed into a small caliber considered the “gold standard”. The main principles of sur- introducer system.105 Most stents are available in an uncov- gical intervention are rapid closure of the esophageal leak, ered form or with a plastic coating on the inside and/or the drainage of mediastinal or pleural collections, and adminis- outside of the stent. Uncovered stents are less liable to mi- tration of parenteral nutrition and broad-spectrum antibiotics. gration, but commonly associated with tumor ingrowth. However, there is no consensus in regard to the optimal Newer generations of metallic self-expanding stents are therapy when the perforation is confined in the absence of equipped with antireflux valves and retrievable threads, and systemic infection. Several treatment methodologies have

Volume 63 • Number 5 1181 The Journal of TRAUMA௡ Injury, Infection, and Critical Care evolved over the years, including nonoperative treatment, 18. Brinster CJ, Singhal S, Lee L, et al. Evolving options in the minimally invasive thoracoscopic surgery, endoscopic stent- management of esophageal perforation. Ann Thorac Surg. 2004; ing, and metallic endoclip application. In contrast to nonop- 77:1475–1483. 19. Silvis SE, Nebel O, Rogers G, et al. Results of the 1974 American erative management of esophageal perforation, minimally Society for gastrointestinal endoscopy survey. JAMA. 1976;235:928–930. invasive techniques have the advantages to prevent further 20. Kavic SM, Basson MD. Complications of endoscopy. Am J Surg. contamination of mediastinal and pleural spaces, and resume 2001;181:319–332. oral intake in a timely fashion. The introduction of these 21. Gama AH, Waye JD. Complications and hazards of gastrointestinal therapeutic modalities is potentially a major step forward in endoscopy. World J Surg. 1989;13:193–201. 22. Vaezi MF, Richter JE. Current therapies for achalasia. J Clin the management of esophageal perforation. The clinical effi- Gastroenterol. 1998;27:21–35. cacy of minimally invasive techniques is promising enough to 23. Nair LA, Reynolds JC, Parkman HP, et al. Complications during warrant further clinical investigation directed at defining pneumatic dilation for achalasia or diffuse esophageal spasm. these evolving modalities as invaluable ancillary adjuncts in Analysis of risk factors, early clinical characteristics, and outcome. the management of early esophageal perforation. Dig Dis Sci. 1993;38:1893–1904. 24. Terblanche J, Bornman PC, Kahn D, et al. Failure of repeated injection sclerotherapy to improve long-term survival after REFERENCES oesophageal variceal bleeding. A five-year prospective controlled clinical trial. 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Surgical aspects of 78. Mayer JE Jr, Murray CA, Varco RL. The treatment of esophageal esophageal disease. Am J Respir Crit Care Med. 2001;16:1037– perforation with delayed recognition and continuing sepsis. Ann 1040. Thorac Surg. 1977;23:568–573. 55. Meyer JP, Barrett JA, Schuler JJ, et al. Mandatory vs selective 79. Bufkin BL, Miller JI Jr, Mansour KA. Esophageal perforation: exploration for penetrating neck trauma. Arch Surg. 1987;122:592– emphasis on management. Ann Thorac Surg. 1996;61:1447–1452. 597. 80. Iannettoni MD, Whyte RI, Orringer MB. Catastrophic 56. Nesbitt JC, Sawyers JL. Surgical management of esophageal complications of the cervical esophagogastric anastomosis. perforation. Am Surg. 1987;53:183–191. J Thorac Cardiovasc Surg. 1995;110:1493–1500. 57. Flynn AE, Verrier ED, Way LW, et al. Esophageal perforation. 81. Grillo HC, Wilkins EW Jr. Esophageal repair following late Arch Surg. 1989;124:1211–1214. diagnosis in intrathoracic perforation. Ann Thorac Surg. 1975; 58. White RK, Morris DM. Diagnosis and management of esophageal 20:387–399. perforations. Am Surg. 1992;58:112–119. 82. Kotsis L, Agocs L. The effectiveness of diaphragmatic pedicled 59. Sarr MD, Pemberton JH, Payne WS. Management of instrumental grafts in esophageal injuries and wall reconstruction. Eur perforations of the esophagus. J Thorac Cardiovasc Surg. 1982; J Cardiothorac Surg. 1998;14:218–220. 84:211–218. 83. Sabanathan S, Eng J, Richardson J. Surgical management of 60. Jones WG II, Ginsberg RJ. Esophageal perforation: a continuing intrathoracic oesophageal rupture. Br J Surg. 1994;81:863–865. challenge. Ann Thorac Surg. 1992;53:534–543. 84. Richarson JD, Martin LF, Borzotta AP, et al. Unifying concepts in 61. Barrett N, Allison PR, Jonestone AS, et al. Discussion on unusual treatment of esophageal leaks. Am J Surg. 1985;149:157–162. aspects of esophageal disease. Proc R Soc Med. 1956;49:529–544. 85. Gouge TH, Depan HJ, Spencer FC. Experience with the Grillo 62. Han SY, McElvein RB, Aldrete JS, et al. Perforation of the pleural wrap procedure in 18 patients with perforation of the esophagus: correlation of site and cause with plain film findings. thoracic esophagus. Ann Surg. 1989;209:612–617. AJR Am J Roentgenol. 1985;145:537–540. 86. Wang N, Razzouk AJ, Safavi A, et al. Delayed primary repair of 63. Panzini L, Burrell MI, Traube M. Instrumental esophageal perforation: intrathoracic esophageal perforation: is it safe? J Thorac chest film findings. Am J Gastroenterol. 1994;89:367–370. Cardiovasc Surg. 1996;111:114–121. 64. Naclerio EA. The “V-sign” in the diagnosis of spontaneous rupture 87. Moghissi K, Pender D. Instrumental perforations of the oesophagus of the esophagus. Am J Surg. 1957;93:291–298. and their management. Thorax. 1988;43:642–646. 65. Gimenez A, Franquet T, Erasmus J, et al. Thoracic complications 88. Urbani M, Mathisen DJ. Repair of esophageal perforation after of esophageal disorders. Radiographics. 2002;22:S247–258. treatment for achalasia. Ann Thorac Surg. 2000;69:1609–1611.

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89. Orringer MB, Stirling MB. Esophagectomy for esophageal 112. Bethge N, Kleist DV, Vakil N. Treatment of esophageal perforation disruption. Ann Thorac Surg. 1990;49:35–42. with a covered expandable metal stent. Gastrointest Endosc. 1996; 90. Banks JG, Bancewicz J. Perforation of the esophagus: experience in 43:161–163. a general hospital. Br J Surg. 1981;68:580–584. 113. Dormann AJ, Wigginghaus B, Deppe H, et al. Successful treatment 91. Matthews HR, Mitchell IM, McGuigan JA. Emergency subtotal of esophageal perforation with a removable self-expanding plastic oesophagectomy. Br J Surg. 1989;76:918–920. stent. Am J Gastroenterol. 2001;96:923–924. 92. Urschel HC Jr, Razzuk MA, Wood RE, et al. Improved management 114. Nana AM, Stefanidis C, Chami JP, et al. Esophageal perforation by of esophageal perforation: exclusion and diversion in continuity. Ann echoprobe during cardiac surgery: treatment by endoscopic stenting. Surg. 1974;179:587–591. Ann Thorac Surg. 2003;75:1955–1957. 93. Menguy R. Near-total esophageal exclusion by cervical 115. Bunch TJ, Nelson J, Foley T, et al. Temporary esophageal stenting esophagostomy and tube gastrostomy in the management of allows healing of esophageal perforations following atrial massive esophageal perforation: report of a case. Ann Surg. 1971; fibrillation ablation procedures. J Cardiovasc Electrophysiol. 2006; 173:613–616. 17:435–439. 94. Fell SC. Esophageal perforation. In: Pearson FG, Cooper JD, 116. Choong CK, Martinez C, Meyers BF. Simple and useful Deslauriers J, eds. Esophageal Surgery. New York: Churchill endoscopic technique in the re-establishment of esophageal patency Livingstone; 2002:615–636. for the treatment of a completely obstructed esophagus. Ann Thorac 95. Brewer LA III, Carter R, Mulder GA, et al. Options in the Surg. 2006;81:1519–1521. management of perforations of the esophagus. Am J Surg. 1986; 117. Mason GR. Esophageal perforations, anastomotic leaks, and 152:62–69. strictures; the role of prosthesis. Am J Surg. 2001;181:195–197. 96. Lawrence DR, Ohri SK, Moxon RE, et al. Iagrogenic oesophageal 118. Chambers AS, Jordan T, McGranahan T, et al. A new management perforations: a clinical review. Ann R Coll Surg Engl. 1998;80:115– approach for esophageal perforation. J Thorac Cardiovasc Surg. 118. 2005;130:1470–1471. 97. Altorjay A, Kiss J, Voros A, et al. Nonoperative management of 119. Segalin A, Bonavina L, Lazzerini M, et al. Endoscopic Ann Surg. esophageal perforations. Is it justified? 1997;225:415–421. management of inveterate esophageal perforations and leaks. Surg 98. Cameron JL, Kieffer RF, Hendrix TR, et al. Selective nonoperative Endosc. 1996;10:928–932. management of contained intrathoracic esophageal disruptions. Ann 120. Mumtaz H, Barone GW, Ketel BL, et al. Successful management Thorac Surg. 1979;27:404–408. of a nonmalignant esophageal perforation with a coated stent. Ann 99. Nguyen NT, Follette DM, Roberts PF, et al. Thoracoscopic Thorac Surg. 2002;74:1233–1235. management of postoperative esophageal leak. J Thorac Cardiovasc 121. Pajarinen J, Ristkari SK, Mokka RE. A report of three cases with Surg. 2001;121:391–392. an oesophageal perforation treated with a coated self-expanding 100. Scott HJ, Rosin RD. Thoracoscopic repair of a transmural rupture stent. Ann Chir Gynaecol. 1999;88:332–334. of the oesophagus. J R Soc Med. 1995;88:414–415. 122. Serna DL, Vovan TT, Roum JH, et al. Successful nonoperative 101. Landen S, El Nakadi I. Minimally-invasive approach to management of delayed spontaneous esophageal perforation in Boerhaave’s syndrome: a pilot study of three cases. Surg Endosc. patients with human immunodeficiency virus. Crit Care Med. 2000; 2002;16:1354–1357. 28:2634–2637. 102. Chung DA, Ritchie AJ. Videothoracoscopic drainage of mediastinal 123. Fisher A, Thomusch O, Benz S, et al. Nonoperative treatment of 15 abscess: an alternative to thoracotomy. Ann Thorac Surg. 2000; 69:1574–1576. benign esophageal perforations with self-expandable covered metal 103. Celestin LR. Permanent inbutation in inoperative cancer of the stents. Ann Thorac Surg. 2006;81:467–473. oesophagus and cardia. Ann R Coll Surg Eng. 1959;25:165–170. 124. Soehendra N, Sriram PV, Ponchon T, et al. Hemostatic clip in 104. Atkinson M, Ferguson R. Fibre-optic endoscopic palliative gastrointestinal bleeding. Endoscopy. 2001;33:172–180. intubation of inoperable oesophogastric neoplasm. Br Med J. 1997; 125. Wewalka FW, Clodi PH, Haidinger D. Endoscopic clipping of 1:266–267. esophageal perforation after pneumatic dilation for achalasia. 105. Lee SH. The role of oesophageal stenting in the non-surgical Endoscopy. 1995;27:608–611. management of oesophageal strictures. Br J Radiol. 2001;74:891–900. 126. Cipolletta L, Biano MA, Rotondano G, et al. Endoscopic clipping 106. Nicholson AA, Royston CMS, Wedgewood K, et al. Palliation of of perforation following pneumatic dilation of esophagojejunal malignant oesophageal perforation and proximal oesophageal anastomotic strictures. Endoscopy. 2000;32:720–722. malignant dysphagia with covered metal stents. Clin Radiol. 1995; 127. Shimizu Y, Kato M, Yamamoto J, et al. Endoscopic clip 50:11–14. application for closure of esophageal perforations caused by EMR. 107. Morgan RA, Ellul JPM, Denton ERE, et al. Malignant esophageal Gastrointest Endosc. 2004;60:636–639. fistulas and perforations: management with plastic-covered metallic 128. Shimamoto C, Hirata I, Umegaki E, et al. Closure of an esophageal endoprosthesis. Radiology. 1997;204:527–532. perforation due to fish bone ingestion by endoscopic clip 108. Bisgaard T, Wojdemann M, Heindorff H, et al. Nonsurgical application. Gastrointest Endosc. 2000;51:736–739. treatment of esophageal perforations after endoscopic palliation in 129. Parupudi VJ, Guduru R, Nageshwar D. Successful closure of advanced esophageal cancer. Endoscopy. 1997;29:155–159. spontaneous esophageal perforation (Boerhaave’s syndrome) by 109. Liedman B, Johnsson E, Lundell L. Treatment of iatrogenic endoscopic clipping. Indian J Gastroenterol. 2006;25:39–41. perforations with covered stents in patients with oesophageal 130. Raymer GS, Sadana A, Campbell DB, et al. Endoscopic clip cancer. Eur J Surg. 2001;167:672–674. application as an adjunct to closure of mature esophageal perforation 110. Adamek HE, Jakobs R, Dorlars D, et al. Management of with fistulae. Clin Gastroenterol Hepatol. 2003;1:44–50. esophageal perforations after therapeutic upper gastrointestinal 131. Abe N, Sugiyama M, Hashimoto Y, et al. Endoscopic nasomediastinal endoscopy. Scan J Gastroenterol. 1997;32:411–414. drainage followed by clip application for treatment of delayed 111. Fernandez FF, Richter A, Freudenberg S, et al. Treatment of esophageal perforation with mediastinitis. Gastrointest Endosc. 2001; endoscopic esophageal perforation. Surg Endosc. 1999;13:962–966. 54:646–648.

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A Simplified Technique of Using Bipedicled Fasciocutaneous Flaps in Closure of Soft Tissue Defects of the Anterior Leg in Patients With Fasciotomy Wounds Deemesh Oudit, MRCSEd, Omar Tillo, MS, MRCS, Gavin McCoubrey, MBBS, Louise Crawford, MRCSEd, and Ali Juma, FRCS

J Trauma. 2007;63:1185–1186.

any cases of lower limb trauma present with com- To create these flaps, the bridge of tissue is undermined pound fractures and the patients undergo fascioto- by dissecting the plane between the fascia and the muscle to Mmies to relieve intracompartmental pressure in the include the fascia into the flap. On raising the flap, the muscular compartments of the leg at the time of bony fixa- musculocutaneous perforators, if found, are sacrificed be- tion. A fraction of these patients also present with soft tissue cause the blood supply to these flaps is derived from the defects of the leg with exposed bone or tendons after mod- direct cutaneous vessels that run parallel above the muscle erate to severe lower extremity injuries. Bone is often ex- and fascia and are included in the flaps.2–4 posed in such wounds on the anterior aspect of the leg The flaps can be raised along part or the entire length of because in this area the anterior tibia is a subcutaneous the fasciotomy wound. This is dictated by the safe length to structure. The exposure of bone demands complex recon- width ratio of the flap and the amount of flap mobility needed structive procedures such as microvascular tissue transfer to to provide adequate soft tissue closure of the defect in a treat these wounds. tension free manner. The safe length to width ratio of the The options for soft tissue reconstruction of these trau- bipedicled fasciocutaneous flap still remains indeterminate.2 matic defects of the leg depend on several factors including Ponten and Barcklay found a 3:1 length to breadth ratio to be the location and size of the defect, the nature of the tissues at satisfactory in unilateral fasciocutaneous flap.3,4 However, the base of the wound (viable fascia or muscle, tendons, or extrapolation to assume a 6:1 ratio would be safe may be bone), the condition of the adjacent tissues, and the presence invalid as tissue viability of the distal pedicle variants has of patent vascular structures. The solutions range from simple been less reliable.5 The ratio we advise is the one used by to complex procedures and include direct closure, split-skin Hallock, which is 3:1 or less. grafting, local fasciocutaneous flaps, and free microvascular This technique would not be possible if the fasciotomy tissue transfer. wounds were either absent or directly closed. In this regard, We suggest a relatively simple, and often overlooked every attempt should be made to resist the urge to directly Ͻ option for reconstruction of relatively narrow ( 2.5 cm) close fasciotomy wounds in such cases since this would longitudinal defects involving the middle third of the anterior impair the mobility of the bipedicled fasciocutaneous flaps. leg in patients who have undergone fasciotomies. Instead, these fasciotomy wounds should be closed using There have been several reports in the literature of the split-thickness skin grafts (Fig. 1). use of bipedicled fasciocutaneous flaps to cover soft tissue 1,2 The usefulness of this technique is, however, limited to defects of the leg. However, to the best of our knowledge, defects, which are relatively narrow (Ͻ2.5 cm) and shorter none has commented on the usefulness of these already- than the fasciotomy wounds with healthy surrounding soft created flaps after fasciotomies of the leg. The strips of intact tissues and with the presence of fasciotomy wounds. As in all soft tissue between the traumatic and fasciotomy wounds, on cases of reconstructive surgery, because of these limitations, each side, when undermined, are in effect bipedicled fascio- careful patient selection is important. cutaneous flaps. Although the cosmetic outcome of split-skin grafting of the fasciotomy wounds is not superior to the linear scar of Submitted for publication October 3, 2004. direct closure, this technique, if applicable, can prevent more Accepted for publication July 6, 2007. complex reconstructive procedures that may be associated Copyright © 2007 by Lippincott Williams & Wilkins with less than ideal cosmetic and functional implications. From the Lancashire Teaching Hospitals, Royal Preston Hospital, Despite the numerous reports in the literature of the Manchester, United Kingdom. Address for reprints: Deemesh Oudit, MRCSEd, Apt 1006 Sovereign various techniques to close fasciotomy wounds to avoid skin 5–10 Point, 31 The Quays, Salford, Manchester M50 3AY, United Kingdom; grafting, this may not be applicable to all cases. We think email: [email protected]. that this relatively simple principle of sacrificing direct clo- DOI: 10.1097/TA.0b013e31814da9e8 sure of fasciotomy wounds can result in the direct closure of

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Fig. 1. Mobilization of the bipedicled fasciocutaneous flaps bilaterally (A) facilitates direst closure of the traumatic wound (B). The fasciotomy wounds are subsequently skin grafted. narrow longitudinal defects of the anterior leg. It is an easily indications and limitations in 12 cases. Scand J Plast Reconstr Surg overlooked solution to a potentially challenging problem that Hand Surg. 1996;30:187–193. may avoid the need for more sophisticated forms of tissue 2. Hallock GG. Bipedicled fasciocutaneous flaps in the lower extremity. 1992;29:397–401. transfer. 3. Ponten B. The fasciocutaneous flap: its use in soft tissue defects of This method avoids the patient having to undergo more the lower leg. Br J Plast Surg. 1981;34:215–220. complex reconstructive procedures (such as free microvascu- 4. Barclay TL, Cardoso E, Sharpe DT, et al. Repair of lower leg lar tissue transfer) to reconstruct the anterior leg defect, injuries with fascio-cutaneous flaps. Br J Plast Surg. 1982;35:127– because the more complex procedures are associated with 132. 5. Amarante J, Costa H, Reis J, et al. A new distally based significantly greater morbidity and mortality. Furthermore, it fasciocutaneous flap of the leg. Br J Plast Surg. 1986;39:338–340. is possible for this procedure to be performed by the ortho- 6. Dahners LE. The running near-near-far-far stitch for closure of pedic team, thus providing early coverage of exposed bone fascitomies and other large wounds. Orthopaedics. 2003;26:383–384. and other vital structures bypassing the unnecessary delays in 7. Janzing HM, Broos PL. Dermatotraction: an effective technique for having the patient transferred to the regional plastic surgery the closure of fasciotomy wounds: a preliminary report of fifteen patients. J Orthop Trauma. 2001;15:438–441. unit. 8. Chiverton N, Redden JF. A new technique for delayed primary closure of fasciotomy wounds. 2000;31:21–24. 9. Asgari MM, Spinelli HM. The vessel loop shoelace technique for REFERENCES closure of fasciotomy wounds. Ann Plast Surg. 2000;44:225–229. 1. Schwabegger A, Ninkovic M, Wechselberger G, et al. The 10. McKenny MG, Nir I, Fee T, et al. A simple device for closure of bipedicled flap on the lower leg, a valuable old method? Its fasciotomy wounds. Am J Surg. 1996;172:275–277.

1186 November 2007 ௡ Brief Report The Journal of TRAUMA Injury, Infection, and Critical Care

Carboxyhemoglobin Monitored by Bedside Continuous CO-Oximetry Troilus Plante, MD, Darcy Harris, MD, Julie Savitt, Fatemeh Akhlaghi, PharmD, PhD, James Monti, MD, and Gregory D. Jay, MD, PhD

J Trauma. 2007;63:1187–1190.

arbon monoxide (CO) poisoning remains a significant We used the RAD-57 pulse CO-oximeter (Masimo, Irvine, and common cause of mortality and morbidity in in- CA) to measure SpCO continuously and noninvasively Cdustrialized countries. Approximately 15,000 patients while simultaneously obtaining a serum specimen for stan- are treated for CO poisoning yearly in emergency depart- dard co-oximetry. Serial SpCO readings were recorded ments (EDs), and roughly 480 of those cases are fatal.1 noninvasively every 5 minutes. Her initial COHb level was Historically, venous co-oximetry has been the mainstay of 35% by standard CO-oximetry compared with 37% by diagnosis. Co-oximetry measures the relative concentrations continuous pulse CO-oximetry. An arterial blood gas re-

of oxygenated and deoxygenated hemoglobin, as well as vealed a pH of 7.36, PaO2 of 339, and a calculated O2 carboxyhemoglobin (COHb) and methemoglobin. Recently, saturation of 64%. During 90 minutes of continuous pulse a noninvasive pulse CO-oximeter with a pulse oximetry CO-oximetry, her SpCO decreased from 23% to 6% at 150 configuration was developed offering the possibility of minutes postintubation. Once reaching 6% COHb, a repeat performing rapid, photospectroscopic COHB (SpCO) mea- blood sample was drawn for standard co-oximetry, which was surements. This technology obtains as SpCO while sim- 5% (Fig. 1). The remainder of her evaluation was significant plifying testing from the traditional venipuncture based only for peribronchial cuffing on chest radiograph. assay to performance of a vital sign not unlike standard After completion of her trauma evaluation, the patient pulse oximetry. We think this case is the first instance in was taken to the trauma intensive care unit for monitoring which such a device was used in the diagnosis and man- and further evaluation of presumed inhalation injury. On agement of a severe CO poisoning. bronchoscopy, the patient was found to have suffered a significant inhalation injury with moderate bronchial air- CASE way edema. Copious amounts of carbonaceous material were An 81-year-old nonsmoking, previously independent suctioned from her bronchial tree. During her 1-month hospital- woman presented to the ED after being trapped in a house ization, the patient underwent tracheostomy and gastrostomy fire. Upon arrival to the ED, she was awake but combative, placement. She developed a moderate oxygen requirement tem- with a Glasgow Coma Scale score of 9. She was breathing porarily, but steadily improved and was able to be discharged to spontaneously with normal vital signs and an oxygen satura- a rehabilitation hospital on oral feeding and supplemental oxy- tion of 98% according to pulse oximetry on high-flow oxygen. At this time, there are no further records available for her gen. Otherwise, her physical examination was normal except survival or neuropsychiatric evaluation. for thick carbonaceous sputum in her nares and oropharynx. After her primary survey, she was intubated and placed on DISCUSSION 100% oxygen for airway protection and the completion of her These data were modeled with a one-compartment (first- trauma evaluation. order or monoexponential decay) or two-compartment (biexpo- After intubation, routine laboratory and radiographic nential decay) model using WinNonlin version 4.1 (Pharsight, examinations were obtained in addition to blood COHb. CA). The available data best fits monoexponential decay kinetics (one compartment model or first order kinetics) with an Submitted for publication November 29, 2005. estimated half-life of 57.6 Ϯ 1.7 minutes. This differs from the Accepted for publication August 10, 2006. commonly cited half-life of 74 minutes, which was actually Copyright © 2007 by Lippincott Williams & Wilkins obtained from experimentally poisoned volunteers.2 From the Department of Emergency Medicine, Brown Medical School, Providence; and the Department of Pharmacy Practice, the University of Patients suffering from acute CO exposure are com- Rhode Island, Kingston, Rhode Island. monly treated with near 100% O2 for 3 hours by nonre- 3 Address for reprints: Troilus Plante, MD, DUMC Box 3096, Durham, breather mask oxygen (NBO2). The implication is that by NC 27710; email: [email protected]. allowing patients to undergo two dissociation half-lives at

DOI: 10.1097/01.ta.0000242769.04246.5d NBO2 (1 atmosphere pressure), there will be a significant

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Fig. 1. Graph of carboxyhemoglobin concentration versus time measured by both noninvasive pulse CO-oximeter and standard venous co-oximetry. reduction in concentration of COHb. The most often cited onstrates a two-compartmental, monoexponential model of half-lives for COHb elimination are 320 minutes at 1.0 at- decay.11 To date, however, no such inquiry has been per- mosphere absolute (ATA) pressure and FIO2 0.21, 74 minutes formed in accidentally poisoned human subjects. at 1.0 ATA and FIO2 1.0, and 23 minutes at 2.8 ATA and FIO2 Our case illustrates the collection of multiple data 2,4,5 1.0 (HBO2). points from the same, non-experimentally poisoned patient Early pharmacokinetic studies applied logarithmic expres- over time from which the decrease in COHb can be studied sions (first-order kinetics) to describe COHb elimination.6,7 and exposed to multiple kinetic models using WinNonlin. Other studies have extended this finding and introduced a The present case, though typical for a severe CO poison- two-point determination of COHb elimination using the ing, is novel as it is the first reported poisoning managed same logarithmic expressions.8,9 Peterson and Stewart with the aid of bedside, noninvasive pulse CO-oximetry. studied two experimentally poisoned human subjects pro- The available data best fits monoexponential decay kinetics (one-compartment model or first-order kinetics) with spectively in a double cross-over design between NBO2 6 an estimated half-life of 57.6 Ϯ 1.7 minutes (Fig. 2). The and HBO2 (1 atmosphere and 2–2.8 atmospheres, respectively). Their analysis was limited by singular application of first-order more physiologically meaningful value of mean residence time (the average time each molecule resides in the body) kinetics to COHb elimination profiles, which resulted in the was estimated at 83.1 Ϯ 2.5 minutes (Table 1). above half-lives. These values have been perpetuated in the Early detection of CO exposure is considered by the literature and not been rigorously tested. Centers for Disease Control and Prevention (CDC) and Jay and McKindley scrutinized these prior kinetic American Association of Poison Control Centers to be “a studies and found that zero-order elimination properties chemical exposure of public health importance”.12 Recent may better describe COHb dissociation under NBO2, 10 CDC reports have focused on CO poisoning from hurricane- whereas first-order elimination prevails under HBO2. associated generator use. The implementation of a noninva- This is an important consideration as a debate continues sive co-oximetry device would be an invaluable tool in whether and when the pressure should be on or off in patient assessment in a disaster situation. Hurricane Katrina treating CO poisoning with 100% oxygen. Multiple phys- swept the Gulf Coast on August 29, 2005 causing widespread iologic compartments cleared by mono- or biexponential property damage and power outages.12 Fifty-one cases of CO decay kinetics is the desirable type of elimination mecha- poisoning among residents of Alabama, Louisiana, and Mis- nism in CO poisoning, which affects myoglobin, hemoglo- sissippi were reported by the hyperbaric oxygen facilities in bin, and the mitochondrial electron transport chain. By those states (46 nonfatal and 5 fatal exposures) from August contrast, zero-order elimination theoretically clears CO 29 through September 24, 2005. All fire or smoke-related from a single compartment. Subsequently, Shimazu et al. exposures were excluded. Exhaust from a portable generator investigated the potential kinetic differences between was deemed the source in all but one of the cases, which was short-term and long-term CO exposure in experimentally found to be from a gasoline-powered pressure washer.12 A poisoned sheep.11 Their results showed that COHb dem- 2004 Behavioral Risk Factor Surveillance System Survey in

1188 November 2007 COHb Monitored by Bedside Continuous Co-Oximetry

Fig. 2. Modeling of elimination of COHb against time assuming a monoexponential decay model: C(T) ϭ D/V ϫ EXP(-K10 ϫ T). Model diagnostic values were 55.8 (Akaike Information Criteria) and 57.6 (Schwarz’s criteria).

will facilitate a better understanding of CO toxicokinetics Table 1 Calculations for Multiple Carboxyhemoglobin and the formation of methemoglobinemia, which can occur Elimination Kinetics iatrogenically or through toxicologic means. The value of Parameter Mean SE CV% adding these features to a device that functions similar to Elimination half-life (min) 57.6 1.7 2.98 a pulse oximeter cannot be overstated. Because signs and Area under the concentration time 6820.3 129.1 1.89 symptoms of mild to moderate CO poisoning can be con- curve (% ϫ min) fused with flu-like symptoms, particularly during the win- Maximum concentration/C (%) 82.1 3.6 4.37 max ter months, there is justification in screening every patient Mean residence time (min) 83.1 2.5 2.98 in ED triage practice for occult CO poisoning.

Florida reported 17.5% of adult respondents used a generator for powering household appliances after at least one of REFERENCES four major hurricanes from August 13 through September 1. MMWR [database online]. CDC. Unintentional non-fire-related carbon 25, 2004.13 A 5.5 kW generator produces as much CO as monoxide exposures-United States. 2001–2003. 2005;54:36–39. that of six idling automobiles.13–15 The CDC and the Con- 2. Weaver LK, Howe S, Hopkins R, et al. Carboxyhemoglobin sumer Product Safety Commission are working to educate the half-life in carbon monoxide poisoned patients treated with 100% oxygen at atmospheric pressure. Chest. March 2000;117: public about CO poisoning and emphasize proper guidelines for 801–808. generator use. Posthurricane conditions including fear of theft 3. Smith GI, Sharp GR. Treatment of carbon monoxide poisoning with and nonweatherized devices in wet conditions create challenges oxygen under pressure. Lancet. 1960;2:905–906. for consumers and consequently heighten the public health risk 4. Goulon M, Barois A, Rapin M, et al. Intoxication oxy carbonee at 12 anoxie aique par inhalation de gay de charbon et d’hydrocarbures. of CO poisoning. Cases of CO poisoning in a disaster setting Ann Med Interne (Paris) 1969;120:335–439. English translation: are undoubtedly underreported and misdiagnosed. J Hyperbaric Med. 1986;1:23–41. The RAD-57 pulse CO-oximeter is a portable, hand- 5. Blumenthal I. Carbon monoxide poisoning. J R Soc Med. 2001; held device, which combines traditional pulse oximetry 94:270–272. 6. Meyers RAM, Snyder SK, Lindberg S, et al. Value of hyperbaric with transmission spectrophotometric detection of SpCO oxygen in suspected carbon monoxide poisoning. JAMA. 1981; into a single finger probe. Both pieces of data, pulse 246:2478–2480. oximetry and SpCO percentage are available concurrently. 7. Thom SR, Taber RL, Mendiguren II, et al. Delayed The use of noninvasive co-oximetry will aid in rapid di- neuropsychologic sequelae after carbon monoxide poisoning: agnosis and early treatment of CO poisoning by emergency prevention by treatment with hyperbaric oxygen. Ann Emerg Med. 1995;25:474–480. healthcare personnel and will enable numerous future stud- 8. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl ies on elimination kinetics in CO poisoning. Many of the J Med. 1996;334:1642–1648. previous publications in this area were conducted on ex- 9. Peterson JE, Stewart RD. Absorption and elimination of carbon perimentally poisoned humans and animals. These models monoxide by inactive young men. Arch Environ Health. 1970; 21:165–171. are not necessarily clinically relevant as smoke inhalation 10. Jay GD, McKindley DS. Alterations in pharmacokinetics of produces a variety of poisonings including cyanide. The carboxyhemoglobin produced by oxygen under pressure. Undersea availability of rapid and continuous bedside co-oximetry Hyperb Med. 1997;165–173.

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11. Shimazu T, Ikeuchi H, Sugimoto H, et al. Half-life of blood 14. Consumer Product Safety Commission. Memorandum to Janet Buyer carboxyhemoglobin after short-term and long-term exposure to from Sandra E. Inkster: Health hazard assessment of CO poisoning carbon monoxide. J Trauma. 2000;49:126–131. associated with emissions from a portable, 5.5 kilowatt, gasoline- 12. MMWR [database online]. CDC. Carbon monoxide poisoning after powered generator. Washington, D.C.: Consumer Product Safety hurricane Katrina—Alabama, Louisiana, and Mississippi, August– Commission; September 21, 2004. Available at http://www.cpsc.gov/ September 2005. 2005;54:996–998. LIBRARY/FOIA/FOIA04/os/ecportgen.pdf. 13. MMWR [database online]. CDC. Carbon monoxide poisoning from 15. US Environmental Protection Agency. Emission facts: idling vehicle hurricane-associated use of portable generators—Florida, 2004. 2005; emissions. Publication EPA420-F-98-014; Washington, DC: US 54:697–700. Environmental Protection Agency; 1998.

Erratum

In Klc¸coc¸lu SS, Erdemli E. New addition to the Statin’s effect J Trauma. 2007;63:187–191.

Sibel Serin-Kilicoglu’s name was cited incorrectly. The correct citation is as follows:

Serin-Kilicoglu S, Erdemli E. New addition to the Statin’s effect J Trauma. 2007;63:187–191.

Erratum

In Chang YH, Wang LJ, Chuang CK, Wong YC, Wu CT, Hsieh ML. The Efficacy and Outcomes of Urgent Superselective Transcatheter Arterial Embolization of Patients With Ruptured Renal Angiomyolipomas. J Trauma. 2007;62:1487–1490.

There was an error in the table. Please see the corrected table below:

Postembolization Age/Sex Presentation Hb/Hct Before 3 After TAE Hospitalization TAE Materials Syndrome 29/F Left flank pain 9.5/29.4 3 12.0/36.3 7d Gelfoam Presence 40/F Right flank pain, hematuria 8.9/27.1 3 10.9/32.8 3d Coil Absence 30/F Right flank pain, hematuria 8.7/26.0 3 10.9/32.0 6d Gelfoam, coil Presence 30/F Right flank pain, traffic crash, shock 6.2/18.4 3 10.9/31.3 38d Coil Absence 63/F Left flank pain, hematuria 8.9/27.1 3 10.7/31.8 8d Lipidol, alcohol Absence 62/F Left flank pain, traffic crash, hematuria, shock 6.6/23.6 3 10.2/27.6 8d Coil Absence 81/F Left flank pain 8.5/26.4 3 10.4/31.5 7d Lipidol, alcohol Presence

1190 November 2007 ௡ Book Review The Journal of TRAUMA Injury, Infection, and Critical Care

Medicinal Leech Therapy, by Andreas Michalsen, MD, Manfred Roth, MD, and Gustav Dobos, MD, Editors, Thieme-Stuttgart, New York; 2007: 178 Pages, 53 Illustrations, 3 Tables.

Medicinal Leech Therapy is a nifty little book that will tell you everything you ever wanted to know about leeches and their use in medical treatment. If you enjoy reading or viewing information about nature and science, the medical uses of this fascinating little creature will make for very enjoyable reading indeed. It is presented as a paperback of high quality on bright heavy stock, with a pleasantly legible font and clear color illustrations. I approached this book wondering how much could possibly be said about a novelty treatment useful only for relieving venous congestion. Then I realized my ignorance of the long history and many uses leeches have. For clarity while you read this review, do not confuse leeches with maggots, another biologic treatment whose use is very different from that of leeches. Maggots debride wounds and encourage healing.1 Leeches have a wide variety of indications touched upon in this book, none of which are wound debridement. Leeches are used for varicose veins, arthrosis of multiple joints, tendonitis, vertebrogenic pain syndromes, and rheumatic disease, in addition to their use in relieving venous congestion in flaps. The authors point out that the Food and Drug Administration classify leeches as a medical device, and that up to 1.2 tons of leeches are used per annum in Germany. The book begins with a brief introduction and history of leeches. The authors describe the near extinction of leeches in the early 19th century, when up to 100 leeches could be used in a single session, earning the therapy the moniker of “vampirism”. It was also interesting to learn that chemical prophylaxis of deep venous thrombosis was first practiced by applying leeches, whose anticoagulant, hirudin, which keeps their meal from clotting, also would prevent postoperative thrombosis. The chapter on biology of leeches includes more than just the biology, including a treatise on the etymology of the word “leech”, which, in German, has phonetic resemblance to the word for “disgusting”, but has entirely different etymologic roots. There is also a discussion of calin, a protein that allows for persistent bleeding after the leech has gone off to nap after his meal. It is thought that the persistent bleeding allows the Aeromonas left behind by the leech to be washed out of the wound, preventing sepsis, and making the host available for another meal. That meal, by the way, may come after a 2-year fast! The technique of leech therapy is described in detail, and can be used as an instruction guide should you choose to use this therapy. It is clearly written by a practitioner with experience, with detail on the dos and don’ts of leech application and removal (never squeeze the leech!), although some comments seem to be rationalizations not supported by logic, to wit... “The patients should be warned that their blood pressure will be slightly lower after treatment due to posttreatment resting and wound bleeding”. I doubt rest and a few milliliters of blood loss to the leech lead to Class 3 shock. Other chapters cover contraindications, adverse effects, legal aspects of leech therapy, and appendixes that could be the basis for a leech therapy pamphlet for occasional practitioners. Overall, the book is an interesting read even if you never intend to use leeches. It is informative, entertaining, well referenced, and well indexed. I will keep the copy sent to me for review on a table in my office. Nicholas Namias, MD, FACS Division of Burns University of Miami/Jackson Memorial Medical Center Miami, Florida

REFERENCE 1. Namias N, Varela JE, Varas RP, Quintana O, Ward CG. Biodebridement: a case report of maggot therapy for limb salvage after fourth-degree burns. J Burn Care Rehabil. 2000;1:254–257.

Volume 63 • Number 5 1191 ௡ The Image of Trauma The Journal of TRAUMA Injury, Infection, and Critical Care

Lung Torsion Associated With Complete Bronchial Transection After Blunt Chest Trauma Ming-Shian Lu, MD, Yao-Kuang Huang, MD, Chiung-Lun Kao, MD, and Hui-Ping Liu, MD, FACS

J Trauma. 2007;63:1192.

23-year-old man was brought to our emergency room after sustaining a motor vehicle crush against a tele- Aphone pole. He was alert, dyspneic, and hypotensive. Physical examination revealed chest wall subcutaneous emphysema and decreased breathing sound with tympanism over the right, aside of superficial abrasions. Chest X-ray film revealed the presence of right pneumohemothorax. After the insertion of a chest tube, profuse bleeding was noted. An emergent chest computed tomography disclosed right main bronchus interruption with posterior wall rupture (Fig 1A), upside down torsion of the right lung with right upper lobe consolidation and pneumopericardium (Fig 1B). Because of massive hemothorax (1,200 mL in Ͻ1 hr) and suspicious bronchial transection, he was rushed to the operating room without further studies. Through a standard posterolateral thoracotomy incision, the fifth intercostals muscle was harvested before chest retraction. Consolidation of the right upper lobe with two deep parenchymal lacerations with active bleeding from the pulmonary vein was noted. Also, the right middle lobe and lower lobe were pushed back and upward with down displacement of the right upper lobe. Right upper Fig. 1. (A) Transection of right main bronchus with disruption of lobectomy was performed because of severe damage of the posterior wall. (B) Upside down rotation of right upper lobe with lung consolidation and pneumopericardium. Submitted for publication March 9, 2006. Accepted for publication March 14, 2006. Copyright © 2007 by Lippincott Williams & Wilkins right upper lobe that we were unable to repair. After opening From the Division of Thoracic and Cardiovascular Surgery (M.-S.L., the mediastinal pleura, a complete transection of the right C.-L.K.), Chang Gung Memorial Hospital, Chia-Yi Center, Taiwan; the main bronchus 1 cm away from the carina was found with the Division of Thoracic and Cardiovascular Surgery (Y.-K.H., H.-P.L.), Chang lumen filled with blood clot. The right main bronchus was Gung Memorial Hospital, Linkuo Medical Center, Taiwan; and Chang Gung Institute of Technology (C.-L.K.), Chia-Yi Campus, Taiwan. repaired with end-to-end anastomosis using interrupted ab- Address for reprints: Dr Hui-Ping Liu, Div. of Thoracic and Cardio- sorbable suture and buttressed with intercostal muscle flap. vascular Surgery, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, The patient recovered uneventfully and was discharged from Kweishan, Taoyuan, Taiwan 333; email: [email protected]. hospital on day 9. A follow-up bronchoscope 1 month later DOI: 10.1097/01.ta.0000221540.55409.d9 revealed patent right main bronchus without obstruction.

1192 November 2007 ௡ Letters to the Editor The Journal of TRAUMA Injury, Infection, and Critical Care

To the Editor: The Authors’ Reply: to be an independent cause of renal im- Successful clinical follow-up for Dr. Silberzweig’s observation that pairment, ranking in importance behind trauma patients with retrievable inferior some patients simply do not want to sepsis, hypotension, and an age of vena cava (IVC) filters can be challenging have another procedure for filter re- greater than 60 years.4 to achieve. Patients are not aware of moval is correct. If this is obvious Given the cost, length of stay, mor- the presence of an IVC filter unless a before the procedure, it might be rea- bidity, and mortality implications of re- complication occurs, such as IVC sonable to use a permanent type at the nal dysfunction, it is vital that we invest thrombosis. A patient who had suffered outset. As far as an effective protocol, in research on renal failure and be com- a significant trauma may not be moti- it did appear in this relatively small prehensive and inclusive when listing its vated to undergo an additional inva- sample that, as with any other invasive causes, especially in trauma and surgical sive procedure to have an IVC filter procedure, the team performing the patients. Recent published guidelines removed. This is in contrast with trauma procedure if tasked with follow-up recommend criteria for defining intra- patients who have had interventions that re- was more reliable. This was indepen- abdominal hypertension and abdominal sult in external devices, such as incision skin dent of whether it was the trauma compartment syndrome.6 This may help staples, a cast, or an ostomy. team, vascular surgery, or interven- reduce the incidence of renal failure In the January 2007 issue of Jour- tional radiology, which placed the fil- through a comprehensive awareness of nal of Trauma, Dr. Karmy-Jones and ters. Of course, as long as there truly is potential causes. colleagues (Practice patterns and out- a systematic method, it probably does Madhuri Anupindi comes of retrievable vena cava filters in not matter how the follow-up is orga- Michael Sugrue, MB, BCh, trauma patients: an AAST multicenter nized. However, my Interventional BAO, MD, FRCSI, FRACS study. J Trauma 2007; 62:17–24) con- Radiology training was in an environ- Department of Trauma clude that the service placing posttrau- ment where the interventional radiol- matic retrievable inferior vena cava ogy team felt that they were a clinical Liverpool Hospital filters (R-IVCF) should be responsible service, not simply a procedure ser- Sydney, Australia for follow-up. The authors indicate vice, and my mentors demonstrated that failure to retrieve the IVC filter be- that this resulted in better outcomes. cause of loss to follow-up occurred at a Riyad Karmy-Jones, MD REFERENCES significantly lower rate at institutions Southwest Washington Medical 1. Brandt MM, Falvo AJ, Rubinfeld IS, where the service placing the R-IVCF Center Blyden D, Durrani NK, Horst HM. Renal had the primary responsibility for Vancouver, Washington dysfunction in trauma: even a little costs a lot. J Trauma. 2007;62:1362–1364. follow-up compared with institutions 2. Bradley SE, Bradley GP. The effect of that did not have this policy. increased intra-abdominal pressure on renal The authors grouped together patients function in man. J Clin Invest. 1947; from institutions with no policy for clini- To the Editor: 26:1010–1022. cal follow-up and follow-up provided by We congratulate Brandt et al. on 3. Sugrue M, Buist MD, Hourihan F, Deane the trauma service. It is not surprising that their study “Renal dysfunction in trau- S, Bauman A, Hillman K. Prospective 1 study of intra-abdominal hypertension and the retrieval rate was poor in this group ma: even a little costs a lot”. This is an renal function after laparotomy. Br J Surg. since 8 of the 18 institutions had no important article that demonstrates the 1995;82:235–238. follow-up routine. Therefore, it is unrea- cost of renal dysfunction to both the 4. Sugrue M, Jones F, Deane SA, Bishop G, sonable for the authors to group these patient and the health care system. How- Bauman A, Hillman K. Intra-abdominal patients together and imply that the ever, to optimize patient management, hypertension is an independent cause of trauma services were incapable of emphasis needs to be placed on the postoperative renal impairment. Arch Surg. 1999;134:1082–1085. achieving adequate follow up. cause of renal failure. The authors cor- 5. Biancofiore G, Bindi ML, Romanelli AM, Methods used to achieve successful rectly state that there are many causes of et al. Postoperative intra-abdominal patient follow-up in this challenging pa- renal failure but intra-abdominal hyper- pressure and renal function after liver tient population are worthy of further tension is an often forgotten member of transplantation. Arch Surg. 2003;138:703– detailed investigation. this list. 706. James E. Silberzweig, MD Several studies have found an asso- 6. Malbrain ML, Cheatham ML, Kirkpatrick St. Luke’s-Roosevelt Hospital ciation between raised intra-abdominal A, et al. Results from the International 2–5 Conference of Experts on Intra-abdominal Center pressure and renal dysfunction. In a Hypertension and Abdominal Compartment Department of Radiology study of 276 postoperative patients, Syndrome. I. Definitions. Intensive Care New York City, New York intra-abdominal hypertension was found Med. 2006;32:1722–1732.

Volume 63 • Number 5 1193 ௡ Meetings/Courses The Journal of TRAUMA Injury, Infection, and Critical Care

2007 INTERNATIONAL U.S. AND CANADA June 28–July 2, 2008 International Shock Congress. November 12–13, 2007 G¨urzenich Convention Center, Cologne, Harvard Critical Care and Trauma Germany. Fees vary (€40–€570). Infor- Symposium. mation: Post: Edmund A.M. Neuge- Fairmont Copley Plaza Hotel–Boston, bauer, PhD, University of Witten/ MA. Information: Contact 1–George Herdeke, Professor and Chairman of Velmahos, MD, PhD, Phone: (617) 726- Surgical Research, Institute for Research 9591; E-mail: [email protected]; in Operative Medicine, Ostmerheimer Str. Website: http://massgeneral.org/trauma; 200, 51109 Cologne, Germany; E-mail: Contact 2–Harvard CME, Phone: (617) [email protected]; Web- 384-8600; Website: http://cme.med. site: http://www.shock2008-cologne.org. harvard.edu.

1194 November 2007