- Email: [email protected]
Thrombosis Incidence in Unilateral vs. Simultaneous Bilateral Total Knee Arthroplasty with Compression Device Prophylaxis
The Journal of Arthroplasty 28 (2013) 474–478
Contents lists available at SciVerse ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Thrombosis Incidence in Unilateral vs. Simultaneous Bilateral Total Knee Arthroplasty with Compression Device Prophylaxis Yadin D. Levy MD a, Mary E. Hardwick MSN a, Steven N. Copp MD b, Adam S. Rosen DO b, Clifford W. Colwell Jr. MD a a b
Shiley Center for Orthopaedic Research & Education at Scripps Clinic, La Jolla, California Division of Orthopaedics, Scripps Clinic, La Jolla, California
a r t i c l e
i n f o
Article history: Received 30 January 2012 Accepted 5 August 2012 Keywords: simultaneous bilateral total knee arthroplasty unilateral total knee arthroplasty thrombosis mobile compression device
a b s t r a c t This study compares the incidence of venous thromboembolic event (VTE) in 55 patients (110 knees) undergoing simultaneous bilateral TKA with 287 patients (287 knees) undergoing unilateral TKA using a mobile compression device as monotherapy prophylaxis in both groups. All patients were clinically evaluated 3 months after surgery with symptomatic confirmed VTE as an endpoint. Deep venous thrombosis (DVT) was documented by duplex ultrasound and pulmonary embolism (PE) was documented by spiral CT. The simultaneous bilateral TKA group had 6 VTEs (10.9%) with 2 PEs (3.6%). The unilateral TKA group had 9 VTEs (3.1%), and 0 PE. Patients undergoing simultaneous bilateral TKA yielded more than twice the rate of VTE compared with patients undergoing unilateral TKA using a mobile compression device as sole thromboprophylactic modality. © 2013 Elsevier Inc. All rights reserved.
Background Total knee arthroplasty (TKA) is a successful procedure that significantly improves the quality of the patient's life. The estimated number of TKAs performed annually in the USA is more than 500,000 and more than 1 million in Europe. TKA can be performed as a unilateral, a staged bilateral or a simultaneous bilateral procedure. Though controversial, simultaneous bilateral TKA can possess advantages for both patients and surgeons. These advantages include single hospital admission, one anesthetic session, treatment of bilateral knee disease, alleviating pain and shorter recovery/rehabilitation time [1]. Venous thromboembolic events (VTEs) are a common and potentially fatal complication in patients undergoing TKA. Previous studies have shown that the rate of VTE in patients undergoing TKA without any prophylaxis can be as high as 88% [2,3]. Prophylaxis can reduce the rate of VTE, which includes deep vein thrombosis (DVT) and / or pulmonary emboli (PE). Consequently, prophylaxis has become the standard of care following TKA [4]. Prophylaxis can be achieved with the use of chemotherapeutic agents or mechanical devices. Several prophylactic antithrombotic agents including, low molecular heparin [5], warfarin [6], fondaparinux [7] and the new oral anticoagulant drugs dabigatran and rivaroxaban [8] are effective in
patients undergoing arthroplasty. Although chemical prophylaxis reduces the VTE rate, it increases the risk for bleeding complications, which deters many surgeons from using this form of prophylaxis. These concerns have resulted in an increase in use of mechanical prophylaxis. Intermittent pneumatic compression devices have been found to decrease venous stasis, accelerate emptying of the venous system [9,10], and increase systemic and local fibrinolysis [11,12]. The absolute risk of thromboembolic events after simultaneous bilateral TKA is still in question. Several studies show a higher VTE rate in patients undergoing bilateral TKA compared with patients undergoing unilateral TKA [13–15]. Other studies show similar DVT rates following simultaneous TKA [16,17] and others show lower rates [18,19]. Recent publications on patients undergoing unilateral arthroplasty utilizing a mobile compression device report VTE rates similar to those of patients utilizing chemical prophylaxis [20,21]. However the literature lacks reports on patients undergoing simultaneous bilateral TKA using mechanical devices as a sole prophylaxis. In light of the aforementioned, we investigated and report on the VTE rate in patients undergoing simultaneous bilateral TKA compared with patients undergoing unilateral TKA using a mobile compression device as monotherapy for VTE prophylaxis. Methods
The Conflict of Interest statement associated with this article can be found at http:// dx.doi.org/10.1016/j.arth.2012.08.002. Reprint requests: Clifford W. Colwell, Jr., MD, Shiley Center for Orthopaedic Research & Education at Scripps Clinic, 11025 North Torrey Pines Road, Suite 200, La Jolla, CA 92037. 0883-5403/2803-0017$36.00/0 – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.arth.2012.08.002
Study Design This was a retrospective non-randomized study evaluating consecutive patients at a single medical center. The study was
Y.D. Levy et al. / The Journal of Arthroplasty 28 (2013) 474–478
475
designed to compare the VTE rates of patient undergoing simultaneous bilateral TKA with rates of patients undergoing unilateral TKA using a mobile compression device as a monotherapy for VTE prophylaxis.
Patient Selection Following approval from our Institutional Review Board we retrospectively reviewed charts of consecutive patients undergoing TKA. All surgeries were performed between January 2009 and June 2011 at a single medical center. Inclusion criteria included patients older than eighteen and undergoing primary TKA. Exclusion criteria included a history of VTE, a known coagulation disorder, major surgery in the preceding three months and undergoing staged bilateral surgery. We identified 342 patients who met our study criteria. Of those 55 patients (110 knees) underwent simultaneous bilateral TKA and 287 patients (287 knees) underwent unilateral TKA. The indications for bilateral TKA surgery were the presence of bilateral knee disease and failure of prior conservative therapy, the patient's desire to undergo simultaneous bilateral TKA, and satisfactory health to undergo a simultaneous surgical procedure. The indication for unilateral TKA was the presence of unilateral knee disease refractory to conservative therapy.
Treatment Protocol Patients in both groups were treated with a mobile compression device plus synchronized flow technology (Active Care+SFT®; Medical Compression Systems, Or Akiva, Israel) as monotherapy for VTE prophylaxis. In the unilateral group, prophylaxis of the unoperated leg was initiated immediately after induction of anesthesia utilizing a calf sleeve. In the operated leg of the unilateral group and in the simultaneous bilateral TKA group, prophylaxis was initiated with the use of calf sleeve immediately after skin closure. Treatment was continued for ten days following surgery. This included time in the hospital and post-discharge to home or to an extended care facility. Details regarding the device and its performance in clinical trials have been previously reported [20–22]. The device used in this study is small, mobile and light weight (0.74-kg or 1.6 lb). The device is battery operated, can hold up to six hours of operation, and recharges when attached to an external power source with an AC adapter. The device can be carried with a shoulder strap (Fig.) and delivers continuous therapy to the patient throughout the recovery whether ambulatory or at bed rest. This mobile compression device functions in synchronization with the patient respiratory phase. The device monitors respiratory related venous phasic flow and generates the compression with this flow. The device does not pump during inspiration with low right heart filling, but pumps during the expiratory phase with greater right heart filling. This in turn increases the peak venous velocity and decreases venous stasis.
Surgical Procedure and Post Operative Management All patients underwent cemented TKA using medial parapatellar approach, under tourniquet. All surgeries were performed by two surgeons (SNC, ASR). In the bilateral group, surgery was performed by the same team in consecutive fashion under the same anesthesia. The postoperative physiotherapy protocol was identical in the two groups. Physiotherapy was initiated on postoperative day one. Treatment was focused on early mobilization of the patients out of the bed, full weight bearing ambulation, quadriceps strengthening, and range of motion exercises.
Fig. Patient ambulating while wearing the lightweight miniature mobile compression device.
Outcomes The primary outcome measure was the incidence of VTE events in both groups. Throughout their hospitalization the patients were monitored for any clinical signs and symptoms of DVT or PE. After patients were discharged home or to an extended care facility, they continued their treatment with the mobile compression device for a total period of ten days. All patients were clinically evaluated by the surgeon at time of hospital discharge, at one month, and at three months after surgery documenting any VTE events as an endpoint. Clinical symptoms of DVT were increased swelling, tenderness and redness over what one would expect following a total knee replacement. PE symptoms included unexpected tachypnea, tachycardia, drop in blood pressure, or significant change in anemia. Patients with clinical suspicion of DVT underwent duplex ultrasonography of both legs. Patients with clinical suspicion of PE were evaluated with spiral CT of the lungs. Each VTE event was recorded separately. Standard protocol for a diagnosed proximal DVT or PE was treatment with anticoagulant (low molecular heparin and warfarin). Standard protocol for a diagnosed distal DVT was serial duplex ultrasound and no pharmacological treatments unless thrombus progression to a proximal clot was documented. Patients diagnosed with distal DVT continued to use the compression device for a period of 10 days. Statistical Analysis Demographics of the bilateral and unilateral groups were compared by calculating means, standard deviations and frequencies. Chi-square tests were used to assess group differences in categorical
476
Y.D. Levy et al. / The Journal of Arthroplasty 28 (2013) 474–478
Table 1 Patients’ Demographics in the Bilateral and Unilateral Groups.
Mean age (years) Mean BMI (kg/m2) Female sex (%) Diagnosis of OA (%) ASA classification (%) 2 — Mild systemic disease 3 — Severe systemic disease Mean duration of surgery (min) Mean length of hospital stay (days)
Simultaneous Bilateral TKA Unilateral TKA (N=58 ) (N=287)
P Value
67.3±9.9 30.7±6.3 50 % 99.1 %
69.1±9.6 29.8±5.8 56.1 % 93.9 %
0.08 0.2 0.26 0.25 0.84
53.8 % 46.2 % 169±37
50 % 50 % 84±14
0.00
3.35±0.8 days
2.9±0.6 days
0.00
variables and independent t-tests were used to compare continuous variables. For calculation of the VTE rate each DVT or PE event was recorded separately. We calculated the VTE rates both per knee and per patient. Chi-square tests and Fisher's exact test (when appropriate) were used to compare VTE incidence rates between the bilateral and unilateral groups. A p-value of 0.05 was used to determine statistical significance. Results Demographics were similar between the two groups, except for the length of surgery, the length of hospital stay, and the discharge disposition, which showed a statistically significant difference between the two groups (Table 1). Diagnosis was predominantly OA in both groups. The American Society of Anesthesiologists (ASA) classification was evenly divided between 2 and 3 in both groups. The incidence of VTE was greater in the bilateral TKA group than in the unilateral TKA group (Table 2). One patient undergoing unilateral TKA died on post operative day 3. This patient had a history of congestive heart failure, coronary artery disease with myocardial infarction, and multiple co-morbidities. During the post operative period the patient was 100% compliant with the compression device with no apparent difficulties. The cause of death was summarized as acute cardiopulmonary arrest with subsequent death; however, no autopsy was performed. No other deaths occurred in either group. PE events were documented in only two patients both undergoing simultaneous bilateral surgery. Diagnosis was established with clinical symptoms and confirmed with chest spiral CT scan. Of those two patients, one was diagnosed with concomitant proximal and distal DVT while the other was diagnosed with PE only. Both patients were further treated initially with LMWH and warfarin. Upon reaching target warfarin levels in the blood LMWH was discontinued. Neither patient had any further sequelae. In the bilateral group, all of the patients diagnosed with DVT had bilateral leg involvement. In the unilateral group, thrombi were diagnosed in the operated leg of eight patients while bilateral involvement was documented in one patient.
In both groups all the patients diagnosed with VTE had a general anesthesia with a regional femoral block. In the bilateral group one patient also had a single intrathecal morphine injection. No serious complications were reported from the use of the device; however, one patient reported discomfort using the device and his therapy was switched to low-molecular-weight heparin. Discussion In this study we found that the VTE rates were more than twice as high in patients undergoing simultaneous bilateral TKA than in unilateral TKA patients using a mobile mechanical compression device as the sole prophylaxis for VTE. PE and proximal DVT occurred only in patients undergoing simultaneous bilateral TKA with none in the unilateral TKA group. However, based on the small number in this unilateral population we cannot make any recommendation on the use of this device in unilateral total knee patients. A variety of chemical and mechanical prophylactic methods are recommended for VTE prevention in patients undergoing TKA [23,24]. The American Academy of Orthopedic Surgeons and the American College of Chest Physicians have published guidelines for VTE prevention in patients undergoing TKA [25,26]. However, neither guideline offers specific recommendations for patients undergoing simultaneous bilateral TKA. Surgeons commonly use similar approaches to prophylaxis for patients undergoing simultaneous bilateral TKA as is used for patients undergoing unilateral TKA procedures. Two PE events (3.4%) were documented in two patients undergoing bilateral TKA and no PE events in patients undergoing unilateral TKA. The risk of PE following bilateral TKA is controversial with several studies reporting higher PE rates than in unilateral TKA [27– 29]. Barrett et al. [30] reviewed 122,385 USA Medicare patients who underwent TKA. Of those, 96,065 patients underwent unilateral TKA and 8324 patients had undergone simultaneous bilateral TKA. The remainder of the patients underwent staged bilateral TKA. Using the ICD-9 code and making actuarial projections to estimate the PE rate, they found that the probability of a PE developing in the first three months after simultaneous bilateral TKA and unilateral TKA was 1.44% and 0.81%, respectively. Memtsoudis et al. [31] studied the outcomes after bilateral and unilateral TKA in nationwide inpatient sample (670,305 patients) and found the PE rate of patients undergoing simultaneous bilateral TKA and patients undergoing unilateral TKA to be 0.82% and 0.39%, respectively. Thus, these large cohort studies indicate that the risk of PE after simultaneous bilateral TKA appears to be double the risk of PE after unilateral TKA. These studies did not specify the method of VTE prophylaxis used or even whether VTE prophylaxis was used. Bullock et al. [18] reported on patients undergoing TKA and utilizing LMWH or warfarin for prophylaxis. The PE rate of patients undergoing simultaneous bilateral TKA was 0.39% while the rate for patients undergoing unilateral TKA was 0%. By contrast, other studies did not find a statistical difference in the incidence of PE between the two groups [16,32–34]. Morrey et al. [16] found a similar PE rate (1%) for patients
Table 2 Incidence of VTE in the Bilateral and Unilateral Groups. Rate Per Patient Bilateral (N=58)
Total VTEs Total DVTs Proximal Distal Total PEs
Rate Per Knee
Unilateral (N=287)
N
%
N
%
9 7 1 6 2
12.1% 10.3% 1.7% 10.3% 3.4%
9 9 9 -
3.1 % 3.1 % 3.1 % -
P value 0.003 0.014
0.002
Rates are reported per number of patients and number of knees. ⁎ One patient undergoing unilateral TKA had a DVT in both legs, counted as two thromboses.
Bilateral (N=116)
Unilateral (N=287)
N
%
N
%
13 11 1 10 2
11.2% 9.5% 0.9% 8.6% 1.7%
10⁎ 10⁎ 10⁎
3.1 % 3.1 % 3.1 % -
-
P Value 0.008 0.019
0.028
Y.D. Levy et al. / The Journal of Arthroplasty 28 (2013) 474–478
undergoing simultaneous bilateral TKA (145 patients) and unilateral TKA (501 patients). Larson et al. [33] report a PE rate of zero in patients undergoing simultaneous bilateral TKA treated with a knee-high intermittent compression device combined with 650mg aspirin twice daily. Our study is in concordance with studies reporting a higher incidence of PE in patients undergoing bilateral simultaneous TKA compared with unilateral TKA whatever method of prophylaxis was used. Only one patient in either group had a proximal DVT. This patient in the simultaneous bilateral TKA group also had a distal DVT and a PE. None of the patients undergoing unilateral procedures were diagnosed with proximal DVT or PE. The rate of distal DVT was 5.5% (3 of 55 patients) in the bilateral group and 3.1% (9 of 287 patients) in the unilateral group. The current literature lacks reports on patients who underwent simultaneous bilateral TKA, utilized mechanical compression devices as a monotherapy for VTE prophylaxis and were evaluated only if they showed clinical symptoms. Hass et al. [35] evaluated 47 patients who underwent staged bilateral TKA and 72 patients who underwent unilateral TKA. Both groups received prophylaxis either with aspirin or with pneumatic sequential compression boots. Thrombi formation was evaluated with bilateral venography performed between post operative days four to six. The VTE rate of patients treated only with the compression device and underwent staged bilateral TKA and unilateral TKA was 48% and 22%, respectively. The rate for patients treated with aspirin was higher, 68% and 47%, respectively. Larson et al. reported a DVT rate of 12.5% per patient and a rate of 6.3% per knee in patients undergoing simultaneous bilateral TKA and screened by duplex ultrasound. Prophylaxis was provided perioperatively with a knee-high intermittent compression device combined with 650 mg aspirin twice daily. Lachiewicz et al. [36] used intermittent compression devices and aspirin as prophylaxis following bilateral and unilateral primary or revision TKA. Patients were screened with duplex prior to discharge. The reported DVT rate was 9.3% in the entire cohort. No specific rate was provided for patients undergoing simultaneous bilateral TKA. Our DVT rate of 12.1% in the bilateral group is lower than the results of the study evaluating patients with venography and comparable with those other studies that screened the patients with duplex ultrasound. This study used clinical assessment followed by duplex to screen for DVT, which will miss asymptomatic clots. The three month clinical follow-up in this patient population identifies the consequences of missing asymptomatic clots. The lack of literature evaluating patients only with clinical symptoms prevents comparison with our results. Another possible explanation for the high DVT rate in our bilateral TKA group may be the time the therapy was initiated. For the bilateral TKA group, therapy was started only after the surgery had been completed in both legs. In the unilateral group prophylaxis was initiated at the induction of anesthesia in the form of a calf sleeve on the non-operated side. This raises the question whether use of a calf sleeve on the non-operated leg at time of surgery can help prevent thrombi formation. This requires further study. Conclusion The rate of VTE in patients undergoing simultaneous bilateral TKA was increased more than two-fold compared with patients undergoing unilateral TKA using a mobile compression device as the sole thromboprophylactic modality. A future study will be necessary to verify that use of additional pharmacologic agents or use of pharmacological agents alone would improve this outcome. Acknowledgments The authors thank Julie C. McCauley, MPHc, for assistance in managing the data and statistics.
477
References 1. Powell RS, Pulido P, Tuason MS, et al. Bilateral vs unilateral total knee arthroplasty: a patient-based comparison of pain levels and recovery of ambulatory skills. J Arthroplasty 2006;21(5):642. 2. Sculco TP. Establishing a universal protocol for deep vein thrombosis following orthopedic surgery: total knee arthroplasty. Orthopedics 1996; 19(Suppl):6. 3. McKenna R, Bachmann F, Kaushal SP, et al. Thromboembolic disease in patients undergoing total knee replacement. J Bone Joint Surg Am 1976;58(7):928. 4. 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 2009;135(2):513. 5. Fitzgerald Jr RH, Spiro TE, Trowbridge AA, et al. Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin. J Bone Joint Surg Am 2001;83-A(6):900. 6. Robinson KS, Anderson DR, Gross M, et al. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the postarthroplasty screening study. A randomized, controlled trial. Ann Intern Med 1997;127(6):439. 7. Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332(7537):325. 8. Friedman RJ. Novel oral anticoagulants for VTE prevention in orthopedic surgery: overview of phase 3 trials. Orthopedics 2011;34(10):795. 9. Sculco TP, Bottner F. Current concepts of nonpharmacologic thromboembolic prophylaxis. Instr Course Lect 2002;51:481. 10. Jacobs DG, Piotrowski JJ, Hoppensteadt DA, et al. Hemodynamic and fibrinolytic consequences of intermittent pneumatic compression: preliminary results. J Trauma 1996;40(5):710. 11. Vanhoutte PM, Boulanger CM, Mombouli JV. Endothelium-derived relaxing factors and converting enzyme inhibition. Am J Cardiol 1995;76(15):3E. 12. Allenby F, Boardman L, Pflug JJ, et al. Effects of external pneumatic intermittent compression on fibrinolysis in man. Lancet 1973;2(7843):1412. 13. Stulberg BN, Insall JN, Williams GW, et al. Deep-vein thrombosis following total knee replacement. An analysis of six hundred and thirty-eight arthroplasties. J Bone Joint Surg Am 1984;66(2):194. 14. Mantilla CB, Horlocker TT, Schroeder DR, et al. Frequency of myocardial infarction, pulmonary embolism, deep venous thrombosis, and death following primary hip or knee arthroplasty. Anesthesiology 2002;96(5):1140. 15. March LM, Cross M, Tribe KL, et al. Two knees or not two knees? Patient costs and outcomes following bilateral and unilateral total knee joint replacement surgery for OA. Osteoarthritis Cartilage 2004;12(5):400. 16. Morrey BF, Adams RA, Ilstrup DM, et al. Complications and mortality associated with bilateral or unilateral total knee arthroplasty. J Bone Joint Surgery Am 1987;69(4):484. 17. Luscombe JC, Theivendran K, Abudu A, et al. The relative safety of one-stage bilateral total knee arthroplasty. Int Orthop 2009;33(1):101. 18. Bullock DP, Sporer SM, Shirreffs Jr TG. Comparison of simultaneous bilateral with unilateral total knee arthroplasty in terms of perioperative complications. J Bone Joint Surg Am 1981;85-A(10):2003. 19. Restrepo C, Parvizi J, Dietrich T, et al. Safety of simultaneous bilateral total knee arthroplasty. A meta-analysis. J Bone Joint Surg Am 2007;89(6):1220. 20. Colwell Jr CW, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am 2010; 92(3):527. 21. Gelfer Y, Tavor H, Oron A, et al. Deep vein thrombosis prevention in joint arthroplasties: continuous enhanced circulation therapy vs low molecular weight heparin. J Arthroplasty 2006;21(2):206. 22. Froimson MI, Murray TG, Fazekas AF. Venous thromboembolic disease reduction with a portable pneumatic compression device. J Arthroplasty 2009; 24(2):310. 23. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest 2001;119(1 Suppl):132S. 24. Bottner F, Sculco TP. Nonpharmacologic thromboembolic prophylaxis in total knee arthroplasty. Clin Orthop Relat Res 2001(392):249. 25. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008;133(6 Suppl):381S. 26. AAOS Workgroup Jacobs JJ, Bozic KJ, et al. Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty: evidence-based guideline and evidence report. AAOS clinical practice guidelines unit. Rosemont, IL: AAOS; 2011:43. 27. Lombardi AV, Mallory TH, Fada RA, et al. Simultaneous bilateral total knee arthroplasties: who decides? Clin Orthop Relat Res 2001(392):319. 28. Lane GJ, Hozack WJ, Shah S, et al. Simultaneous bilateral versus unilateral total knee arthroplasty. Outcomes analysis. Clin Orthop Relat Res 1997(345):106. 29. Adili A, Bhandari M, Petruccelli D, et al. Sequential bilateral total knee arthroplasty under 1 anesthetic in patients N or = 75 years old: complications and functional outcomes. J Arthroplasty 2001;16(3):271. 30. Barrett J, Baron JA, Losina E, et al. Bilateral total knee replacement: staging and pulmonary embolism. J Bone Joint Surg Am 2006;88(10):2146.
478
Y.D. Levy et al. / The Journal of Arthroplasty 28 (2013) 474–478
31. Memtsoudis SG, Ma Y, Gonzalez Della Valle A, et al. Perioperative outcomes after unilateral and bilateral total knee arthroplasty. Anesthesiology 2009;111(6): 1206. 32. Kim YH, Choi YW, Kim JS. Simultaneous bilateral sequential total knee replacement is as safe as unilateral total knee replacement. J Bone Joint Surg Br 2009;91(1):64. 33. Larson CM, MacMillan DP, Lachiewicz PF. Thromboembolism after total knee arthroplasty: intermittent pneumatic compression and aspirin prophylaxis. J South Orthop Assoc 2001;10(3):155.
34. Kim YH, Oh SH, Kim JS. Incidence and natural history of deep-vein thrombosis after total hip arthroplasty. A prospective and randomised clinical study. J Bone Joint Surg Br 2003;85(5):661. 35. Haas SB, Insall JN, Scuderi GR, et al. Pneumatic sequential-compression boots compared with aspirin prophylaxis of deep-vein thrombosis after total knee arthroplasty. J Bone Joint Surgery Am 1990;72(1):27. 36. Lachiewicz PF, Soileau ES. Mechanical calf compression and aspirin prophylaxis for total knee arthroplasty. Clin Orthop Relat Res 2007;464:61.
Contents lists available at SciVerse ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Thrombosis Incidence in Unilateral vs. Simultaneous Bilateral Total Knee Arthroplasty with Compression Device Prophylaxis Yadin D. Levy MD a, Mary E. Hardwick MSN a, Steven N. Copp MD b, Adam S. Rosen DO b, Clifford W. Colwell Jr. MD a a b
Shiley Center for Orthopaedic Research & Education at Scripps Clinic, La Jolla, California Division of Orthopaedics, Scripps Clinic, La Jolla, California
a r t i c l e
i n f o
Article history: Received 30 January 2012 Accepted 5 August 2012 Keywords: simultaneous bilateral total knee arthroplasty unilateral total knee arthroplasty thrombosis mobile compression device
a b s t r a c t This study compares the incidence of venous thromboembolic event (VTE) in 55 patients (110 knees) undergoing simultaneous bilateral TKA with 287 patients (287 knees) undergoing unilateral TKA using a mobile compression device as monotherapy prophylaxis in both groups. All patients were clinically evaluated 3 months after surgery with symptomatic confirmed VTE as an endpoint. Deep venous thrombosis (DVT) was documented by duplex ultrasound and pulmonary embolism (PE) was documented by spiral CT. The simultaneous bilateral TKA group had 6 VTEs (10.9%) with 2 PEs (3.6%). The unilateral TKA group had 9 VTEs (3.1%), and 0 PE. Patients undergoing simultaneous bilateral TKA yielded more than twice the rate of VTE compared with patients undergoing unilateral TKA using a mobile compression device as sole thromboprophylactic modality. © 2013 Elsevier Inc. All rights reserved.
Background Total knee arthroplasty (TKA) is a successful procedure that significantly improves the quality of the patient's life. The estimated number of TKAs performed annually in the USA is more than 500,000 and more than 1 million in Europe. TKA can be performed as a unilateral, a staged bilateral or a simultaneous bilateral procedure. Though controversial, simultaneous bilateral TKA can possess advantages for both patients and surgeons. These advantages include single hospital admission, one anesthetic session, treatment of bilateral knee disease, alleviating pain and shorter recovery/rehabilitation time [1]. Venous thromboembolic events (VTEs) are a common and potentially fatal complication in patients undergoing TKA. Previous studies have shown that the rate of VTE in patients undergoing TKA without any prophylaxis can be as high as 88% [2,3]. Prophylaxis can reduce the rate of VTE, which includes deep vein thrombosis (DVT) and / or pulmonary emboli (PE). Consequently, prophylaxis has become the standard of care following TKA [4]. Prophylaxis can be achieved with the use of chemotherapeutic agents or mechanical devices. Several prophylactic antithrombotic agents including, low molecular heparin [5], warfarin [6], fondaparinux [7] and the new oral anticoagulant drugs dabigatran and rivaroxaban [8] are effective in
patients undergoing arthroplasty. Although chemical prophylaxis reduces the VTE rate, it increases the risk for bleeding complications, which deters many surgeons from using this form of prophylaxis. These concerns have resulted in an increase in use of mechanical prophylaxis. Intermittent pneumatic compression devices have been found to decrease venous stasis, accelerate emptying of the venous system [9,10], and increase systemic and local fibrinolysis [11,12]. The absolute risk of thromboembolic events after simultaneous bilateral TKA is still in question. Several studies show a higher VTE rate in patients undergoing bilateral TKA compared with patients undergoing unilateral TKA [13–15]. Other studies show similar DVT rates following simultaneous TKA [16,17] and others show lower rates [18,19]. Recent publications on patients undergoing unilateral arthroplasty utilizing a mobile compression device report VTE rates similar to those of patients utilizing chemical prophylaxis [20,21]. However the literature lacks reports on patients undergoing simultaneous bilateral TKA using mechanical devices as a sole prophylaxis. In light of the aforementioned, we investigated and report on the VTE rate in patients undergoing simultaneous bilateral TKA compared with patients undergoing unilateral TKA using a mobile compression device as monotherapy for VTE prophylaxis. Methods
The Conflict of Interest statement associated with this article can be found at http:// dx.doi.org/10.1016/j.arth.2012.08.002. Reprint requests: Clifford W. Colwell, Jr., MD, Shiley Center for Orthopaedic Research & Education at Scripps Clinic, 11025 North Torrey Pines Road, Suite 200, La Jolla, CA 92037. 0883-5403/2803-0017$36.00/0 – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.arth.2012.08.002
Study Design This was a retrospective non-randomized study evaluating consecutive patients at a single medical center. The study was
Y.D. Levy et al. / The Journal of Arthroplasty 28 (2013) 474–478
475
designed to compare the VTE rates of patient undergoing simultaneous bilateral TKA with rates of patients undergoing unilateral TKA using a mobile compression device as a monotherapy for VTE prophylaxis.
Patient Selection Following approval from our Institutional Review Board we retrospectively reviewed charts of consecutive patients undergoing TKA. All surgeries were performed between January 2009 and June 2011 at a single medical center. Inclusion criteria included patients older than eighteen and undergoing primary TKA. Exclusion criteria included a history of VTE, a known coagulation disorder, major surgery in the preceding three months and undergoing staged bilateral surgery. We identified 342 patients who met our study criteria. Of those 55 patients (110 knees) underwent simultaneous bilateral TKA and 287 patients (287 knees) underwent unilateral TKA. The indications for bilateral TKA surgery were the presence of bilateral knee disease and failure of prior conservative therapy, the patient's desire to undergo simultaneous bilateral TKA, and satisfactory health to undergo a simultaneous surgical procedure. The indication for unilateral TKA was the presence of unilateral knee disease refractory to conservative therapy.
Treatment Protocol Patients in both groups were treated with a mobile compression device plus synchronized flow technology (Active Care+SFT®; Medical Compression Systems, Or Akiva, Israel) as monotherapy for VTE prophylaxis. In the unilateral group, prophylaxis of the unoperated leg was initiated immediately after induction of anesthesia utilizing a calf sleeve. In the operated leg of the unilateral group and in the simultaneous bilateral TKA group, prophylaxis was initiated with the use of calf sleeve immediately after skin closure. Treatment was continued for ten days following surgery. This included time in the hospital and post-discharge to home or to an extended care facility. Details regarding the device and its performance in clinical trials have been previously reported [20–22]. The device used in this study is small, mobile and light weight (0.74-kg or 1.6 lb). The device is battery operated, can hold up to six hours of operation, and recharges when attached to an external power source with an AC adapter. The device can be carried with a shoulder strap (Fig.) and delivers continuous therapy to the patient throughout the recovery whether ambulatory or at bed rest. This mobile compression device functions in synchronization with the patient respiratory phase. The device monitors respiratory related venous phasic flow and generates the compression with this flow. The device does not pump during inspiration with low right heart filling, but pumps during the expiratory phase with greater right heart filling. This in turn increases the peak venous velocity and decreases venous stasis.
Surgical Procedure and Post Operative Management All patients underwent cemented TKA using medial parapatellar approach, under tourniquet. All surgeries were performed by two surgeons (SNC, ASR). In the bilateral group, surgery was performed by the same team in consecutive fashion under the same anesthesia. The postoperative physiotherapy protocol was identical in the two groups. Physiotherapy was initiated on postoperative day one. Treatment was focused on early mobilization of the patients out of the bed, full weight bearing ambulation, quadriceps strengthening, and range of motion exercises.
Fig. Patient ambulating while wearing the lightweight miniature mobile compression device.
Outcomes The primary outcome measure was the incidence of VTE events in both groups. Throughout their hospitalization the patients were monitored for any clinical signs and symptoms of DVT or PE. After patients were discharged home or to an extended care facility, they continued their treatment with the mobile compression device for a total period of ten days. All patients were clinically evaluated by the surgeon at time of hospital discharge, at one month, and at three months after surgery documenting any VTE events as an endpoint. Clinical symptoms of DVT were increased swelling, tenderness and redness over what one would expect following a total knee replacement. PE symptoms included unexpected tachypnea, tachycardia, drop in blood pressure, or significant change in anemia. Patients with clinical suspicion of DVT underwent duplex ultrasonography of both legs. Patients with clinical suspicion of PE were evaluated with spiral CT of the lungs. Each VTE event was recorded separately. Standard protocol for a diagnosed proximal DVT or PE was treatment with anticoagulant (low molecular heparin and warfarin). Standard protocol for a diagnosed distal DVT was serial duplex ultrasound and no pharmacological treatments unless thrombus progression to a proximal clot was documented. Patients diagnosed with distal DVT continued to use the compression device for a period of 10 days. Statistical Analysis Demographics of the bilateral and unilateral groups were compared by calculating means, standard deviations and frequencies. Chi-square tests were used to assess group differences in categorical
476
Y.D. Levy et al. / The Journal of Arthroplasty 28 (2013) 474–478
Table 1 Patients’ Demographics in the Bilateral and Unilateral Groups.
Mean age (years) Mean BMI (kg/m2) Female sex (%) Diagnosis of OA (%) ASA classification (%) 2 — Mild systemic disease 3 — Severe systemic disease Mean duration of surgery (min) Mean length of hospital stay (days)
Simultaneous Bilateral TKA Unilateral TKA (N=58 ) (N=287)
P Value
67.3±9.9 30.7±6.3 50 % 99.1 %
69.1±9.6 29.8±5.8 56.1 % 93.9 %
0.08 0.2 0.26 0.25 0.84
53.8 % 46.2 % 169±37
50 % 50 % 84±14
0.00
3.35±0.8 days
2.9±0.6 days
0.00
variables and independent t-tests were used to compare continuous variables. For calculation of the VTE rate each DVT or PE event was recorded separately. We calculated the VTE rates both per knee and per patient. Chi-square tests and Fisher's exact test (when appropriate) were used to compare VTE incidence rates between the bilateral and unilateral groups. A p-value of 0.05 was used to determine statistical significance. Results Demographics were similar between the two groups, except for the length of surgery, the length of hospital stay, and the discharge disposition, which showed a statistically significant difference between the two groups (Table 1). Diagnosis was predominantly OA in both groups. The American Society of Anesthesiologists (ASA) classification was evenly divided between 2 and 3 in both groups. The incidence of VTE was greater in the bilateral TKA group than in the unilateral TKA group (Table 2). One patient undergoing unilateral TKA died on post operative day 3. This patient had a history of congestive heart failure, coronary artery disease with myocardial infarction, and multiple co-morbidities. During the post operative period the patient was 100% compliant with the compression device with no apparent difficulties. The cause of death was summarized as acute cardiopulmonary arrest with subsequent death; however, no autopsy was performed. No other deaths occurred in either group. PE events were documented in only two patients both undergoing simultaneous bilateral surgery. Diagnosis was established with clinical symptoms and confirmed with chest spiral CT scan. Of those two patients, one was diagnosed with concomitant proximal and distal DVT while the other was diagnosed with PE only. Both patients were further treated initially with LMWH and warfarin. Upon reaching target warfarin levels in the blood LMWH was discontinued. Neither patient had any further sequelae. In the bilateral group, all of the patients diagnosed with DVT had bilateral leg involvement. In the unilateral group, thrombi were diagnosed in the operated leg of eight patients while bilateral involvement was documented in one patient.
In both groups all the patients diagnosed with VTE had a general anesthesia with a regional femoral block. In the bilateral group one patient also had a single intrathecal morphine injection. No serious complications were reported from the use of the device; however, one patient reported discomfort using the device and his therapy was switched to low-molecular-weight heparin. Discussion In this study we found that the VTE rates were more than twice as high in patients undergoing simultaneous bilateral TKA than in unilateral TKA patients using a mobile mechanical compression device as the sole prophylaxis for VTE. PE and proximal DVT occurred only in patients undergoing simultaneous bilateral TKA with none in the unilateral TKA group. However, based on the small number in this unilateral population we cannot make any recommendation on the use of this device in unilateral total knee patients. A variety of chemical and mechanical prophylactic methods are recommended for VTE prevention in patients undergoing TKA [23,24]. The American Academy of Orthopedic Surgeons and the American College of Chest Physicians have published guidelines for VTE prevention in patients undergoing TKA [25,26]. However, neither guideline offers specific recommendations for patients undergoing simultaneous bilateral TKA. Surgeons commonly use similar approaches to prophylaxis for patients undergoing simultaneous bilateral TKA as is used for patients undergoing unilateral TKA procedures. Two PE events (3.4%) were documented in two patients undergoing bilateral TKA and no PE events in patients undergoing unilateral TKA. The risk of PE following bilateral TKA is controversial with several studies reporting higher PE rates than in unilateral TKA [27– 29]. Barrett et al. [30] reviewed 122,385 USA Medicare patients who underwent TKA. Of those, 96,065 patients underwent unilateral TKA and 8324 patients had undergone simultaneous bilateral TKA. The remainder of the patients underwent staged bilateral TKA. Using the ICD-9 code and making actuarial projections to estimate the PE rate, they found that the probability of a PE developing in the first three months after simultaneous bilateral TKA and unilateral TKA was 1.44% and 0.81%, respectively. Memtsoudis et al. [31] studied the outcomes after bilateral and unilateral TKA in nationwide inpatient sample (670,305 patients) and found the PE rate of patients undergoing simultaneous bilateral TKA and patients undergoing unilateral TKA to be 0.82% and 0.39%, respectively. Thus, these large cohort studies indicate that the risk of PE after simultaneous bilateral TKA appears to be double the risk of PE after unilateral TKA. These studies did not specify the method of VTE prophylaxis used or even whether VTE prophylaxis was used. Bullock et al. [18] reported on patients undergoing TKA and utilizing LMWH or warfarin for prophylaxis. The PE rate of patients undergoing simultaneous bilateral TKA was 0.39% while the rate for patients undergoing unilateral TKA was 0%. By contrast, other studies did not find a statistical difference in the incidence of PE between the two groups [16,32–34]. Morrey et al. [16] found a similar PE rate (1%) for patients
Table 2 Incidence of VTE in the Bilateral and Unilateral Groups. Rate Per Patient Bilateral (N=58)
Total VTEs Total DVTs Proximal Distal Total PEs
Rate Per Knee
Unilateral (N=287)
N
%
N
%
9 7 1 6 2
12.1% 10.3% 1.7% 10.3% 3.4%
9 9 9 -
3.1 % 3.1 % 3.1 % -
P value 0.003 0.014
0.002
Rates are reported per number of patients and number of knees. ⁎ One patient undergoing unilateral TKA had a DVT in both legs, counted as two thromboses.
Bilateral (N=116)
Unilateral (N=287)
N
%
N
%
13 11 1 10 2
11.2% 9.5% 0.9% 8.6% 1.7%
10⁎ 10⁎ 10⁎
3.1 % 3.1 % 3.1 % -
-
P Value 0.008 0.019
0.028
Y.D. Levy et al. / The Journal of Arthroplasty 28 (2013) 474–478
undergoing simultaneous bilateral TKA (145 patients) and unilateral TKA (501 patients). Larson et al. [33] report a PE rate of zero in patients undergoing simultaneous bilateral TKA treated with a knee-high intermittent compression device combined with 650mg aspirin twice daily. Our study is in concordance with studies reporting a higher incidence of PE in patients undergoing bilateral simultaneous TKA compared with unilateral TKA whatever method of prophylaxis was used. Only one patient in either group had a proximal DVT. This patient in the simultaneous bilateral TKA group also had a distal DVT and a PE. None of the patients undergoing unilateral procedures were diagnosed with proximal DVT or PE. The rate of distal DVT was 5.5% (3 of 55 patients) in the bilateral group and 3.1% (9 of 287 patients) in the unilateral group. The current literature lacks reports on patients who underwent simultaneous bilateral TKA, utilized mechanical compression devices as a monotherapy for VTE prophylaxis and were evaluated only if they showed clinical symptoms. Hass et al. [35] evaluated 47 patients who underwent staged bilateral TKA and 72 patients who underwent unilateral TKA. Both groups received prophylaxis either with aspirin or with pneumatic sequential compression boots. Thrombi formation was evaluated with bilateral venography performed between post operative days four to six. The VTE rate of patients treated only with the compression device and underwent staged bilateral TKA and unilateral TKA was 48% and 22%, respectively. The rate for patients treated with aspirin was higher, 68% and 47%, respectively. Larson et al. reported a DVT rate of 12.5% per patient and a rate of 6.3% per knee in patients undergoing simultaneous bilateral TKA and screened by duplex ultrasound. Prophylaxis was provided perioperatively with a knee-high intermittent compression device combined with 650 mg aspirin twice daily. Lachiewicz et al. [36] used intermittent compression devices and aspirin as prophylaxis following bilateral and unilateral primary or revision TKA. Patients were screened with duplex prior to discharge. The reported DVT rate was 9.3% in the entire cohort. No specific rate was provided for patients undergoing simultaneous bilateral TKA. Our DVT rate of 12.1% in the bilateral group is lower than the results of the study evaluating patients with venography and comparable with those other studies that screened the patients with duplex ultrasound. This study used clinical assessment followed by duplex to screen for DVT, which will miss asymptomatic clots. The three month clinical follow-up in this patient population identifies the consequences of missing asymptomatic clots. The lack of literature evaluating patients only with clinical symptoms prevents comparison with our results. Another possible explanation for the high DVT rate in our bilateral TKA group may be the time the therapy was initiated. For the bilateral TKA group, therapy was started only after the surgery had been completed in both legs. In the unilateral group prophylaxis was initiated at the induction of anesthesia in the form of a calf sleeve on the non-operated side. This raises the question whether use of a calf sleeve on the non-operated leg at time of surgery can help prevent thrombi formation. This requires further study. Conclusion The rate of VTE in patients undergoing simultaneous bilateral TKA was increased more than two-fold compared with patients undergoing unilateral TKA using a mobile compression device as the sole thromboprophylactic modality. A future study will be necessary to verify that use of additional pharmacologic agents or use of pharmacological agents alone would improve this outcome. Acknowledgments The authors thank Julie C. McCauley, MPHc, for assistance in managing the data and statistics.
477
References 1. Powell RS, Pulido P, Tuason MS, et al. Bilateral vs unilateral total knee arthroplasty: a patient-based comparison of pain levels and recovery of ambulatory skills. J Arthroplasty 2006;21(5):642. 2. Sculco TP. Establishing a universal protocol for deep vein thrombosis following orthopedic surgery: total knee arthroplasty. Orthopedics 1996; 19(Suppl):6. 3. McKenna R, Bachmann F, Kaushal SP, et al. Thromboembolic disease in patients undergoing total knee replacement. J Bone Joint Surg Am 1976;58(7):928. 4. 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 2009;135(2):513. 5. Fitzgerald Jr RH, Spiro TE, Trowbridge AA, et al. Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin. J Bone Joint Surg Am 2001;83-A(6):900. 6. Robinson KS, Anderson DR, Gross M, et al. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the postarthroplasty screening study. A randomized, controlled trial. Ann Intern Med 1997;127(6):439. 7. Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332(7537):325. 8. Friedman RJ. Novel oral anticoagulants for VTE prevention in orthopedic surgery: overview of phase 3 trials. Orthopedics 2011;34(10):795. 9. Sculco TP, Bottner F. Current concepts of nonpharmacologic thromboembolic prophylaxis. Instr Course Lect 2002;51:481. 10. Jacobs DG, Piotrowski JJ, Hoppensteadt DA, et al. Hemodynamic and fibrinolytic consequences of intermittent pneumatic compression: preliminary results. J Trauma 1996;40(5):710. 11. Vanhoutte PM, Boulanger CM, Mombouli JV. Endothelium-derived relaxing factors and converting enzyme inhibition. Am J Cardiol 1995;76(15):3E. 12. Allenby F, Boardman L, Pflug JJ, et al. Effects of external pneumatic intermittent compression on fibrinolysis in man. Lancet 1973;2(7843):1412. 13. Stulberg BN, Insall JN, Williams GW, et al. Deep-vein thrombosis following total knee replacement. An analysis of six hundred and thirty-eight arthroplasties. J Bone Joint Surg Am 1984;66(2):194. 14. Mantilla CB, Horlocker TT, Schroeder DR, et al. Frequency of myocardial infarction, pulmonary embolism, deep venous thrombosis, and death following primary hip or knee arthroplasty. Anesthesiology 2002;96(5):1140. 15. March LM, Cross M, Tribe KL, et al. Two knees or not two knees? Patient costs and outcomes following bilateral and unilateral total knee joint replacement surgery for OA. Osteoarthritis Cartilage 2004;12(5):400. 16. Morrey BF, Adams RA, Ilstrup DM, et al. Complications and mortality associated with bilateral or unilateral total knee arthroplasty. J Bone Joint Surgery Am 1987;69(4):484. 17. Luscombe JC, Theivendran K, Abudu A, et al. The relative safety of one-stage bilateral total knee arthroplasty. Int Orthop 2009;33(1):101. 18. Bullock DP, Sporer SM, Shirreffs Jr TG. Comparison of simultaneous bilateral with unilateral total knee arthroplasty in terms of perioperative complications. J Bone Joint Surg Am 1981;85-A(10):2003. 19. Restrepo C, Parvizi J, Dietrich T, et al. Safety of simultaneous bilateral total knee arthroplasty. A meta-analysis. J Bone Joint Surg Am 2007;89(6):1220. 20. Colwell Jr CW, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am 2010; 92(3):527. 21. Gelfer Y, Tavor H, Oron A, et al. Deep vein thrombosis prevention in joint arthroplasties: continuous enhanced circulation therapy vs low molecular weight heparin. J Arthroplasty 2006;21(2):206. 22. Froimson MI, Murray TG, Fazekas AF. Venous thromboembolic disease reduction with a portable pneumatic compression device. J Arthroplasty 2009; 24(2):310. 23. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest 2001;119(1 Suppl):132S. 24. Bottner F, Sculco TP. Nonpharmacologic thromboembolic prophylaxis in total knee arthroplasty. Clin Orthop Relat Res 2001(392):249. 25. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008;133(6 Suppl):381S. 26. AAOS Workgroup Jacobs JJ, Bozic KJ, et al. Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty: evidence-based guideline and evidence report. AAOS clinical practice guidelines unit. Rosemont, IL: AAOS; 2011:43. 27. Lombardi AV, Mallory TH, Fada RA, et al. Simultaneous bilateral total knee arthroplasties: who decides? Clin Orthop Relat Res 2001(392):319. 28. Lane GJ, Hozack WJ, Shah S, et al. Simultaneous bilateral versus unilateral total knee arthroplasty. Outcomes analysis. Clin Orthop Relat Res 1997(345):106. 29. Adili A, Bhandari M, Petruccelli D, et al. Sequential bilateral total knee arthroplasty under 1 anesthetic in patients N or = 75 years old: complications and functional outcomes. J Arthroplasty 2001;16(3):271. 30. Barrett J, Baron JA, Losina E, et al. Bilateral total knee replacement: staging and pulmonary embolism. J Bone Joint Surg Am 2006;88(10):2146.
478
Y.D. Levy et al. / The Journal of Arthroplasty 28 (2013) 474–478
31. Memtsoudis SG, Ma Y, Gonzalez Della Valle A, et al. Perioperative outcomes after unilateral and bilateral total knee arthroplasty. Anesthesiology 2009;111(6): 1206. 32. Kim YH, Choi YW, Kim JS. Simultaneous bilateral sequential total knee replacement is as safe as unilateral total knee replacement. J Bone Joint Surg Br 2009;91(1):64. 33. Larson CM, MacMillan DP, Lachiewicz PF. Thromboembolism after total knee arthroplasty: intermittent pneumatic compression and aspirin prophylaxis. J South Orthop Assoc 2001;10(3):155.
34. Kim YH, Oh SH, Kim JS. Incidence and natural history of deep-vein thrombosis after total hip arthroplasty. A prospective and randomised clinical study. J Bone Joint Surg Br 2003;85(5):661. 35. Haas SB, Insall JN, Scuderi GR, et al. Pneumatic sequential-compression boots compared with aspirin prophylaxis of deep-vein thrombosis after total knee arthroplasty. J Bone Joint Surgery Am 1990;72(1):27. 36. Lachiewicz PF, Soileau ES. Mechanical calf compression and aspirin prophylaxis for total knee arthroplasty. Clin Orthop Relat Res 2007;464:61.