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© 1999 The Journal of Bone and Joint Surgery, Inc. Thromboembolic Prophylaxis with Use of Aspirin, Exercise, and Graded Elastic Stockings or Intermittent Compression Devices in Patients Managed with Total Hip Arthroplasty* , CORAL GABLES, FLORIDA , LOS ANGELES, CALIFORNIAInvestigation performed at the Arthritis and Joint Replacement Institute, Coral Gables, and Orthopaedic Hospital of Los Angeles, Los Angeles
Background: Prophylaxis against pulmonary embolism as a complication of total hip arthroplasty remains controversial. Our experience suggests that an inexpensive protocol of prophylaxis that includes aspirin and exercise is effective. Methods: We investigated the effectiveness of aspirin, a program of intraoperative and postoperative exercises, and graded elastic stockings or intermittent compression devices as prophylaxis against thromboembolic disease in a series of 1267 patients who had had 1492 total hip arthroplasties. All of the operations were done through a posterior approach. For the purpose of this review, the duration of follow-up was limited to a minimum of three months. No patient was lost to follow-up. Any thromboembolic complications that may have occurred after the third postoperative month were not considered to be related to the operation and were not recorded. Results: A fatal pulmonary embolism occurred after two arthroplasties (0.13 percent), a nonfatal pulmonary embolism was diagnosed after fourteen (0.94 percent), and deep venous thrombosis developed after fifteen (1.01 percent). Regional (epidural) anesthesia was used for 1099 arthroplasties (73.7 percent), and general anesthesia was used for 393 procedures (26.3 percent). A fatal pulmonary embolism occurred after two (0.18 percent) of the 1099 arthroplasties that had been performed with regional anesthesia and after none that had been performed with general anesthesia (chi square = 0.22; p > 0.05). A nonfatal pulmonary embolism occurred after two procedures (0.18 percent) that had been done with regional anesthesia and after twelve (3.05 percent) that had been done with general anesthesia (chi square = 25.3; p < 0.001). Deep venous thrombosis was diagnosed after seven procedures (0.64 percent) that had been performed with regional anesthesia and after eight (2.04 percent) that had been performed with general anesthesia (chi square = 5.45; p < 0.025). We detected a significant difference between men and women with respect to the rate of nonfatal pulmonary embolism (chi square = 4.36; p < 0.05). With the numbers available, we found no significant differences between the 774 arthroplasties (51.9 percent) in patients who had worn graded elastic stockings and the 718 arthroplasties (48.1 percent) in patients who had used intermittent compression devices, between the 774 arthroplasties (51.9 percent) that had been performed in Florida and the 718 (48.1 percent) that had been done in California, or between the 1313 primary arthroplasties (88 percent) and the 179 revision arthroplasties (12 percent), with regard to the prevalence of fatal pulmonary embolism, nonfatal pulmonary embolism, or deep venous thrombosis (p > 0.05 for all comparisons). In summary, we found that the type of compression (graded elastic stockings or intermittent compression devices), the geographic location (California or Florida), and the type of operation (primary or revision) had no significant effect, with the numbers available, on the rate of thromboembolic complications. Compared with general anesthesia, the use of regional anesthesia was associated with a significantly lower rate of nonfatal pulmonary embolism (p < 0.001) and deep venous thrombosis (p < 0.025). Both patients who had a fatal pulmonary embolism had had regional anesthesia (p > 0.05). Conclusions: This inexpensive method of prophylaxis against thromboembolic disease after total hip arthroplasty, which was based primarily on the use of aspirin as the pharmacological agent and the performance of intraoperative and postoperative exercises, produced good clinical results.
Total hip arthroplasty is associated with a well known risk of deep venous thrombosis, which is the primary source of pulmonary embolism. Orthopaedic surgeons generally believe that it is desirable to employ pharmacological or mechanical methods, or both, as prophylaxis against this complication. However, although a variety of prophylactic methods have been described in the literature, there is no consensus on the most effective protocol. The purpose of the present study was to determine the rates of fatal pulmonary embolism, nonfatal pulmonary embolism, and clinically symptomatic deep venous thrombosis in a group of patients who had been managed with a program of prophylaxis consisting of the administration of aspirin, the performance of intraoperative and postoperative exercises, and the use of graded elastic stockings or intermittent compression devices.
The original cohort consisted of 1304 patients who were managed with total hip arthroplasty. Thirty-seven patients (2.8 percent) were excluded because of hypersensitivity to aspirin, previous thromboembolic disease, chronic venous stasis, active peptic-ulcer disease, or a disorder affecting platelet function. The remaining 1267 patients, who had 1492 total hip arthroplasties (1313 primary procedures and 179 revision procedures), form the basis of the present study. The patients were followed for a minimum of three months, and no patient was lost to follow-up during this three-month period. Any thromboembolic complications that may have occurred after the third postoperative month were not considered to be related to the operation and were not recorded. Eight hundred and sixty-five arthroplasties (58 percent) were performed in women, and 627 arthroplasties (42 percent) were done in men. The average age of the patients at the time of the index operation was sixty-three years. Nine hundred and seventy arthroplasties (65 percent) were performed because of osteoarthritis; 179 (12 percent), because of the failure of a previous total hip arthroplasty; 149 (10 percent), because of rheumatoid arthritis; 149 (10 percent), because of avascular necrosis; and forty-five (3 percent), because of other conditions, such as ankylosing spondylitis, failed osteotomy, and failed internal fixation of a fracture of the proximal part of the femur. Two hundred and twenty-five patients had a bilateral procedure. All arthroplasties were performed through a posterior approach, without trochanteric osteotomy, and all hips were dislocated posteriorly by means of flexion, adduction, and internal rotation. Regional (epidural) anesthesia was used for 1099 procedures (73.7 percent) and general anesthesia, for 393 (26.3 percent). During the operation, the member of the operative team who was assigned to hold the lower limb was instructed to avoid extreme degrees of flexion of the hip and knee as well as internal rotation of the hip and was responsible for carrying out passive exercises of the hip, knee, and ankle in an effort to avoid damage to the intimal layer of the popliteal and femoral vessels. These exercises were conducted throughout the entire procedure when the passive motions did not interfere with the surgeon's work. Graded elastic stockings or intermittent compression devices were used by all patients. Graded elastic stockings were applied after 774 procedures (51.9 percent) and intermittent compression devices, after 718 (48.1 percent). The first 644 arthroplasties (43.2 percent) were performed in Miami, Florida, from 1976 to 1978. These patients were managed with graded elastic stockings, which were worn during hospitalization and no longer worn after discharge. The next 718 arthroplasties (48.1 percent) were performed in Los Angeles, California, from 1978 to 1993, and the patients were managed with intermittent compression devices. The remaining 130 arthroplasties (8.7 percent) were performed in Miami from 1995 to 1997, and graded elastic stockings were used. Walking was begun on the first or second postoperative day. Active isometric and isotonic exercises of the gluteus maximus, the quadriceps, and the dorsiflexors and plantar flexors of the ankle were performed for two minutes at fifteen-minute intervals in the immediate postoperative period. Deep-breathing exercises and exercises of the upper extremities with use of a trapeze attached to the bed frame were also encouraged. Patients were given an aspirin suppository (600 milligrams) immediately after the operation and continued to receive 325 milligrams of aspirin twice a day until discharge. The actual data on the duration of hospitalization were not available, but on the basis of information provided by the hospitals we estimated that the average duration of hospitalization was seven days. Because the duration of hospitalization decreased over the years, the patients who were managed earlier in the study received prophylaxis for a longer period of time than did those who were managed more recently. The clinical diagnosis of deep venous thrombosis was made when at least one symptom was present. These symptoms included tenderness of the calf or the inner part of the thigh; edema of the leg, ankle, or foot; a positive Homans sign; or a slight elevation of temperature. When any of these findings were documented, the patient was evaluated by an internist, who determined whether venography or Doppler studies, or both, were needed to confirm the diagnosis. The diagnosis of pulmonary embolism was established on the basis of clinical findings (pleuritic chest pain, dyspnea, discomfort in the chest, hemoptysis, or the presence of a friction rub on auscultation), blood-gas determinations (a low PO2 or PCO2 or respiratory alkalosis), suggestive changes seen on radiographs of the chest (increased density of the pulmonary parenchyma), and electrocardiographic findings. The diagnosis was confirmed with a ventilation-perfusion lung scan. If a diagnosis of pulmonary embolism or deep venous thrombosis was made, the patient was managed with therapeutic doses of heparin or warfarin.
The study group consisted of 1267 patients who had had 1492 total hip arthroplasties.
Fatal Pulmonary Embolism
Nonfatal Pulmonary Embolism All pulmonary emboli were confirmed with use of a ventilation-perfusion lung scan. One patient also had a confirmatory pulmonary angiogram. All of these patients were managed with therapeutic doses of heparin or warfarin. Three of these patients (three hips) also had deep venous thrombosis. The pulmonary embolism was diagnosed during hospitalization for seven patients (seven hips) and after discharge from the hospital (between the twentieth and sixtieth postoperative days) for the other six patients (seven hips).
Deep Venous Thrombosis
Other Complications
Geographic Location
Anesthesia
Compression Devices
Type of Operation
Coventry et al. reported that the rate of fatal pulmonary embolism was 0.05 percent after 1950 total hip arthroplasties in patients who had received warfarin compared with 3.4 percent after fifty-eight procedures in patients who had not received any prophylactic medication11. Johnson et al., in a review of a series of 7959 total hip arthroplasties, reported a rate of fatal pulmonary embolism of 1.04 percent19. In another review, Weinmann and Salzman noted that one or two fatal pulmonary emboli can be expected to develop among 100 patients who have had a general operative procedure (including an orthopaedic procedure) when prophylaxis is not used36. In a meta-analysis of 130,000 patients who had had a total hip arthroplasty, Murray et al. found that the overall mortality rate was 0.30 percent (ten of 3355) among patients who had not received prophylaxis, 0.40 percent (forty of 10,105) among those who had received heparin, 0.29 percent (eleven of 3763) among those who had received warfarin, 0.15 percent (four of 2649) among those who had received aspirin, and 0.50 percent (thirteen of 2618) among those who had received dextran27. In comparison, the rate of fatal pulmonary embolism ranged from 0.26 percent (seven of 2730) among patients who had been managed with dextran to 0.04 percent (two of 5162) among patients who had been managed with warfarin. The rates of fatal pulmonary embolism associated with heparin, aspirin, and no prophylaxis were within that range, and none of the differences among the groups were found to be significant (p = 0.051)27. Those authors stated that during the period between 1980 and the mid-1990s the overall mortality rate after total hip arthroplasty was 0.38 percent and the rate of fatal pulmonary embolism was 0.11 percent. Their study suggested that there is not enough evidence to conclude that any form of thromboembolic prophylaxis decreases the mortality rate after total hip arthroplasty. Warwick et al., in a review of 1162 consecutive total hip arthroplasties that had been performed without the use of pharmacological prophylaxis, reported that the rate of fatal pulmonary embolism was 0.34 percent (four hips)35. In our study, the rate of fatal pulmonary embolism was 0.13 percent (two hips), the rate of nonfatal pulmonary embolism was 0.94 percent (fourteen hips), and the rate of deep venous thrombosis was 1.01 percent (fifteen hips). The rate of deep venous thrombosis in our study was low; however, venograms were made only for patients who had clinical symptoms that were suggestive of deep venous thrombosis, and routine venography was not performed. Other investigators have reported higher rates of deep venous thrombosis. Turpie et al. reported that deep venous thrombosis developed after 42 percent of fifty total hip arthroplasties34, and Colwell et al. reported that this complication developed after 21 percent of 203 such procedures10. The clinical importance of these findings has yet to be determined, as some investigators have reported that the rate of fatal pulmonary embolism is very low. Nurmohamed et al., for example, reported that a fatal pulmonary embolism occurred in only eleven (0.13 percent) of 8172 patients who had had a general or orthopaedic operation28. A variety of prophylactic agents have been used over the years, and many have been associated with lower rates of mortality and morbidity. These agents have included low-molecular-weight heparin1,5,10,20,23,34, warfarin2,14, low-dose warfarin9, subcutaneously administered heparin12,13,21, dextran14, aspirin7,15,16,18, hydroxychloroquine8, and combination modalities such as dihydroergotamine-heparin3,22 and aspirin-dipyridamole30. The use of hypotensive epidural anesthesia also has been suggested as a way to reduce thromboembolic disease by reducing blood loss, preserving blood volume, and increasing blood flow to the lower extremities6,24-26. Our experience supports this hypothesis as we found significant differences between regional anesthesia and general anesthesia with respect to the rates of pulmonary nonfatal embolism (p < 0.001) and deep venous thrombosis (p < 0.025). Mechanical devices, such as graded elastic stockings37 and intermittent compression devices33,38,39, have also been recommended for the prevention of thromboembolic disease. We found no difference between the results of the 774 procedures (51.9 percent) performed in patients who were managed with graded elastic stockings and those of the 718 procedures (48.1 percent) performed in patients who were managed with intermittent compression devices (p > 0.05). Imperiale and Speroff performed a meta-analysis on the data from fifty-six clinical trials, which included a total of 7976 patients who had been managed with various treatment modalities (aspirin, dextran, heparin, low-molecular-weight heparin, warfarin, compression stockings, and no prophylaxis)17. They found that low-molecular-weight heparin and warfarin were more effective for the prevention of proximal thrombi than the other methods were. However, these two modalities were associated with high rates of clinically important bleeding (1.3 percent [eleven of 864] for warfarin and 1.8 percent [thirty-seven of 2065] for low-molecular-weight heparin). Only heparin was associated with a higher rate of bleeding complications (2.6 percent [forty-five of 1745])17. Paiement et al. claimed that low-dose warfarin is associated with a minimum risk of bleeding29. In the present study, in which aspirin was used, a large hematoma developed after three arthroplasties (0.2 percent), and it was necessary to ligate moderately large vessels that had been repaired at the time of the original procedure. The second operation was performed on the same day as the initial operation. In some instances, the postoperative dressings were found to be saturated with blood a few days after the operation. No records were kept of the number of saturated dressings, and we considered such findings to be inconsequential. The administration of aspirin was discontinued in three patients (three hips; 0.2 percent) because of an allergy and in two patients (two hips; 0.13 percent) because of gastrointestinal bleeding. In our series, prophylaxis with aspirin was not continued after the time of discharge. It is common knowledge that a large and increasing number of people in recent years have begun to use aspirin as prophylaxis against coronary artery disease29. We do not know how many of our patients had taken aspirin before the operation and continued to take it for that purpose after discharge from the hospital. Therefore, we are unable to determine the most effective dosage or the duration of time that aspirin should be administered as prophylaxis against thromboembolic disease. In some studies, aspirin has not been shown to be as effective as other measures for the prevention of deep venous thombosis31,32,34. Stamatakis et al. reported that the rate of deep venous thrombosis was 25 percent for sixty-eight control patients and 36 percent for sixty-four patients who had received aspirin and dipyridamole, which suggested that such prophylaxis had a poor efficacy31. In the meta-analysis by Imperiale and Speroff, the difference between the risk of deep venous thrombosis in a group of patients who had used aspirin and that in a control group of patients who had not received prophylaxis was 0.15, which suggested that aspirin had a poor efficacy17. In a previous study by one of us (A. S.) and colleagues, 528 patients (574 hips) received aspirin as prophylaxis against thromboembolic disease after total hip arthroplasty18. None of the patients had a fatal pulmonary embolism, seven patients (seven hips; 1.22 percent) had a nonfatal pulmonary embolism, and thirty-four patients (thirty-four hips; 5.92 percent) had clinical evidence of deep venous thrombosis18. Unlike the operations in the present study, those in the earlier study were performed through a lateral approach with trochanteric osteotomy and anterior dislocation of the hip. In a comparison of the findings of the earlier study with those of the present study, we found a significantly lower rate of deep venous thrombosis associated with a posterior approach (chi square = 45.5; p < 0.01) (Table III). We acknowledge that, because the two studies were conducted at different times and because other variables besides the operative approach were not controlled, the validity of the comparison can be questioned. However, aspirin was used in both studies and the same surgeon (A. S.) performed all of the arthroplasties.
Our data revealed slight differences between primary and revision procedures with respect to the rates of fatal pulmonary embolism, nonfatal pulmonary embolism, and deep venous thrombosis. A fatal pulmonary embolism occurred in two patients who had had a primary arthroplasty and in no patient who had had a revision arthroplasty (chi square = 0.27; p > 0.05). A nonfatal pulmonary embolism was associated with eleven (0.84 percent) of the 1313 primary arthroplasties and three (1.68 percent) of the 179 revision arthroplasties (chi square = 1.19; p > 0.05). Deep venous thrombosis developed after eleven primary arthroplasties (0.84 percent) compared with four revision arthroplasties (2.23 percent) (chi square = 1.49; p > 0.05). It has been suggested, although it has not been documented in the literature, that there may be a difference in the prevalence of thromboembolic disease in different sections of the country. Our patients were almost equally divided between Miami on the East Coast and Los Angeles on the West Coast. With the numbers available, we found no significant difference between the geographic location of the patients and the prevalence of fatal pulmonary embolism, nonfatal pulmonary embolism, or deep venous thrombosis (p > 0.05 for all comparisons). The currently used prophylactic methods, whether pharmacological or mechanical, seem to be at least partially effective for reducing the prevalence of thromboembolic complications after total hip arthroplasty. Our data suggest that an inexpensive protocol, consisting of aspirin, exercises, and the use of graded elastic stockings or intermittent compression devices, is associated with few thromboembolic complications. Furthermore, we did not detect any relationship between the occurrence of such complications and the age or geographic location of the patient, the type of compression device used, or the type of operation (primary or revision) performed. Our experience does not allow us to state that the administration of aspirin was totally responsible for the low rate of thromboembolic complications. It is likely that the use of regional anesthesia, the posterior approach, an intensive intraoperative and postoperative program of physical exercises, and the use of stockings (graded elastic stockings or intermittent compression devices) were also important features. The avoidance of extreme positions of flexion of the hip and knee and internal rotation of the hip is likely to prevent or minimize damage to the femoral and popliteal vessels, which initiates the pathological process. The passive exercises conducted during the operation and the active exercises performed postoperatively may also prevent blood stagnation and subsequent thromboembolic disease. The present study did not include a rigorous analysis of the cost of pharmacological prophylaxis. However, prophylaxis with aspirin is an inexpensive prophylactic method, and prophylaxis with drugs that need parenteral administration (such as low-molecular-weight heparin) is more expensive.
NOTE: The authors thank Jorge Corona, M.D., for his assistance in the preparation of this manuscript.
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.
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