- Email: [email protected]
AAOS Guidelines for the Prevention of Symptomatic Pulmonary Embolism After Total Hip and Total Knee Arthroplasty: Advantages and Disadvantages
AAOS Guidelines for the Prevention of Symptomatic Pulmonary Embolism After Total Hip and Total Knee Arthroplasty: Advantages and Disadvantages Paul F. Lachiewicz, MD*,† The American Academy of Orthopedic Surgeons has published a clinical guideline for the prevention of symptomatic pulmonary embolism in patients undergoing total hip and total knee arthroplasty. This guideline includes recommendations from a consensus process and a review and analysis of 42 publications since 1996. The end points for analysis were symptomatic and fatal pulmonary embolism rates, total death rates, and major bleeding complications. The guideline recommends preoperative risk stratification of all patients for “standard” and “high” risks of both pulmonary embolism and major bleeding complications. The use of regional anesthesia, mechanical prophylaxis, rapid mobilization, and patient education were consensus recommendations. The choice of a specific medication postoperatively by the surgeon should be based on an individual risk– benefit analysis of pulmonary embolism and major bleeding complications. The advantages of this guideline include a greater concern for bleeding and other local wound complications that could affect overall patient outcome, and the ability of the surgeon to treat each patient as an individual. The disadvantages of this guideline include placing hip and knee arthroplasty patients into a single group, the lower levels of evidence for the recommendations, and the relative lack of acceptance by other specialty groups and governmental agencies. Semin Arthro 20:230-234 Published by Elsevier Inc. KEYWORDS symptomatic pulmonary embolism, total hip arthroplasty, total knee arthroplasty
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linical guidelines in medicine have been devised to standardize and improve patient care for a variety of disorders. A clinical guideline addresses key clinical problems or questions, and has a defined evidence base and strength of recommendations. These recommendations are reached by both a review of available medical literature and, when no such data exist, through a consensus process of experts in the field. A clinical guideline should also encourage and guide future research in the field. It is important to remember that a clinical guideline is not a predefined protocol or dogmatic statement that is incapable of changing, nor is it a substitute for sound clinical judgment. There are now 3 clinical guidelines for venous thromboembolism prophylaxis after total
*Section of Orthopaedics, Department of Surgery, Duke University School of Medicine, Durham VA Medical Center, Durham, NC, USA. †Chapel Hill Orthopedics Surgery & Sports Medicine, Chapel Hill, NC, USA. Address reprint requests to Paul F. Lachiewicz, MD, Section of Orthopaedics, Department of Surgery, Duke University School of Medicine, Durham VA Medical Center, 508 Fulton Street, Durham, NC 27705. E-mail: [email protected]
230
1045-4527/09/$-see front matter Published by Elsevier Inc. doi:10.1053/j.sart.2009.10.006
hip and knee arthroplasty. These are the guidelines of the American College of Chest physicians (ACCP), Surgical Care Improvement Project, and most recently, the American Academy of Orthopedic Surgeons (AAOS). This article will describe the AAOS clinical guideline: Prevention of Symptomatic Pulmonary Embolism in Patients undergoing Total Hip or Knee Arthroplasty and discuss its advantages and disadvantages.
Orthopedic Concerns with ACCP Guidelines Orthopedic surgeons who perform total hip and knee arthroplasty have been impacted by the American College of Chest Physicians guidelines for the prevention of deep-vein thrombosis, with the most recent edition 8 published in June 2008.1 Deep venous thrombosis, detected by venography or ultrasonography, was the primary outcome measure in the development of these guidelines. The strongest or Grade 1-A recommendations are based on data from only prospective, randomized studies, with most of these comparing the effi-
AAOS guidelines for prevention of symptomatic pulmonary embolism cacy of one pharmacologic agent to another or to a placebo. Few studies were related to mechanical or multimodal (combined) prophylaxis. Surgical patients are grouped as “low,” “medium,” or “high” risk, but all total hip and knee arthroplasty patients are considered “high” risk, despite patient age, activity level, or comorbidities. Several orthopedic surgeons have voiced concerns with the ACCP guidelines, which emphasize prophylaxis with strong pharmacologic agents.2 Asymptomatic thrombi, detected by venography or ultrasonography, are considered as important an outcome as symptomatic thromboembolism. Only data from prospective, randomized studies were used to obtain a Grade 1-A recommendation. Thus, the data from even large (⬎1000 patient) cohort studies of 1 prophylactic method or multimodal prophylaxis cannot be given or obtain a Grade 1-A recommendation. Because prospective, randomized studies of pharmaceutical agent efficacy include only carefully selected patients with few comorbidities, these guidelines may not be applicable to the wide spectrum of patients undergoing total hip or knee arthroplasty. The ACCP guidelines appear to underestimate the risks of bleeding complications and other adverse outcomes, such as prolonged wound drainage or deep infection, related to the use of pharmacologic anticoagulants.2 Symptomatic pulmonary embolism is relatively rare after total hip or knee arthroplasty. The 90-day rate of fatal pulmonary embolism was 0.22% after 44,785 total hip arthroplasties and 0.15% after 27,000 total knee arthroplasties in the Scottish Registry.3 In a review of over 200,000 total knee arthroplasties in a California database, the 90-day rate of symptomatic pulmonary embolism was 0.41%.4 The risk of serious bleeding complications has been described in a nonselected group of total hip and knee arthroplasty patients given the ACCP 1-A level recommended 10day course of low-molecular-weight heparin.5 In this study of 290 patients, major bleeding occurred in 9% of patients, with 4.7% requiring readmission. Efficacy of this protocol was also questioned, as symptomatic deep-vein thrombosis occurred in 3.8% and nonfatal, symptomatic pulmonary embolism occurred in 1.3%. A recent study showed that patients who return to the operating room within 30 days after total knee arthroplasty for evacuation of a postoperative hematoma are at significantly increased risk for the development of deep infection or other major surgery.6
AAOS Guidelines Rationale and Methodology The primary concerns of orthopedic surgeons after total hip and knee arthroplasty are the prevention of fatal and nonfatal symptomatic pulmonary embolism and minimizing serious joint bleeding and wound drainage that adversely affect the patient’s outcome. The AAOS formed a working group in 2006 to develop a consensus guideline for the prevention of symptomatic pulmonary embolism after total hip and total knee arthroplasty.7-9 The working group comprised 8 members of the AAOS with known expertise in the field. The
231 group consulted an evidence review team from the Center for Clinical Evidence Synthesis at Tufts-New England Medical Center, which has assisted other medical specialty groups with the development of guidelines. The key goals or questions were to determine the rates of fatal and symptomatic pulmonary embolism after total hip and knee arthroplasty with several interventions (aspirin, warfarin, low molecular weight heparins, pentasaccharides, and mechanical methods) and the rates of adverse events (bleeding or death) associated with these interventions. The evidence base, determined by a consensus of the working group, was a review of published studies that met certain strict criteria: a prospective study of hip or knee arthroplasties performed since 1996 only; a cohort study with at least 100 patients per group; or a randomized controlled trial with at least 10 patients per treatment group.9 There were no recent studies of the natural history (pulmonary embolism without prophylaxis) that included at least 1000 patients. Older studies were excluded, as the consensus of the working group was that techniques and postoperative rehabilitation had greatly changed in more recent times. The review of published data included 2713 citations from search engines and 10 other articles that the working group was aware of but had not been retrieved.10 Of these 2723 citations, only 42 articles met the previously specified criteria of the working group. Of the 42 articles, 26 articles with cohorts totalling 16,304 total hip arthroplasties and 16 articles with cohorts totalling 11,665 total knee arthroplasties were reviewed by the evidence review team. The individual studies were graded according to levels of evidence (I-V). The strength of recommendation was graded on the basis of the quality of the collection of studies from which the recommendation was derived (A-D). The reviewed studies were heterogeneous in multiple areas, including treatment doses, intensity and timing, cotreatments, and anesthetic techniques. The results of review of published data were presented as separate forest plots for total hip and knee arthroplasty.7-9 These include all pulmonary embolism after total hip and knee arthroplasty; any pulmonary embolism, fatal pulmonary embolism, and all deaths after total hip and knee arthroplasty; and major bleeding and death related to bleeding after total hip and knee arthroplasty.7-9 Conclusions from review of published data of both total hip and total knee arthroplasty patients were described together. The rate of fatal pulmonary embolism was approximately 1 per 1700 arthroplasties, and there was no difference among prophylactic methods. The rate of nonfatal pulmonary embolism was approximately 1 per 300 arthroplasties with any prophylactic method. The rate of death from bleeding was approximately 1 per 3000 arthroplasties. Major bleeding complications were more common in patients treated with systemic pharmacologic prophylaxis (REM summary estimate 1.8%, 95% confidence interval, 1.4%-2.5%) than in those treated with mechanical prophylaxis and aspirin (REM summary estimate, 0.14%, 95% confidence interval, 0.03%-0.8%). There were numerous limitations of review of published data, including clinical heterogeneity, outcome measures, and sample sizes.
P.F. Lachiewicz
232
Recommendations The AAOS guideline recommendations are derived from both the working group consensus process and review and analysis process of published data. All aspects of the guideline are to be followed, rather than selective implementation. From the working group consensus process, there are 9 recommendations (Table 1). Most important are the preoperative evaluation of the patient by the orthopedic surgeon to assess the risk of pulmonary embolism (standard or elevated, Grade III B) and the risk of bleeding complications (standard or elevated, Grade III C), another recommendation was that the patient and surgeon consider (in consultation with the anesthesiologist) the use of regional anesthesia (Grade IV C). The surgeon should consider using mechanical prophylaxis intraoperatively or immediately postoperatively (Grade III B) with continuation until discharge (Grade IV C). The AAOS guideline recommendations for postoperative medication were derived from the literature review and analysis. These recommendations are stratified into 4 groups, with choices based on both the preoperative risk assessment of pulmonary embolism and the risk for major bleeding (Table 2). The AAOS Board of Directors approved these guidelines in May 2007, and they have been published in many formats.7-9 The review and analysis of published AAOS guideline showed no important differences among the different thromboembolism prophylactic methods in terms of rate of total pulmonary embolism, rate of fatal pulmonary embolism, rate of total death, or rate of death from bleeding. The prevalence of major bleeding was very low with the combined intervention of mechanical prophylaxis and aspirin compared with the prevalence of the other pharmacologic interventions. Orthopedic surgeons should evaluate and carefully document preoperatively each patient’s risk for pulmonary embolism and major bleeding. Some examples of patients who may be at elevated risk for pulmonary embolism include those with a previous symptomatic thromboembolism, especially pulmonary embolism; those with a known heritable thrombophilia or hypercoagulable state (protein S or C deficiency); and those who cannot mobilize rapidly after surgery. Some examples of patients who may be at a higher risk for bleeding include those having revision total hip or knee arthroplasty, Table 1 AAOS Guidelines Recommendations (Consensus Process) ● Assess pre-op for PE risk (III B) ● Assess pre-op for bleeding risk (III C) ● Consider patients with contraindications for anticoagulation for IVC filter (V C) ● Consider intra-op and/or immediate post-op mechanical compression (III B) ● Consider regional anesthesia (IV C) (in consultation with anesthesiologist) ● Mechanical prophylaxis post-op (IV C) ● Rapid mobilization (V C) ● DVT/PE screening not recommended (III B) ● Educate patient on DVT/PE symptoms (V B)
Table 2 AAOS Guidelines Recommendations for Medication (Literature Review—Analysis) 1. Standard risk PE and major bleeding
2. Elevated risk PE; standard risk bleeding
3. Standard risk PE; elevated risk bleeding 4. Elevated risk PE and bleeding
Aspirin LMWH Pentasaccharide Warfarin, INR <2 (III B) (C dosing, timing) LMWH Pentasaccharide Warfarin, INR <2 (III B) (C dosing, timing) Aspirin Warfarin, INR <2 None (III C) Aspirin Warfarin, INR <2 None (III C)
or a complex primary arthroplasty with extensive soft tissue dissection; and those with a history of bleeding in other locations, such as gastrointestinal and cerebral, or with a history of a bleeding disorder.9 These examples are not exhaustive. The orthopedic surgeon should consider the overall patient risk– benefit ratio before prescribing any specific pharmacologic intervention. Some published data support preoperative risk assessment and multimodal thromboprophylaxis, the cornerstone of the AAOS guidelines. Lotke and Lonner reported the results of 3473 total knee arthroplasties treated with foot pumps and aspirin.10 High-risk patients identified preoperatively were excluded and given warfarin prophylaxis. With multimodal prophylaxis, the rate of nonfatal pulmonary embolism was 0.26% and the rate of fatal pulmonary embolism was 0.06%0.14%. Dorr et al reported preoperative assessment and use of calf compression and aspirin in 1179 total hip and knee arthroplasty patients, with no fatal pulmonary embolism and 0.25% nonfatal pulmonary embolism.11 Lachiewicz and Soileau reported 0.5% nonfatal pulmonary embolism in 856 total knee arthroplasties given calf mechanical compression and aspirin.12 Westrich et al reported 0.04% fatal and 1% nonfatal pulmonary embolism in 2592 total hip arthroplasties.13 Lachiewicz and Soileau reported 0.09% fatal and 0.7% nonfatal pulmonary embolism.14 Both of these studies used multimodal prophylaxis, including mechanical prophylaxis and aspirin.
Advantages and Disadvantages of AAOS Guidelines The AAOS guideline has encountered some criticism. In a commentary by Eikelboom et al, supporting the continued use of the ACCP guidelines for hip and knee arthroplasty patients, the use of asymptomatic deep-vein thrombosis as a valid surrogate outcome measure for pulmonary embolism was again proposed.15 There are some non-arthroplasty studies that show a parallel reduction of deep-vein thrombosis and pulmonary embolism when antithrombotic agents are
AAOS guidelines for prevention of symptomatic pulmonary embolism compared with placebo or untreated controls. However, the position of the AAOS remains that there is insufficient evidence to conclude that, in total hip and knee arthroplasty patients, asymptomatic deep-vein thrombosis meets the criterion of a valid surrogate marker. The harmful effect of treatment, especially bleeding, was also not addressed in that commentary. There are several important advantages of the AAOS guidelines. The guideline recommendations were written by the specialty organization of the orthopedic surgeons, rather than the specialty organization of physicians who provide clinical respiratory, sleep, critical care, and cardiothoracic patient care. These physicians may not appreciate the complexities of certain surgical procedures and the effect of strong pharmacologic agents on local bleeding complications and overall patient outcome. A standard regimen for postoperative care by one subspecialty group for a different specialty group may thus be a dubious contribution and may create legal implications that are difficult to ignore.2 Orthopedic surgeons have been concerned with the diagnosis and prophylaxis of venous thromboembolism after total hip and knee arthroplasty for almost 4 decades. The orthopedic specialty has resisted 1 standard regimen for all patients because of the bleeding risks of a large variety of pharmacologic agents, in favor of individualized risk– benefit analysis. The AAOS guidelines consensus recommendations include a preoperative risk assessment by the surgeon for symptomatic pulmonary embolism as standard or elevated risk and the risk for clinically relevant local bleeding complications as standard or elevated. The patients may then be grouped into 4 specific categories, and each of these has several choices for pharmacologic prophylaxis. Finally, the guideline places the greatest emphasis on the outcome measures of symptomatic pulmonary embolism and bleeding complications rather than asymptomatic deep-vein thrombosis. There are several disadvantages and criticisms of the AAOS guidelines. Although the studies dealing with total hip and total knee arthroplasty patients were analyzed separately, these 2 groups of patients are considered as 1 for the risk assessment analysis and for the recommendations for medication. Because of the lack of prospective randomized studies of symptomatic pulmonary embolism after total hip and knee arthroplasty, most of the recommendations only have a level of evidence of III or IV, rather than level I, as do the strongest recommendations of the ACCP guidelines. The AAOS guidelines do not offer any recommendations concerning prophylaxis of asymptomatic deep-vein thrombosis other than recommending against routine postoperative screening with ultrasonography. Another disadvantage is that the AAOS guideline is a relatively new document, having been approved by the Board of Directors in May 2007, while the ACCP guideline has been in existence since 1986 and a recent edition 8 was published in June 2008. Finally, the AAOS guideline has had, to date, limited influence on governmental and other agencies that propose regulations and requirements on hospitals, which may affect reimbursement for the inpatient care of total hip and knee arthroplasty patients.
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Conclusions The AAOS Clinical Guideline for the prevention of symptomatic pulmonary embolism after total hip and total knee arthroplasty is a relatively new document. To fully comply with this guideline, all the recommendations for preoperative risk assessment and intraoperative and postoperative modalities should be followed in addition to the recommendation for medication. Surgeons should carefully document the use of this guideline in the computerized medical record or hospital chart. The AAOS working group encourages future prospective, randomized, multicenter studies comparing the various interventions presently in use, as well as new pharmacologic agents, with the outcome measures of symptomatic pulmonary embolism and major bleeding. The AAOS plans a new working group to review the guideline at regular intervals in the future.
References 1. Geerts WH, Bergqvist D, Pineo GF, et al; American College of Chest Physicians: Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Ed). Chest 133:381S-453S, 2008 (6 suppl) 2. Callaghan JJ, Dorr LD, Engh GA, et al: Prophylaxis for thromboembolic disease. Recommendations from the American College of Chest Physicians—Are they appropriate for orthopaedic surgery? (Editorial). J Arthroplasty 20:273-274, 2005 3. Howie C, Hughes H, Watts AC: Venous thromboembolism associated with hip and knee replacement over a ten-year period: A populationbased study. J Bone Joint Surg Br 87:1675-1680, 2005 4. Soohoo NF, Lieberman JR, Ko CY, et al: Factors predicting complication rates following total knee replacement. J Bone Joint Surg Am 88: 480-485, 2006 5. Burnett RSJ, Clohisy JC, Wright RW, et al: Failure of the American College of Chest Physicians––1A protocol for Lovenox in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty 22:317-324, 2007 6. Galat DD, McGovern SC, Hanssen AD, et al: Early return to surgery for evacuation of a postoperative hematoma after primary total knee arthroplasty. J Bone Joint Surg Am 90:2331-2336, 2008 7. Haas SB, Barrack RL, Westrich G, et al: Venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg Am 90: 2764-2780, 2008 8. Johanson NA, Lachiewicz PF, Lieberman JR, et al: Prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty. J Am Acad Orthop Surg 17:183-196, 2009 9. Lachiewicz PF: Prevention of symptomatic pulmonary embolism in patients undergoing total hip and knee arthroplasty: Clinical guideline of the American Academy of Orthopaedic Surgeons, in Azar F, O’Connor M (eds): Instructional Course Lectures, Volume 58. Rosemont, IL, American Academy of Orthopedic Surgeons, 2009, pp 795804 10. Lotke PA, Lonner JH: The benefit of aspirin chemoprophylaxis for thromboembolism after total knee arthroplasty. Clin Orthop Relat Res 452:175-180, 2006 11. Dorr LD, Gendelman V, Maheshwari AV, et al: Multimodal thromboprophylaxis for total hip and knee arthroplasty based on risk assessment. J Bone Joint Surg Am 89:2648-2657, 2007 12. Lachiewicz PF, Soileau ES: Mechanical calf compression and aspirin prophylaxis for total knee arthroplasty. Clin Orthop 464:61-64, 2007
234 13. Westrich GH, Farrell C, Bono JV, et al: The incidence of venous thromboembolism after total hip arthroplasty: A specific hypotensive anesthesia protocol. J Arthroplasty 14:456-463, 1999 14. Lachiewicz PF, Soileau ES: Multimodal prophylaxis for THA with mechanical compression. Clin Orthop 453:225-230, 2006
P.F. Lachiewicz 15. Eikelboom JW, Karthikeyan G, Fagel N, et al: American Association of Orthopedic Surgeons and American College of Chest Physicians guidelines for venous thromboembolism prevention in hip and knee arthroplasty differ. What are the implications for clinicians and patients? Chest 135:513-520, 2009
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linical guidelines in medicine have been devised to standardize and improve patient care for a variety of disorders. A clinical guideline addresses key clinical problems or questions, and has a defined evidence base and strength of recommendations. These recommendations are reached by both a review of available medical literature and, when no such data exist, through a consensus process of experts in the field. A clinical guideline should also encourage and guide future research in the field. It is important to remember that a clinical guideline is not a predefined protocol or dogmatic statement that is incapable of changing, nor is it a substitute for sound clinical judgment. There are now 3 clinical guidelines for venous thromboembolism prophylaxis after total
*Section of Orthopaedics, Department of Surgery, Duke University School of Medicine, Durham VA Medical Center, Durham, NC, USA. †Chapel Hill Orthopedics Surgery & Sports Medicine, Chapel Hill, NC, USA. Address reprint requests to Paul F. Lachiewicz, MD, Section of Orthopaedics, Department of Surgery, Duke University School of Medicine, Durham VA Medical Center, 508 Fulton Street, Durham, NC 27705. E-mail: [email protected]
230
1045-4527/09/$-see front matter Published by Elsevier Inc. doi:10.1053/j.sart.2009.10.006
hip and knee arthroplasty. These are the guidelines of the American College of Chest physicians (ACCP), Surgical Care Improvement Project, and most recently, the American Academy of Orthopedic Surgeons (AAOS). This article will describe the AAOS clinical guideline: Prevention of Symptomatic Pulmonary Embolism in Patients undergoing Total Hip or Knee Arthroplasty and discuss its advantages and disadvantages.
Orthopedic Concerns with ACCP Guidelines Orthopedic surgeons who perform total hip and knee arthroplasty have been impacted by the American College of Chest Physicians guidelines for the prevention of deep-vein thrombosis, with the most recent edition 8 published in June 2008.1 Deep venous thrombosis, detected by venography or ultrasonography, was the primary outcome measure in the development of these guidelines. The strongest or Grade 1-A recommendations are based on data from only prospective, randomized studies, with most of these comparing the effi-
AAOS guidelines for prevention of symptomatic pulmonary embolism cacy of one pharmacologic agent to another or to a placebo. Few studies were related to mechanical or multimodal (combined) prophylaxis. Surgical patients are grouped as “low,” “medium,” or “high” risk, but all total hip and knee arthroplasty patients are considered “high” risk, despite patient age, activity level, or comorbidities. Several orthopedic surgeons have voiced concerns with the ACCP guidelines, which emphasize prophylaxis with strong pharmacologic agents.2 Asymptomatic thrombi, detected by venography or ultrasonography, are considered as important an outcome as symptomatic thromboembolism. Only data from prospective, randomized studies were used to obtain a Grade 1-A recommendation. Thus, the data from even large (⬎1000 patient) cohort studies of 1 prophylactic method or multimodal prophylaxis cannot be given or obtain a Grade 1-A recommendation. Because prospective, randomized studies of pharmaceutical agent efficacy include only carefully selected patients with few comorbidities, these guidelines may not be applicable to the wide spectrum of patients undergoing total hip or knee arthroplasty. The ACCP guidelines appear to underestimate the risks of bleeding complications and other adverse outcomes, such as prolonged wound drainage or deep infection, related to the use of pharmacologic anticoagulants.2 Symptomatic pulmonary embolism is relatively rare after total hip or knee arthroplasty. The 90-day rate of fatal pulmonary embolism was 0.22% after 44,785 total hip arthroplasties and 0.15% after 27,000 total knee arthroplasties in the Scottish Registry.3 In a review of over 200,000 total knee arthroplasties in a California database, the 90-day rate of symptomatic pulmonary embolism was 0.41%.4 The risk of serious bleeding complications has been described in a nonselected group of total hip and knee arthroplasty patients given the ACCP 1-A level recommended 10day course of low-molecular-weight heparin.5 In this study of 290 patients, major bleeding occurred in 9% of patients, with 4.7% requiring readmission. Efficacy of this protocol was also questioned, as symptomatic deep-vein thrombosis occurred in 3.8% and nonfatal, symptomatic pulmonary embolism occurred in 1.3%. A recent study showed that patients who return to the operating room within 30 days after total knee arthroplasty for evacuation of a postoperative hematoma are at significantly increased risk for the development of deep infection or other major surgery.6
AAOS Guidelines Rationale and Methodology The primary concerns of orthopedic surgeons after total hip and knee arthroplasty are the prevention of fatal and nonfatal symptomatic pulmonary embolism and minimizing serious joint bleeding and wound drainage that adversely affect the patient’s outcome. The AAOS formed a working group in 2006 to develop a consensus guideline for the prevention of symptomatic pulmonary embolism after total hip and total knee arthroplasty.7-9 The working group comprised 8 members of the AAOS with known expertise in the field. The
231 group consulted an evidence review team from the Center for Clinical Evidence Synthesis at Tufts-New England Medical Center, which has assisted other medical specialty groups with the development of guidelines. The key goals or questions were to determine the rates of fatal and symptomatic pulmonary embolism after total hip and knee arthroplasty with several interventions (aspirin, warfarin, low molecular weight heparins, pentasaccharides, and mechanical methods) and the rates of adverse events (bleeding or death) associated with these interventions. The evidence base, determined by a consensus of the working group, was a review of published studies that met certain strict criteria: a prospective study of hip or knee arthroplasties performed since 1996 only; a cohort study with at least 100 patients per group; or a randomized controlled trial with at least 10 patients per treatment group.9 There were no recent studies of the natural history (pulmonary embolism without prophylaxis) that included at least 1000 patients. Older studies were excluded, as the consensus of the working group was that techniques and postoperative rehabilitation had greatly changed in more recent times. The review of published data included 2713 citations from search engines and 10 other articles that the working group was aware of but had not been retrieved.10 Of these 2723 citations, only 42 articles met the previously specified criteria of the working group. Of the 42 articles, 26 articles with cohorts totalling 16,304 total hip arthroplasties and 16 articles with cohorts totalling 11,665 total knee arthroplasties were reviewed by the evidence review team. The individual studies were graded according to levels of evidence (I-V). The strength of recommendation was graded on the basis of the quality of the collection of studies from which the recommendation was derived (A-D). The reviewed studies were heterogeneous in multiple areas, including treatment doses, intensity and timing, cotreatments, and anesthetic techniques. The results of review of published data were presented as separate forest plots for total hip and knee arthroplasty.7-9 These include all pulmonary embolism after total hip and knee arthroplasty; any pulmonary embolism, fatal pulmonary embolism, and all deaths after total hip and knee arthroplasty; and major bleeding and death related to bleeding after total hip and knee arthroplasty.7-9 Conclusions from review of published data of both total hip and total knee arthroplasty patients were described together. The rate of fatal pulmonary embolism was approximately 1 per 1700 arthroplasties, and there was no difference among prophylactic methods. The rate of nonfatal pulmonary embolism was approximately 1 per 300 arthroplasties with any prophylactic method. The rate of death from bleeding was approximately 1 per 3000 arthroplasties. Major bleeding complications were more common in patients treated with systemic pharmacologic prophylaxis (REM summary estimate 1.8%, 95% confidence interval, 1.4%-2.5%) than in those treated with mechanical prophylaxis and aspirin (REM summary estimate, 0.14%, 95% confidence interval, 0.03%-0.8%). There were numerous limitations of review of published data, including clinical heterogeneity, outcome measures, and sample sizes.
P.F. Lachiewicz
232
Recommendations The AAOS guideline recommendations are derived from both the working group consensus process and review and analysis process of published data. All aspects of the guideline are to be followed, rather than selective implementation. From the working group consensus process, there are 9 recommendations (Table 1). Most important are the preoperative evaluation of the patient by the orthopedic surgeon to assess the risk of pulmonary embolism (standard or elevated, Grade III B) and the risk of bleeding complications (standard or elevated, Grade III C), another recommendation was that the patient and surgeon consider (in consultation with the anesthesiologist) the use of regional anesthesia (Grade IV C). The surgeon should consider using mechanical prophylaxis intraoperatively or immediately postoperatively (Grade III B) with continuation until discharge (Grade IV C). The AAOS guideline recommendations for postoperative medication were derived from the literature review and analysis. These recommendations are stratified into 4 groups, with choices based on both the preoperative risk assessment of pulmonary embolism and the risk for major bleeding (Table 2). The AAOS Board of Directors approved these guidelines in May 2007, and they have been published in many formats.7-9 The review and analysis of published AAOS guideline showed no important differences among the different thromboembolism prophylactic methods in terms of rate of total pulmonary embolism, rate of fatal pulmonary embolism, rate of total death, or rate of death from bleeding. The prevalence of major bleeding was very low with the combined intervention of mechanical prophylaxis and aspirin compared with the prevalence of the other pharmacologic interventions. Orthopedic surgeons should evaluate and carefully document preoperatively each patient’s risk for pulmonary embolism and major bleeding. Some examples of patients who may be at elevated risk for pulmonary embolism include those with a previous symptomatic thromboembolism, especially pulmonary embolism; those with a known heritable thrombophilia or hypercoagulable state (protein S or C deficiency); and those who cannot mobilize rapidly after surgery. Some examples of patients who may be at a higher risk for bleeding include those having revision total hip or knee arthroplasty, Table 1 AAOS Guidelines Recommendations (Consensus Process) ● Assess pre-op for PE risk (III B) ● Assess pre-op for bleeding risk (III C) ● Consider patients with contraindications for anticoagulation for IVC filter (V C) ● Consider intra-op and/or immediate post-op mechanical compression (III B) ● Consider regional anesthesia (IV C) (in consultation with anesthesiologist) ● Mechanical prophylaxis post-op (IV C) ● Rapid mobilization (V C) ● DVT/PE screening not recommended (III B) ● Educate patient on DVT/PE symptoms (V B)
Table 2 AAOS Guidelines Recommendations for Medication (Literature Review—Analysis) 1. Standard risk PE and major bleeding
2. Elevated risk PE; standard risk bleeding
3. Standard risk PE; elevated risk bleeding 4. Elevated risk PE and bleeding
Aspirin LMWH Pentasaccharide Warfarin, INR <2 (III B) (C dosing, timing) LMWH Pentasaccharide Warfarin, INR <2 (III B) (C dosing, timing) Aspirin Warfarin, INR <2 None (III C) Aspirin Warfarin, INR <2 None (III C)
or a complex primary arthroplasty with extensive soft tissue dissection; and those with a history of bleeding in other locations, such as gastrointestinal and cerebral, or with a history of a bleeding disorder.9 These examples are not exhaustive. The orthopedic surgeon should consider the overall patient risk– benefit ratio before prescribing any specific pharmacologic intervention. Some published data support preoperative risk assessment and multimodal thromboprophylaxis, the cornerstone of the AAOS guidelines. Lotke and Lonner reported the results of 3473 total knee arthroplasties treated with foot pumps and aspirin.10 High-risk patients identified preoperatively were excluded and given warfarin prophylaxis. With multimodal prophylaxis, the rate of nonfatal pulmonary embolism was 0.26% and the rate of fatal pulmonary embolism was 0.06%0.14%. Dorr et al reported preoperative assessment and use of calf compression and aspirin in 1179 total hip and knee arthroplasty patients, with no fatal pulmonary embolism and 0.25% nonfatal pulmonary embolism.11 Lachiewicz and Soileau reported 0.5% nonfatal pulmonary embolism in 856 total knee arthroplasties given calf mechanical compression and aspirin.12 Westrich et al reported 0.04% fatal and 1% nonfatal pulmonary embolism in 2592 total hip arthroplasties.13 Lachiewicz and Soileau reported 0.09% fatal and 0.7% nonfatal pulmonary embolism.14 Both of these studies used multimodal prophylaxis, including mechanical prophylaxis and aspirin.
Advantages and Disadvantages of AAOS Guidelines The AAOS guideline has encountered some criticism. In a commentary by Eikelboom et al, supporting the continued use of the ACCP guidelines for hip and knee arthroplasty patients, the use of asymptomatic deep-vein thrombosis as a valid surrogate outcome measure for pulmonary embolism was again proposed.15 There are some non-arthroplasty studies that show a parallel reduction of deep-vein thrombosis and pulmonary embolism when antithrombotic agents are
AAOS guidelines for prevention of symptomatic pulmonary embolism compared with placebo or untreated controls. However, the position of the AAOS remains that there is insufficient evidence to conclude that, in total hip and knee arthroplasty patients, asymptomatic deep-vein thrombosis meets the criterion of a valid surrogate marker. The harmful effect of treatment, especially bleeding, was also not addressed in that commentary. There are several important advantages of the AAOS guidelines. The guideline recommendations were written by the specialty organization of the orthopedic surgeons, rather than the specialty organization of physicians who provide clinical respiratory, sleep, critical care, and cardiothoracic patient care. These physicians may not appreciate the complexities of certain surgical procedures and the effect of strong pharmacologic agents on local bleeding complications and overall patient outcome. A standard regimen for postoperative care by one subspecialty group for a different specialty group may thus be a dubious contribution and may create legal implications that are difficult to ignore.2 Orthopedic surgeons have been concerned with the diagnosis and prophylaxis of venous thromboembolism after total hip and knee arthroplasty for almost 4 decades. The orthopedic specialty has resisted 1 standard regimen for all patients because of the bleeding risks of a large variety of pharmacologic agents, in favor of individualized risk– benefit analysis. The AAOS guidelines consensus recommendations include a preoperative risk assessment by the surgeon for symptomatic pulmonary embolism as standard or elevated risk and the risk for clinically relevant local bleeding complications as standard or elevated. The patients may then be grouped into 4 specific categories, and each of these has several choices for pharmacologic prophylaxis. Finally, the guideline places the greatest emphasis on the outcome measures of symptomatic pulmonary embolism and bleeding complications rather than asymptomatic deep-vein thrombosis. There are several disadvantages and criticisms of the AAOS guidelines. Although the studies dealing with total hip and total knee arthroplasty patients were analyzed separately, these 2 groups of patients are considered as 1 for the risk assessment analysis and for the recommendations for medication. Because of the lack of prospective randomized studies of symptomatic pulmonary embolism after total hip and knee arthroplasty, most of the recommendations only have a level of evidence of III or IV, rather than level I, as do the strongest recommendations of the ACCP guidelines. The AAOS guidelines do not offer any recommendations concerning prophylaxis of asymptomatic deep-vein thrombosis other than recommending against routine postoperative screening with ultrasonography. Another disadvantage is that the AAOS guideline is a relatively new document, having been approved by the Board of Directors in May 2007, while the ACCP guideline has been in existence since 1986 and a recent edition 8 was published in June 2008. Finally, the AAOS guideline has had, to date, limited influence on governmental and other agencies that propose regulations and requirements on hospitals, which may affect reimbursement for the inpatient care of total hip and knee arthroplasty patients.
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Conclusions The AAOS Clinical Guideline for the prevention of symptomatic pulmonary embolism after total hip and total knee arthroplasty is a relatively new document. To fully comply with this guideline, all the recommendations for preoperative risk assessment and intraoperative and postoperative modalities should be followed in addition to the recommendation for medication. Surgeons should carefully document the use of this guideline in the computerized medical record or hospital chart. The AAOS working group encourages future prospective, randomized, multicenter studies comparing the various interventions presently in use, as well as new pharmacologic agents, with the outcome measures of symptomatic pulmonary embolism and major bleeding. The AAOS plans a new working group to review the guideline at regular intervals in the future.
References 1. Geerts WH, Bergqvist D, Pineo GF, et al; American College of Chest Physicians: Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Ed). Chest 133:381S-453S, 2008 (6 suppl) 2. Callaghan JJ, Dorr LD, Engh GA, et al: Prophylaxis for thromboembolic disease. Recommendations from the American College of Chest Physicians—Are they appropriate for orthopaedic surgery? (Editorial). J Arthroplasty 20:273-274, 2005 3. Howie C, Hughes H, Watts AC: Venous thromboembolism associated with hip and knee replacement over a ten-year period: A populationbased study. J Bone Joint Surg Br 87:1675-1680, 2005 4. Soohoo NF, Lieberman JR, Ko CY, et al: Factors predicting complication rates following total knee replacement. J Bone Joint Surg Am 88: 480-485, 2006 5. Burnett RSJ, Clohisy JC, Wright RW, et al: Failure of the American College of Chest Physicians––1A protocol for Lovenox in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty 22:317-324, 2007 6. Galat DD, McGovern SC, Hanssen AD, et al: Early return to surgery for evacuation of a postoperative hematoma after primary total knee arthroplasty. J Bone Joint Surg Am 90:2331-2336, 2008 7. Haas SB, Barrack RL, Westrich G, et al: Venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg Am 90: 2764-2780, 2008 8. Johanson NA, Lachiewicz PF, Lieberman JR, et al: Prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty. J Am Acad Orthop Surg 17:183-196, 2009 9. Lachiewicz PF: Prevention of symptomatic pulmonary embolism in patients undergoing total hip and knee arthroplasty: Clinical guideline of the American Academy of Orthopaedic Surgeons, in Azar F, O’Connor M (eds): Instructional Course Lectures, Volume 58. Rosemont, IL, American Academy of Orthopedic Surgeons, 2009, pp 795804 10. Lotke PA, Lonner JH: The benefit of aspirin chemoprophylaxis for thromboembolism after total knee arthroplasty. Clin Orthop Relat Res 452:175-180, 2006 11. Dorr LD, Gendelman V, Maheshwari AV, et al: Multimodal thromboprophylaxis for total hip and knee arthroplasty based on risk assessment. J Bone Joint Surg Am 89:2648-2657, 2007 12. Lachiewicz PF, Soileau ES: Mechanical calf compression and aspirin prophylaxis for total knee arthroplasty. Clin Orthop 464:61-64, 2007
234 13. Westrich GH, Farrell C, Bono JV, et al: The incidence of venous thromboembolism after total hip arthroplasty: A specific hypotensive anesthesia protocol. J Arthroplasty 14:456-463, 1999 14. Lachiewicz PF, Soileau ES: Multimodal prophylaxis for THA with mechanical compression. Clin Orthop 453:225-230, 2006
P.F. Lachiewicz 15. Eikelboom JW, Karthikeyan G, Fagel N, et al: American Association of Orthopedic Surgeons and American College of Chest Physicians guidelines for venous thromboembolism prevention in hip and knee arthroplasty differ. What are the implications for clinicians and patients? Chest 135:513-520, 2009