Antithrombotic Therapies in Spine Surgery 1 North American Spine Society Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care

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NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 1 North American Spine Society Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care

Antithrombotic Therapies in Spine Surgery

NASS Evidence-Based Guideline Development Committee Christopher M. Bono, MD, Committee Chair Robert Fernand, MD William C. Watters III, MD, Committee Chair Tim Lamer, MD Michael H. Heggeness, MD, PhD Paul G. Matz, MD Daniel K. Resnick, MD, Richard C. Mendel, MD William O. Shaffer, MD Rajeev K. Patel, MD Jamie Baisden, MD Charles A. Reitman, MD Peleg Ben-Galim, MD John F. Toton, MD John E. Easa, MD

Financial Statement This clinical guideline was developed and funded in its entirety by the North American Spine Society (NASS). All participating authors have submitted a disclosure form relative to potential conflicts of interest which is kept on file at NASS.

Comments Comments regarding the guideline may be submitted to the North American Spine Society and will be considered in development of future revisions of the work.

North American Spine Society Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care Antithrombotic Therapies in Spine Surgery

7075 Veterans Boulevard Burr Ridge, IL 60527 630.230.3600 www.spine.org

ISBN: 1-929988-26-5

I. Introduction ...... 4

II. Guideline Development Methodology ...... 5

III. Incidence of DVT/PE in Spine Surgery A. Unprophylaxed Patient...... 9 B. Prophylaxed Patient ...... 15

IV. Recommendations Regarding Appropriate Use of Antithrombotic Therapies in Spine Surgery A. Efficacy of Antithrombotic Therapies...... 17 B. Mechanical Prophylaxis...... 21 C. Chemoprophylaxis...... 22 D. Wound Complications...... 25 E. Risk/Benefit Analysis...... 26

V. Appendices A. Levels of Evidence for Primary Research Questions...... 28 B. Grades of Recommendations for Summaries or Reviews of Studies...... 29 C. NASS Literature Search Protocol ...... 30 D. Literature Search Parameters...... 32 E. Evidentiary Tables...... 39

VI. References...... 93

Objective with discussion of wound complications and risks The objective of the North American Spine So- associated with prophylactic measures. ciety (NASS) Evidence-Based Clinical Guideline on Antithrombotic Therapies in Spine Surgery is THIS GUIDELINE DOES NOT REPRESENT to provide evidence-based recommendations to A “STANDARD OF CARE,” nor is it intended address key clinical questions surrounding the use as a fixed treatment protocol. It is anticipated that of antithrombotic therapies in spine surgery. The there will be patients who will require less or more guideline is intended to address these questions extensive prophylaxis than the average. It is also ac- based on the highest quality clinical literature avail- knowledged that in atypical cases, treatment falling able on this subject as of February 2008. The goals outside this guideline will sometimes be necessary. of the guideline recommendations are to assist in This guideline should not be seen as prescribing the delivering optimum, efficacious treatment with the type, frequency or duration of intervention. Treat- goal of preventing thromboembolic events. ment should be based on the individual patient’s need and doctor’s professional judgment. This Scope, Purpose and Intended User document is designed to function as a guideline and This document was developed by the North should not be used as the sole reason for denial of American Spine Society Evidence-based Guideline treatment and services. This guideline is not in- Development Committee as an educational tool tended to expand or restrict a health care provider’s to assist spine surgeons in minimizing the risk of scope of practice or to supersede applicable ethical deep venous thrombosis (DVT) and pulmonary standards or provisions of law. embolism (PE). The NASS Clinical Guideline on Antithrombotic Therapies in Spine Surgery dis- Patient Population cusses the incidence of DVT/PE in the population The patient population for this guideline encom- of patients undergoing spinal surgery. Recom- passes adults (18 years or older) undergoing spine mendations are made to address the utilization of surgery. chemoprophylaxis and mechanical prophylaxis,

Through objective evaluation of the evidence and ing includes a series of readings and exercises, or transparency in the process of making recom- interactivities, to prepare guideline developers for mendations, it is NASS’ goal to develop evidence- systematically evaluating literature and developing based clinical practice guidelines for the diagnosis evidence-based guidelines. The online course takes and treatment of adult patients with various spinal approximately 15-30 hours to complete and partici- conditions. These guidelines are developed for pants are awarded CME credit upon completion of educational purposes to assist practitioners in their the course. clinical decision-making processes. It is anticipated that where evidence is very strong in support of Disclosure of Potential Conflicts of recommendations, these recommendations will be Interest operationalized into performance measures. All participants involved in guideline development have disclosed potential conflicts of interest to their Multidisciplinary Collaboration colleagues and their potential conflicts have been With the goal of ensuring the best possible care documented for future reference. They will not be for adult patients suffering with back pain, NASS published in any guideline, but kept on file for ref- is committed to multidisciplinary involvement in erence, if needed. Participants have been asked to the process of guideline and performance measure update their disclosures regularly throughout the development. To this end, NASS has ensured that guideline development process. representatives from medical, interventional and surgical spine specialties have participated in the development and review of all NASS guidelines. Levels of Evidence and Grades of It is also important that primary care providers and musculoskeletal specialists who care for pa- Recommendation tients with spinal complaints are represented in the NASS has adopted standardized levels of evidence development and review of guidelines that address (Appendix B) and grades of recommendation treatment by first contact physicians, and NASS (Appendix C) to assist practitioners in easily un- has involved these providers in the development derstanding the strength of the evidence and rec- process as well. To ensure broad-based representa- ommendations within the guidelines. The levels of tion, NASS has invited and welcomes input from evidence range from Level I (high quality random- other societies and specialties. ized controlled trial) to Level V (expert consensus). Grades of recommendation indicate the strength of Evidence Analysis Training of All the recommendations made in the guideline based on the quality of the literature. NASS Guideline Developers NASS has initiated, in conjunction with the Uni- Grades of Recommendation: versity of Alberta’s Centre for Health Evidence, an online training program geared toward educat- A: Good evidence (Level I studies with consistent ing guideline developers about evidence analysis finding) for or against recommending intervention. and guideline development. All participants in guideline development for NASS have completed B: Fair evidence (Level II or III studies with the training prior to participating in the guide- consistent findings) for or against recommending line development program at NASS. This train- intervention.

Level I therapeutic study. This same study, howev- C: Poor quality evidence (Level IV or V studies) er, might be classified as giving Level II prognostic for or against recommending intervention. evidence if the data for the untreated controls were extracted and evaluated prognostically. I: Insufficient or conflicting evidence not allowing a recommendation for or against intervention. Guideline Development Process

The criteria for assigning these levels of evidence  Step 1: Identification of Clinical Questions and grades of recommendation are the same as Trained guideline participants were asked to submit those used by the Journal of Bone and Joint Sur- a list of clinical questions that the guideline should gery, the American Academy of Orthopaedic address. The lists were compiled into a master list, Surgeons, Clinical Orthopaedics and Related Re- which was then circulated to each member with a search, the journal Spine and the Pediatric Ortho- request that they independently rank the questions paedic Society of North America. in order of importance for consideration in the guideline. The most highly ranked questions, as In evaluating studies as to levels of evidence for determined by the participants, served to focus the this guideline, the study design was interpreted guideline. as establishing only a potential level of evidence. As an example, a therapeutic study designed as a  Step 2: Identification of Work Groups randomized controlled trial would be considered Multidisciplinary teams were assigned to work a potential Level I study. The study would then be groups and assigned specific clinical questions to further analyzed as to how well the study design address. Because NASS is comprised of surgical, was implemented and significant short comings in medical and interventional specialists, it is impera- the execution of the study would be used to down- tive to the guideline development process that a grade the levels of evidence for the study’s conclu- cross section of NASS membership is represented sions. In the example cited previously, reasons to on each group whenever feasible. This also helps downgrade the results of a potential Level I ran- to ensure that the potential for inadvertent biases domized controlled trial to a Level II study would in evaluating the literature and formulating recom- include, among other possibilities, an underpow- mendations is minimized. ered study (patient sample too small, variance too high), inadequate randomization or masking of the  Step 3: Identification of Search Terms and group assignments and lack of validated outcome Parameters measures. One of the most crucial elements of evidence analysis to support development of recommenda- In addition, a number of studies were reviewed tions for appropriate clinical care is the compre- several times in answering different questions hensive literature search. Thorough assessment of within this guideline. How a given question was the literature is the basis for the review of existing asked might influence how a study was evaluated evidence and the formulation of evidence-based and interpreted as to its level of evidence in an- recommendations. In order to ensure a thorough swering that particular question. For example, a literature search, NASS has instituted a Literature randomized control trial reviewed to evaluate the Search Protocol (Appendix D) which has been fol- differences between the outcomes of patients who lowed to identify literature for evaluation in guide- received antibiotic prophylaxis with those who line development. In keeping with the Literature did not might be a well designed and implemented Search Protocol, work group members have iden-

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 7 tified appropriate search terms and parameters to literature using the NASS levels of evidence. Any direct the literature search. discrepancies in scoring have been addressed by two or more reviewers. The consensus level (the Specific search strategies, including search terms, level upon which two thirds of reviewers were in parameters and databases searched, are documented agreement) was then assigned to the article. in the appendices (Appendix E). As a final step in the evidence analysis process,  Step 4: Completion of the Literature members identified and documented gaps in the Search evidence to educate guideline readers about where After each work group identified search terms/ evidence is lacking and help guide further needed parameters, the literature search was implemented research by NASS and other societies. by a medical/research librarian, consistent with the Literature Search Protocol.  Step 7: Formulation of Evidence-Based Recommendations and Incorporation of Following these protocols ensures that NASS rec- Expert Consensus ommendations (1) are based on a thorough review Work groups held Web casts to discuss the evi- of relevant literature; (2) are truly based on a uni- dence-based answers to the clinical questions, the form, comprehensive search strategy; and (3) rep- grades of recommendations and the incorporation resent the current best research evidence available. of expert consensus. Expert consensus has been NASS maintains a search history in EndNote,™ incorporated only where Level I-IV evidence is for future use or reference. insufficient and the work group has deemed that a recommendation is warranted. Transparency in the  Step 5: Review of Search Results/ incorporation of consensus is crucial, and all con- Identification of Literature to Review sensus-based recommendations made in this guide- Work group members reviewed all abstracts yield- line very clearly indicate that Level I-IV evidence is ed from the literature search and identified the insufficient to support a recommendation and that literature they would review in order to address the the recommendation is based only on expert con- clinical questions, in accordance with the Litera- sensus. ture Search Protocol. Members identified the best research evidence available to answer the targeted Consensus Development Process clinical questions. That is, if Level I, II and/or III Voting on guideline recommendations was con- literature is available to answer specific questions, ducted using a modification of the nominal group the work group was not required to review Level technique in which each work group member IV or V studies. independently and anonymously ranked a recommendation on a scale ranging from 1 (“extremely  Step 6: Evidence Analysis inappropriate”) to 9 (“extremely appropriate”). Members of the work group independently devel- Consensus was obtained when at least 80% of oped evidentiary tables summarizing study conclu- work group members ranked the recommendation sions, identifying strengths and weaknesses and as 7, 8 or 9. When the 80% threshold was not at- assigning levels of evidence. In order to systemati- tained, up to three rounds of discussion and voting cally control for potential biases, at least two work were held to resolve disagreements. If disagree- group members reviewed each article selected and ments were not resolved after these rounds, no independently assigned levels of evidence to the recommendation was adopted.

After the recommendations were established, work  Step 10: Submission for Endorsement, group members developed the guideline content, Publication and National Guideline addressing the literature which supports the recom- Clearinghouse (NGC) Inclusion mendations. Following NASS Board approval, the guidelines were slated for publication, submitted for endorse-  Step 8: Submission of the Draft Guidelines ment to all appropriate societies and submitted for for Review/Comment inclusion in the National Guidelines Clearinghouse Guidelines were submitted to the full Evidence- (NGC). No revisions were made at this point in based Guideline Development Committee, the the process, but comments have been and will be Research Council Director and the Advisory Panel saved for the next iteration. for review and comment. The Advisory Panel is comprised of representatives from physical medi-  Step 11: Identification and Development of cine and rehab, pain medicine/management, or- Performance Measures thopedic surgery, neurosurgery, anesthesiology, The recommendations will be reviewed by a group rheumatology, psychology/psychiatry and family experienced in performance measure development practice. Revisions to recommendations were con- (eg, the AMA Physician’s Consortium for Per- sidered for incorporation only when substantiated formance Improvement) to identify those recom- by a preponderance of appropriate level evidence. mendations rigorous enough for measure development. All relevant medical specialties involved in  Step 9: Submission for Board Approval the guideline development and at the Consortium After any evidence-based revisions were incorpo- will be invited to collaborate in the development rated, the drafts were prepared for NASS Board of evidence-based performance measures related to review and approval. Edits and revisions to recom- spine care. mendations and any other content were considered for incorporation only when substantiated by a  Step 12: Review and Revision Process preponderance of appropriate level evidence. The guideline recommendations will be reviewed every three years by an EBM-trained multidisciplinary team and revised as appropriate based on a thorough review and assessment of relevant literature published since the development of this ver- sion of the guideline.

The body of scientific and clinical literature on the Managing this risk in patients undergoing spinal topic of deep vein thrombosis (DVT) and pulmonary surgery can pose substantial challenges. Treatment of embolism (PE) is extensive. Either can occur spon- DVT or a PE using anticoagulants in the immediate taneously or after a risk-enhancing event such as an postoperative period may potentially lead to cata- injury or a surgical procedure. A variety of factors, strophic neurologic decline from epidural bleeding at including the patient’s health and genetic background, the surgical site. can influence the risk of this life threatening complication.

A. Incidence of DVT/PE in Unprophylaxed Patients In order to appreciate the incidence of these thrombo- or ultrasound-based imaging. Thus, comparison sis-related complications in patients undergoing spinal of outcomes between different studies that use surgery without antithrombotic prophylaxis, the work distinctly different diagnostic criteria is of ques- group performed a comprehensive literature search tionable validity. and analysis. The group reviewed 45 articles that were 3. The patient populations addressed in the world selected from a search of MEDLINE (PubMed), Co- literature vary widely. The study groups varied chrane Register of Controlled Trials, Web of Science in age, ethnicity (potentially influencing genetic and EMBASE Drugs & Pharmacology that addressed susceptibility), magnitude and length of surgery, the incidence and natural history of DVT and PE as- and postoperative mobilization, all of which might sociated with spinal surgery. influence the risk for thromboembolic disease. For example, it is well-established that bed rest is Analysis of the questions related to the natural history a risk factor for DVT. However, the pace at which of DVT in spinal surgery patients not receiving any patients are mobilized after spinal surgery varies prophylactic therapies was difficult due to a number of widely. Mobilization protocols are rarely reported issues. in detail in spine surgical studies.

1. Very few studies have been done in recent years in Because of these issues, the work group was unable which absolutely no prophylaxis was used. Me- to definitively answer the posed questions related to chanical pumps and/or compressive stockings are incidence of DVT/PE in spinal surgery patients not re- widely and routinely used after spinal surgery so ceiving prophylactic antithrombotic therapies. How- that studies without such are rare. ever, the work group felt that several important sug- 2. The diagnostic method for DVT and PE vary gestions can be made based on the literature reviewed. widely between publications. Older studies report These are included below along with a detailed analy- only clinically evident thrombotic events. More sis of the small subset of papers that met the guide- recent studies, in large part due to evolving tech- line’s inclusion criteria and provided information that nology, rely on a variety of different diagnostic was germane to the discussion of incidence in this methods including radionuclide scans, venograms patient population.

What is the overall Gruber et al18 performed a prospective comparative study to determine the incidence of bleeding compli- rate (symptomatic and cations in patients undergoing lumbar disc surgery asymptomatic) of DVT or PE treated with minidose heparin-dihydroergotamine (DHE) or placebo. Of the 50 patients included in the following elective spinal surgery study, 25 received 2500IU heparin-DHE twice daily without any form of prophylaxis? and 25 were assigned to the placebo group. Injections were administered two hours preoperatively, with postoperative administration at 12-hour intervals for What are the relative rates of at least seven days or until the patient was discharged clinically symptomatic DVT or PE from the hospital. Of the 25 assigned to the control group, five had received heparin at another hospi- (including fatal PE) without any tal and were excluded from the analysis. Surgeons form or prophylaxis following reported bleeding and, if clinically suspected, DVT was diagnosed by phlebogram, plethysmography, elective cervical, thoracic, and Doppler ultrasound or I125 fibrinogen test. If a PE lumbar surgery? was suspected, a chest radiograph, ECG, ventilation- perfusion scan or pulmonary angiogram was obtained. Work Group Conclusions/Suggestions: The authors reported no clinically evident DVT or 1. Deep vein thrombosis and subsequent PE events in this small series of consecutive patients. pulmonary embolus can occur following spinal The authors noted increased intraoperative bleeding in surgery, which in turn can lead to morbidity 24% (6/25) of patients in the heparin-DHE group and and death. Anyone participating in the care 28% in the placebo group, a difference that was not of spinal surgery patients should be aware of statistically significant. these conditions as known potential events. In critique of this study, diagnostic methods for DVT 2. The incidence of DVT and PE in patients were not standardized and only conducted when undergoing spinal surgery likely varies prompted by clinical suspicion. Furthermore, patient according to the magnitude of the surgery and numbers were quite low and the definition of “lum- perioperative mobilization. bar disc operations” was unclear. Due to these meth- 3. The use of “historical controls” to address odological limitations, this potential Level II study the incidence of DVT or PE in a perioperative provides Level III evidence of a low risk of DVT/PE population is probably not appropriate. in patients undergoing lumbar disc surgery. 4. Clinical examination alone is not a reliable method to confirm the diagnosis Joffe et al20 reported results of a prospective case se- of a DVT. Objective diagnostic methods, ries investigating the incidence of DVT in patients un- such as venography or Doppler ultrasound, dergoing elective neurosurgical procedures. Of the 23 should be used to confirm a suspected DVT neurosurgical patients included in the study, only 10 in postoperative spine patients. Future were spinal cases. All patients were screened daily for studies to characterize the incidence of the duration of their hospital stay (which was at least DVT in postoperative spine patients should seven days) for DVT with an I125 fibrinogen test and use objective diagnostic methods such as Doppler ultrasound. The authors reported that 60% venography or Doppler ultrasound. of the spinal patients (6/10) developed asymptomatic postoperative DVT. They concluded that neurosurgical patients are at risk for DVT and that these patients This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 11

are often asymptomatic. Based on their findings, the documenting the prevalence of DVT after posterior authors further suggested that DVT will be underdiag- spinal surgery in patients not receiving antithrombotic nosed by clinical criteria alone. therapies. Of the 134 patients included in the study, 110 were screened for DVT by venography within 14 In critique, this was a very small study consisting of days of surgery (mean = 7.2 days) and clinically fol- only a few spinal patients without details about the lowed for at least three months. Authors reported that type and extent of spine surgery. Due to these weak- 15.5% (17/110) of patients had venographic evidence nesses, this potential Level IV study provides Level of DVT, while none had clinical manifestations of V evidence that asymptomatic DVT is not uncommon DVT. The authors also indicated the prevalence of in a nonselect group of patients undergoing elective DVT by surgical region; 26.5% of lumbar, 14.3% of spinal surgery likely followed by prolonged periods thoracic and 5.6% of cervical patients had venograph- of bed rest, an assumption made based on the year the ic evidence of DVT. Statistical comparison between study was published. The applicability of these find- patients who did and did not have DVT demonstrated ings today is questionable given that prolonged peri- that increased age was a statistically significant risk ods of bed rest are no longer recommended following factor (Mann–Whitney test; P< 0.05). The authors surgery. concluded that the incidence of DVT after posterior spinal surgery is higher than generally appreciated. Lee et al22 conducted a prospective comparative study Therefore, they felt that further study is necessary to to determine the rate of DVT following elective major clarify the appropriate screening method for and pro- reconstructive spinal surgery without antithrombotic phylaxis of DVT after spinal surgery. therapies in an East Asian (Korean) population. All 313 patients included in the study were screened via This study provides Level II evidence that the rate duplex ultrasonography between the fifth and seventh of DVT in postoperative spine surgery patients may postoperative days. Authors reported a 1.3% (4/313) be underestimated. Clinical manifestations are not overall incidence of DVT, with a clinically symptom- reliable for the diagnosis of DVT. Increased age and atic presentation in only 0.3% (1/313) of patients. The posterior lumbar surgery are risk factors. It should authors concluded that East Asians undergoing these also be noted that all patients included in this study procedures do not get DVT often enough to warrant had an interval of bed rest following surgery. The prophylaxis. The authors further suggested that rou- applicability of these findings today is questionable tine screening and prophylaxis in this specific patient given that prolonged periods of bed rest are no longer population is not warranted. recommended following surgery.

In critique of this study, an unknown number of pe- Uden et al40 described a retrospective case series diatric patients were included. A subgroup analysis documenting the rate of clinically evident DVT in a addressing the adult population was not provided. In population of 1229 patients treated surgically with addition, patients were treated with postoperative bed Harrington instrumentation followed by three to five rest for a mean of 7.4 days. This potential Level I weeks of bed rest. Diagnosis of DVT was confirmed study provides Level II evidence suggesting a lower via contrast and/or isotope phlebography only when incidence of DVT after elective major reconstructive clinically suspected or by autopsy. The authors re- spinal surgery without antithrombotic therapy than ported a 0.65% (8/1229) incidence of DVT and 0.08% previously reported. Although the authors concluded (1/1229) incidence of PE in this scoliosis patient this incidence was related to the ethnicity of the pa- population. tient group, it should be noted that other unidentified factors may have influenced the DVT rate. In critique of this study, patients were not enrolled at Oda et al30 reported a prospective comparative study the same point in their disease and some patients were This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 12 younger than 18 years. Some patients had two sepa- surgery for spine trauma or rate surgeries performed, though subgroup analyses were not provided. Diagnostic methods were variably malignancy without any form of applied to only those patients with clinical suspicion prophylaxis? of DVT, with no standardized follow-up or duration identified. Because of these methodological weaknesses, this potential Level III study provides Level What is the rate of clinically IV evidence that clinically evident DVT can occur in scoliosis patients managed with postoperative bed symptomatic DVT or PE rest. Because this rate is based upon screening of (including fatal PE) following only those patients with clinical suspicion of DVT, the incidence was likely underestimated in this patient nonelective spinal surgery for population. spine trauma or malignancy Future Directions for Research without any form of prophylaxis? The North American Spine Society believes that delib- A systematic review of the literature did not reveal erately withholding antithrombotic therapies, thereby any high-quality studies with appropriate subgroup exposing patients to increased risks of DVT and PE, in analyses to address these specific questions. order to more thoroughly investigate the rate of DVT/ PE in an unprophylaxed patient population undergoing elective spine surgery is unethical. For practical Future Directions for Research purposes, the North American Spine Society is satis- The North American Spine Society believes that delib- fied to base its recommendations for the use of anti- erately withholding antithrombotic therapies, thereby thrombotic therapies on the results of existing data, exposing patients to increased risks of DVT and PE in and does not call for a definitive natural history study order to more thoroughly investigate the rate of DVT/ to be conducted of patients receiving no mechanical PE in an unprophylaxed patient population undergoing prophylaxis. nonelective spine surgery is unethical. For practical purposes, the North American Spine Society is satis- fied to base its recommendations for the use of anti- What is the overall thrombotic therapies on the results of existing data, rate (symptomatic and and does not call for a definitive natural history study asymptomatic) of DVT or PE to be conducted. in nonsurgically treated acute References 1. 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A pro- Combined radionuclide phlebography and lung scanning spective study of venous thromboembolism after major in patients operated on for scoliosis with the Harrington trauma. N Engl J Med. Dec 15 1994;331(24):1601-1606. procedure. Clin Orthop Relat Res. Oct 1980(152):241- 17. Gerlach R, Raabe A, Beck J, Woszczyk A, Seifert V. 246. Postoperative nadroparin administration for prophy- 30. Oda T, Fuji T, Kato Y, Fujita S, Kanemitsu N. Deep laxis of thromboembolic events is not associated with an venous thrombosis after posterior spinal surgery. Spine. increased risk of hemorrhage after spinal surgery. Eur Nov 15 2000;25(22):2962-2967. Spine J. Feb 2004;13(1):9-13. 31. Platzer P, Thalhammer G, Jaindl M, et al. Throm- 18. Gruber UF, Rem J, Meisner C, Gratzl O. Prevention of boembolic complications after spinal surgery in trauma thromboembolic complications with miniheparin-dihy- patients. Acta Orthop. Oct 2006;77(5):755-760. droergotamine in patients undergoing lumbar disc opera- 32. Rosner MK, Kuklo TR, Tawk R, Moquin R, Ondra SL. tions. Eur Arch Psychiatry Neurol Sci. 1984;234(3):157- Prophylactic placement of an inferior vena cava filter 161. in high-risk patients undergoing spinal reconstruction.

Neurosurg Focus. Oct 15 2004;17(4):E6. 39. Tetzlaff JE, Yoon HJ, O’Hara J, Bell GR, Boumphrey 33. Samama CM, Albaladejo P, Benhamou D, et al. Venous FR, Graor RA. Influence of anesthetic technique on the thromboembolism prevention in surgery and obstetrics: incidence of deep venous thrombosis after elective lum- Clinical practice guidelines. European Journal of Anaes- bar spine surgery. Regional Anesthesia; 1994:28. thesiology. 2006;23(2):95-116. 40. Uden A. Thromboembolic complications following 34. Soreff J, Axdorph G, Bylund P, Odeen I, Olerud S. scoliosis surgery in Scandinavia. Acta Orthop Scand. Apr Treatment of patients with unstable fractures of the 1979;50(2):175-178. thoracic and lumbar spine: a follow-up study of surgi- 41. Vavilala MS, Nathens AB, Jurkovich GJ, Mackenzie E, cal and conservative treatment. Acta Orthop Scand. Jun Rivara FP. Risk factors for venous thromboembolism in 1982;53(3):369-381. pediatric trauma. J Trauma. May 2002;52(5):922-927. 35. Stawicki SP, Grossman MD, Cipolla J, et al. Deep venous 42. Waters RL, Meyer PR, Jr., Adkins RH, Felton D. Emer- thrombosis and pulmonary embolism in trauma pa- gency, acute, and surgical management of spine trauma. tients: an overstatement of the problem? Am Surg. May Arch Phys Med Rehabil. Nov 1999;80(11):1383-1390. 2005;71(5):387-391. 43. Wedge JH, Kirkaldy-Willis WH, Hayton RC. Dextran 36. Stokes JM. Vascular complications of disc surgery. J Bone 75 in the prophylaxis of deep venous thrombosis and Joint Surg Am. Mar 1968;50(2):394-399. pulmonary embolism. Can J Surg. Jan 1974;17(1):45-48. 37. Szilagyi DE, Smith RF, Scerpella JR, Hoffman K. 44. Wood JP. Lumbar disk surgery: complications. J Am Lumbar sympathectomy. Current role in the treatment Osteopath Assoc. Nov 1974;74(3):234-240. of arteriosclerotic occlusive disease. Arch Surg. Nov 45. Yoshimoto H, Sato S, Nakagawa I, et al. Deep vein 1967;95(5):753-761. thrombosis due to migrated graft bone after posterior 38. Tetzlaff JE, Dilger JA, Kodsy M, al-Bataineh J, Yoon lumbosacral interbody fusion. Case report. J Neurosurg HJ, Bell GR. Spinal anesthesia for elective lumbar spine Spine. Jan 2007;6(1):47-51. surgery. J Clin Anesth. Dec 1998;10(8):666-669.

B. Incidence of DVT/PE in Prophylaxed Patients

What is the rate of clinically practice in spinal units in the British Isles. Injury. May 2002;33(4):353-355. symptomatic DVT and/or PE 5. Deep K, Jigajinni MV, McLean AN, Fraser MH. Pro- phylaxis of thromboembolism in spinal injuries--results (including fatal PE) following of enoxaparin used in 276 patients. Spinal Cord. Feb 2001;39(2):88-91. elective spinal surgery with one 6. Epstein NE. A review of the risks and benefits of dif- fering prophylaxis regimens for the treatment of deep or more of the following pro- venous thrombosis and pulmonary embolism in neuro- phylaxis measures: compression surgery. Surgical Neurology. 2005;64(4):295-301. 7. Epstein NE. Intermittent pneumatic compression stockings, mechanical sequential stocking prophylaxis against deep venous thrombosis in anterior cervical spinal surgery: a prospective efficacy compression devices, chemopro- study in 200 patients and literature review. Spine. Nov 15 2005;30(22):2538-2543. phylaxis medication? 8. Epstein NE. Efficacy of pneumatic compression stocking prophylaxis in the prevention of deep venous thrombosis (PROGNOSTIC QUESTION) and pulmonary embolism following 139 lumbar laminectomies with instrumented fusions. J Spinal Disord Tech. The few eligible studies reviewed by the work group Feb 2006;19(1):28-31. provided limited information regarding the relative 9. Ferree BA. Deep venous thrombosis following lum- incidence of venous thromboembolism (VTE) com- bar laminotomy and laminectomy. Orthopedics. Jan 1994;17(1):35-38. plications for specific antithrombotic prophylactic 10. Ferree BA, Stern PJ, Jolson RS, Roberts JMt, Kahn A, measures within specific spine surgery patient sub- 3rd. Deep venous thrombosis after spinal surgery. Spine. populations (eg, single-level corpectomy patients). Mar 1 1993;18(3):315-319. Furthermore, there is not enough data to definitively 11. Ferree BA, Wright AM. Deep venous thrombosis fol- state the rate of clinically symptomatic DVT and/or lowing posterior lumbar spinal surgery. Spine. Jun 15 1993;18(8):1079-1082. PE for each type of spinal surgical intervention and 12. Geerts WH, Pineo GF, Heit JA, et al. Prevention of ve- prophylactic measure. Given the inability to general- nous thromboembolism: The Seventh ACCP Conference ize reported incidences to the variety of surgeries with on Antithrombotic and Thrombolytic Therapy. Chest. different prophylactic protocols, the work group was 2004;126(3 SUPPL.):338S-400S. unable to address this question. 13. Gerlach R, Raabe A, Beck J, Woszczyk A, Seifert V. Postoperative nadroparin administration for prophylaxis of thromboembolic events is not associated with an References increased risk of hemorrhage after spinal surgery. Eur 1. Agnelli G. Prevention of venous thromboembolism in Spine J. Feb 2004;13(1):9-13. surgical patients. Circulation. Dec 14 2004;110(24 Suppl 14. Green D. Prevention of thromboembolism in spinal 1):IV4-12. injury. Blood. 1996;88(10):3054-3054. 2. Cain JE, Jr., Major MR, Lauerman WC, West JL, Wood 15. Gruber UF, Rem J, Meisner C, Gratzl O. Prevention of KB, Fueredi GA. The morbidity of heparin therapy after thromboembolic complications with miniheparin-dihy- development of pulmonary embolus in patients undergo- droergotamine in patients undergoing lumbar disc opera- ing thoracolumbar or lumbar spinal fusion. Spine. Jul 15 tions. Eur Arch Psychiatry Neurol Sci. 1984;234(3):157- 1995;20(14):1600-1603. 161. 3. Dearborn JT, Hu SS, Tribus CB, Bradford DS. Throm- 16. Harris S, Chen D, Green D. Enoxaparin for thromboem- boembolic complications after major thoracolumbar bolism prophylaxis in spinal injury: preliminary report spine surgery. Spine. Jul 15 1999;24(14):1471-1476. on experience with 105 patients. Am J Phys Med Reha- 4. Deep K, Jigajinni MV, Fraser MH, McLean AN. Prophy- bil. Sep-Oct 1996;75(5):326-327. laxis of thromboembolism in spinal injuries--survey of

17. Lee HM, Suk KS, Moon SH, Kim DJ, Wang JM, Kim 23. Scaduto AA, Gamradt SC, Yu WD, Huang J, Delamarter NH. Deep vein thrombosis after major spinal surgery: RB, Wang JC. Perioperative complications of threaded incidence in an East Asian population. Spine. Jul 15 cylindrical lumbar interbody fusion devices: anterior 2000;25(14):1827-1830. versus posterior approach. Journal of spinal disorders & 18. Leon L, Rodriguez H, Tawk RG, Ondra SL, Labropou- techniques; 2003:502-507. los N, Morasch MD. The prophylactic use of inferior 24. Smith MD, Bressler EL, Lonstein JE, Winter R, Pinto vena cava filters in patients undergoing high-risk spinal MR, Denis F. Deep venous thrombosis and pulmonary surgery. Ann Vasc Surg. May 2005;19(3):442-447. embolism after major reconstructive operations on the 19. Nelson LD, Jr., Montgomery SP, Dameron TB, Jr., spine. A prospective analysis of three hundred and seven- Nelson RB. Deep vein thrombosis in lumbar spinal fu- teen patients. J Bone Joint Surg Am. Jul 1994;76(7):980- sion: a prospective study of antiembolic and pneumatic 985. compression stockings. J South Orthop Assoc. Fall 25. Turpie AG, Gent M, Doyle DJ, et al. An evaluation 1996;5(3):181-184. of suloctidil in the prevention of deep vein throm- 20. Oskouian RJ, Jr., Johnson JP. Vascular complications in bosis in neurosurgical patients. Thromb Res. Jul 15 anterior thoracolumbar spinal reconstruction. J Neuro- 1985;39(2):173-181. surg. Jan 2002;96(1 Suppl):1-5. 26. Voth D, Schwarz M, Hahn K, Dei-Anang K, al Butmeh 21. Rokito SE, Schwartz MC, Neuwirth MG. Deep vein S, Wolf H. Prevention of deep vein thrombosis in neu- thrombosis after major reconstructive spinal surgery. rosurgical patients: a prospective double-blind com- Spine. Apr 1 1996;21(7):853-858; discussion 859. parison of two prophylactic regimen. Neurosurg Rev. 22. Samama CM, Albaladejo P, Benhamou D, et al. Venous 1992;15(4):289-294. thromboembolism prevention in surgery and obstetrics: 27. Wood KB, Kos PB, Abnet JK, Ista C. Prevention of Clinical practice guidelines. European Journal of Anaes- deep-vein thrombosis after major spinal surgery: a com- thesiology. 2006;23(2):95-116. parison study of external devices. J Spinal Disord. Jun 1997;10(3):209-214.

A. Efficacy of Antithrombotic Therapies Do prophylactic antithrombotic decrease the incidence of thromboembolic complications. measures, including compression stockings, mechanical sequential GRADE OF RECOMMENDATION: B compression devices and Rokito et al21 prospectively studied the incidence chemoprophylaxis medications, of DVT after elective major adult spinal surgery in order to identify the optimal mode of prophylaxis. Of decrease the rate of clinically the 329 patients included in the study, 110 patients symptomatic DVT and/or PE were prospectively randomized to one of three study groups. Group 1 (42 patients) received bilateral thigh- (including fatal PE) following high thrombosis embolic deterrent (TED) compression elective spinal surgery? stockings. Group 2 (33 patients) received TED stockings and thigh-length cuffs that provided sequential (THERAPEUTIC QUESTION) pneumatic compression to the calf and thigh. Group 3 (35 patients) received TED stockings and low-dose A comprehensive review of the literature suggests that Coumadin (warfarin). The 219 patients not random- most commonly-performed elective spine surgeries ized received either TED stockings alone or TED done through a posterior approach are associated with stockings and pneumatic compression boots for DVT a very low risk of VTE. In this setting, chemoprophy- prophylaxis. The authors reported that 0.3% (1/329) laxis may not be warranted as it is accompanied by of patients were diagnosed with a DVT. Moreover, a definable risk of serious wound and bleeding com- they also found that 5.7% of patients treated with Cou- plications. Postoperative chemoprophylaxis may be madin experienced bleeding complications. considered for long and complex surgeries, such as anterior or combined anterior-posterior approaches, and Due to the unstated randomization process, this po- in patients with known thromboembolic risk factors, tential Level II case control study provides Level III such as paralysis, spinal cord injury, malignancy, or therapeutic evidence that low-dose Coumadin is no hypercoagulable state. However, mechanical prophy- more effective than mechanical prophylaxis in reduc- laxis of any type, such as pneumatic sequential com- ing DVT risks. Given the increased risk of hemor- pression boots or compression stockings, should be rhage with Coumadin, mechanical prophylaxis with considered following any in-patient spine surgery due graduated compression stockings and pneumatic com- to the documented efficacy and low complication rates pression boots is preferable to anticoagulation therapy. of these devices. Wood et al27 reported results of an RCT conducted RECOMMENDATION: Mechanical on patients undergoing elective anterior or posterior compression devices in the lower extremities thoracic, thoracolumbar, or lumbar multilevel de- are suggested in elective spinal surgery to compressions and/or spinal fusions. They compared two different types of prophylactic protocols (elastic This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 18

stockings/foot wraps versus elastic stockings/pneumatic compression boots) for the prevention of DVT/ Due to unstated randomization techniques and the PE after complex spinal surgery. Of the 136 con- small sample size, this potential Level I study pro- secutively assigned patients, data were available on vides Level II therapeutic evidence supporting the use 134. Mechanical prophylaxis via elastic stockings of TED stockings in combination with ASA 600mg and foot wraps was used for 75 patients, while 59 bid to decrease the incidence of DVT. These results received elastic stockings and pneumatic compression suggest that the addition of pneumatic compression boots. The authors reported a 1.5% (2/136) incidence boots does not provide any added protection against of DVT and a 0.7% (1/136) incidence of PE and DVT. concluded that mechanical prophylaxis is effective in reducing DVT risk after major spinal surgery. RECOMMENDATION: Most commonly- performed elective spine surgeries done Due to the unclear randomization process utilized, this through a posterior approach are associated potential Level I study provides Level II therapeutic with a very low risk of VTE. In this setting, evidence that mechanical prophylaxis is effective in chemoprophylaxis may not be warranted as it reducing DVT risk after major spine surgery. The is accompanied by a definable risk of serious findings suggest that one form of mechanical prophy- wound and bleeding complications. Low laxis is not superior to the other. molecular weight heparin (LMWH) or low- dose warfarin may be used postoperatively RECOMMENDATION: TED stockings in to lower the risk of thromboembolic combination with acetylsalicylic acid (ASA) complications following elective combined are an option in elective spinal surgery to anterior-posterior (circumferential) spine decrease the incidence of thromboembolic surgery or in patients identified as having complications. a high risk for thromboembolic disease, such as multiple trauma, malignancy or GRADE OF RECOMMENDATION: I hypercoagulable state. These therapies should (Insufficient Evidence) be considered carefully and on an individual case-by-case basis, as use may place patients at Nelson et al19 described a prospective randomized increased risk of bleeding complications. controlled trial evaluating the incidence of DVT following posterior lumbar decompression with instru- GRADE OF RECOMMENDATION: mented fusion in patients using TED stockings and Work Group Consensus Statement acetylsalicylic acid (ASA) compared with those using TED stockings, pneumatic compression boots and Future Directions for Research ASA during surgery. Of the 117 patients included in Recommendation #1: A randomized controlled trial the study, 60 were randomly assigned to receive ASA comparing mechanical prophylaxis alone (i.e. pneu- 600mg bid and TED stockings and 57 were randomly matic compression boots or compression stockings) assigned to receive ASA 600mg bid, TED stockings with combined LMWH and mechanical prophylaxis and pneumatic compression boots. The authors found in high-risk patients can be performed to assess the that at two to six days postoperatively, no patients in respective incidence of DVT, PE, neurological dete- either group were diagnosed via clinical exam and rioration secondary to epidural hematoma, postopera- ultrasound with DVT, and concluded that the use of tive bleeding, and wound complications. TED stockings in combination with ASA 600mg bid is sufficient for DVT prophylaxis in this patient popula- Recommendation #2: A randomized controlled trial tion. This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 19 comparing mechanical prophylaxis alone (i.e. pneu- 2005;30(22):2538-2543. matic compression boots or compression stockings) 8. Epstein NE. Efficacy of pneumatic compression stocking with combined low-dose warfarin and mechanical prophylaxis in the prevention of deep venous thrombosis and pulmonary embolism following 139 lumbar lamine- prophylaxis in high-risk patients can be performed to ctomies with instrumented fusions. J Spinal Disord Tech. assess the respective incidence of DVT, PE, neuro- Feb 2006;19(1):28-31. logical deterioration secondary to epidural hematoma, 9. Ferree BA. Deep venous thrombosis following lum- postoperative bleeding, and wound complications. bar laminotomy and laminectomy. Orthopedics. Jan 1994;17(1):35-38. 10. Ferree BA, Stern PJ, Jolson RS, Roberts JMt, Kahn A, Recommendation #3: A prospective, uncontrolled, 3rd. Deep venous thrombosis after spinal surgery. Spine. prognostic multicenter study of a high number of pa- Mar 1 1993;18(3):315-319. tients undergoing a wide variety of spine surgeries can 11. Ferree BA, Wright AM. Deep venous thrombosis fol- be undertaken to quantify the relative risk of a number lowing posterior lumbar spinal surgery. Spine. Jun 15 of suspected predisposing factors for VTE that would 1993;18(8):1079-1082. 12. Geerts WH, Pineo GF, Heit JA, et al. Prevention of ve- include, but not be limited to, length of surgery, num- nous thromboembolism: The Seventh ACCP Conference ber of levels fused, underlying diagnosis, traumatic on Antithrombotic and Thrombolytic Therapy. Chest. injury, paralysis and SCI. In addition, the relative 2004;126(3 SUPPL.):338S-400S. risks of postoperative neurological deterioration from 13. Gerlach R, Raabe A, Beck J, Woszczyk A, Seifert V. epidural hematoma, bleeding, wound complications, Postoperative nadroparin administration for prophylaxis of thromboembolic events is not associated with an and transfusion requirements should be scrupulously increased risk of hemorrhage after spinal surgery. Eur defined for each subgroup. Spine J. Feb 2004;13(1):9-13. 14. Green D. Prevention of thromboembolism in spinal injury. Blood. 1996;88(10):3054-3054. References 15. Gruber UF, Rem J, Meisner C, Gratzl O. Prevention of 1. Agnelli G. Prevention of venous thromboembolism in thromboembolic complications with miniheparin-dihy- surgical patients. Circulation. Dec 14 2004;110(24 Suppl droergotamine in patients undergoing lumbar disc opera- 1):IV4-12. tions. Eur Arch Psychiatry Neurol Sci. 1984;234(3):157- 2. Cain JE, Jr., Major MR, Lauerman WC, West JL, Wood 161. KB, Fueredi GA. The morbidity of heparin therapy after 16. Harris S, Chen D, Green D. Enoxaparin for thromboem- development of pulmonary embolus in patients undergo- bolism prophylaxis in spinal injury: preliminary report ing thoracolumbar or lumbar spinal fusion. Spine. Jul 15 on experience with 105 patients. Am J Phys Med Reha- 1995;20(14):1600-1603. bil. Sep-Oct 1996;75(5):326-327. 3. Dearborn JT, Hu SS, Tribus CB, Bradford DS. Throm- 17. Lee HM, Suk KS, Moon SH, Kim DJ, Wang JM, Kim boembolic complications after major thoracolumbar NH. Deep vein thrombosis after major spinal surgery: spine surgery. Spine. Jul 15 1999;24(14):1471-1476. incidence in an East Asian population. Spine. Jul 15 4. Deep K, Jigajinni MV, Fraser MH, McLean AN. Prophy- 2000;25(14):1827-1830. laxis of thromboembolism in spinal injuries--survey of 18. Leon L, Rodriguez H, Tawk RG, Ondra SL, Labropou- practice in spinal units in the British Isles. Injury. May los N, Morasch MD. The prophylactic use of inferior 2002;33(4):353-355. vena cava filters in patients undergoing high-risk spinal 5. Deep K, Jigajinni MV, McLean AN, Fraser MH. Pro- surgery. Ann Vasc Surg. May 2005;19(3):442-447. phylaxis of thromboembolism in spinal injuries--results 19. Nelson LD, Jr., Montgomery SP, Dameron TB, Jr., of enoxaparin used in 276 patients. Spinal Cord. Feb Nelson RB. Deep vein thrombosis in lumbar spinal fu- 2001;39(2):88-91. sion: a prospective study of antiembolic and pneumatic 6. Epstein NE. A review of the risks and benefits of dif- compression stockings. J South Orthop Assoc. Fall fering prophylaxis regimens for the treatment of deep 1996;5(3):181-184. venous thrombosis and pulmonary embolism in neuro- 20. Oskouian RJ, Jr., Johnson JP. Vascular complications in surgery. Surgical Neurology. 2005;64(4):295-301. anterior thoracolumbar spinal reconstruction. J Neuro- 7. Epstein NE. Intermittent pneumatic compression surg. Jan 2002;96(1 Suppl):1-5. stocking prophylaxis against deep venous thrombosis 21. Rokito SE, Schwartz MC, Neuwirth MG. Deep vein in anterior cervical spinal surgery: a prospective efficacy thrombosis after major reconstructive spinal surgery. study in 200 patients and literature review. Spine. Nov 15

Spine. Apr 1 1996;21(7):853-858; discussion 859. teen patients. J Bone Joint Surg Am. Jul 1994;76(7):980- 22. Samama CM, Albaladejo P, Benhamou D, et al. Venous 985. thromboembolism prevention in surgery and obstetrics: 25. Turpie AG, Gent M, Doyle DJ, et al. An evaluation Clinical practice guidelines. European Journal of Anaes- of suloctidil in the prevention of deep vein throm- thesiology. 2006;23(2):95-116. bosis in neurosurgical patients. Thromb Res. Jul 15 23. Scaduto AA, Gamradt SC, Yu WD, Huang J, Delamarter 1985;39(2):173-181. RB, Wang JC. Perioperative complications of threaded 26. Voth D, Schwarz M, Hahn K, Dei-Anang K, al Butmeh cylindrical lumbar interbody fusion devices: anterior S, Wolf H. Prevention of deep vein thrombosis in neu- versus posterior approach. Journal of spinal disorders & rosurgical patients: a prospective double-blind com- techniques; 2003:502-507. parison of two prophylactic regimen. Neurosurg Rev. 24. Smith MD, Bressler EL, Lonstein JE, Winter R, Pinto 1992;15(4):289-294. MR, Denis F. Deep venous thrombosis and pulmonary 27. Wood KB, Kos PB, Abnet JK, Ista C. Prevention of embolism after major reconstructive operations on the deep-vein thrombosis after major spinal surgery: a com- spine. A prospective analysis of three hundred and seven- parison study of external devices. J Spinal Disord. Jun 1997;10(3):209-214.

B. Mechanical Prophylaxis

spine surgery. Spine. Jul 15 1999;24(14):1471-1476. When indicated, what is the 2. Epstein NE. Intermittent pneumatic compression ideal time to begin mechanical stocking prophylaxis against deep venous thrombosis in anterior cervical spinal surgery: a prospective efficacy prophylaxis in relation to spinal study in 200 patients and literature review. Spine. Nov 15 2005;30(22):2538-2543. surgery? 3. Epstein NE. Efficacy of pneumatic compression stocking prophylaxis in the prevention of deep venous thrombosis and pulmonary embolism following 139 lumbar laminectomies with instrumented fusions. J Spinal Disord Tech. When indicated, how long should Feb 2006;19(1):28-31. mechanical prophylaxis continue 4. Ferree BA. Deep venous thrombosis following lumbar laminotomy and laminectomy. Orthopedics. Jan following spinal surgery? 1994;17(1):35-38. 5. Ferree BA, Stern PJ, Jolson RS, Roberts JMt, Kahn A, RECOMMENDATION: Although evidence 3rd. Deep venous thrombosis after spinal surgery. Spine. Mar 1 1993;18(3):315-319. in the spine literature is limited regarding 6. Ferree BA, Wright AM. Deep venous thrombosis fol- timing and duration of mechanical prophylaxis, lowing posterior lumbar spinal surgery. Spine. Jun 15 initiation of mechanical compression just 1993;18(8):1079-1082. prior to or at the beginning of surgery 7. Geerts WH, Pineo GF, Heit JA, et al. Prevention of ve- and continuation until the patient is fully nous thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. ambulatory is a reasonable practice. While 2004;126(3 SUPPL.):338S-400S. several studies cited start and stop times 8. Nelson LD, Jr., Montgomery SP, Dameron TB, Jr., consistent with this recommendation, no Nelson RB. Deep vein thrombosis in lumbar spinal fu- studies specifically assessed this issue in a sion: a prospective study of antiembolic and pneumatic comparative fashion. compression stockings. J South Orthop Assoc. Fall 1996;5(3):181-184. 9. Rokito SE, Schwartz MC, Neuwirth MG. Deep vein GRADE OF RECOMMENDATION: thrombosis after major reconstructive spinal surgery. Work Group Consensus Statement Spine. Apr 1 1996;21(7):853-858; discussion 859. 10. Samama CM, Albaladejo P, Benhamou D, et al. Venous thromboembolism prevention in surgery and obstetrics: Future Directions for Research Clinical practice guidelines. European Journal of Anaes- After careful consideration of this literature, the work thesiology. 2006;23(2):95-116. group determined that a future prospective compara- 11. Smith MD, Bressler EL, Lonstein JE, Winter R, Pinto tive study would be highly impractical as it would be MR, Denis F. Deep venous thrombosis and pulmonary embolism after major reconstructive operations on the invariably underpowered due to the large number of spine. A prospective analysis of three hundred and seven- patients required to demonstrate a statistically signifi- teen patients. J Bone Joint Surg Am. Jul 1994;76(7):980- cant difference. 985. 12. Wood KB, Kos PB, Abnet JK, Ista C. Prevention of deep-vein thrombosis after major spinal surgery: a com- References parison study of external devices. J Spinal Disord. Jun 1. Dearborn JT, Hu SS, Tribus CB, Bradford DS. Throm- 1997;10(3):209-214. boembolic complications after major thoracolumbar

C. Chemoprophylaxis

RECOMMENDATION: The utility and safety recommendation that LMWH be used of chemoprophylaxis following spinal surgery cautiously prior to routine, elective spinal is controversial. Because of the hazardous surgery, and withheld unless there are other risk of symptomatic epidural hematoma, risk factors for thromboembolism. the potential consequences may confound the benefits of these agents. Unfortunately, GRADE OF RECOMMENDATION: Work scientific scrutiny of chemoprophylaxis in Group Consensus Statement elective spinal surgery has been limited to case series involving discectomy and decompression. Evidence is better established When indicated, how long should in higher risk patients undergoing spinal chemoprophylaxis be continued surgery for traumatic or neoplastic conditions, although safety and efficacy have not been following spinal surgery? thoroughly studied in these conditions either. Most commonly-performed elective RECOMMENDATION: The available literature spine surgeries done through a posterior does not support an ideal duration for which approach are associated with a very low risk chemoprophylaxis should be continued of VTE. In this setting, chemoprophylaxis may following spinal surgery. It is the work not be warranted as it is accompanied by a group’s recommendation that this parameter definable risk of serious wound and bleeding be decided based upon the underlying complications. When chemoprophylaxis is pathological condition being treated, co- utilized, neurological status should be closely morbidities (eg, heart valve, previous DVT, monitored. stent restenosis prophylaxis), and other host factors, such as ambulatory and neurological GRADE OF RECOMMENDATION: status. Work Group Consensus Statement GRADE OF RECOMMENDATION: Work Group Consensus Statement When indicated, what is the ideal time to begin chemoprophylaxis In patients who are being treated in relation to spinal surgery? with chemical anticoagulants for a non-spine related disorder (eg, RECOMMENDATION: Although the literature does not support an ideal time to begin valve replacement), what is the chemoprophylaxis, initiating low molecular ideal “bridge” therapy between weight heparin (LMWH) preoperatively can decrease the incidence of thromboembolic stopping and starting the usual disease. However, this is associated with an increased risk of bleeding complications. agent before and after surgery? There is Level IV evidence that LMWH can RECOMMENDATION: The literature reviewed be started safely the day of elective spine does not support an ideal perioperative surgery. 4,9,10,22,25 It is the work group’s “bridge” therapy. Candidate agents, such

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 23 as warfarin, therapeutic heparin, LMWH, tients discontinuing clopidogrel ten days, seven days clopidogrel or acetylsalicylic acid (ASA) and one day prior to elective spinal surgery. all increase bleeding risk in postoperative spinal surgery patients. It is the work group’s Recommendation #4: recommendation that the magnitude of The work group recommends a prospective study surgical insult and underlying thromboembolic investigating optimum duration of postoperative risk be balanced against the risk for epidural prophylaxis comparing three groups of spine surgery bleeding and wound complications. Though patients treated with LMWH, ASA or clopidogrel for not substantiated by evidence, the work group one week and another three groups of patients treated agreed that the use of intravenous heparin is with LMWH, ASA or clopidogrel for four weeks. a reasonable bridge therapy for those patients being indefinitely treated with warfarin for Recommendation #5: a non-spine condition. The rationale for The work group recommends a comparative study this statement is that intravenous heparin investigating the incidence of bleeding complications is more controllable and more predictable in spinal patients receiving LMWH immediately post- than LMWH, though LMWH is a reasonable operatively with another group of patients receiving alternative bridge therapy. The ideal time to LMWH three days postoperatively. discontinue agents such as clopidogrel and ASA is unique to the pharmacokinetics of References the particular medication as it is influenced 1. Agnelli G. Prevention of venous thromboembolism in by the clearance half-life, however, an interval surgical patients. Circulation. Dec 14 2004;110(24 Suppl of approximately one week prior to surgery 1):IV4-12. seems prudent. 2. Cain Jr JE, Major MR, Lauerman WC, West JL, Wood KB, Fueredi GA. The morbidity of heparin therapy after development of pulmonary embolus in patients under- GRADE OF RECOMMENDATION: going thoracolumbar or lumbar spinal fusion. Spine. Work Group Consensus Statement 1995;20(14):1600-1603. 3. Catre MG. Anticoagulation in spinal surgery. A critical review of the literature. Can J Surg. Dec 1997;40(6):413- Future Directions for Research 419. Recommendation #1: 4. Deep K, Jigajinni MV, McLean AN, Fraser MH. Pro- The work group recommends a randomized controlled phylaxis of thromboembolism in spinal injuries--results trial of LMWH vs. heparin as a bridge therapy for of enoxaparin used in 276 patients. Spinal Cord. Feb 2001;39(2):88-91. patients on long term warfarin prophylaxis for cardiac 5. Deep K, Jigajinni MV, Fraser MH, McLean AN. Prophy- or other vascular conditions. laxis of thromboembolism in spinal injuries--survey of practice in spinal units in the British Isles. Injury. May Recommendation #2: 2002;33(4):353-355. The work group recommends a comparative study 6. Ee PL, Kempen PM. Elective surgery days after myocar- dial infarction: clinical and ethical considerations. J Clin identifying the risks of perioperative bleeding com- Anesth. Aug 2006;18(5):363-366. plications in spinal surgery patients with clopidogrel- 7. Epstein NE. A review of the risks and benefits of dif- coated stents compared with those taking ASA and fering prophylaxis regimens for the treatment of deep controls. venous thrombosis and pulmonary embolism in neurosurgery. Surgical Neurology. 2005;64(4):295-301. 8. Geerts WH, Pineo GF, Heit JA, et al. Prevention of ve- Recommendation #3: nous thromboembolism: The Seventh ACCP Conference The work group recommends a comparative study on Antithrombotic and Thrombolytic Therapy. Chest. investigating the rate of bleeding complications in pa- 2004;126(3 SUPPL.):338S-400S.

9. Gerlach R, Raabe A, Beck J, Woszczyk A, Seifert V. 18. Macouillard G, Castagnera L, Claverie JP, Janvier G, Postoperative nadroparin administration for prophy- Maurette P. Prevention of deep venous thrombosis in laxis of thromboembolic events is not associated with an spinal surgery: Comparison of intermittent sequential increased risk of hemorrhage after spinal surgery. Eur pneumatic compression versus low molecular weight Spine J. Feb 2004;13(1):9-13. heparin. Thrombosis & Haemostasis; 1993:646-Abstract 10. Gruber UF, Rem J, Meisner C, Gratzl O. Prevention of no: 373. thromboembolic complications with miniheparin-dihy- 19. Macouillard G, Castagnera L, Claverie JP, Simeon F. droergotamine in patients undergoing lumbar disc opera- Comparative efficacy of two dosages of a low molecular tions. Eur Arch Psychiatry Neurol Sci. 1984;234(3):157- weight heparin for prevention of deep venous throm- 161. bosis in spinal surgery. Thrombosis & Haemostasis; 11. Harris S, Chen D, Green D. Enoxaparin for thromboem- 1995:979-Abstract no: 306. bolism prophylaxis in spinal injury: preliminary report 20. Nelson LD, Jr., Montgomery SP, Dameron TB, Jr., on experience with 105 patients. Am J Phys Med Reha- Nelson RB. Deep vein thrombosis in lumbar spinal fu- bil. Sep-Oct 1996;75(5):326-327. sion: a prospective study of antiembolic and pneumatic 12. Janni W, Bergauer F, Rjosk D, Lohscheidt K, Hagena compression stockings. J South Orthop Assoc. Fall FW. A randomized controlled study evaluating the safety 1996;5(3):181-184. and efficacy of different low molecular weight hepa- 21. Rocha E, Imberti D, Paschina E. Low-molecular-weight rins for high risk patients. Zentralblatt fur Chirurgie; heparins: Before or after surgery? New concepts and 2001:32-38. evidence: Congress report from the SIGMA TAU/ROVI 13. Korinth MC, Gilsbach JM, Weinzierl MR. Low- satellite symposium (Rome, Italy, 13 November 2006). dose aspirin before spinal surgery: results of a survey Clinical Drug Investigation. 2007;27(5):357-366. among neurosurgeons in Germany. Eur Spine J. Mar 22. Rokito SE, Schwartz MC, Neuwirth MG. Deep vein 2007;16(3):365-372. thrombosis after major reconstructive spinal surgery. 14. Layton KF, Kallmes DF, Horlocker TT. Recommenda- Spine. Apr 1 1996;21(7):853-858; discussion 859. tions for anticoagulated patients undergoing image-guid- 23. Samama CM, Albaladejo P, Benhamou D, et al. Venous ed spinal procedures. American Journal of Neuroradiol- thromboembolism prevention in surgery and obstetrics: ogy. 2006;27(3):468-470. Clinical practice guidelines. European Journal of Anaes- 15. Lee HM, Suk KS, Moon SH, Kim DJ, Wang JM, Kim thesiology. 2006;23(2):95-116. NH. Deep vein thrombosis after major spinal surgery: 24. Turpie AG, Gent M, Doyle DJ, et al. An evaluation incidence in an East Asian population. Spine. Jul 15 of suloctidil in the prevention of deep vein throm- 2000;25(14):1827-1830. bosis in neurosurgical patients. Thromb Res. Jul 15 16. Leitao LM, Isaac JB. Anaesthesia for scoliosis surgery 1985;39(2):173-181. in a patient on anticoagulant therapy. Paediatr Anaesth. 25. Voth D, Schwarz M, Hahn K, Dei-Anang K, al Butmeh 1998;8(6):512-515. S, Wolf H. Prevention of deep vein thrombosis in neu- 17. Leon L, Rodriguez H, Tawk RG, Ondra SL, Labropou- rosurgical patients: a prospective double-blind com- los N, Morasch MD. The prophylactic use of inferior parison of two prophylactic regimen. Neurosurg Rev. vena cava filters in patients undergoing high-risk spinal 1992;15(4):289-294. surgery. Ann Vasc Surg. May 2005;19(3):442-447.

D. Wound Complications

nous thromboembolism: The Seventh ACCP Conference Does the use of chemoprophylaxis on Antithrombotic and Thrombolytic Therapy. Chest. increase the risk of wound 2004;126(3 SUPPL.):338S-400S. 5. Gurkanlar D, Acikbas C, Cengiz GK, Tuncer R. Lumbar complications or neurologic decline epidural hematoma following lumbar puncture: the role of high dose LMWH and late surgery. A case report. from epidural hematoma in patients Neurocirugia (Astur). Feb 2007;18(1):52-55. 6. Harris S, Chen D, Green D. Enoxaparin for thromboem- receiving chemoprophylaxis after bolism prophylaxis in spinal injury: preliminary report on experience with 105 patients. Am J Phys Med Reha- spinal surgery? bil. Sep-Oct 1996;75(5):326-327. 7. Kirazli Y, Akkoc Y, Kanyilmaz S. Spinal epidural hema- A comprehensive review of the spine literature did toma associated with oral anticoagulation therapy. Am J not yield sufficient evidence to address the question Phys Med Rehabil. Mar 2004;83(3):220-223. related to the risk of wound complications or neuro- 8. Kotani N, Tanioka F, Tsubo T, Ishibara H, Matsuki A. Systemic heparinization during postoperative pulmonary logic decline from epidural hematoma following use embolism induces fatal complications. Eur J Anaesthe- of chemoprophylaxis. siol. May 2002;19(5):382-384. 9. Layton KF, Kallmes DF, Horlocker TT. Recommenda- Future Directions for Research tions for anticoagulated patients undergoing image-guid- ed spinal procedures. American Journal of Neuroradiol- Controlled studies documenting rates of wound ogy. 2006;27(3):468-470. complications in spinal surgical patients who received 10. Morse K, Weight M, Molinari R. Extensive postopera- specific chemoprophylaxis protocols are suggested. tive epidural hematoma after full anticoagulation: case Data recorded for each patient should include type report and review of the literature. J Spinal Cord Med. of procedure as well as specific chemoprophylaxis 2007;30(3):282-287. 11. Nelson LD, Jr., Montgomery SP, Dameron TB, Jr., protocol (chemoprophylaxis agent, dosage, timing and Nelson RB. Deep vein thrombosis in lumbar spinal fu- duration). sion: a prospective study of antiembolic and pneumatic compression stockings. J South Orthop Assoc. Fall 1996;5(3):181-184. References 12. Rocha E, Imberti D, Paschina E. Low-molecular-weight 1. Cain Jr JE, Major MR, Lauerman WC, West JL, Wood heparins: Before or after surgery? New concepts and KB, Fueredi GA. The morbidity of heparin therapy after evidence: Congress report from the SIGMA TAU/ROVI development of pulmonary embolus in patients under- satellite symposium (Rome, Italy, 13 November 2006). going thoracolumbar or lumbar spinal fusion. Spine. Clinical Drug Investigation. 2007;27(5):357-366. 1995;20(14):1600-1603. 13. Samama CM, Albaladejo P, Benhamou D, et al. Venous 2. Deep K, Jigajinni MV, McLean AN, Fraser MH. Pro- thromboembolism prevention in surgery and obstetrics: phylaxis of thromboembolism in spinal injuries--results Clinical practice guidelines. European Journal of Anaes- of enoxaparin used in 276 patients. Spinal Cord. Feb thesiology. 2006;23(2):95-116. 2001;39(2):88-91. 14. Sreerama V, Ivan LP, Dennery JM, Richard MT. Neu- 3. Epstein NE. A review of the risks and benefits of dif- rosurgical complications of anticoagulant therapy. Can fering prophylaxis regimens for the treatment of deep Med Assoc J. Feb 3 1973;108(3):305-307. venous thrombosis and pulmonary embolism in neuro- 15. Turpie AG, Gent M, Doyle DJ, et al. An evaluation surgery. Surgical Neurology. 2005;64(4):295-301. of suloctidil in the prevention of deep vein throm- 4. Geerts WH, Pineo GF, Heit JA, et al. Prevention of ve- bosis in neurosurgical patients. Thromb Res. Jul 15 1985;39(2):173-181.

E. Risk/Benefit Analysis

What is the ideal measure by Mar 1 1993;18(3):315-319. 6. Ferree BA, Wright AM. Deep venous thrombosis fol- which to gauge the risk/benefit lowing posterior lumbar spinal surgery. Spine. Jun 15 1993;18(8):1079-1082. ratio of chemoprophylaxis in 7. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: The Seventh ACCP Conference patients undergoing spinal on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 SUPPL.):338S-400S. surgery? 8. Gerlach R, Raabe A, Beck J, Woszczyk A, Seifert V. Postoperative nadroparin administration for prophy- A comprehensive review of the spine literature did laxis of thromboembolic events is not associated with an not yield sufficient evidence to address the previous increased risk of hemorrhage after spinal surgery. Eur question related to the risk of wound complications or Spine J. Feb 2004;13(1):9-13. 9. Green D, Sullivan S, Simpson J, Soltysik RC, Yarnold neurologic decline from epidural hematoma follow- PR. Evolving risk for thromboembolism in spinal cord ing use of chemoprophylaxis. With limited evidence injury (SPIRATE Study). Am J Phys Med Rehabil. Jun on efficacy of chemoprophylaxis, the work group was 2005;84(6):420-422. unable to address this question. 10. Harris S, Chen D, Green D. Enoxaparin for thromboembolism prophylaxis in spinal injury: preliminary report on experience with 105 patients. Am J Phys Med Reha- Future Directions for Research bil. Sep-Oct 1996;75(5):326-327. Additional studies are suggested in previous sec- 11. Ho WK, Baccala M, Thom J, Eikelboom JW. High tions of this guideline to both address the efficacy of prevalence of abnormal preoperative coagulation tests in chemoprophylaxis as well as provide a detailed docu- patients with adolescent idiopathic scoliosis. J Thromb mentation of rates of wound complications for specific Haemost. May 2005;3(5):1094-1095. 12. Kleindienst A, Harvey HB, Mater E, et al. Early an- populations and chemoprophylaxis protocols. Until tithrombotic prophylaxis with low molecular weight additional information is available to address both of heparin in neurosurgery. Acta Neurochir (Wien). Dec these issues, questions related to risk/benefit analysis 2003;145(12):1085-1090; discussion 1090-1081. cannot be adequately or accurately addressed. 13. Korinth MC, Gilsbach JM, Weinzierl MR. Low- dose aspirin before spinal surgery: results of a survey among neurosurgeons in Germany. Eur Spine J. Mar References 2007;16(3):365-372. 1. Cain Jr JE, Major MR, Lauerman WC, West JL, Wood 14. Layton KF, Kallmes DF, Horlocker TT. Recommenda- KB, Fueredi GA. The morbidity of heparin therapy after tions for anticoagulated patients undergoing image-guid- development of pulmonary embolus in patients under- ed spinal procedures. American Journal of Neuroradiol- going thoracolumbar or lumbar spinal fusion. Spine. ogy. 2006;27(3):468-470. 1995;20(14):1600-1603. 15. Leon L, Rodriguez H, Tawk RG, Ondra SL, Labropou- 2. Catre MG. Anticoagulation in spinal surgery. A critical los N, Morasch MD. The prophylactic use of inferior review of the literature. Can J Surg. Dec 1997;40(6):413- vena cava filters in patients undergoing high-risk spinal 419. surgery. Ann Vasc Surg. May 2005;19(3):442-447. 3. Deep K, Jigajinni MV, McLean AN, Fraser MH. Pro- 16. Nelson LD, Jr., Montgomery SP, Dameron TB, Jr., phylaxis of thromboembolism in spinal injuries--results Nelson RB. Deep vein thrombosis in lumbar spinal fu- of enoxaparin used in 276 patients. Spinal Cord. Feb sion: a prospective study of antiembolic and pneumatic 2001;39(2):88-91. compression stockings. J South Orthop Assoc. Fall 4. Epstein NE. A review of the risks and benefits of dif- 1996;5(3):181-184. fering prophylaxis regimens for the treatment of deep 17. O’Donnell M, Weitz JI. Thromboprophylaxis in surgical venous thrombosis and pulmonary embolism in neuro- patients. Can J Surg. Apr 2003;46(2):129-135. surgery. Surgical Neurology. 2005;64(4):295-301. 18. Rocha E, Imberti D, Paschina E. Low-molecular-weight 5. Ferree BA, Stern PJ, Jolson RS, Roberts JMt, Kahn A, heparins: Before or after surgery? New concepts and 3rd. Deep venous thrombosis after spinal surgery. Spine. evidence: Congress report from the SIGMA TAU/ROVI This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 27

satellite symposium (Rome, Italy, 13 November 2006). bar spine surgery. Regional Anesthesia; 1994:28. Clinical Drug Investigation. 2007;27(5):357-366. 23. Turpie AG, Gent M, Doyle DJ, et al. An evaluation 19. Rokito SE, Schwartz MC, Neuwirth MG. Deep vein of suloctidil in the prevention of deep vein throm- thrombosis after major reconstructive spinal surgery. bosis in neurosurgical patients. Thromb Res. Jul 15 Spine. Apr 1 1996;21(7):853-858; discussion 859. 1985;39(2):173-181. 20. Samama CM, Albaladejo P, Benhamou D, et al. Venous 24. Valladares JB, Hankinson J. Incidence of lower extremity thromboembolism prevention in surgery and obstetrics: deep vein thrombosis in neurosurgical patients. Neuro- Clinical practice guidelines. European Journal of Anaes- surgery. Feb 1980;6(2):138-141. thesiology. 2006;23(2):95-116. 25. Voth D, Schwarz M, Hahn K, Dei-Anang K, al Butmeh 21. Sonaglia F, Agnelli G, Baroni M, Severi P, Quintavalla S, Wolf H. Prevention of deep vein thrombosis in neu- R, D’Angelo SV. Pre-operative plasma levels of soluble rosurgical patients: a prospective double-blind com- fibrin polymers correlate with the development of deep parison of two prophylactic regimen. Neurosurg Rev. vein thrombosis after elective neurosurgery. Blood Co- 1992;15(4):289-294. agul Fibrinolysis. Dec 1999;10(8):459-463. 26. Wood KB, Kos PB, Abnet JK, Ista C. Prevention of 22. Tetzlaff JE, Yoon HJ, O’Hara J, Bell GR, Boumphrey deep-vein thrombosis after major spinal surgery: a com- FR, Graor RA. Influence of anesthetic technique on the parison study of external devices. J Spinal Disord. Jun incidence of deep venous thrombosis after elective lum- 1997;10(3):209-214.

Types of Studies Therapeutic Studies – Prognostic Studies – Diagnostic Studies – Economic and Decision Investigating the results of Investigating the effect of a Investigating a diagnostic Analyses – treatment patient characteristic on the test Developing an economic or outcome of disease decision model Level I • High quality randomized • High quality prospective • Testing of previously • Sensible costs and trial with statistically study4 (all patients were developed diagnostic alternatives; values significant difference or enrolled at the same criteria on consecutive obtained from many no statistically significant point in their disease patients (with universally studies; with multiway difference but narrow with ≥ 80% follow-up of applied reference “gold” sensitivity analyses confidence intervals enrolled patients) standard) • Systematic review2 of • Systematic Review2 of • Systematic review2 of • Systematic review2 of Level I studies Level I RCTs (and study Level I studies Level I studies results were homogenous3) Level II • Lesser quality RCT (eg, < • Retrospective6 study • Development of • Sensible costs and 80% follow-up, no • Untreated controls from diagnostic criteria on alternatives; values blinding, or improper an RCT consecutive patients obtained from limited randomization) • Lesser quality (with universally applied studies; with multiway • Prospective4 comparative prospective study (eg, reference “gold” sensitivity analyses study5 patients enrolled at standard) • Systematic review2 of • Systematic review2 of different points in their • Systematic review2 of Level II studies Level II studies or Level 1 disease or <80% follow- Level II studies studies with inconsistent up.) results • Systematic review2 of Level II studies Level III • Case control study7 • Case control study7 • Study of non- • Analyses based on limited • Retrospective6 consecutive patients; alternatives and costs; comparative study5 without consistently and poor estimates • Systematic review2 of applied reference “gold” • Systematic review2 of Level III studies standard Level III studies • Systematic review2 of Level III studies Level IV Case series8 Case series • Case-control study • Analyses with no • Poor reference standard sensitivity analyses Level V Expert Opinion Expert Opinion Expert Opinion Expert Opinion

1. A complete assessment of quality of individual studies requires critical appraisal of all aspects of the study design. 2. A combination of results from two or more prior studies. 3. Studies provided consistent results. 4. Study was started before the first patient enrolled. 5. Patients treated one way (eg, cemented hip arthroplasty) compared with a group of patients treated in another way (eg, uncemented hip arthroplasty) at the same institution. 6. The study was started after the first patient enrolled. 7. Patients identified for the study based on their outcome, called “cases”; eg, failed total arthroplasty, are compared to those who did not have outcome, called “controls”; eg, successful total hip arthroplasty. 8. Patients treated one way with no comparison group of patients treated in another way.

A: Good evidence (Level I studies with consistent finding) for or against recommending intervention.

B: Fair evidence (Level II or III studies with consistent findings) for or against recommending intervention.

C: Poor quality evidence (Level IV or V studies) for or against recommending intervention.

I: Insufficient or conflicting evidence not allowing a recommendation for or against intervention.

One of the most crucial elements of evidence ship with Northwestern University’s Galter Health analysis to support development of recommenda- Sciences Library. When it is determined that a tions for appropriate clinical care or use of new literature search is needed, NASS research staff will technologies is the comprehensive literature search. work with the requesting parties and Galter to run Thorough assessment of the literature is the basis a comprehensive search employing at a minimum for the review of existing evidence, which will be the following search techniques: instrumental to these activities. 1. A preliminary search of the evidence will be Background conducted using the following clearly defined It has become apparent that the number of litera- search parameters (as determined by the con- ture searches being conducted at NASS is increas- tent experts). The following parameters are to ing and that they are not necessarily conducted in be provided to research staff to facilitate this a consistent manner between committees/projects. search. Because the quality of a literature search directly • Time frames for search affects the quality of recommendations made, a • Foreign and/or English language comparative literature search was undertaken to • Order of results (chronological, by journal, help NASS refine the process and make recom- etc.) mendations about how to conduct future literature • Key search terms and connectors, with or searches on a NASS-wide basis. without MeSH terms to be employed • Age range In November-December 2004, NASS conducted a • Answers to the following questions: trial run at new technology assessment. As part of o Should duplicates be eliminated between the analysis of that pilot process, the same litera- searches? ture searches were conducted by both an experi- o Should searches be separated by term or enced NASS member and a medical librarian for as one large package? comparison purposes. After reviewing the results o Should human studies, animal studies or of that experiment and the different strategies em- cadaver studies be included? ployed for both searches, it was the recommenda- This preliminary search should encompass a search tion of NASS Research staff that a protocol be de- of the Cochrane database when access is available. veloped to ensure that all future NASS searches be conducted consistently to yield the most compre- 2. Search results with abstracts will be compiled hensive results. While it is recognized that some by Galter in EndNote™ software. Galter typi- searches occur outside the Research and Clinical cally responds to requests and completes the Care Councils, it is important that all searches searches within two to five days. Results will conducted at NASS employ a solid search strategy, be forwarded to the research staff, who will regardless of the source of the request. To this end, share it with the appropriate NASS staff mem- this protocol has been developed and NASS-wide ber or requesting party(ies). (Research staff implementation is recommended. have access to EndNote™ software and will maintain a database of search results for future Protocol for NASS Literature Searches use/documentation.) The NASS Research Department has a relation- This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 31

3. NASS staff shares the search results with an 8. NASS members reviewing full-text articles appropriate content expert (NASS Committee should also review the references at the end of member or other) to assess relevance of articles each article to identify additional articles which and identify appropriate articles to review and should be reviewed, but may have been missed on which to run a “related articles” search. in the search.

4. Based on content expert’s review, NASS re- Protocol for Expedited Searches search staff will then coordinate with the Galter At a minimum, numbers 1, 2 and 3 should be fol- medical librarian the second level searching to lowed for any necessary expedited search. Fol- identify relevant “related articles.” lowing #3, depending on the time frame allowed, deeper searching may be conducted as described by 5. Galter will forward results to research staff to the full protocol or request of full-text articles may share with appropriate NASS staff member. occur. If full-text articles are requested, #8 should also be included. Use of the expedited protocol 6. NASS staff share related articles search results or any deviation from the full protocol should be with an appropriate content expert (NASS documented with explanation. Committee member or other) to assess relevance of this second set of articles, and identify Following these protocols will help ensure that appropriate articles to review and on which to NASS recommendations are (1) based on a thor- run a second “related articles” search. ough review of relevant literature; (2) are truly based on a uniform, comprehensive search strategy; 7. NASS research staff will work with Galter and (3) represent the current best research evidence library to obtain the 2nd related articles search available. Research staff will maintain a search his- results and any necessary full-text articles for tory in EndNote,™ for future use or reference. review.

SUGGESTED SEARCH PARAMETERS FOR ALL QUESTIONS: • Time frames for search: 1966-PRESENT • Foreign and/or English language: ENGLISH ONLY • Order of results (chronological, by journal, etc.): CHRONOLOGICAL • Key search terms and connectors, with or without MeSH terms to be employed: LISTED WITH EACH QUESTION • Age range: 18+ • Should duplicates be eliminated between searches? NO • Should searches be separated by term or as one large package? ONE PACKAGE PER QUESTION • Should human studies, animal studies or cadaver studies be included? HUMAN STUDIES ONLY

Incidence of DVT or PE in Spine Surgery

Without Antithrombotic Prophylaxis – Work Group 1 1. What is the overall rate (symptomatic and asymptomatic) of DVT or PE following elective spinal surgery without any form of prophylaxis? (((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neo- plasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((“Pulmonary Embolism”[Mesh] OR “Venous Thrombosis”[Mesh]) OR “Thrombophlebitis”[Mesh] OR pulmonary embolism[title] OR PE[title] OR deep vein thrombosis[title] OR DVT[title] AND ((Humans[Mesh]) AND (English[lang])))) NOT ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombo- sis/drug therapy”[Mesh] OR “Thrombosis/prevention and control”[Mesh] OR “Thrombosis/ therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Ac- tion])) OR (“Fibrinolytic Agents”[Mesh] OR “Fibrinolytic Agents “[Pharmacological Ac- tion] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) in PubMed Addendum: ((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord

Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neo- plasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((“Pulmonary Embolism”[Mesh] OR “Venous Thrombosis”[Mesh]) OR “Thrombophlebitis”[Mesh] OR pulmonary embolism[title] OR PE[title] OR deep vein thrombosis[title] OR DVT[title] AND ((Humans[Mesh]) AND (English[lang]))) in PubMed

2. What are the relative rates of clinically symptomatic DVT or PE (including fatal PE) without any form or prophylaxis following elective cervical, thoracic and lumbar surgery? (((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neo- plasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((“Pulmonary Embolism”[Mesh] OR “Venous Thrombosis”[Mesh]) OR “Thrombophlebitis”[Mesh] OR pulmonary embolism[title] OR PE[title] OR deep vein thrombosis[title] OR DVT[title] AND ((Humans[Mesh]) AND (English[lang])))) AND “clinically symptomatic” in PubMed

With Antithrombotic Prophylaxis – Work Group 2 3. What is the rate of clinically symptomatic DVT and/or PE (including fatal PE) following elective spinal surgery with one or more of the following prophylaxis measures: compression stockings, mechanical sequential compression devices, chemoprophylaxis medication? (((((“Stockings, Compression”[Mesh] OR “Intermittent Pneumatic Compression Devices”[Mesh])) OR “Bandages”[Mesh]) OR (“venous thrombosis/prevention and control”[Mesh] AND (compression OR bandages OR bandage)) OR compression stockings[all fields] OR compression hose[all fields] OR sequential compression devices[all fields] OR intermittent pneumatic compression[all fields] AND ((Humans[Mesh]) AND (English[lang]))) OR ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombosis/drug therapy”[Mesh] OR “Thrombosis/ prevention and control”[Mesh] OR “Thrombosis/therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Action])) OR (“Fibrinolytic Agents”[Mesh] OR “Fi- brinolytic Agents “[Pharmacological Action] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) AND ((Humans[Mesh]) AND (English[lang]))) AND (((“Spine/surgery”[Mesh] OR “Spinal Diseases/ surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/ surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/ surgery”[Mesh] OR “Spinal Neoplasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((“Pulmonary Embolism”[Mesh] OR “Venous Thrombosis”[Mesh]) OR “Thrombophlebitis”[Mesh] OR pulmonary embolism[title] OR PE[title] OR deep vein thrombosis[title] OR DVT[title] AND ((Humans[Mesh]) AND (English[lang])))) AND ((Humans[Mesh]) AND (English[lang])) in PubMed

Incidence of DVT or PE in High Risk Patient Populations

Without Antithrombotic Prophylaxis – Work Group 1 4. What is the overall rate (symptomatic and asymptomatic) of DVT or PE in nonsurgically treated acute spine trauma or tumor patients without any form of prophylaxis? ((((((“Spinal Injuries”[Mesh] OR “Spinal Neoplasms”[Mesh]) NOT “Spinal Neoplasms/ surgery”[Mesh]) NOT “Spinal Injuries/surgery”[Mesh] AND ((Humans[Mesh]) AND (English[lang]))) AND ((“Pulmonary Embolism”[Mesh] OR “Venous Thrombosis”[Mesh]) OR “Thrombophlebitis”[Mesh] OR pulmonary embolism[title] OR PE[title] OR deep vein thrombosis[title] OR DVT[title] AND ((Humans[Mesh]) AND (English[lang]))) AND ((Humans[Mesh]) AND (English[lang]))) NOT ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombosis/drug therapy”[Mesh] OR “Thrombosis/ prevention and control”[Mesh] OR “Thrombosis/therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Action])) OR (“Fibrinolytic Agents”[Mesh] OR “Fi- brinolytic Agents “[Pharmacological Action] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) AND ((Humans[Mesh]) AND (English[lang]))) NOT (spinal neoplasms/secondary AND ((Humans[Mesh]) AND (English[lang]))) AND ((Humans[Mesh]) AND (English[lang]))) NOT (“surgery”[Subheading]) in PubMed

5. What is the overall rate (symptomatic and asymptomatic) of DVT or PE following nonelective spinal surgery for spine trauma or malignancy without any form of prophylaxis? ((((“Spinal Neoplasms”[Mesh] OR “Spinal Injuries”[Mesh]) AND “surgery”[subheading]) OR ((tumor[title] OR tumors[title] OR malignancy[title] OR malignancies[title] OR trauma[title]) AND (spinal[all fields] OR (“spine”[MeSH Terms] OR spine[Text Word])))) AND ((“Pulmo- nary Embolism”[Mesh] OR “Venous Thrombosis”[Mesh]) OR “Thrombophlebitis”[Mesh] OR pulmonary embolism[title] OR PE[title] OR deep vein thrombosis[title] OR deep venous thrombosis[title] OR DVT[title] AND (“humans”[MeSH Terms] AND English[lang]))) NOT ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombo- sis/drug therapy”[Mesh] OR “Thrombosis/prevention and control”[Mesh] OR “Thrombosis/ therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Ac- tion])) OR (“Fibrinolytic Agents”[Mesh] OR “Fibrinolytic Agents “[Pharmacological Ac- tion] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) in PubMed

6. What is the rate of clinically symptomatic DVT or PE (including fatal PE) following nonelective spinal surgery for spine trauma or malignancy without any form of prophylaxis? ((((“Spinal Neoplasms”[Mesh] OR “Spinal Injuries”[Mesh]) AND “surgery”[subheading]) OR ((tumor[title] OR tumors[title] OR malignancy[title] OR malignancies[title] OR trauma[title]) AND (spinal[all fields] OR (“spine”[MeSH Terms] OR spine[Text Word])))) AND ((“Pulmo- nary Embolism”[Mesh] OR “Venous Thrombosis”[Mesh]) OR “Thrombophlebitis”[Mesh] OR pulmonary embolism[title] OR PE[title] OR deep vein thrombosis[title] OR deep venous thrombosis[title] OR DVT[title] AND (“humans”[MeSH Terms] AND English[lang]))) NOT This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Antithrombotic Therapies in Spine Surgery 35

((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombo- sis/drug therapy”[Mesh] OR “Thrombosis/prevention and control”[Mesh] OR “Thrombosis/ therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Ac- tion])) OR (“Fibrinolytic Agents”[Mesh] OR “Fibrinolytic Agents “[Pharmacological Ac- tion] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) in PubMed

With Antithrombotic Prophylaxis – Work Group 2 7. What is the rate of clinically symptomatic DVT and/or PE (including fatal PE) following nonelective spinal surgery for spine trauma or malignancy with one or more of the following prophylaxis measures: compression stockings, mechanical sequential compression devices, chemoprophylaxis medication? ((“Pulmonary Embolism”[Mesh] OR “Venous Thrombosis”[Mesh]) OR “Thrombophlebitis”[Mesh] OR pulmonary embolism[title] OR PE[title] OR deep vein thrombosis[title] OR deep venous thrombosis[title] OR DVT[title] AND (“humans”[MeSH Terms] AND English[lang])) AND (((“Spinal Neoplasms”[Mesh] OR “Spinal Injuries”[Mesh]) AND “surgery”[subheading]) OR ((tumor[title] OR tumors[title] OR malignancy[title] OR malignancies[title] OR trauma[title]) AND (spinal[all fields] OR (“spine”[MeSH Terms] OR spine[Text Word])))) AND (((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombosis/drug therapy”[Mesh] OR “Thrombosis/ prevention and control”[Mesh] OR “Thrombosis/therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Action])) OR (“Fibrinolytic Agents”[Mesh] OR “Fibrin- olytic Agents “[Pharmacological Action] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) OR ((((“Stock- ings, Compression”[Mesh] OR “Intermittent Pneumatic Compression Devices”[Mesh])) OR “Bandages”[Mesh]) OR (“venous thrombosis/prevention and control”[Mesh] AND (compression OR bandages OR bandage)) OR compression stockings[all fields] OR compression hose[all fields] OR sequential compression devices[all fields] OR intermittent pneumatic compression[all fields] AND ((Humans[Mesh]) AND (English[lang])))) in PubMed

Prophylaxis Protocol – Work Group 2

Chemoprophylaxis 8. When indicated, what is the ideal time to begin chemoprophylaxis in relation to spinal surgery? ((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neoplasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombosis/drug therapy”[Mesh] OR “Thrombosis/ prevention and control”[Mesh] OR “Thrombosis/therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Action])) OR (“Fibrinolytic Agents”[Mesh] OR “Fibrin-

olytic Agents “[Pharmacological Action] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) in PubMed

9. When indicated, how long should chemoprophylaxis be continued following spinal surgery? ((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neoplasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombosis/drug therapy”[Mesh] OR “Thrombosis/ prevention and control”[Mesh] OR “Thrombosis/therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Action])) OR (“Fibrinolytic Agents”[Mesh] OR “Fibrin- olytic Agents “[Pharmacological Action] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) in PubMed

10. In patients who are being treated with chemical anticoagulants for a non-spine related disorder (eg, valve replacement), what is the ideal “bridge” therapy between stopping and starting the usual agent before and after surgery? ((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neoplasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombosis/drug therapy”[Mesh] OR “Thrombosis/ prevention and control”[Mesh] OR “Thrombosis/therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Action])) OR (“Fibrinolytic Agents”[Mesh] OR “Fibrin- olytic Agents “[Pharmacological Action] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) in PubMed

Mechanical Prophylaxis 11. When indicated, what is the ideal time to begin mechanical prophylaxis in relation to spinal surgery?

((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neo- plasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((((“Stockings, Compression”[Mesh] OR “Intermittent Pneumatic Com-

pression Devices”[Mesh])) OR “Bandages”[Mesh]) OR (“venous thrombosis/prevention and control”[Mesh] AND (compression OR bandages OR bandage)) OR compression stockings[all fields] OR compression hose[all fields] OR sequential compression devices[all fields] OR- in termittent pneumatic compression[all fields] AND ((Humans[Mesh]) AND (English[lang]))) in PubMed

12. When indicated, how long should mechanical prophylaxis be continued following spinal surgery? ((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neo- plasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((((“Stockings, Compression”[Mesh] OR “Intermittent Pneumatic Com- pression Devices”[Mesh])) OR “Bandages”[Mesh]) OR (“venous thrombosis/prevention and control”[Mesh] AND (compression OR bandages OR bandage)) OR compression stockings[all fields] OR compression hose[all fields] OR sequential compression devices[all fields] OR- in termittent pneumatic compression[all fields] AND ((Humans[Mesh]) AND (English[lang]))) in PubMed

Complications and Risk/Benefit Analysis – Work Group 3 13. Does the use of chemoprophylaxis increase the risk of wound complications or neurologic decline from epidural hematoma in patients receiving chemoprophylaxis after spinal surgery? ((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh] OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND ((Humans[Mesh]) AND (English[lang]))) NOT (“Spinal Cord Injuries/surgery”[Mesh] OR “Spinal Cord Neoplasms/surgery”[Mesh] OR “Spinal Neoplasms/surgery”[Mesh] OR “Spinal Injuries/surgery”[Mesh]) AND ((Humans[Mesh]) AND (English[lang]))) AND ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Thrombosis/drug therapy”[Mesh] OR “Thrombosis/ prevention and control”[Mesh] OR “Thrombosis/therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacological Action])) OR (“Fibrinolytic Agents”[Mesh] OR “Fi- brinolytic Agents “[Pharmacological Action] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) AND (“He- matoma, Epidural, Cranial”[Mesh] OR “Hematoma, Epidural, Spinal”[Mesh] OR epidural hematoma[title] AND ((Humans[Mesh]) AND (English[lang]))) AND ((Humans[Mesh]) AND (English[lang])) in PubMed

14. What is the ideal measure by which to gauge the risk/benefit ratio of chemoprophylaxis in patients undergoing spinal surgery? ((“Spine/surgery”[Mesh] OR “Spinal Diseases/surgery”[Mesh] OR “Spinal Fusion”[Mesh]

OR “Diskectomy”[Mesh] OR “Laminectomy”[Mesh] OR “Spinal Nerves/surgery”[Mesh] OR “Spinal Cord/surgery”[Mesh] OR “Spinal Cord Diseases/surgery”[Mesh] OR spine surgery[title] OR spinal surgery[title] AND (“humans”[MeSH Terms] AND English[lang])) AND ((((“Thrombolytic Therapy”[Mesh] OR “Chemoprevention”[Mesh:noexp]) OR (“Throm- bosis/drug therapy”[Mesh] OR “Thrombosis/prevention and control”[Mesh] OR “Throm- bosis/therapy”[Mesh])) OR (“Anticoagulants”[Mesh] OR “Anticoagulants “[Pharmacologi- cal Action])) OR (“Fibrinolytic Agents”[Mesh] OR “Fibrinolytic Agents “[Pharmacological Action] OR anticoagulation[title] OR antithrombotic[title] OR chemoprophylaxis[title]) AND (“humans”[MeSH Terms] AND English[lang])) AND (“humans”[MeSH Terms] AND English[lang])) AND (((“Risk Assessment”[Mesh] OR (“Risk”[Mesh] OR “Risk Reduc- tion Behavior”[Mesh] OR “Risk Factors”[Mesh]) OR risk[title] OR benefit[title]) OR (“Out- come Assessment (Health Care)”[Mesh] OR “Treatment Outcome”[Mesh])) OR “Epide- miologic Measurements”[Mesh] AND (“humans”[MeSH Terms] AND English[lang])) AND (“humans”[MeSH Terms] AND English[lang]) in PubMed

Appendix E: Evidentiary Tables

Article Level Description of study Conclusion Explanation (Alpha by Author) (I-V) of failure to meet Type of guideline evidence inclusion criteria (when applicable) Gruber UF, Rem Level III Prospective Retrospective – check Critique of methodology Justification J, Meisner C, one Patients not enrolled at same point in (check all Gratzl O. Type of their disease that apply): Prevention of evidence: Study design (select one): comparative <80% follow-up Level V thromboembolic prognostic No validated outcome measures used (expert complications with Stated objective of study: Determine the Small sample size consensus) miniheparin- incidence of bleeding complications in Lacked subgroup analysis Level IV in dihydroergotamin patients undergoing lumbar spine surgery Diagnostic method(s) not described presence e in patients treated with minidose heparin-DHE Follow-up was not standardized. of higher undergoing compared with those receiving placebo. Other: only performed test on patients quality lumbar disc with clinically suspicious presentation studies operations. Eur Total number of patients: 50 Subgroup Arch Psychiatry Number of patients not receiving Work group conclusions analysis Neurol Sci. prophylaxis: 20 (5 patients in the control Potential Level (select one): II data not 1984;234(3):157- group of 25 were found to have received Downgraded Level (select one): III available 161. heparin at another hospital) Not Conclusions relative to question relevant to Duration of follow-up: 7 days This paper provides evidence that:in this question

small series of consecutive patients Validated outcome measures used (list): undergoing "lumbar disc operations," no Ultrasound or I125 scan, only performed, clinically evident DVT or PE events were however, on patients in whom clinical documented. findings (not described) suggested possible DVT

Nonvalidated outcome measures used (list):

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify): 125 Fibrinogen, CXR, EEG, VQ Scan, pulmonary angiogram if PE suspect

Results/subgroup analysis (relevant to question): Incidence of DVT: Zero Incidence of PE: Zero Other:

Author conclusions (relative to question): In this small series of consecutive patients undergoing "lumbar disc operations," no clinically evident DVT or PE events were documented.

Joffe SN. Level V Prospective Retrospective – check Critique of methodology Justification

Incidence of one Patients not enrolled at same point in (check all postoperative Type of their disease that apply): deep vein evidence: Study design (select one): case series <80% follow-up Level V thrombosis in prognostic No validated outcome measures used (expert neurosurgical Stated objective of study: Investigate the Small sample size consensus) patients. J incidence of DVT in patients undergoing Lacked subgroup analysis Level IV in Neurosurg. Feb elective neurosurgical procedures. Diagnostic method(s) not described presence 1975;42(2):201- of higher 203. Total number of patients: 23 (only 10 spinal quality cases) Work group conclusions studies Number of patients not receiving Potential Level (select one): IV Subgroup prophylaxis: 23 (10 spinal cases) Downgraded Level (select one): V analysis data not Duration of follow-up: Hospitalization Conclusions relative to question available (greater than 7 days) This paper provides evidence Not that:asymptomatic DVT is not uncommon relevant to Validated outcome measures used (list): in a nonselect group of patients question undergoing elective spinal surgery followed by a prolonged period of Nonvalidated outcome measures used postoperative bedrest. The applicability (list): of these findings today is questionable given that prolonged periods of bed rest Diagnosis of DVT/PE made by (check all are no longer recommended following that apply): surgery. The paper also suggests that Clinical exam clinical manifestations are not reliable for Ultrasound the diagnosis of DVT. Venography Other (please specify): I-125 Fibrinogen

Results/subgroup analysis (relevant to

question): Incidence of DVT: 60%, 6/10 with spinal surgery Incidence of PE: not stated Other:

Author conclusions (relative to question): Neurosurgical patients are at risk for DVT; these patients are often asymptomatic. DVT will be underdiagnosed by clinical criteria alone, but this conclusion was based on a mix of cranial and spinal data.

Lee HM, Suk KS, Level II Prospective Retrospective – check Critique of methodology Justification Moon SH, Kim one Patients not enrolled at same point in (check all DJ, Wang JM, Type of their disease that apply): Kim NH. Deep evidence: Study design (select one): comparative <80% follow-up Level V vein thrombosis prognostic No validated outcome measures used (expert after major spinal Stated objective of study: To determine the Small sample size consensus) surgery: incidence rate of DVT after elective spinal surgery Lacked subgroup analysis Level IV in in an East Asian (without prophylaxis) in an east Asian Diagnostic method(s) not described presence population. Spine. (Korean) population. Other: included an unknown number of higher Jul 15 of pediatric patients with subgroup quality 2000;25(14):1827 Total number of patients: 313 analysis not provided studies -1830. Number of patients not receiving Subgroup prophylaxis: 313 Work group conclusions analysis Potential Level (select one): I data not Duration of follow-up: 5 to 7 days Downgraded Level (select one): II available Not Validated outcome measures used (list): Conclusions relative to question relevant to ultrasound This paper provides evidence that:in this question series of east Asian patients who

Nonvalidated outcome measures used underwent elective spinal surgery without (list): antithrombotic prophylaxis, a very low rate of DVT was observed, using Diagnosis of DVT/PE made by (check all ultrasound screening. Although the that apply): authors concluded that these results were Clinical exam related to the ethnicity of the patient Ultrasound group, it is possible that other unidentified Venography factors (other than ethnicity) may have Other (please specify): had a role in this finding.

Results/subgroup analysis (relevant to question): Incidence of DVT: The overall incidence of thrombotic complications was 1.3% and the incidence of symptomatic DVT was 0.3% Incidence of PE: none clinically seen Other: Some patients were pediatric.

Author conclusions (relative to question): East Asians do not get DVT often enough to warrant prophylaxis. Routine screening and prophylaxis for the east Asian patients undergoing elective spinal surgery is not warranted.

Oda T, Fuji T, Level II Prospective Retrospective – check Critique of methodology Justification Kato Y, Fujita S, one Patients not enrolled at same point in (check all Kanemitsu N. Type of their disease that apply): Deep venous evidence: Study design (select one): comparative <80% follow-up Level V thrombosis after prognostic No validated outcome measures used (expert

posterior spinal Stated objective of study: To document the Small sample size consensus) surgery. Spine. prevalence of DVT after posterior spinal Lacked subgroup analysis Level IV in Nov 15 surgery with no prophylaxis Diagnostic method(s) not described presence 2000;25(22):2962 of higher -2967. Total number of patients: 134/110 studied quality with venography Work group conclusions studies Number of patients not receiving Potential Level (select one): II Subgroup prophylaxis: 134 Downgraded Level (select one): analysis data not Duration of follow-up: Venography Conclusions relative to question available performed within 14 days of surgery This paper provides evidence that:the Not (average 7.2 days). Clinical follow-up of at rate of DVT in postoperative spine relevant to least 3 months. surgery patients may be underestimated. question Clinical manifestations are not reliable for Validated outcome measures used (list): the diagnosis of DVT. Increased age and venography posterior approach to the lumbar spine are risk factors. It should be noted that all Nonvalidated outcome measures used patients had an interval of bed rest (list): following surgery.

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 17/110 (15.5%) had venographic evidence of DVT;

0/110 patients had clinical manifestations of DVT. Incidence of PE: none Other: The prevalence of DVT after posterior spinal surgery: lumbar 26.5% > thoracic 14.3% > cervical 5.6%. Increased age is a risk factor for DVT.

Author conclusions (relative to question): The prevalence of DVT after posterior spinal surgery is higher than generally recognized (15.5%); therefore, further study is necessary to clarify the appropriate method for screening and the efficacy of DVT prophylaxis after spinal surgery.

Uden A. Level IV Prospective Retrospective – check Critique of methodology Justification Thromboembolic one Patients not enrolled at same point in (check all complications Type of their disease that apply): following scoliosis evidence: Study design (select one): case series <80% follow-up Level V surgery in prognostic No validated outcome measures used (expert Scandinavia. Acta Stated objective of study: to document the Small sample size consensus) Orthop Scand. rate of clinically evident DVT in a Lacked subgroup analysis Level IV in Apr population of patients treated surgically Diagnostic method(s) not described presence of 1979;50(2):175- with Harrington instrumentation and 3 to 5 Other: Some patients had 2 separate higher quality 178. weeks of bed rest. surgeries with this subgroup analysis studies data not provided. Variable diagnostic Subgroup Total number of patients: 1229 methods implemented, but no analysis data Number of patients not receiving standardized follow up or duration not available prophylaxis: 1229 identified. Not relevant to question

Duration of follow-up: at least 5 weeks Work group conclusions Potential Level (select one): III Validated outcome measures used (list): Downgraded Level (select one): IV venography was used, but only on patients who had clinical findings. They also used Conclusions relative to question autopsy findings. This paper provides evidence that:clinically evident DVT can occur in Nonvalidated outcome measures used scoliosis patients managed with (list): postoperative bed rest.

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify): Contrast phlebography, isotope phlebography, autopsy

Results/subgroup analysis (relevant to question): Incidence of DVT: 8/1229 (0.65%) Incidence of PE: 1/1229 (0.08%) Other: All 8 DVTs were proximal on the left side. The incidence of thromboembolic complications increases with age and the number of vertebrae fused. Patients may present with pain in the leg or lower abdominal region. PE may occur with minimal clinical evidence of DVT.

Author conclusions (relative to question): Incidence is low in this group of patients but probably higher than stated (venography done only when clinical diagnosis was made).

Article Level Description of study Conclusion Explanation of (Alpha by Author) (I-V) failure to meet guideline Type of inclusion evidence criteria (when applicable) Lee HM, Suk KS, Level II Prospective Retrospective – check Critique of methodology Justification Moon SH, Kim one Patients not enrolled at same point in (check all DJ, Wang JM, Type of their disease that apply): Kim NH. Deep evidence: Study design (select one): comparative <80% follow-up Level V vein thrombosis prognostic No validated outcome measures used (expert after major spinal Stated objective of study: To determine the Small sample size consensus) surgery: incidence rate of DVT after elective spinal Lacked subgroup analysis Level IV in in an East Asian surgery(without prophylaxis) in an east Diagnostic method(s) not described presence of population. Spine. Asian (Korean) population. higher quality Jul 15 studies 2000;25(14):1827 Total number of patients: 313 Work group conclusions Subgroup -1830. Number of patients not receiving Potential Level (select one): I analysis data prophylaxis: 313 Downgraded Level (select one): II not available Not relevant Duration of follow-up: 5 to 7 days Conclusions relative to question to question This paper provides evidence that:In this Validated outcome measures used (list): series of east Asian patients who ultrasound underwent elective spinal surgery without

antithrombotic prophylaxis, a very low Nonvalidated outcome measures used rate of clinically symptomatic DVT was (list): observed, using ultrasound screening. Although the authors concluded that Diagnosis of DVT/PE made by (check all these results were related to the ethnicity that apply): of the patient group, it is possible that Clinical exam other unidentified factors (other than Ultrasound ethnicity) may have had a role in this Venography finding. Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: The incidence of symptomatic DVT was 0.3% (1/313) Incidence of PE: 0 Other: Some patients were pediatric.

surgery. Spine. prevalence of DVT after posterior spinal Lacked subgroup analysis Level IV in Nov 15 surgery with no prophylaxis Diagnostic method(s) not described presence of 2000;25(22):2962 higher quality -2967. Total number of patients: 134/110 studied studies with venography Work group conclusions Subgroup Number of patients not receiving Potential Level (select one): II analysis data prophylaxis: 134 Downgraded Level (select one): not available Not relevant Duration of follow-up: Venography Conclusions relative to question to question performed within 14 days of surgery This paper provides evidence (average 7.2 days). Clinical follow-up of at that:clinically evident DVT can be very least 3 months. low post spinal surgery, although the rate of clinically silent DVT can be significant. Validated outcome measures used (list): Clinical exam is not reliable in the venography diagnosis of DVT in the postoperative spinal surgery patient. Nonvalidated outcome measures used (list):

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 17/110 (15.5%) had venographic evidence of DVT; 0/110 patients had clinical manifestations of DVT.

Incidence of PE: none Other: The prevalence of DVT after posterior spinal surgery: lumbar 26.5% > thoracic 14.3% > cervical 5.6%. Increased age is a risk factor for DVT.

Author conclusions (relative to question): DVT was venographically evident in 3/54 patients (5.6%) who underwent cervical procedures. DVT was evident in 13/49 patients (26.5%) who underwent lumbar procedures. These differences were statisticaly significant. Increased age was established as a risk factor. The prevalence of DVT after posterior spinal surgery is higher than generally recognized (15.5%); therefore, further study is necessary to clarify the appropriate method for screening and the efficacy of DVT prophylaxis after spinal surgery.

Article Level Description of study Conclusion Explanation of (Alpha by Author) (I-V) failure to meet guideline Type of inclusion evidence criteria (when applicable) Dearborn JT, Hu Level II Prospective Retrospective -- (check Critique of Methodology/ Justification SS, Tribus CB, one) Justification for Downgrading (check all Bradford DS. Type of (Check all that apply): that apply): Thromboembolic evidence: Study design (select one): comparative Nonconsecutive patients Level V complications prognostic Nonrandomized (expert after major Stated objective of study: To determine the Nonmasked reviewers consensus) thoracolumbar ~~~~~~~ incidence of symptomatic and asymptomatic Nonmasked patients Level IV in spine surgery. venous thromboembolism by PE or DVT No validated outcome measures presence of Spine. Jul 15 Level IV after thoracolumbar fusion surgery. used higher quality 1999;24(14):1471 Small sample size studies -1476. Type of Type(s) of prophylaxis: Mechanical: <80% follow-up Subgroup evidence stockings or pneumatic compression Lacked subgroup analysis analysis data therapeutic stockings. Diagnostic method(s) not detailed not available

Other: Not relevant Total number of patients: 116 to question Number of patients in relevant subgroups: PROGNOSTIC ASSESSMENT 49 A/P (circumferential) surgery with 67 Work group conclusions unilateral (62 PSF/3 ASF/ 2 hardware Potential Level (select one): I removal) Downgraded Level (select one): II

Consecutive series (select one)? Yes Conclusions relative to question This paper provides evidence Type(s) of surgery: that:combined posterior and anterior ASF/PSF/Circumferential or hardware spinal procedures had a greater removal incidence of PE than posterior only cases using elastic stockings and Duration of follow-up: 3-20 days for duplex pneumatic compression as prophylaxis. with 2-year retrospective review of group None of the patients with PE had been identified by Doppler ultrasound as Validated outcome measures used (list): having DVT, so this DVT screening may Duplex Doppler and V/Q in 73/116; no clear not be useful for looking at PE in this functional outcome measure used population. Anterior surgery was a definite risk factor, and there was a Nonvalidated outcome measures used (list): trend for older age to be a risk factor.

THERAPEUTIC ASSESSMENT Diagnosis of DVT/PE made by (check all that Work group conclusions apply): Potential Level (select one): III Clinical exam Downgraded Level (select one): IV Ultrasound Venography Conclusions relative to question Other (please specify): Ventilation- This paper provides evidence that:the perfusion (V/Q) scans in 73/116, region and degree/type of spinal surgery should play a role in prophylaxis

Results/subgroup analysis (relevant to choice. question): Incidence of DVT: 0.9% (in retrospective group, 0.3%) Incidence of PE: 2.6% (in retrospective group, 2.5%) Incidence of Tx Related Complications:

Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): Duplex ultrasounds appear insensitive to identifying clots in patients subsequently diagnosed with PE.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Simple mechanical prophylaxis for thromboembolism, which may be adequate for patients undergoing posterior procedures, may not be as protective for patients undergoing combined anterior/posterior spine surgery.

Epstein NE. Level II Prospective Retrospective -- (check Critique of Methodology/ Justification Intermittent one) Justification for Downgrading (check all pneumatic Type of (Check all that apply): that apply): compression evidence: Study design (select one): comparative Nonconsecutive patients Level V stocking prognostic Nonrandomized (expert prophylaxis Stated objective of study: To examine the Nonmasked reviewers consensus)

against deep ~~~~~~~ incidence of VTE after one-level and multi- Nonmasked patients Level IV in venous level cervical corpectomy. No validated outcome measures presence of thrombosis in Level IV used higher quality anterior cervical Type(s) of prophylaxis: Intermittent Small sample size studies spinal surgery: a Type of pneumatic compression stockings <80% follow-up Subgroup prospective evidence: Lacked subgroup analysis analysis data efficacy study in therapeutic Total number of patients: 200 Diagnostic method(s) not detailed not available 200 patients and Number of patients in relevant subgroups: Other: Downgraded due to short Not relevant literature review. 100 one-level, 100 multi-level corpectomies follow-up of two days. to question Spine. Nov 15 2005;30(22):2538 Consecutive series (select one)? Yes PROGNOSTIC ASSESSMENT -2543. Work group conclusions Type(s) of surgery: Cervical corpectomy Potential Level (select one): I Downgraded Level (select one): II Duration of follow-up: 2 days post-op; 2.5 year one-level, 5.3 year multi-level Conclusions relative to question This paper provides evidence Validated outcome measures used (list): that:mechanical prophylaxis is None associated with a 1-7% risk of DVT and 0-2% risk of PE depending on type of Nonvalidated outcome measures used (list): cervical surgery. The study of None prognosis did not stratify for other high- risk factors (age, smoking). Diagnosis of DVT/PE made by (check all that apply): THERAPEUTIC ASSESSMENT Clinical exam Work group conclusions Ultrasound Potential Level (select one): IV Venography Downgraded Level (select one): IV Other (please specify): CT angiogram of chest on patients with suspected PE Conclusions relative to question This paper provides evidence

Results/subgroup analysis (relevant to that:Mechanical prophylaxis is an question): attractive option given that there is a Incidence of DVT: 1% one-level, 7% multi- risk of hemorrhage after surgery with level heparin. Incidence of PE: 0% one-level, 2% multilevel Incidence of Tx Related Complications: 0% Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): The rates of DVT (1% and 7%, respectively) and PE (1% and 2%, respectively) were comparable with frequencies encountered in other cranial/spinal series using mini-heparin and/or low-dose heparin regimens but avoided the 2% to 4% risk of major postoperative hemorrhage.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Intermittent compression pneumatic stockings were equally effective to literature reported rates of prophylaxis with low-dose heparin and avoided the risks of postoperative hemorrhage.

Epstein NE. Level IV Prospective Retrospective -- (check Critique of Methodology/ Justification Efficacy of one) Justification for Downgrading (check all pneumatic Type of (Check all that apply): that apply): compression evidence: Study design (select one): case series Nonconsecutive patients Level V

stocking prognostic Nonrandomized (expert prophylaxis in the Stated objective of study: To examined the Nonmasked reviewers consensus) prevention of ~~~~~~~ incidence of VTE with pneumatic Nonmasked patients Level IV in deep venous compression stockings No validated outcome measures presence of thrombosis and Level IV used higher quality pulmonary Type(s) of prophylaxis: Pneumatic Small sample size studies embolism Type of compression stockings <80% follow-up Subgroup following 139 evidence Lacked subgroup analysis analysis data lumbar therapeutic Total number of patients: 139 Diagnostic method(s) not detailed not available laminectomies Number of patients in relevant subgroups: Other: Unable to ascertain whether Not relevant with instrumented None this was a prospective study, thus the to question fusions. J Spinal work group had to assume it was Disord Tech. Feb Consecutive series (select one)? No retrospective. 2006;19(1):28-31. Type(s) of surgery: Lumbar laminectomies PROGNOSTIC ASSESSMENT with fusion Work group conclusions Potential Level (select one): IV Duration of follow-up: Postoperative period Downgraded Level (select one): IV

Validated outcome measures used (list): Conclusions relative to question This paper provides evidence that:With lumbar decompression and stabilization, Nonvalidated outcome measures used (list): mechanical prophylaxis has low rate of VTE. Incidence of DVT following elective decompression and fusion in Diagnosis of DVT/PE made by (check all that patients wearing SCD postoperatively apply): was 2.9%. Clinical exam Ultrasound THERAPEUTIC ASSESSMENT Venography Work group conclusions Other (please specify): Potential Level (select one): IV

Downgraded Level (select one): IV Results/subgroup analysis (relevant to question): Conclusions relative to question Incidence of DVT: 2.9% (4/139) This paper provides evidence Incidence of PE: 0.7% (1/139) that:mechanical prophylaxis with Incidence of Tx Related Complications: elective lumbar surgery minimizes DVT risk. Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): The rate of DVT is 2.9% in elective lumbar decompressions and fusion when using compression stockings for prophylaxis.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Pneumatic compression stockings provided effective prophylaxis for DVT in elective lumbar fusion surgery, almost comparable to low-dose heparin regimens without the associated risk of hematomas and neurological compromise.

Ferree BA. Deep Level II Prospective Retrospective -- (check Critique of Methodology/ Justification venous one) Justification for Downgrading (check all thrombosis Type of (Check all that apply): that apply): following lumbar evidence: Study design (select one): comparative Nonconsecutive patients Level V laminotomy and prognostic Nonrandomized (expert laminectomy. Stated objective of study: Investigate the Nonmasked reviewers consensus) Orthopedics. Jan ~~~~~~~ incidence of DVT after lumbar Nonmasked patients Level IV in

1994;17(1):35-38. decompressive surgery No validated outcome measures presence of Level IV used higher quality Type(s) of prophylaxis: Sequential Small sample size studies Type of compression stockings <80% follow-up Subgroup evidence: Lacked subgroup analysis analysis data therapeutic Total number of patients: 60 Diagnostic method(s) not detailed not available Number of patients in relevant subgroups: 6 Other: Not relevant patients were greater than 62 years old and to question 54 were less than 62 years old PROGNOSTIC ASSESSMENT Work group conclusions Consecutive series (select one)? Yes Potential Level (select one): I Downgraded Level (select one): II Type(s) of surgery: lumbar laminotomy and laminectomy with some fusion Conclusions relative to question This paper provides evidence that: DVT Duration of follow-up: Studies within 14 days is more common in older patients and preoperatively and 2-5 days postoperatively there is a 5% incidence of Doppler- identified, but asymptomatic DVT on Validated outcome measures used (list): Doppler surveillance in elective laminectomy and laminotomy with compression stockings. Nonvalidated outcome measures used (list): THERAPEUTIC ASSESSMENT Work group conclusions Diagnosis of DVT/PE made by (check all that Potential Level (select one): IV apply): Downgraded Level (select one): IV Clinical exam Ultrasound Conclusions relative to question Venography This paper provides evidence Other (please specify): that:mechanical prophylaxis via sequential compression stockings is

Results/subgroup analysis (relevant to effective in reducing thromboembolism question): in elective laminectomy and Incidence of DVT: 5% (3/60). Age stratified laminotomy. results: in the six patients greater than 62 years of age, there were two DVTs; of the 54 patients under 62 years old, there was only one DVT (p<.05). Incidence of PE: none described Incidence of Tx Related Complications:

Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): Clinically significant DVT after lumbar decompression appears unusual

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Mechanical prophylaxis in the setting of lumbar decompression appears as an attractive alternative.

Ferree BA, Stern Level II Prospective Retrospective -- (check Critique of Methodology/ Justification PJ, Jolson RS, one) Justification for Downgrading (check all Roberts JMt, Type of (Check all that apply): that apply): Kahn A, 3rd. evidence: Study design (select one): comparative Nonconsecutive patients Level V Deep venous prognostic Nonrandomized (expert thrombosis after Stated objective of study: Determine the Nonmasked reviewers consensus) spinal surgery. ~~~~~~~ incidence of DVT after spine surgery Nonmasked patients Level IV in Spine. Mar 1 No validated outcome measures presence of

1993;18(3):315- Level IV Type(s) of prophylaxis: Pneumatic used higher quality 319. compression stockings Small sample size studies Type of <80% follow-up Subgroup evidence: Total number of patients: 86 Lacked subgroup analysis analysis data therapeutic Number of patients in relevant subgroups: Diagnostic method(s) not detailed not available 86 Other: Since not clearly articulated, Not relevant the work group was required to to question Consecutive series (select one)? Yes assume that this was a retrospective study. Type(s) of surgery: Lumbar and thoracic decompressions (40) with additional fusion PROGNOSTIC ASSESSMENT (46) Work group conclusions Potential Level (select one): II Duration of follow-up: Studies within 14 days Downgraded Level (select one): II preoperatively and 7 days postoperatively Conclusions relative to question Validated outcome measures used (list): This paper provides evidence that:there is a low incidence of DVT in patients treated with pneumatic compression Nonvalidated outcome measures used (list): stockings. Age does not appear to correlate with increased incidence of DVT. Diagnosis of DVT/PE made by (check all that apply): THERAPEUTIC ASSESSMENT Clinical exam Work group conclusions Ultrasound Potential Level (select one): IV Venography Downgraded Level (select one): IV Other (please specify): Conclusions relative to question Results/subgroup analysis (relevant to This paper provides evidence question): that:pneumatic compression stockings

Incidence of DVT: 6% are effective in preventing DVT. Incidence of PE: 0% Incidence of Tx Related Complications: 0% Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): Pneumatic compression stockings are effective in preventing DVT. Age does not appear to correlated with DVT

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Pneumatic compression stockings are effective in preventing DVT.

Ferree BA, Wright Level III Prospective Retrospective -- (check Critique of Methodology/ Justification AM. Deep venous one) Justification for Downgrading (check all thrombosis Type of (Check all that apply): that apply): following posterior evidence: Study design (select one): comparative Nonconsecutive patients Level V lumbar spinal prognostic Nonrandomized (expert surgery. Spine. Stated objective of study: determine the Nonmasked reviewers consensus) Jun 15 ~~~~~~~ incidence of DVT/PE comparing the use of Nonmasked patients Level IV in 1993;18(8):1079- elastic stockings to intermittent pneumatic No validated outcome measures presence of 1082. Level IV compression boots used higher quality Small sample size studies Type of Type(s) of prophylaxis: elastic stockings <80% follow-up Subgroup evidence: versus intermittent pneumatic compression Lacked subgroup analysis analysis data therapeutic stockings Diagnostic method(s) not detailed not available Other: heterogeneous prophylaxis Not relevant Total number of patients: 185 methods and heterogeneous patient to question

Number of patients in relevant subgroups: populations. Selection bias: one 74 patients received elastic stockings and surgeon used one method and one 111 received intermittent pneumatic used another. Also, groups were not compression (differed by surgeon) balanced with respect to type of surgery (decompression versus Consecutive series (select one)? No decompression and fusion).

Type(s) of surgery: lumbar laminectomies PROGNOSTIC ASSESSMENT and lumbar fusions Work group conclusions Potential Level (select one): II Duration of follow-up: 2-7 days Downgraded Level (select one): III postoperatively Conclusions relative to question Validated outcome measures used (list): This paper provides evidence that:the use of IPC boots appears to significantly lower the incidence of DVT. Nonvalidated outcome measures used (list): THERAPEUTIC ASSESSMENT Work group conclusions Diagnosis of DVT/PE made by (check all that Potential Level (select one): III apply): Downgraded Level (select one): IV Clinical exam Ultrasound Conclusions relative to question Venography This paper provides evidence that:IPC Other (please specify): boots can significantly lower the incidence of DVT. Results/subgroup analysis (relevant to question): Incidence of DVT: 5% in the elastic stocking group; 0% in the IPC group Incidence of PE: 0%

Incidence of Tx Related Complications: 0% Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): No correlation between operation type, length of bed rest, age, tobacco use, or length of procedure and incidence of DVT.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): IPC are more effective than elastic stocking in preventing DVT (p<0.05). No differences in DVT by operation type, length of bed rest, age, tobacco use or length of procedure.

Gerlach R, Raabe Level II Prospective Retrospective -- (check Critique of Methodology/ Justification A, Beck J, one) Justification for Downgrading (check all Woszczyk A, Type of (Check all that apply): that apply): Seifert V. evidence: Study design (select one): case series Nonconsecutive patients Level V Postoperative prognostic Nonrandomized (expert nadroparin Stated objective of study: Evaluate the Nonmasked reviewers consensus) administration for ~~~~~~~ incidence of clinically significant hematoma Nonmasked patients Level IV in prophylaxis of after use of anticoagulation. No validated outcome measures presence of thromboembolic Level IV used higher quality events is not Type(s) of prophylaxis: Nadroparin + Small sample size studies associated with Type of compression stockings <80% follow-up Subgroup an increased risk evidence Lacked subgroup analysis analysis data of hemorrhage therapeutic Total number of patients: 1954 Diagnostic method(s) not detailed not available after spinal Number of patients in relevant subgroups: Other: Not relevant surgery. Eur cervical surgery 503, thoracic 152, lumbar to question

Spine J. Feb 1299 2004;13(1):9-13. PROGNOSTIC ASSESSMENT Consecutive series (select one)? No Work group conclusions Potential Level (select one): II Type(s) of surgery: Any spinal surgery in Downgraded Level (select one): II any region Conclusions relative to question Duration of follow-up: Duration of This paper provides evidence that:there hospitalization is a very low incidence of DVT/PE in this retrospectively selected patient Validated outcome measures used (list): population which received nadroparin for anticoagulation and compression stockings. Nonvalidated outcome measures used (list): Neurological exam THERAPEUTIC ASSESSMENT Work group conclusions Diagnosis of DVT/PE made by (check all that Potential Level (select one): IV apply): Downgraded Level (select one): IV Clinical exam Ultrasound Conclusions relative to question Venography This paper provides evidence that:use Other (please specify): of nadroparin and compression stockings results in a very low incidence Results/subgroup analysis (relevant to of DVT/PE with no increased risk of question): hematoma. Incidence of DVT: 0.05% (1/1954) Incidence of PE: 0% Incidence of Tx Related Complications: 0.4% (8/1954); total hematomas=13 (5 prior to nadroparin) Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): Early nadroparin is safe and does not appear to increase hematoma risk.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Early nadroparin is safe and does not appear to increase hematoma risk.

Gruber UF, Rem Level II Prospective Retrospective -- (check Critique of Methodology/ Justification J, Meisner C, one) Justification for Downgrading (check all Gratzl O. Type of (Check all that apply): that apply): Prevention of evidence: Study design (select one): RCT Nonconsecutive patients Level V thromboembolic prognostic Nonrandomized (expert complications with Stated objective of study: Evaluate the Nonmasked reviewers consensus) miniheparin- ~~~~~~~ incidence of bleeding complications using Nonmasked patients Level IV in dihydroergotamin miniheparin starting preoperatively compared No validated outcome measures presence of e in patients Level to none in a control group used higher quality undergoing Small sample size studies lumbar disc Type of Type(s) of prophylaxis: heparin DHE 2500 <80% follow-up Subgroup operations. Eur evidence: Lacked subgroup analysis analysis data Arch Psychiatry therapeutic Total number of patients: 50 Diagnostic method(s) not detailed not available Neurol Sci. Number of patients in relevant subgroups: Other: Not relevant 1984;234(3):157- n=25 heparin DHE 2500 BID to question 161. PROGNOSTIC ASSESSMENT Consecutive series (select one)? Yes Work group conclusions Evaluted only to Potential Level (select one): I address the Type(s) of surgery: lumbar discectomy Downgraded Level (select one): II incidence of

DVT/PE, rather Duration of follow-up: until discharge or up to Conclusions relative to question than therapeutic 7 days postoperatively This paper provides evidence efficacy. that:preoperatively and postoperatively Validated outcome measures used (list): administered miniheparin DHE (2500u Intraoperative bleeding by volume bid) did not increase bleeding complications nor did this method of Nonvalidated outcome measures used (list): chemoprophylaxis result in decreased incidence of DVT/PE when compared with controls. Diagnosis of DVT/PE made by (check all that apply): THERAPEUTIC ASSESSMENT Clinical exam Work group conclusions Ultrasound Potential Level (select one): Venography Downgraded Level (select one): Other (please specify): I125 fibrinogen; V/Q scan or pulmonary angiogram. Conclusions relative to question This paper provides evidence that:. Results/subgroup analysis (relevant to question): Incidence of DVT: 4% (1/25) with heparin and 0% (0/25) without Incidence of PE: 0 Incidence of Tx Related Complications: 24% (6/25) with heparin and 28% (7/25) without Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): None

THERAPEUTIC ASSESSMENT

Author conclusions (relative to question): Pre- and postoperative heparinization @ 2500u bid with DHE does not increase bleeding complications.

Leon L, Rodriguez Level IV Prospective Retrospective -- (check Critique of Methodology/ Justification H, Tawk RG, one) Justification for Downgrading (check all Ondra SL, Type of (Check all that apply): that apply): Labropoulos N, evidence: Study design (select one): case series Nonconsecutive patients Level V Morasch MD. The prognostic Nonrandomized (expert prophylactic use Stated objective of study: Determine if Nonmasked reviewers consensus) of inferior vena ~~~~~~~ inferior vena cava filters (IVCF) reduce the Nonmasked patients Level IV in cava filters in incidence of PE in a patient population at No validated outcome measures presence of patients Level IV high risk for VTE. used higher quality undergoing high- Small sample size studies risk spinal Type of Type(s) of prophylaxis: elastic stockings, <80% follow-up Subgroup surgery. Ann Vasc evidence: pneumatic compression boots, IVCF Lacked subgroup analysis analysis data Surg. May therapeutic Diagnostic method(s) not detailed not available 2005;19(3):442- Total number of patients: 74 Other: no subgroup analysis data Not relevant 447. Number of patients in relevant subgroups: provided on which patients received to question Stratified by risk factors I (n=4), II (n=19), III prophylaxis in addition to IVCF (n=19), IV (n=18), V (n=8), VI (n=6) PROGNOSTIC ASSESSMENT Consecutive series (select one)? No Work group conclusions Potential Level (select one): IV Type(s) of surgery: Major spinal surgery Downgraded Level (select one): IV

Duration of follow-up: 11 months consisting Conclusions relative to question of weekly Doppler ultrasound while in the This paper provides evidence that:IVCF hospital and 1 month clinical follow-up are associated with a low incidence of standardized PE in patients at high risk for VTE.

Validated outcome measures used (list): THERAPEUTIC ASSESSMENT none Work group conclusions Potential Level (select one): IV Nonvalidated outcome measures used (list): Downgraded Level (select one): IV none Conclusions relative to question Diagnosis of DVT/PE made by (check all that This paper provides evidence that:IVCF apply): can significantly reduce the incidence of Clinical exam PE in patients at high risk for VTE. Ultrasound Venography Other (please specify): Abdominopelvic CT and Chest CTA in some patinets

Results/subgroup analysis (relevant to question): Incidence of DVT: 31% (23/74) Incidence of PE: 1.3% (1/74) Incidence of Tx Related Complications: misplaced IVCF in 2 patients Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): Incidence of DVT is elevated in this high risk group.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): IVC filters minimize the incidence of PE

Nelson LD, Jr., Level II Prospective Retrospective -- (check Critique of Methodology/ Justification Montgomery SP, one) Justification for Downgrading (check all Dameron TB, Jr., Type of (Check all that apply): that apply): Nelson RB. Deep evidence: Study design (select one): RCT Nonconsecutive patients Level V vein thrombosis in prognostic Nonrandomized (expert lumbar spinal Stated objective of study: To evaluate Nonmasked reviewers consensus) fusion: a ~~~~~~~ incidence of DVT following degenerative Nonmasked patients Level IV in prospective study lumbar spine surgery in patients using TED No validated outcome measures presence of of antiembolic and Level II stockings and acetylsalicylic acid (ASA) used higher quality pneumatic compared with those using TED stockings, Small sample size studies compression Type of pneumatic compression boots and ASA <80% follow-up Subgroup stockings. J South evidence: (group II) during surgery Lacked subgroup analysis analysis data Orthop Assoc. therapeutic Diagnostic method(s) not detailed not available Fall Type(s) of prophylaxis: TED, pneumatic Other: Method of randomization not Not relevant 1996;5(3):181- compression boots and ASA clearly stated: authors do not state to question 184. the randomization technique; Total number of patients: 117 therefore, it is uncertain how Number of patients in relevant subgroups: allocation was concealed. 60 with stockings and ASA 600 mg bid and PROGNOSTIC ASSESSMENT 57 with stockings and boots plus ASA 600 Work group conclusions mg bid Potential Level (select one): I Downgraded Level (select one): II Consecutive series (select one)? Yes Conclusions relative to question Type(s) of surgery: posterior lumbar This paper provides evidence decompression with fusion and fixation that:elastic stockings along with ASA sufficiently reduce the DVT risk. Duration of follow-up: 2-6 days postoperatively THERAPEUTIC ASSESSMENT Work group conclusions

Validated outcome measures used (list): Potential Level (select one): I Downgraded Level (select one): II

Nonvalidated outcome measures used (list): Conclusions relative to question This paper provides evidence that:the use of TED stockings and ASA 600 mg Diagnosis of DVT/PE made by (check all that is effective in reducing the risk of DVT. apply): Pneumatic compression stockings do Clinical exam not provide additional prophylactic Ultrasound benefits. Venography Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 0 Incidence of PE: 0 Incidence of Tx Related Complications: None Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): The use of elastic stockings and ASA 600mg bid is satisfactory for DVT prophylaxis

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): The use of elastic stockings and ASA 600mg bid is satisfactory for DVT prophylaxis

Rokito SE, Level II Prospective Retrospective -- (check Critique of Methodology/ Justification Schwartz MC, one) Justification for Downgrading (check all Neuwirth MG. Type of (Check all that apply): that apply): Deep vein evidence: Study design (select one): comparative Nonconsecutive patients Level V thrombosis after prognostic Nonrandomized (expert major Stated objective of study: determine the Nonmasked reviewers consensus) reconstructive ~~~~~~~ incidence of deep vein thrombosis after Nonmasked patients Level IV in spinal surgery. major adult spinal surgery and the optimal No validated outcome measures presence of Spine. Apr 1 Level III mode of prophylaxis in this surgical used higher quality 1996;21(7):853- population. Small sample size studies 858; discussion Type of <80% follow-up Subgroup 859. evidence: Type(s) of prophylaxis: compression Lacked subgroup analysis analysis data therapeutic stockings, IPC devices, low-dose Coumadin Diagnostic method(s) not detailed not available Other: Unstated randomization Not relevant Total number of patients: 329 patients. process. to question Number of patients in relevant subgroups: 110 patients were prospectively randomized PROGNOSTIC ASSESSMENT to one of three study groups. Group 1 (42 Work group conclusions patients) received bilateral thigh-high Potential Level (select one): II thrombosis embolic deterrent (TED) Downgraded Level (select one): II compression stockings. Group 2 (33 patients) received TED stockings and thigh- Conclusions relative to question length cuffs that provided sequential This paper provides evidence that: pneumatic compression to the calf and thigh. Pneumatic compression stockings with Group 3 (35 patients) received TED TEDS and/or TEDS alone are stockings and low-dose Coumadin. The 219 associated with a low incidence of DVT. not randomized received either TED stockings alone or TED stockings and THERAPEUTIC ASSESSMENT pneumatic compression boots for DVT Work group conclusions prophylaxis. Potential Level (select one): II Downgraded Level (select one): III

Consecutive series (select one)? Yes Conclusions relative to question Type(s) of surgery: Anterior and/or posterior This paper provides evidence that:low- spinal fusions and/or decompression dose Coumadin is no more effective than mechanical prophylaxis in reducing Duration of follow-up: 5-7 days for ultrasound DVT risks. Given the increased risk of and 1 year clinically hemorrhage with Coumadin, mechanical prophylaxis with graduated Validated outcome measures used (list): compression stockings and pneumatic compression boots is preferable to anticoagulation therapy. Nonvalidated outcome measures used (list):

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 0.3% overall (1/329), 0% in RCT Incidence of PE: 0 Incidence of Tx Related Complications: 5.7% (2/35) with Coumadin but 0% without Other:

PROGNOSTIC ASSESSMENT

Author conclusions (relative to question): Pneumatic compression boots and TEDS were associated with a low incidence of DVT/PE.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Pneumatic compression boots and TEDS provide sufficient VTE prophylaxis.

Smith MD, Level II Prospective Retrospective -- (check Critique of Methodology/ Justification Bressler EL, one) Justification for Downgrading (check all Lonstein JE, Type of (Check all that apply): that apply): Winter R, Pinto evidence: Study design (select one): case series Nonconsecutive patients Level V MR, Denis F. prognostic Nonrandomized (expert Deep venous Stated objective of study: Examine the Nonmasked reviewers consensus) thrombosis and ~~~~~~~ incidence in complex spine surgery of VTE Nonmasked patients Level IV in pulmonary with compression stockings and pneumatic No validated outcome measures presence of embolism after Level IV boots used higher quality major Small sample size studies reconstructive Type of Type(s) of prophylaxis: compression <80% follow-up Subgroup operations on the evidence: stockings and pneumatic boots Lacked subgroup analysis analysis data spine. A therapeutic Diagnostic method(s) not detailed not available prospective Total number of patients: 317 (126 received Other: Inconsistently applied Not relevant analysis of three USG and 191 did not) diagnostic methods. to question hundred and Number of patients in relevant subgroups: seventeen Cervical lesion (32), Infection (3), Lumbar PROGNOSTIC ASSESSMENT patients. J Bone lesion (122), Scoliosis (77), Spinal trauma Work group conclusions Joint Surg Am. Jul (34), Spondylolisthesis (31), Thoracic lesion Potential Level (select one): I 1994;76(7):980- (18) Downgraded Level (select one): II 985.

Consecutive series (select one)? No Conclusions relative to question This paper provides evidence that:there Type(s) of surgery: Complex surgeries is a very low incidence of DVT (0.6%) anterior and/or posterior and PE (0.3%) with use of compression stockings and pneumatic boots. Duration of follow-up: 6 days postoperatively and as outpatient for a few weeks. THERAPEUTIC ASSESSMENT Work group conclusions Validated outcome measures used (list): Potential Level (select one): IV Downgraded Level (select one): IV

Nonvalidated outcome measures used (list): Conclusions relative to question This paper provides evidence that:compression stockings and Diagnosis of DVT/PE made by (check all that pneumatic boots are effective in apply): preventing DVT and PE. Additionally, Clinical exam routine postoperative ultrasound is not Ultrasound warranted in patients treated with Venography mechanical prophylaxis. Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 0.6% (2/317) Incidence of PE: 0.3% (1/317) Incidence of Tx Related Complications: None Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question):

Low incidence of VTE with compression stockings and pneumatic boots. Routine ultrasound not warranted.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Mechanical prophylaxis is effective in preventing VTE. Routine ultrasound not warranted.

Voth D, Schwarz Level I Prospective Retrospective -- (check Critique of Methodology/ Justification M, Hahn K, Dei- one) Justification for Downgrading (check all Anang K, al Type of (Check all that apply): that apply): Butmeh S, Wolf evidence: Study design (select one): RCT Nonconsecutive patients Level V H. Prevention of prognostic Nonrandomized (expert deep vein Stated objective of study: determine the Nonmasked reviewers consensus) thrombosis in ~~~~~~~ incidence of DVT and PE comparing use of Nonmasked patients Level IV in neurosurgical once daily dosing of low molecular weight No validated outcome measures presence of patients: a Level II heparin (LMWH) with dihydroergotamine used higher quality prospective (DHE) to twice daily dosing of heparin with Small sample size studies double-blind Type of DHE as prophylaxis in routine, elective <80% follow-up Subgroup comparison of two evidence: lumbar disc surgery. Lacked subgroup analysis analysis data prophylactic therapeutic Diagnostic method(s) not detailed not available regimen. Type(s) of prophylaxis: LMWH/DHE once Other: two chemoprophylaxis Not relevant Neurosurg Rev. daily versus heparin/DHE twice daily regimens compared (no control group); to question 1992;15(4):289- lack of power; randomization method 294. Total number of patients: 179 not specified; screening only Number of patients in relevant subgroups: immediately postoperatively LMWH/DHE (87 patients) and heparin/DHE (92 patients) PROGNOSTIC ASSESSMENT Work group conclusions

Consecutive series (select one)? Yes Potential Level (select one): I Downgraded Level (select one): I Type(s) of surgery: lumbar disc surgery- laminectomy for herniated disc Conclusions relative to question This paper provides evidence that: Duration of follow-up: not specified LMWH/DHE regimen and heparin/DHE both have low incidence of DVT but Validated outcome measures used (list): seem to have some mild bleeding sequelae.

Nonvalidated outcome measures used (list): THERAPEUTIC ASSESSMENT Work group conclusions Potential Level (select one): I Diagnosis of DVT/PE made by (check all that Downgraded Level (select one): II apply): Clinical exam Conclusions relative to question Ultrasound This paper provides evidence Venography that:LMWH/DHE regimen and Other (please specify): I125 fibrinogen heparin/DHE reduce the risk of DVT, but can result in bleeding complications. Results/subgroup analysis (relevant to question): Incidence of DVT: 4.6% (3/87) with LMWH/DHE and 3.3% (3/92) with heparin/DHE Incidence of PE: Incidence of Tx Related Complications: Excessive intraoperative bleeding in 4/92 (4.3%) of the heparin/DHE patients; Intraoperative blood transfusion 5.8% with LMWH and 4.4% with heparin/DHE

Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): Low but real incidence of DVT in posterior decompression surgery

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): LMWH with DHE is highly safe and effective.

Wood KB, Kos Level I Prospective Retrospective -- (check Critique of Methodology/ Justification PB, Abnet JK, Ista one) Justification for Downgrading (check all C. Prevention of Type of (Check all that apply): that apply): deep-vein evidence: Study design (select one): RCT Nonconsecutive patients Level V thrombosis after prognostic Nonrandomized (expert major spinal Stated objective of study: To compare two Nonmasked reviewers consensus) surgery: a ~~~~~~~ different types of compressive devices Nonmasked patients Level IV in comparison study (elastic stockings/foot wraps and elastic No validated outcome measures presence of of external Level II stockings/pneumatic compression boots) in used higher quality devices. J Spinal the prevention of DVT/PE after complex Small sample size studies Disord. Jun Type of spinal surgery <80% follow-up Subgroup 1997;10(3):209- evidence: Lacked subgroup analysis analysis data 214. therapeutic Type(s) of prophylaxis: elastic Diagnostic method(s) not detailed not available stockings+foot wraps (n=75) or elastic Other: Randomization method not Not relevant stockings+pneumatic boots (n=59) clearly stated. to question

Total number of patients: 134 PROGNOSTIC ASSESSMENT Number of patients in relevant subgroups: Work group conclusions n=75 with foot wraps and n=59 with boots Potential Level (select one): I Downgraded Level (select one): I

Consecutive series (select one)? Yes Conclusions relative to question Type(s) of surgery: Anterior or posterior This paper provides evidence thoracic, thoracolumbar or lumbar multilevel that:mechanical prophylaxis is decompressions and/or spinal fusions associated with minimal DVT risk and one form is not superior to the other. Duration of follow-up: At least about a week, otherwise not specified. All patients received THERAPEUTIC ASSESSMENT duplex study 5 to 7 days postoperatively. Work group conclusions Potential Level (select one): I Validated outcome measures used (list): Downgraded Level (select one): II visual analog comfort scale Conclusions relative to question Nonvalidated outcome measures used (list): This paper provides evidence that:mechanical prophylaxis is effective in reducing DVT risk after major spine Diagnosis of DVT/PE made by (check all that surgery, and one form is not superior to apply): the other. Clinical exam Ultrasound Venography Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 2/136 (1.5%) Incidence of PE: 1/136 (0.7%) Incidence of Tx Related Complications: 36/136 (complained of redness/itching) Other:

PROGNOSTIC ASSESSMENT Author conclusions (relative to question): The rate of DVT after major spinal surgery is low with mechanical prophylaxis.

THERAPEUTIC ASSESSMENT Author conclusions (relative to question): Mechanical prophylaxis is effective in reducing DVT risk after major spinal surgery.

In patients who are being treated with chemical anticoagulants for a non-spine related disorder (eg, valve replacement), what is the ideal "bridge" therapy between stopping and starting the usual agent before and after surgery?

Article Level Description of study Conclusion Explanation of (Alpha by Author) (I-V) failure to meet guideline Type of inclusion evidence criteria (when applicable) Gerlach R, Raabe Level IV Prospective Retrospective -- (check Critique of Methodology/ Justification A, Beck J, one) Justification for Downgrading (check all Woszczyk A, Type of (Check all that apply): that apply): Seifert V. evidence: Study design (select one): case series Nonconsecutive patients Level V Postoperative therapeutic Nonrandomized (expert nadroparin Stated objective of study: Evaluate the Nonmasked reviewers consensus) administration for incidence of clinically significant hematoma Nonmasked patients Level IV in prophylaxis of after use of anticoagulation No validated outcome measures presence of thromboembolic used higher quality events is not Type(s) of prophylaxis: Nadroparin 0.3ml Small sample size studies associated with within 24 hours of surgery continued through <80% follow-up Subgroup an increased risk hospitalization with compression stockings; Lacked subgroup analysis analysis data of hemorrhage hypercoagulable and/or valve patients Diagnostic method(s) not detailed not available

after spinal received 0.3-0.6ml every 12 hours; those on Other: Not relevant surgery. Eur anticoagulants received 0.6ml every 12 to questions Spine J. Feb hours with medication stopped 12 hours prior Work group conclusions 2004;13(1):9-13. to surgery and begun 12 hours after surgery. Potential Level (select one): IV 0.3ml = 2850 IU Downgraded Level (select one): IV

Total number of patients: 1954 Conclusions relative to question Number of patients in relevant subgroups: This paper provides evidence cervical surgery 503, thoracic 152, lumbar that:Nadroparin 0.3ml may be 1299 administered within 24 hours of surgery and continued for the duration of Consecutive series (select one)? Yes hospitalization. Nadroparin 0.6ml can be used for those patients on Type(s) of surgery: Any spinal surgery in anticoagulants every 12 hours with any region medication stopped 12 hours prior to surgery and resumed 12 hours after Duration of follow-up: Duration of surgery. hospitalization

Validated outcome measures used (list):

Nonvalidated outcome measures used (list): Neurological exam

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography

Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 0.05% (1/1954) Incidence of PE: 0% Incidence of Tx Related Complications: 8/1954 (0.4%); total hematomas 13 (5 prior to nadroparin) Other:

Author conclusions (relative to question): Early nadroparin is safe and does not appear to increase hematoma risk.

Gruber UF, Rem Level IV Prospective Retrospective -- (check Critique of Methodology/ Justification J, Meisner C, one) Justification for Downgrading (check all Gratzl O. Type of (Check all that apply): that apply): Prevention of evidence: Study design (select one): RCT Nonconsecutive patients Level V thromboembolic therapeutic Nonrandomized (expert complications with Stated objective of study: Evaluate the Nonmasked reviewers consensus) miniheparin- Although incidence of bleeding complications using Nonmasked patients Level IV in dihydroergotamin designed miniheparin starting preoperatively compared No validated outcome measures presence of e in patients as an RCT, to none in a control group used higher quality undergoing the level of Small sample size studies lumbar disc evidence Type(s) of prophylaxis: heparin DHE 2500 <80% follow-up Subgroup operations. Eur reflects the Lacked subgroup analysis analysis data Arch Psychiatry review of Total number of patients: 50 Diagnostic method(s) not detailed not available Neurol Sci. case series Number of patients in relevant subgroups: Other: Not relevant 1984;234(3):157- level data heparin DHE n=25 and placebo n=25 to questions

161. used to Work group conclusions address Consecutive series (select one)? Yes Potential Level (select one): IV questions Downgraded Level (select one): IV related to Type(s) of surgery: lumbar discectomy chemoprop Conclusions relative to question hylaxis Duration of follow-up: until discharge or up to This paper provides evidence protocol. 7 days postoperatively that:heparin DHE may be started preoperatively and continued at 12 hour Validated outcome measures used (list): intervals throughout hospitalization to intraoperative bleeding by volume reduce VTE risk without an increased risk of bleeding complications. Nonvalidated outcome measures used (list):

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify): I125 fibrinogen; V/Q scan or pulmonary angiogram.

Results/subgroup analysis (relevant to question): Incidence of DVT: 4% (1/25) with heparin and 0% (0/25) without Incidence of PE: 0 Incidence of Tx Related Complications: 24% (6/25) with heparin and 28% (7/25) without Other:

Author conclusions (relative to question): Pre- and postoperative heparinization at 2500u twice daily with DHE does not increase bleeding.

Nelson LD, Jr., Level IV Prospective Retrospective -- (check Critique of Methodology/ Justification Montgomery SP, one) Justification for Downgrading (check all Dameron TB, Jr., Type of (Check all that apply): that apply): Nelson RB. Deep evidence: Study design (select one): RCT Nonconsecutive patients Level V vein thrombosis in therapeutic Nonrandomized (expert lumbar spinal Stated objective of study: To determine the Nonmasked reviewers consensus) fusion: a Although difference in VTE in patients with elastic Nonmasked patients Level IV in prospective study designed stockings compared with stockings and No validated outcome measures presence of of antiembolic and as an RCT, pneumatic compression boots used higher quality pneumatic the level of Small sample size studies compression evidence Type(s) of prophylaxis: elastic stockings and <80% follow-up Subgroup stockings. J South reflects the ASA 600 mg twice daily postoperatively with Lacked subgroup analysis analysis data Orthop Assoc. review of or without pneumatic compression boots Diagnostic method(s) not detailed not available Fall case series Other: Not relevant 1996;5(3):181- level data Total number of patients: 117 to questions 184. used to Number of patients in relevant subgroups: Work group conclusions address 60 with stockings and ASA (600 mg twice Potential Level (select one): IV questions daily) and 57 with stockings, ASA and boots Downgraded Level (select one): IV related to chemoprop Consecutive series (select one)? Yes Conclusions relative to question hylaxis This paper provides evidence protocol. Type(s) of surgery: posterior lumbar that:postoperatively administered ASA decompression with fusion and fixation (600 mg) may be used in combination with elastic stockings to reduce the risk Duration of follow-up: 2-6 days of DVT/PE.

postoperatively

Validated outcome measures used (list):

Nonvalidated outcome measures used (list):

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 0 Incidence of PE: 0 Incidence of Tx Related Complications: None Other:

Author conclusions (relative to question): The use of elastic stockings and ASA 600 mg twice daily is satisfactory for DVT prophylaxis

Rokito SE, Level IV Prospective Retrospective -- (check Critique of Methodology/ Justification Schwartz MC, one) Justification for Downgrading (check all

Neuwirth MG. Type of (Check all that apply): that apply): Deep vein evidence: Study design (select one): RCT Nonconsecutive patients Level V thrombosis after therapeutic Nonrandomized (expert major Stated objective of study: To evaluate the Nonmasked reviewers consensus) reconstructive Although incidence of DVT after elective major adult Nonmasked patients Level IV in spinal surgery. designed spinal surgery in order to identify the optimal No validated outcome measures presence of Spine. Apr 1 as an RCT, mode of prophylaxis used higher quality 1996;21(7):853- the level of Small sample size studies 858; discussion evidence Type(s) of prophylaxis: RCT: elastic <80% follow-up Subgroup 859. reflects the stockings v. elastic stockings and pneumatic Lacked subgroup analysis analysis data review of compression boots v. elastic stockings and Diagnostic method(s) not detailed not available case series Coumadin; Observational: elastic Other: Not relevant level data compression stockings v. elastic to questions used to compression stockings and pneumatic boots Work group conclusions address Potential Level (select one): IV questions Total number of patients: 110 RCT, 219 Downgraded Level (select one): IV related to Observation (n=329) total chemoprop Number of patients in relevant subgroups: Conclusions relative to question hylaxis Group 1 (42 patients) received bilateral thigh- This paper provides evidence protocol. high thrombosis embolic deterrent (TED) that:Coumadin (10mg) administered compression stockings. Group 2 (33 prior to surgery and continued thereafter patients) received TED stockings and thigh- to keep INR at 1.3-1.5 does not reduce length cuffs that provided sequential DVT risks compared to pneumatic pneumatic compression to the calf and thigh. compression boots and/or elastic Group 3 (35 patients) received TED stockings alone, and is associated with stockings and low-dose Coumadin. The 219 a 5.7% incidence of hemorrhage. patients not randomized received either TED Pneumatic compression stockings with stockings alone or TED stockings and TEDS and/or TEDS alone reduce the pneumatic compression boots for DVT risk of DVT without bleeding prophylaxis. complications encountered with Coumadin.

Consecutive series (select one)? Yes

Type(s) of surgery: Anterior and/or posterior spinal fusions and/or decompression

Duration of follow-up: 5-7 days for ultrasound and 1 year clinically

Validated outcome measures used (list):

Nonvalidated outcome measures used (list):

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify):

Results/subgroup analysis (relevant to question): Incidence of DVT: 0.3% overall (1/329), 0% in RCT Incidence of PE: 0 Incidence of Tx Related Complications: 5.7% with Coumadin but 0% without Other:

Author conclusions (relative to question): Addition of Coumadin to prophylaxis for elective spine surgery appeared no better than TEDs alone.

Voth D, Schwarz Level IV Prospective Retrospective -- (check Critique of Methodology/ Justification M, Hahn K, Dei- one) Justification for Downgrading (check all Anang K, al Type of (Check all that apply): that apply): Butmeh S, Wolf evidence: Study design (select one): RCT Nonconsecutive patients Level V H. Prevention of therapeutic Nonrandomized (expert deep vein Stated objective of study: determine the Nonmasked reviewers consensus) thrombosis in Although incidence of DVT and PE comparing use of Nonmasked patients Level IV in neurosurgical designed once daily dosing of low molecular weight No validated outcome measures presence of patients: a as an RCT, heparin (LMWH) with dihydroergotamine used higher quality prospective the level of (DHE) to twice daily dosing of heparin with Small sample size studies double-blind evidence DHE as prophylaxis in routine, elective <80% follow-up Subgroup comparison of two reflects the lumbar disc surgery. Lacked subgroup analysis analysis data prophylactic review of Diagnostic method(s) not detailed not available regimen. case series Type(s) of prophylaxis: LMWH/DHE Other: Not relevant Neurosurg Rev. level data 32mg/0.5mg once daily + placebo versus to questions 1992;15(4):289- used to heparin/DHE 5000IU/0.5mg every 12 hours; Work group conclusions 294. address timing was within 2 hours of surgery and for Potential Level (select one): IV questions 7 days after. Downgraded Level (select one): IV related to chemoprop Total number of patients: 179 Conclusions relative to question hylaxis Number of patients in relevant subgroups: This paper provides evidence protocol. LMWH/DHE=87 Heparin/DHE=92 that:LMWH/DHE regimen and heparin/DHE both have low incidence of Consecutive series (select one)? Yes DVT but seem to have some mild bleeding sequelae. LMWH with DHE Type(s) of surgery: Lumbar disc surgery may be administered for lumbar disc

surgery two hours preoperatively and Duration of follow-up: 8 days maintained for seven days postoperatively to minimize the Validated outcome measures used (list): incidence of VTE.

Nonvalidated outcome measures used (list):

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify): I125 fibrinogen

Results/subgroup analysis (relevant to question): Incidence of DVT: 4.6% (3/87) with LMWH/DHE and 3.3% (3/92) with heparin/DHE Incidence of PE: Incidence of Tx Related Complications: Excessive bleeding in 4/92 (4.3%); Intraoperative blood transfusion 5.8% with LMWH and 4.4% with heparin Other:

Author conclusions (relative to question): LMWH with DHE, as administered in this

surgery two hours preoperatively and Duration of follow-up: 8 days maintained for seven days postoperatively to minimize the Validated outcome measures used (list): incidence of VTE.

Nonvalidated outcome measures used (list):

Diagnosis of DVT/PE made by (check all that apply): Clinical exam Ultrasound Venography Other (please specify): I125 fibrinogen

Author conclusions (relative to question): LMWH with DHE, as administered in this

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