Prospective R a n d o m i z e d Trial of Sequential Compression Devices vs Low-dose Warfarin for Deep Venous Thrombosis Prophylaxis in Total Hip Arthroplasty
James P. Bailey, MD,* Michael P. Kruger, MD, w Francis X. Solano, MD, i Albert B. Zajko, MD,* and Harry E. Rubash, MD*
Abstract: A prospective randomized trial compared the effectiveness of lowdose warfarin (LDW) to sequential compression devices (SCD) for deep venous thrombosis (DVT) prophylaxis in 95 patients after total hip arthroplasty (THA). Patients were 39 years of age or older, with no history of previous venous disease. Bilateral lower-extremity venography was used for thrombi detection. Venous thrombi occurred in 12 patients (all calf) on LDW (26.6%) and 3 patients with SCDs (one calf, two thigh) (6.0%). The incidence of DVT was significantly higher in the LDW group (P < .006). In this stndy of average-risk patients, the use of SCDs significantly outperformed LDW as a prophylactic agent. However, the thrombi that did occur with SCDs were more critical. Key words: deep venous thrombosis, total hip arthroplasty, Coumadin, sequential compression devices
Thromboembolic disease, a well-known complication of total hip arthroplasty (THA), occurs in 4 5 70% of unprotected patients and is associated with 1 - 3 % mortality due to pulmonary emboli (15, 28, 33, 35, 37). Significant reductions in the incidence of deep venous thrombosis (DVT) have been documented with low-dose warfarin (LDW) (8, 11, 15, 22, 26, 28, 39, 48), adjusted-dose heparin (15, 28, 37), low-molecular-weight dextran (9, 15, 22, 23), aspirin (7, 15, 19, 22), and sequential compression From the *Joint Replacement Service, *Departments of Orthopaedics, Medicine and Obstetrics and Gynecology, and *Vascular and Interventional Radiology Service, Unirersity of Pittsburgh, Pittsburgh, Pennsyh.ania, and w of Orthopaedic Stergery, University of Connecticut and 2~It. Sinag Farmington, Connecticut.
Reprint requests: Harry E. Rubash, biD, University Orthopaedics, 3601 Fifth Avenue, Pittsburgh, PA 15213.
devices (SCDs), which include thigh chambers (15, 24, 29, 30, 44). Comparison of studies is h a m p e r e d by varying diagnostic techniques, differing dosage schedules of antithrombotics, and inclusion of highand low-risk patient groups in studies with small sample size. LDW and adjusted-d0se h e p a r i n appear to be the most effective anticoagulant regimens, but require close patient monitoring and carry significant risks-of bleeding complications (22, 28, 41, 43). A~. an advantage, LDW requires less patient monitoring (once daily) and allows greater ease of administration (oral). SCDs appear to have the fewest associated complications, although their ability to prevent thigh thrombi has been questioned (24, 43). It remains to be determined which single or combined regimen is most effective in reducing thrombi and
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pulmonary emboli, while producing the fewest complications. The present study was undertaken to compare the incidence of DVT in a prospective randomized study comparing LDW to SCDs. All patients were at least 40 years of age and were without prior history of venous disease. All patients were scheduled to undergo elective primary or revision THA.
Materials and Methods All patients 40 years of age or older scheduled for elective primary or revision THA on the Joint Replacement Service at Presbyterian University Hospital from November 1987 until August 1989 were evaluated for admission into this study. Patients were excluded if they had previous venous disease, including a history of venous surgery. Patients with active peptic ulcer disease, allergy to iodine contrast dye, underlying breeding disorders, or a history of cerebral vascular accidents were also excluded. All exclusions were documented. After informed consent had been obtained, 95 patients were randomized to one of two treatment regimens by a standard computerized randomization program. Nonsteroidal antiinflammatory drugs (NSAIDs) were stopped 2 weeks prior to admission. If the NSAIDs had not been discontinued, a modified Ivy bleeding time was determined and, if abnormal, admission was cancelled. NSAIDs were not administered during the study.
Treatment Regimens Patients randomized to the SCD group received thigh-length graded elastic compression stockings, T.E.D. hose (Kendall, Inc., Mansfield, MA), which were applied upon admission and continued until discharge. The SCDs were applied immediately after surgery in the recovery ward. They were worn continuously throughout the remainder of the study except during bathing and physical therapy. The SCDs consisted of two six-chambered leggings with popliteal cut-outs for flexion. They were available in three sizes. There were two thigh and four calf chambers. These were attached to a portable controller by means of pneumatic tubing. Complete cycle time of the unit was 71 seconds. The two ankle chambers inflated first, with peak pressure of 55 m m of mercury. The calf chambers inflated 289 seconds later, and the thigh chambers inflated 3 seconds after
the calf, with peak pressure of 40 m m of mercury. The entire device remained inflated for an additional 589 seconds, then the entire unit deflated simultaneously through vents under the sleeves. Both lower extremities received the compression cycle simultaneously and continuously. Patients w h o randomized to the LDW group routinely received warfarin 10 mg the evening before surgery. This was modified to 789mg for w o m e n over the age of 70 and patients with minor abnormalities of liver function tests. Prothrombin and partial thromboplastin times were obtained in the recovery ward, and if less than 15 seconds, 5 mg of warfarin were administered the evening of surgery. Subsequent doses were adjusted to maintain the prothrombin time at 1 4 - 1 6 seconds (189 x control). Partial thromboplastin times were monitored as well, and the warfarin dose was decreased for values greater than 50 seconds, according to the recommendations of Harris, et al. (4). Therapeutic prothrombin times were routinely obtained by postoperative day 2 or 3. Graded elastic compression stockings (T.E.D. hose) were also utilized in this group, both before and after surgery. Sequential compression devices were immediately discontinued on any patient with a positive venogram. Those patients whose venograms d e m o n strated thrombi of t h e popliteal vein or m o r e proximal were heparinized to 289times the control partial thromboplastin time value. This was maintained for 5 days. Oral warfarin was introduced gradually until the prothrombin time was maintained at a level of 1 6 - 1 8 seconds. The warfarin doses of the patients in the warfarin group whose venograms revealed DVT (all distal to the popliteal vein) were increased until prothrombin values were within the 1 6 - 1 8 second range. Any patient with positive venography was anticoagulated for 3 months.
Surgical Procedure All surgical procedures were u n d e r the direction of the senior author (H.E.R.). Perioperative antibiotics, (cephalosporin or vancomycin), were routinely utilized. Surgical exposure was through a lateral non-transtrochanteric (Hardinge) (17) approach, with the patient in a full lateral position with the lower leg flexed 45 ~ All 95 acetabular components were uncemented titanium fiber-metal-coated ingrowth devices with initial screw fixation (Harris Galante Prosthesis, Zimmer, Warsaw, IN). Cemented stems were cobalt-chrome alloy (Precoat, Zimmer, or Precision Howmedica, East Rutherford, NJ), while
Deep Venous Thrombosis After THA
uncemented devices were divided between titanium fiber-metal-coated (Harris Galante Prosthesis or Bias Zimmer) and grooved titanium implants (Macrofit Prosthesis, Zimmer). C o n t e m p o r a r y cement techniques were used in all cemented cases, including the use of an intramedullary plug, cement gun, pressurization seal, and v a c u u m cement mixing. All w o u n d s were closed over suction drains, and the operative leg was placed in balanced Thomas suspension. Bed-to-chair activity was routinely begun on postoperative day I, with patients beginning protected weight bearing on postoperative day 2, using crutches or a walker. Venograms were obtained using a standard technique on postoperativd days 5 - 7 (40). The operative leg was visualized first and, if abnormal, the study was terminated. If the operative leg was negative, the nonoperative leg also u n d e r w e n t venography. All venograms were carried out and interpreted by physicians blinded to the patients' treatment group. Venograms were considered positive if intraluminal filllng defects, abrupt termination of veins, or nonfilling of veins were present. Isolated filling defects in the small muscular calf veins or their c o m m u n i caring branches were not considered positive. Four patients whose v e n o g r a m s could not be completed for technical reasons (lack of venous access) underwent B-mode Doppler ultrasound, and techn e c i u m - p y r o p h o s p h a t e red-cell labeled nuclear venogram with impedance plethysmography, all with negative results.
*
Bailey et al.
The two treatment groups were c o m p a r e d to each other for age, sex, perioperative blood loss, revision or primary surgery, height, weight, operative time, blood transfusions, type of anesthesia, and type of stem by chi-square analysis. Logistic regression analysis methods were used to evaluate the influence of the above variables on the incidence of DVT. Corrected chi-square statistics were used to test independence a m o n g selected variables and the presence or absence of DVT.
Results Patient Population Of the 95 patients w h o met inclusion criteria and agreed to participate, 50 (53%) received SCDs and 45 (47%) received LDW. The treatment groups did not differ significantly w h e n analyzed for differences in age, sex, height, type of anesthesia, revision or primary surgery, duration of surgery, type of implant, perioperative blood loss, or preoperative NSAID use. The groups did differ in weight, the LDW group significantly heavier (mean, 81 kg) than the SCD group (mean, 72 kg) (P = .01). However, the weight of patients w h o developed DVT did not vary significantly from the average weight of those in their treatment group or from that of the study group as a whole. Relevant patient characteristics of the t w o treatment groups are s h o w n in Table 1.
Table 1. Comparison of Treatment Groups
Variable Age (years) Sex Male Female Height (cm) Weight (kg) Blood transfused (units) OR Time (min) Preoperative Hct (%) Postoperative Hct (%) Anesthesia General Epidural General/Epidural Hip Primary Revision Stem Cemented Uncemented
Sequential Compression Devices Mean Range 65.3 24 (48%) 26 (52%) 165 72.2* 1.9 184.5 37.2 33.07 40 (80%) 7 (14%) 3 (6.0%) 27 (54%) 23 (46%) 40 (75.5%) 13 (24.5%)
* statistically significant difference. Hct, hematocrit; OR, operating room.
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41-88
Low-dose Warfarin Mean Range 64.4
45-80
--
22
(49%)
--
--
23
(51%)
i
148-185 42-109 O-9 100-480 30-44 21.8-43.3 m
I
I
m
165.5 81.3" 2.2 208.5 37.3 32.5 37 (82.2%) 3 (6.7%) 5 (11%) 26 (57.8%) 19 (42.2%) 34 (80.9%) 8 (19.1%)
153-185 35.7-120 0-6 120-500 28.7-45.6 26.7-38.5 i
m
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The Journal of Arthroplasty Vol. 6 Supplement October 1991
Frequency and Distribution of Deep Venous Thrombi Venography revealed DVT in 12 of the 45 patients (26.6%) on LDW but in only 3 of the 50 patients (6%) with SCDs. This was highly significant (P < .006). No thigh thrombi occurred in the LDW group. Two of the thrombi in the SCD group consisted of isolated,~ nonocclusive superficial femoral vein thrombi. There were no deaths and no clinically detectable pulmonary emboli in either group. Logistic regression analysis indicated that the treatment regimen had an important effect on the development of DVT. The only other variable found to affect the occurrence of DVT was whether the surgery was a revision or primary operation. Venous thrombi occurred in 12 of 46 (26%) primary THAs and in 3 of 42 (7.1%) revision cases. Thus, 80% of the venous thrombi occurred in primary THA. This approached statistical significance (P = .058). The patients who developed DVT are compared to those who did not in Table 2. Two patients, both in the SCD group, returned to the hospital with late DVT after termination of this study. One patient returned 3 days after venogram with a calf thrombus (peroneal vein). The other patient returned 1 week after venogram with pain and swelling of the operative leg and was readmitted. Repeat venography on both patients revealed thrombi that were not previously present. T a b l e 2. C o m p a r i s o n
No clinically important bleeding occurred in either group. There were 14 cases of transient postoperative serous wound drainage, 6 with SCDs and 8 with LDW, all of which resolved spontaneously. None of these cases required operative intervention. There were no infections. There were no clinically evident thigh hematomas, defined as thigh swelling with a drop in hematocrit, observed in any of the cases. No statistical difference existed in number of blood units transfused or in pre- and postoperative hematocrits between the two groups.
Discussion The need for prophylaxis to reduce DVT, and thereby pulmonary emboli, in patients undergoing THA is well established. The relative safety and effectiveness of various methods continues to be a source of debate and confusion. This report compared in a prospective, randomized fashion LDW, a convenient and relatively safe anticoagulant, and SCDs, an extremely safe mechanical alternative whose effectiveness continues to be debated. Since younger patients develop significantly fewer deep venous thrombi after surgery (10, 12, 22, 28, 31, 32, 34, 38, 41, 45), they were excluded from the study. Patients with prior venous disease were also excluded, as this has been shown to predispose to
of Patients Who Developed
DVT With Those Who Did Not
No DVT Variable Age (years) Sex Male Female Height (cm) Weight (kg) Blood transfused (units) OR Time (rain) Preoperative Hct (%) Postoperative Hct (%) Anesthesia General Epidural General/Epidural Hip Primary Revision Stem Cemented Uncemented Treatment SCD LDW
Mean 64.3
DVT Range 41-84
Mean 68.2
39 (84.7%) 41 (83.6%) 165.1 74.5 2.0 198 37.3 32.9
--150-185 35.7-109 0-9 100-500 28.7-45.6 21.8-43.3
7 (15.2%) 8 (16.3%) 166.6 81.4 2.3 184 37.0 32.3
68 (88.3%) 8 (80%) 4 (50%)
----
9 (11.6%) 2 (20%) 4 (50%)
41 (77.4%) 39 (92.8%)
---
12 (22.6%) 3 (7.1%)
61 (82.4%) 19 (90.5%)
---
13 (17.6%) 2 (9.5%)
47 (94%) 33 (73.4%)
---
3* (6%) 12" (26.6%)
Range 56-88
148-185 55-120 0-4 120-420 30.3-42 27.2-38
m
i
m
i
* statistically significant difference. OR, operating room; Hct, hematocrit; DVT, deep v e n o u s thrombosis; SCD, sequential compression device; LDW, low-dose warfarin.
Deep Venous Thrombosis After THA
DVT (7, 22, 28, 31, 32, 35-38, 41, 47). In addition, LDW has already been shown superior to SCDs in this population (20, 47). Previous literature reports have implicated age (44), use of cement (10), and increased operating time (10, 12, 45) as factors that increase the incidence of DVT. This report found no association between any of these variables and DVT. The nnexpected statistical finding of a disproportionate number of primary THAs with DVT is difficult to interpret. Certainly, the revision THA patients had more traditional risk factors for DVT, such as increased operative time and more blood loss. Although difficult to prove, we suspect there may exist a subtle selection bias in the study design since patients who developed venous disease after primary THA would have been excluded from this study group. The primary THA patients in this study with such a propensity, not having undergone such a challenge to their venous systems, w oul d have no cause for exclusion, and therefore would be enrolled. -The SCDs in this study were significantly more effective than LDW in preventing the total number of DVT cases after THA in patients of average risk. Previous studies have reported a 15-30% incidence of DVT with LDW (4, 9, 11, 18, 19, 21, 22, 43) and a 6 - 2 4 % incidence with SCDs (29, 43). The DVT rate in both groups involved in this study was similar to that of other nonrandomized studies. In contrast to other studies that used SCDs intraoperatively, our method was to apply the SCDs in the recovery ward. This protocol was chosen due to the concern of having the nonoperative leg unmonitored during lengthy revision surgery. The one reported serious complication with SCDs, compartment syndrome, occurred in such a setting (51). The apparent increased incidence of DVT found by Hull et al. (29) using this technique was not supported by this study. The two patients treated with SCDs who returned to the hospital with late DVT are of particular concern. Although the second peak incidence of DVT at 10-14 days after operation has been well described, this has been previously reported in SCDs that included thigh chambers in only two previous cases (29). The patient who developed a calf thrombi 2 days after venogram was thought to have developed phlebitis from the contrast medium. The rate of DVT after venogram has been reported to be 3% (22, 51). Postvenogram DVT has also been reported with LDW in 2 of 51 patients by Harris et al. (22), although it did not occur in our series. The second patient developed a large femoral thrombus after 36 hours of bed rest, possibly contributing to thrombus development. This late thrombus phenomenon has also been reported in patients treated with low-dose hep-
9
Bailey et al.
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arin (44), rheomacrodex (32), and single-chamber calf compression devices (44). Due to the design of this study, the number of asymptomatic thrombi after venogram is unknown. Although the two delayed thrombi may have been related to the sequential compression devices, we could find no objective proof of this, and late thrombi appear to occur with virtually all treatment regimens (22, 29, 32, 44). Although Harris (20) and others (2, 3, 43) have questioned the ability of SCDs to prevent thigh thrombi in this population, Hull et al. (29) showed a statistically significant decrease in thigh thrombi when compared to untreated controls. The 4% of patients who developed thigh thrombi treated with SCDs in this study compares with rates of 1.9-15% (24, 29, 43) in other groups of patients treated with SCDs. The 4% rate in this study is similar to thigh thrombi rates of 2-6. 9% (11, 22, 42) reported with warfarin and to the 10-27% rate reported in unprotected patients (6, 7, 14, 16, 21, 24, 27-29, 47, 50). The number of patients in this study with DVT in or proximal to the popliteal vein is too small to draw meaningful statistical conclusions between the number of SCD and LDW patients. However, it cannot be ignored that in a prospective, randomized trial thigh clots occurred in the SCD group and did not occur in the LDW group. We believe this is cause for concern and an indication for careful postoperative screening of SCD-treated patients. Previous reports of bleeding and wound hematomas with LDW at rates of 4.3-8.7% (3, 4, 11, 26, 28, 43) were not supported by this study. Fourteen patients in this study, including eight on warfarin, did develop transient serous drainage from their wounds, but none had a clinically evident thigh hematoma and none required surgical intervention. Hematocrit before and after surgery, as well as amount of blood transfused, did not vary significantly between the two groups. This is similar to the experience of Amstutz and colleagues who reported a 1.5% incidence of bleeding and hematoma with closer monitoring techniques (2). The lower rates here and in the Amstutz study may be due to the similar methods in which warfarin was administered and monitored. In our study, one coinvestigator was responsible for warfarin administration for 12month intervals during the study. Our treatment protocol of ace wrap hip spica and fresh frozen plasma treatment for prothrombin times greater than 18 and 20 seconds, respectively, is also similar to techniques reported by Amstutz. Accurate thrombi detection is both the cornerstone of diagnosis and the means of evaluating treatment efficacy. We chose venogram for thrombi detection, as this continues to be the gold standard. Four pa-
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The Journal of Arthroplasty Vol. 6 Supplement October 1991
tients w h o could not undergo routine venography for technical reasons (lack of venous access) were evaluated by Duplex doppler ultrasound, impedance plethysmography, and nuclear venography. The accuracy rate of these tests approaches that of venography (27). We did not consider isolated defects in the small muscular and communicating branches of the calf to be significant DVT. These defects have been reported to be transient flow p h e n o m e n o n , and are not thought to propagate or embolize (11, 34). In this prospective randomized study of averagerisk patients undergoing THA, LDW was found to be more protective than SCDs against thigh thrombi. This was accomplished with no increased risk ofperioperative bleeding. SCDs were found to be significantly better then LDW at reducing the overall thrombi rate. However, the thrombi, w h e n present, typically occurred in clinically serious locations. This fact, along with the possible occurrence of late thrombi with SCDs, necessitates routine postoperative screening for thrombi in these patients. Currently, we utilize SCDs for low-risk patients with no previous history of venous disease w h o undergo THA. All patients are evaluated with postoperative venography or Duplex doppler ultrasound studies in the early postoperative period to detect DVT.
Acknowledgments The authors acknowledge the services of Kendall Corporation for their support of this randomized study.
References 1. Allenby F, Pflug J J, Boardman L, Calnan JS: Effects of external pneumatic intermittent compression on fibrinolysis in man. Lancet 2:1412, 1973 2. Amstutz HC, Friscia DA, Dorey F, Carney BT: Warfarin prophylaxis to prevent mortality from pulmonary embolism after total hip replacement. J Bone Joint Surg 71A:321, 1989 3. Askey JM: Hemorrhage during long-term anticoagulafion drug therapy. Calif Med 104:175, 1966 4. Bell DF, Harris WH, Kuter DJ, Wessinger SJ: Elevated partial thromboplastin time as an indicator of hemorrhage risk in postoperative patients on warfarin prophylaxis. J Anhroplasty 3:181, 1988 5. Convery FR, Barnes RW, Krugmire RB Jr., Strandness DE Jr.: Prophylaxis against thromboembolic disease. p. 173. In: The Hip, Proceedings of The Hip Society. C.V. Mosby. St. Louis, 1974
6. Culver D, Crawford JS, Gardiner JH, Wiley AM: Venous thrombosis after fractures of the upper end of the femur: a study of incidence and site. J Bone Joint Surg 52B:61, 1970 7. Delee JC, Rockwood CA: The use of aspirin in thromboembolic disease: current concepts review. J Bone Joint Surg 62A:149, 1980 8. Eskeland G, Solheim K, Skjorten F: Anticoagulant prophylaxis, thromboembolism and mortality in elderly patients with hip fractures: a controlled clinical trial. Acta Chir Scand 131:16, 1966 9. Evarts CM, Feil EJ: Prevention of thromboembolic disease after elective surgery of the hip. J Bone Joint Surg 53A:1271, 1971 10. Francis CW, Evarts CM, Marder VJ: Lower risk of thromboembolic disease after total hip replacement with noncemented than with cemented prostheses. Lancet 1:769, 1986 11. Francis CW, Marper VJ, Evarts CM, Yaukoolbodi S: Two-step warfarin therapy, prevention of postoperative venous thrombosis without excessive bleeding. JAMA 249:374, 1983 12. Francis CW, Pellegrini VD, Marder VJ et al: Prevention of venous thrombosis after total hip arthroplasty: antithrombin III and low-dose heparin compared wit h dextran 40. J Bone Joint Surg 71A:327, 1989 13. Fredin H, Rosberg B: Anaesthetic techniques and thromboembolism in total hip arthroplasty. Eur J Anaesthesiol 3:273, 1986 14. Gallus A, Raman K, Darby T: Venous thrombosis after elective hip replacement: the influence of preventive intermittent calf compression and of surgical technique. BrJ Surg 70:17, 1983 15. Gold EW: Prophylaxis of deep venous thromboembolism literature review. Orthopaedics 11:1197, 1988 16. Hamilton HW, Crawford JS, G~rdiner JH, Wiley AM: Venous thrombosis in patients with fracture of the upper end of the femur: a phlebographic study of the effect of prophylactic anti-coagu!ation. J Bone Joint Surg 52B:268, 1970 17. Hardinge K: The direct lateral approach to the hip. J Bone Joint Surg 64B:17, 1982 18. Harris WH: The incidence and prevention of thromboembolic disease, p. 36. In Instructional course lectures, The American Academy of Orthopaedic Surgeons, Vol. 19, C.V. Mosby, St. Louis, 1970 19. Harris WH, Athanasoulis CA, Waltman AC, Salzman EW: Prophylaxis of deep-vein thrombosis after total hip replacement: dextran and external pneumatic compression compared with 1.2 or 0.3 gram aspirin daily. J Bone Joint Surg 67A:57, 1985 20. Harris WH, Raines JK, Athanasoulis C et al: External pneumation compression versus warfarin in reducing thrombosis in high-risk hip patients, p. 51. In JL Madden, M Hume (eds): Venous thromboembolism: prevention and treatments, .Appleton-Century-Crofts, New York, 1976 21. ttarris WH, Salzman EW, Athanasoulis C et al: Comparison of 125 I fibrinogen count scanning with phle-
Deep Venous Thrombosis After THA
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James P. Bailey, MD,* Michael P. Kruger, MD, w Francis X. Solano, MD, i Albert B. Zajko, MD,* and Harry E. Rubash, MD*
Abstract: A prospective randomized trial compared the effectiveness of lowdose warfarin (LDW) to sequential compression devices (SCD) for deep venous thrombosis (DVT) prophylaxis in 95 patients after total hip arthroplasty (THA). Patients were 39 years of age or older, with no history of previous venous disease. Bilateral lower-extremity venography was used for thrombi detection. Venous thrombi occurred in 12 patients (all calf) on LDW (26.6%) and 3 patients with SCDs (one calf, two thigh) (6.0%). The incidence of DVT was significantly higher in the LDW group (P < .006). In this stndy of average-risk patients, the use of SCDs significantly outperformed LDW as a prophylactic agent. However, the thrombi that did occur with SCDs were more critical. Key words: deep venous thrombosis, total hip arthroplasty, Coumadin, sequential compression devices
Thromboembolic disease, a well-known complication of total hip arthroplasty (THA), occurs in 4 5 70% of unprotected patients and is associated with 1 - 3 % mortality due to pulmonary emboli (15, 28, 33, 35, 37). Significant reductions in the incidence of deep venous thrombosis (DVT) have been documented with low-dose warfarin (LDW) (8, 11, 15, 22, 26, 28, 39, 48), adjusted-dose heparin (15, 28, 37), low-molecular-weight dextran (9, 15, 22, 23), aspirin (7, 15, 19, 22), and sequential compression From the *Joint Replacement Service, *Departments of Orthopaedics, Medicine and Obstetrics and Gynecology, and *Vascular and Interventional Radiology Service, Unirersity of Pittsburgh, Pittsburgh, Pennsyh.ania, and w of Orthopaedic Stergery, University of Connecticut and 2~It. Sinag Farmington, Connecticut.
Reprint requests: Harry E. Rubash, biD, University Orthopaedics, 3601 Fifth Avenue, Pittsburgh, PA 15213.
devices (SCDs), which include thigh chambers (15, 24, 29, 30, 44). Comparison of studies is h a m p e r e d by varying diagnostic techniques, differing dosage schedules of antithrombotics, and inclusion of highand low-risk patient groups in studies with small sample size. LDW and adjusted-d0se h e p a r i n appear to be the most effective anticoagulant regimens, but require close patient monitoring and carry significant risks-of bleeding complications (22, 28, 41, 43). A~. an advantage, LDW requires less patient monitoring (once daily) and allows greater ease of administration (oral). SCDs appear to have the fewest associated complications, although their ability to prevent thigh thrombi has been questioned (24, 43). It remains to be determined which single or combined regimen is most effective in reducing thrombi and
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pulmonary emboli, while producing the fewest complications. The present study was undertaken to compare the incidence of DVT in a prospective randomized study comparing LDW to SCDs. All patients were at least 40 years of age and were without prior history of venous disease. All patients were scheduled to undergo elective primary or revision THA.
Materials and Methods All patients 40 years of age or older scheduled for elective primary or revision THA on the Joint Replacement Service at Presbyterian University Hospital from November 1987 until August 1989 were evaluated for admission into this study. Patients were excluded if they had previous venous disease, including a history of venous surgery. Patients with active peptic ulcer disease, allergy to iodine contrast dye, underlying breeding disorders, or a history of cerebral vascular accidents were also excluded. All exclusions were documented. After informed consent had been obtained, 95 patients were randomized to one of two treatment regimens by a standard computerized randomization program. Nonsteroidal antiinflammatory drugs (NSAIDs) were stopped 2 weeks prior to admission. If the NSAIDs had not been discontinued, a modified Ivy bleeding time was determined and, if abnormal, admission was cancelled. NSAIDs were not administered during the study.
Treatment Regimens Patients randomized to the SCD group received thigh-length graded elastic compression stockings, T.E.D. hose (Kendall, Inc., Mansfield, MA), which were applied upon admission and continued until discharge. The SCDs were applied immediately after surgery in the recovery ward. They were worn continuously throughout the remainder of the study except during bathing and physical therapy. The SCDs consisted of two six-chambered leggings with popliteal cut-outs for flexion. They were available in three sizes. There were two thigh and four calf chambers. These were attached to a portable controller by means of pneumatic tubing. Complete cycle time of the unit was 71 seconds. The two ankle chambers inflated first, with peak pressure of 55 m m of mercury. The calf chambers inflated 289 seconds later, and the thigh chambers inflated 3 seconds after
the calf, with peak pressure of 40 m m of mercury. The entire device remained inflated for an additional 589 seconds, then the entire unit deflated simultaneously through vents under the sleeves. Both lower extremities received the compression cycle simultaneously and continuously. Patients w h o randomized to the LDW group routinely received warfarin 10 mg the evening before surgery. This was modified to 789mg for w o m e n over the age of 70 and patients with minor abnormalities of liver function tests. Prothrombin and partial thromboplastin times were obtained in the recovery ward, and if less than 15 seconds, 5 mg of warfarin were administered the evening of surgery. Subsequent doses were adjusted to maintain the prothrombin time at 1 4 - 1 6 seconds (189 x control). Partial thromboplastin times were monitored as well, and the warfarin dose was decreased for values greater than 50 seconds, according to the recommendations of Harris, et al. (4). Therapeutic prothrombin times were routinely obtained by postoperative day 2 or 3. Graded elastic compression stockings (T.E.D. hose) were also utilized in this group, both before and after surgery. Sequential compression devices were immediately discontinued on any patient with a positive venogram. Those patients whose venograms d e m o n strated thrombi of t h e popliteal vein or m o r e proximal were heparinized to 289times the control partial thromboplastin time value. This was maintained for 5 days. Oral warfarin was introduced gradually until the prothrombin time was maintained at a level of 1 6 - 1 8 seconds. The warfarin doses of the patients in the warfarin group whose venograms revealed DVT (all distal to the popliteal vein) were increased until prothrombin values were within the 1 6 - 1 8 second range. Any patient with positive venography was anticoagulated for 3 months.
Surgical Procedure All surgical procedures were u n d e r the direction of the senior author (H.E.R.). Perioperative antibiotics, (cephalosporin or vancomycin), were routinely utilized. Surgical exposure was through a lateral non-transtrochanteric (Hardinge) (17) approach, with the patient in a full lateral position with the lower leg flexed 45 ~ All 95 acetabular components were uncemented titanium fiber-metal-coated ingrowth devices with initial screw fixation (Harris Galante Prosthesis, Zimmer, Warsaw, IN). Cemented stems were cobalt-chrome alloy (Precoat, Zimmer, or Precision Howmedica, East Rutherford, NJ), while
Deep Venous Thrombosis After THA
uncemented devices were divided between titanium fiber-metal-coated (Harris Galante Prosthesis or Bias Zimmer) and grooved titanium implants (Macrofit Prosthesis, Zimmer). C o n t e m p o r a r y cement techniques were used in all cemented cases, including the use of an intramedullary plug, cement gun, pressurization seal, and v a c u u m cement mixing. All w o u n d s were closed over suction drains, and the operative leg was placed in balanced Thomas suspension. Bed-to-chair activity was routinely begun on postoperative day I, with patients beginning protected weight bearing on postoperative day 2, using crutches or a walker. Venograms were obtained using a standard technique on postoperativd days 5 - 7 (40). The operative leg was visualized first and, if abnormal, the study was terminated. If the operative leg was negative, the nonoperative leg also u n d e r w e n t venography. All venograms were carried out and interpreted by physicians blinded to the patients' treatment group. Venograms were considered positive if intraluminal filllng defects, abrupt termination of veins, or nonfilling of veins were present. Isolated filling defects in the small muscular calf veins or their c o m m u n i caring branches were not considered positive. Four patients whose v e n o g r a m s could not be completed for technical reasons (lack of venous access) underwent B-mode Doppler ultrasound, and techn e c i u m - p y r o p h o s p h a t e red-cell labeled nuclear venogram with impedance plethysmography, all with negative results.
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The two treatment groups were c o m p a r e d to each other for age, sex, perioperative blood loss, revision or primary surgery, height, weight, operative time, blood transfusions, type of anesthesia, and type of stem by chi-square analysis. Logistic regression analysis methods were used to evaluate the influence of the above variables on the incidence of DVT. Corrected chi-square statistics were used to test independence a m o n g selected variables and the presence or absence of DVT.
Results Patient Population Of the 95 patients w h o met inclusion criteria and agreed to participate, 50 (53%) received SCDs and 45 (47%) received LDW. The treatment groups did not differ significantly w h e n analyzed for differences in age, sex, height, type of anesthesia, revision or primary surgery, duration of surgery, type of implant, perioperative blood loss, or preoperative NSAID use. The groups did differ in weight, the LDW group significantly heavier (mean, 81 kg) than the SCD group (mean, 72 kg) (P = .01). However, the weight of patients w h o developed DVT did not vary significantly from the average weight of those in their treatment group or from that of the study group as a whole. Relevant patient characteristics of the t w o treatment groups are s h o w n in Table 1.
Table 1. Comparison of Treatment Groups
Variable Age (years) Sex Male Female Height (cm) Weight (kg) Blood transfused (units) OR Time (min) Preoperative Hct (%) Postoperative Hct (%) Anesthesia General Epidural General/Epidural Hip Primary Revision Stem Cemented Uncemented
Sequential Compression Devices Mean Range 65.3 24 (48%) 26 (52%) 165 72.2* 1.9 184.5 37.2 33.07 40 (80%) 7 (14%) 3 (6.0%) 27 (54%) 23 (46%) 40 (75.5%) 13 (24.5%)
* statistically significant difference. Hct, hematocrit; OR, operating room.
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41-88
Low-dose Warfarin Mean Range 64.4
45-80
--
22
(49%)
--
--
23
(51%)
i
148-185 42-109 O-9 100-480 30-44 21.8-43.3 m
I
I
m
165.5 81.3" 2.2 208.5 37.3 32.5 37 (82.2%) 3 (6.7%) 5 (11%) 26 (57.8%) 19 (42.2%) 34 (80.9%) 8 (19.1%)
153-185 35.7-120 0-6 120-500 28.7-45.6 26.7-38.5 i
m
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Frequency and Distribution of Deep Venous Thrombi Venography revealed DVT in 12 of the 45 patients (26.6%) on LDW but in only 3 of the 50 patients (6%) with SCDs. This was highly significant (P < .006). No thigh thrombi occurred in the LDW group. Two of the thrombi in the SCD group consisted of isolated,~ nonocclusive superficial femoral vein thrombi. There were no deaths and no clinically detectable pulmonary emboli in either group. Logistic regression analysis indicated that the treatment regimen had an important effect on the development of DVT. The only other variable found to affect the occurrence of DVT was whether the surgery was a revision or primary operation. Venous thrombi occurred in 12 of 46 (26%) primary THAs and in 3 of 42 (7.1%) revision cases. Thus, 80% of the venous thrombi occurred in primary THA. This approached statistical significance (P = .058). The patients who developed DVT are compared to those who did not in Table 2. Two patients, both in the SCD group, returned to the hospital with late DVT after termination of this study. One patient returned 3 days after venogram with a calf thrombus (peroneal vein). The other patient returned 1 week after venogram with pain and swelling of the operative leg and was readmitted. Repeat venography on both patients revealed thrombi that were not previously present. T a b l e 2. C o m p a r i s o n
No clinically important bleeding occurred in either group. There were 14 cases of transient postoperative serous wound drainage, 6 with SCDs and 8 with LDW, all of which resolved spontaneously. None of these cases required operative intervention. There were no infections. There were no clinically evident thigh hematomas, defined as thigh swelling with a drop in hematocrit, observed in any of the cases. No statistical difference existed in number of blood units transfused or in pre- and postoperative hematocrits between the two groups.
Discussion The need for prophylaxis to reduce DVT, and thereby pulmonary emboli, in patients undergoing THA is well established. The relative safety and effectiveness of various methods continues to be a source of debate and confusion. This report compared in a prospective, randomized fashion LDW, a convenient and relatively safe anticoagulant, and SCDs, an extremely safe mechanical alternative whose effectiveness continues to be debated. Since younger patients develop significantly fewer deep venous thrombi after surgery (10, 12, 22, 28, 31, 32, 34, 38, 41, 45), they were excluded from the study. Patients with prior venous disease were also excluded, as this has been shown to predispose to
of Patients Who Developed
DVT With Those Who Did Not
No DVT Variable Age (years) Sex Male Female Height (cm) Weight (kg) Blood transfused (units) OR Time (rain) Preoperative Hct (%) Postoperative Hct (%) Anesthesia General Epidural General/Epidural Hip Primary Revision Stem Cemented Uncemented Treatment SCD LDW
Mean 64.3
DVT Range 41-84
Mean 68.2
39 (84.7%) 41 (83.6%) 165.1 74.5 2.0 198 37.3 32.9
--150-185 35.7-109 0-9 100-500 28.7-45.6 21.8-43.3
7 (15.2%) 8 (16.3%) 166.6 81.4 2.3 184 37.0 32.3
68 (88.3%) 8 (80%) 4 (50%)
----
9 (11.6%) 2 (20%) 4 (50%)
41 (77.4%) 39 (92.8%)
---
12 (22.6%) 3 (7.1%)
61 (82.4%) 19 (90.5%)
---
13 (17.6%) 2 (9.5%)
47 (94%) 33 (73.4%)
---
3* (6%) 12" (26.6%)
Range 56-88
148-185 55-120 0-4 120-420 30.3-42 27.2-38
m
i
m
i
* statistically significant difference. OR, operating room; Hct, hematocrit; DVT, deep v e n o u s thrombosis; SCD, sequential compression device; LDW, low-dose warfarin.
Deep Venous Thrombosis After THA
DVT (7, 22, 28, 31, 32, 35-38, 41, 47). In addition, LDW has already been shown superior to SCDs in this population (20, 47). Previous literature reports have implicated age (44), use of cement (10), and increased operating time (10, 12, 45) as factors that increase the incidence of DVT. This report found no association between any of these variables and DVT. The nnexpected statistical finding of a disproportionate number of primary THAs with DVT is difficult to interpret. Certainly, the revision THA patients had more traditional risk factors for DVT, such as increased operative time and more blood loss. Although difficult to prove, we suspect there may exist a subtle selection bias in the study design since patients who developed venous disease after primary THA would have been excluded from this study group. The primary THA patients in this study with such a propensity, not having undergone such a challenge to their venous systems, w oul d have no cause for exclusion, and therefore would be enrolled. -The SCDs in this study were significantly more effective than LDW in preventing the total number of DVT cases after THA in patients of average risk. Previous studies have reported a 15-30% incidence of DVT with LDW (4, 9, 11, 18, 19, 21, 22, 43) and a 6 - 2 4 % incidence with SCDs (29, 43). The DVT rate in both groups involved in this study was similar to that of other nonrandomized studies. In contrast to other studies that used SCDs intraoperatively, our method was to apply the SCDs in the recovery ward. This protocol was chosen due to the concern of having the nonoperative leg unmonitored during lengthy revision surgery. The one reported serious complication with SCDs, compartment syndrome, occurred in such a setting (51). The apparent increased incidence of DVT found by Hull et al. (29) using this technique was not supported by this study. The two patients treated with SCDs who returned to the hospital with late DVT are of particular concern. Although the second peak incidence of DVT at 10-14 days after operation has been well described, this has been previously reported in SCDs that included thigh chambers in only two previous cases (29). The patient who developed a calf thrombi 2 days after venogram was thought to have developed phlebitis from the contrast medium. The rate of DVT after venogram has been reported to be 3% (22, 51). Postvenogram DVT has also been reported with LDW in 2 of 51 patients by Harris et al. (22), although it did not occur in our series. The second patient developed a large femoral thrombus after 36 hours of bed rest, possibly contributing to thrombus development. This late thrombus phenomenon has also been reported in patients treated with low-dose hep-
9
Bailey et al.
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arin (44), rheomacrodex (32), and single-chamber calf compression devices (44). Due to the design of this study, the number of asymptomatic thrombi after venogram is unknown. Although the two delayed thrombi may have been related to the sequential compression devices, we could find no objective proof of this, and late thrombi appear to occur with virtually all treatment regimens (22, 29, 32, 44). Although Harris (20) and others (2, 3, 43) have questioned the ability of SCDs to prevent thigh thrombi in this population, Hull et al. (29) showed a statistically significant decrease in thigh thrombi when compared to untreated controls. The 4% of patients who developed thigh thrombi treated with SCDs in this study compares with rates of 1.9-15% (24, 29, 43) in other groups of patients treated with SCDs. The 4% rate in this study is similar to thigh thrombi rates of 2-6. 9% (11, 22, 42) reported with warfarin and to the 10-27% rate reported in unprotected patients (6, 7, 14, 16, 21, 24, 27-29, 47, 50). The number of patients in this study with DVT in or proximal to the popliteal vein is too small to draw meaningful statistical conclusions between the number of SCD and LDW patients. However, it cannot be ignored that in a prospective, randomized trial thigh clots occurred in the SCD group and did not occur in the LDW group. We believe this is cause for concern and an indication for careful postoperative screening of SCD-treated patients. Previous reports of bleeding and wound hematomas with LDW at rates of 4.3-8.7% (3, 4, 11, 26, 28, 43) were not supported by this study. Fourteen patients in this study, including eight on warfarin, did develop transient serous drainage from their wounds, but none had a clinically evident thigh hematoma and none required surgical intervention. Hematocrit before and after surgery, as well as amount of blood transfused, did not vary significantly between the two groups. This is similar to the experience of Amstutz and colleagues who reported a 1.5% incidence of bleeding and hematoma with closer monitoring techniques (2). The lower rates here and in the Amstutz study may be due to the similar methods in which warfarin was administered and monitored. In our study, one coinvestigator was responsible for warfarin administration for 12month intervals during the study. Our treatment protocol of ace wrap hip spica and fresh frozen plasma treatment for prothrombin times greater than 18 and 20 seconds, respectively, is also similar to techniques reported by Amstutz. Accurate thrombi detection is both the cornerstone of diagnosis and the means of evaluating treatment efficacy. We chose venogram for thrombi detection, as this continues to be the gold standard. Four pa-
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The Journal of Arthroplasty Vol. 6 Supplement October 1991
tients w h o could not undergo routine venography for technical reasons (lack of venous access) were evaluated by Duplex doppler ultrasound, impedance plethysmography, and nuclear venography. The accuracy rate of these tests approaches that of venography (27). We did not consider isolated defects in the small muscular and communicating branches of the calf to be significant DVT. These defects have been reported to be transient flow p h e n o m e n o n , and are not thought to propagate or embolize (11, 34). In this prospective randomized study of averagerisk patients undergoing THA, LDW was found to be more protective than SCDs against thigh thrombi. This was accomplished with no increased risk ofperioperative bleeding. SCDs were found to be significantly better then LDW at reducing the overall thrombi rate. However, the thrombi, w h e n present, typically occurred in clinically serious locations. This fact, along with the possible occurrence of late thrombi with SCDs, necessitates routine postoperative screening for thrombi in these patients. Currently, we utilize SCDs for low-risk patients with no previous history of venous disease w h o undergo THA. All patients are evaluated with postoperative venography or Duplex doppler ultrasound studies in the early postoperative period to detect DVT.
Acknowledgments The authors acknowledge the services of Kendall Corporation for their support of this randomized study.
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Deep Venous Thrombosis After THA
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