Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double-blind study.

BACKGROUND: Prophylaxis is recommended following total joint replacement because of the high risk of venous thromboembolism (VTE). Postoperative low-molecular-weight heparin (LMWH) reduces the incidence of venographically detected deep vein thrombosis (DVT) to about 10-15% in total hip replacement (THR) patients. Ximelagatran is a novel, oral direct thrombin inhibitor that selectively and competitively inhibits both free and clot-bound thrombin. We compared the efficacy and safety of ximelagatran with those of enoxaparin for the prevention of VTE in patients undergoing THR. METHODS: This was a prospective, randomized, multicenter, double-blind study conducted principally in the USA and Canada. Patients received fixed-dose oral ximelagatran 24 mg bid or subcutaneous enoxaparin 30 mg bid and matched placebo for 7-12 days; both regimens were initiated the morning after surgery. The incidence of VTE (by postoperative day 12) included thrombosis determined by mandatory venography of the leg on which surgery was performed and symptomatic, objectively proven DVT or pulmonary embolism (PE). VTE and bleeding events were interpreted by an independent central adjudication committee for primary analysis. RESULTS: Of the 1838 patients randomized, 1557 had either adequate venography or symptomatic, proven VTE (efficacy population). Overall rate of venography acceptable for evaluation was 85.4%. Overall rates of total VTE were 7.9% (62 of 782 patients) in the ximelagatran group and 4.6% (36 of 775 patients) in the enoxaparin group, with an absolute difference of 3.3% and a 95% confidence interval for the difference of 0.9% to 5.7%. Proximal DVT and/or PE occurred in 3.6% (28 of 782 patients) in the ximelagatran group and 1.2% (nine of 774 patients) in the enoxaparin group. Major bleeding events were observed in 0.8% (seven of 906) of the ximelagatran-treated patients and in 0.9% (eight of 910) of the enoxaparin-treated patients (P > 0.95). Non-inferiority of ximelagatran 24 mg bid based on a prespecified margin of 5% was not met, resulting in superiority of the enoxaparin regimen. CONCLUSIONS: Both ximelagatran and enoxaparin decreased the overall rate of VTE compared with that reported historically. However, in this study, enoxaparin 30 mg bid was more effective than ximelagatran 24 mg bid for prevention of VTE in THR. Oral ximelagatran was used without coagulation monitoring, was well tolerated, and had bleeding rates comparable to those of enoxaparin. Further refinement by testing a higher dose of ximelagatran in the patients undergoing THR is warranted.

Role of knee aspiration after resection of the infected total knee arthroplasty.

Recognizing persistent infection after resection arthroplasty and implantation of cement spacers in the infected total knee arthroplasty is often difficult. The purpose of this study was to determine whether aspiration of the knee after resection arthroplasty is valuable for determining the presence of ongoing infection. Thirty-four previously infected knees that were aspirated and cultured after resection arthroplasty, implantation of cement spacers, and intravenous antibiotics for an average of 6.3 weeks were identified. There were 8 cases of persistent infection-none identified on preoperative aspiration. Two preoperative cultures were false positive for Staphylococcus epidermidis. Preoperative cultures were negative in 32 knees, with 8 false-negative results. The antibiotic-free interval among all cases averaged 20 days; the cases with false-negative results from aspiration had an antibiotic-free interval averaging 11.5 days, compared with an average of 26 days among all other cases. Aspiration of knees after resection arthroplasty had sensitivity of 0%, positive predictive value of 0%, and accuracy of 71%. Specificity was 92%, and negative predictive value was 75%. A negative result from joint aspiration after resection arthroplasty does not necessarily rule out the presence of ongoing infection. False-negative results may be observed if joint aspiration is not delayed more than 2 to 3 weeks.

Tibial osteonecrosis.

Spontaneous osteonecrosis of the tibial plateau involves a continuum of change observed in the subchondral zone that is commonly associated with early and mid stages of osteoarthritis. The typical patient is an elderly woman who experiences a sudden onset of pain in the medial aspect of the knee. The diagnosis of this under-appreciated clinical entity may be difficult, but careful examination and judicious use of imaging studies, as well as a high index of suspicion, may facilitate the accurate diagnosis. Although the radiographs may initially be normal (with the exception of mild arthrosis), radionuclide scans and MRI can be of great value. The MRI studies usually show a decreased signal intensity on a T1-weighted image, but may be normal in the early course of the disease. The T2-weighted images and fat suppression views are helpful in establishing a diagnosis and determining the extent of involvement. Recognition of this problem may help to avoid unnecessary intra-articular surgery. Many of these patients have complete or partial resolution of symptoms by 1 year, after a period of protected weight bearing. Nonetheless, surgery may be necessary for more advanced lesions and in those patients with progressive arthrosis.

Changes in bone density after cemented total knee arthroplasty: influence of stem design.

Total knee arthroplasty has shown excellent survivorship in short-term and intermediate-term studies. With longer follow-up, however, aseptic loosening becomes an increasing cause of failure. Dual-energy x-ray absorptiometry scanning has shown that stress shielding occurs from altered mechanical loading. The purpose of this study is to determine if tibial stem design affects bone density in the longterm. Bone densities in the proximal tibia with and without cemented stems were compared at an average of 94 months after surgery. The bone quality under the Miller-Galante I prosthesis, which has 4 0.5-cm pegs, was compared with the bone quality under a Press-Fit Condylar prosthesis with a single 4-cm stem. Each group was also compared with the unoperated contralateral tibia. Results showed that there is a significantly reduced density of bone in the tibial metaphysis in the cemented stemmed group but not in the pegged group. There were no changes distally in the diaphyseal bone. This study supports the contention that the use of a cemented stem reduces proximal stresses and may result in proximal bone resorption. Although the use of a stem provides excellent resistance to lift-off and shear, it comes at a price. The proximal resorption may contribute to the persistence of tibial component loosening as a primary threat to survivorship. This bone loss may complicate revision surgery. Consideration should be given to using shorter tibial stems, less cement, or alternative designs that avoid long-stem fixation.

Total knee arthroplasty in patients 40 years of age and younger with osteoarthritis.

The results of 32 total knee arthroplasties performed for osteoarthritis in 32 patients who were 40 years of age or younger are reviewed. At a mean followup of 7.9 years (minimum, 5 years), the Knee Society knee scores increased from an average of 47 to 88 points, and the function scores increased from 45 to 70 points. Overall, Knee Society knee scores were considered good or excellent in 82% of patients (26 knees) and fair or poor in 18% (six knees). Postoperative function scores were good or excellent in only 40% (13 knees). The average postoperative flexion arc was 110 degrees. If patients involved in worker's compensation cases are excluded from analysis, the results improved substantially, with range of motion averaging 113 degrees, and Knee Society knee scores and function scores averaging 92 points and 77 points, respectively. Excluding the five patients involved in workmen's compensation cases, knee scores were good or excellent in 91% of patients (25 knees) and function scores were good or excellent in 50% of patients (14 knees). Three revisions were performed for aseptic failure; one additional patient has radiographic evidence of tibial loosening, representing an aseptic failure rate of 12.5% at 8 years. Although slightly higher than observed in older patients, this failure rate still may be considered acceptable for this population of patients with severely affected knees who are not considered candidates for nonarthroplasty surgery. Despite a slightly higher tendency for aseptic failures in this group of patients, cemented total knee arthroplasty may provide some patients younger than 40 years of age with severe debilitating and recalcitrant osteoarthrosis, an important option with reasonable mid- and long-term results.

Simultaneous femoral osteotomy and total knee arthroplasty for treatment of osteoarthritis associated with severe extra-articular deformity.

BACKGROUND: In the presence of large extra-articular deformity, complex imbalance of the collateral ligaments may result if standard techniques of soft-tissue releases and intra-articular bone resection are used during total knee arthroplasty. The purpose of this paper is to review our experience with simultaneous corrective osteotomy and total knee arthroplasty for the treatment of severe extra-articular femoral deformity associated with ipsilateral osteoarthritis of the knee. METHODS: The results of simultaneous corrective osteotomy and total knee arthroplasty in eleven knees with osteoarthritis and associated extra-articular angular deformity of the femur were reviewed retrospectively. The femoral deformity resulted from fracture malunion in ten knees and from hypophosphatemic rickets in one. There were five primarily uniplanar deformities (four varus deformities and one antecurvatum deformity), five biplanar (varus and antecurvatum) deformities, and one triplanar (varus, antecurvatum, and internal rotation) deformity. Four knees were approached through a standard medial parapatellar arthrotomy and seven, through an anterolateral subvastus approach with an osteotomy of the tibial tubercle. The site of the femoral osteotomy was fixed with a blade-plate in seven patients, a press-fit long-stemmed femoral component in two, and a retrograde femoral nail in two. An extramedullary alignment system was utilized in eight patients, and intramedullary alignment was used in three. RESULTS: The duration of follow-up averaged forty-six months (range, twenty-six to eighty-eight months). According to the classification system of the Knee Society, the mean function score increased from 22 points preoperatively to 81 points at the time of follow-up and the mean knee score increased from 10 points preoperatively to 87 points at the time of follow-up. The mean flexion contracture decreased from 19 degrees preoperatively to 2 degrees at the time of follow-up. The arc of motion averaged 56 degrees (range, 30 to 75 degrees) preoperatively and 89 degrees (range, 65 to 115 degrees) at the time of follow-up. The mechanical alignment in the coronal plane was restored to within 2 degrees of normal in each patient. Ten femoral osteotomy sites healed, and one, in a patient treated with a press-fit long-stemmed femoral component, had not healed by the time of follow-up. All seven sites of the tibial tubercle osteotomies healed. There were no complete radiolucent lines at the prosthetic interfaces, and no total knee arthroplasty was revised. One patient had a nonfatal postoperative pulmonary embolism. As determined by clinical examination and the patients' assessment of function, no ligament imbalance was noted at the time of the most recent follow-up. CONCLUSIONS: Simultaneous femoral osteotomy and total knee arthroplasty is a technically difficult but effective treatment for patients with severe femoral deformity associated with ipsilateral osteoarthritis of the knee. We recommend that the femoral osteotomy site be secured with a plate or a locked intramedullary nail, depending on the location of the deformity and the subsequent osteotomy.

Subchondral magnetic resonance imaging changes in early osteoarthrosis associated with tibial osteonecrosis.

SUMMARY: The authors report on 41 patients with acute or subacute knee pain and early or midstage degenerative arthrosis with osteonecrotic lesions in the subchondral and metaphyseal region of the medial proximal tibia. Each lesion was identified only on magnetic resonance images (MRI). These MRI changes are classified and the clinical course is defined during a follow-up period averaging 4.5 years. Radiographically, 22 patients had minimal degenerative changes; 12 had moderate arthritis; and 7 were normal. With MRI, 3 distinct types of lesions were identified. Type A lesions had localized areas of decreased signal in the subchondral area. Type B lesions had diffuse signal changes with extension into the metaphysis. Type C lesions had metaphyseal involvement as well as a marginated serpentine subchondral rim usually associated with advanced osteonecrosis. There were 9 type A lesions, 23 type B, and 9 type C. At the end of 1 year, 33 patients (80%) had no or mild symptoms, and 8 (20%) had persistent moderate pain. At 4.5-year follow-up, most patients had symptoms consistent with progressive osteoarthrosis, 12 patients had severe symptoms (29%), 17 (41%) had mild or moderate symptoms, and only 12 (29%) were asymptomatic or had minimal symptoms. The type of MRI change seen initially was predictive of prognosis. Only 6 (19%) of the 32 patients with type A or B findings had severe symptoms at last follow-up. Six (66%) of the 9 patients with a type C MRI lesion had severe symptoms or had an operation by last follow-up. Twelve patients had follow-up MRI at a mean 15 months (range, 12 to 18 months) after the initial evaluation. The type A and B changes were either absent or significantly reduced. The type C subchondral marginated rim changes remained but metaphyseal involvement was reduced. There appears to be a spectrum of tibial subchondral MRI changes associated with sudden onset of medial knee pain in patients with early osteoarthritis of the knee. These changes may be indicative of osteonecrosis. The initial MRI classification is useful in predicting prognosis. Recognition of this problem may avoid unnecessary intra-articular surgery.

Total knee arthroplasty in patients 90 years of age and older.

With increasing longevity, more patients older than age 90 now are becoming candidates for total knee arthroplasty. This article reviews our experience with the perioperative morbidity and early outcomes in 12 patients older than age 90, undergoing 15 total knee surgeries. Postoperative Knee Society clinical and functional scores showed excellent outcomes, and the quality of life is enhanced. There were no significant surgical complications; however, there were several nonsurgical complications, including mental confusion (3), urinary retention (3), atrial fibrillation (2), atrial flutter (1), and gallstone retention and gastrointestinal bleed (1). Most of these complications stemmed directly from the preoperative medical condition. These are predictive and therefore may be recognized early and treated aggressively. Total knee surgery can be performed safely in patients older than 90 years old with excellent pain relief and enhanced quality of life. The surgeon should be aware of the patient's past medical history because this predisposes to postoperative morbidity.

Aseptic complications after total knee arthroplasty.

Aseptic complications after total knee arthroplasty are occurring less frequently than they did one or two decades ago. This is related in part to technical advancements, design improvements, and changes in perioperative management. Extensor mechanism dysfunction is the most frequent complication and the most commonly cited reason for secondary surgery after total knee arthroplasty. Mechanical wear, tibiofemoral instability, periprosthetic fracture, thromboembolic disease, compromised wound healing, neurovascular problems, and stiffness are less common, but nevertheless troublesome, sources of dysfunction after total knee arthroplasty. Complications compromise outcomes, and the most effective way of dealing with complications is prevention.

The role of aspirin for thromboembolic disease in total joint arthroplasty.

Fatal PE is a real problem and cannot be minimized. However, it must be appropriately balanced to other perioperative risks. It appears that fatal PE, as reported in the recent literature, is the same no matter which chemoprophylactic agent is used, with a rate of approximately 0.1% to 0.2%. With the use of aspirin as chemoprophylaxis after TKA, we have demonstrated the risk of fatal PE to be 0.15%. Because of our experience, the current data in the literature, and the need to carefully balance risk, we continue to use aspirin as our prophylactic agent of choice.

Magnetic resonance venography versus contrast venography to diagnose thrombosis after joint surgery.

Magnetic resonance venography is a recently developed, noninvasive means of visualizing the proximal veins of the lower extremity and pelvis. Magnetic resonance venography is compared with standard contrast venography in the diagnosis of proximal deep vein thrombosis after total joint arthroplasty. Two hundred seven extremities were evaluated in a blinded study 5 to 7 days after surgery. Standard contrast venography identified 11 proximal deep vein thromboses. Initial interpretations of the magnetic resonance venographies by staff radiologists identified 5 of the proximal vein thromboses (sensitivity 45%). Two patients with negative standard contrast venographies were identified as positive (specificity 99%). A retrospective review of all magnetic resonance venographies by a dedicated magnetic resonance angiographer identified 10 of 11 deep vein thromboses seen on standard contrast venography (sensitivity 91%). Both false negatives were identified as positives. Standard contrast venography remains the gold standard for identifying proximal vein thromboses. Emerging magnetic resonance imaging techniques have created a potential alternative modality by which to identify deep vein thrombosis. The present study suggests that standard contrast venography continues to be the most accurate modality currently available. Although magnetic resonance venography seems to be accurate, its interpretation requires experience. As costs diminish and experience increases, magnetic resonance venography will have increased importance in the clinical recognition of deep vein thrombosis.

Total knee arthroplasty in a previously ankylosed or arthrodesed knee.

Few reports address the reconstructive challenge of total knee arthroplasty after a surgically fused or ankylosed knee. The long term results and complications of a large series of patients who have had their ankylosed or arthrodesed knee converted to a total knee replacement were evaluated. Thirty-seven knees (35 patients, 28 female and 7 male) without any motion in the knee were retrospectively reviewed in a multicenter study after total knee arthroplasty. The mean age was 53 years, and the average length of followup was 90 months. The results at followup showed an average 7 degrees lack of extension and 62 degrees flexion. Complications included 24% short term complications and 35% major complications with a 14% infection rate. The total complication rate was 57%. A satisfactory outcome (no pain and an unlimited ambulation distance) was obtained in only 10 patients (29%). Patients with a satisfactory outcome had an average age of 45, and postoperative knee flexion of 87 degrees, significantly different from those with an unsatisfactory outcome. There was no relationship between results and the angle at which the knee was ankylosed preoperatively. This analysis indicates that although success in reconstructing a previously ankylosed or arthrodesed knee is possible, the lack of consistent adequate motion and the complication rate may suggest that the surgeon reconsider the risks and benefits of this difficult procedure.

Deep venous thrombosis after total joint arthroplasty. The role of compression ultrasonography and the importance of the experience of the technician.

We evaluated the influence of the expertise of the technician on the accuracy of compression ultrasonography as a screening test to detect postoperative deep venous thrombosis in patients who had had primary or revision arthroplasty of the hip or the knee. The study was performed in two phases on two groups of patients who were evaluated with both compression ultrasonography and conventional venography. All of the patients received prophylaxis for deep venous thrombosis. In the first phase of the study, adequate venograms and ultrasonograms were made for 126 extremities (121 patients). Venography demonstrated seven thrombi in the proximal veins. Only three ultrasonograms were considered positive. Ultrasonography had a sensitivity of 0 per cent because none of the seven proximal thrombi identified with venography were detected with ultrasonography. Three ultrasonograms were false-positive (that is, the ultrasonogram was positive and the venogram was negative), so the specificity was 97 per cent. The accuracy of compression ultrasonography was 92 per cent. Both tests were performed on a second group of eight-seven extremities (eighty-four patients). Proximal clots were detected with venography in five extremities. The ultrasonogram was positive for seven extremities, including the five in which a clot had been identified with venography. There were no false-negative and two false-positive results. In this phase of the study, ultrasonography had a sensitivity of 100 per cent, a specificity of 98 per cent, and an accuracy of 98 per cent. The only difference that was identified between the two groups of patients was the experience of the ultrasonography technician. It appears that the reliability of compression ultrasonography is directly dependent on the experience of the technician.

Aspirin and warfarin for thromboembolic disease after total joint arthroplasty.

This study compares the benefits of aspirin and warfarin prophylactic agents for patients with thromboembolic disease after total joint arthroplasty. It is a prospective randomized study of 388 patients having total hip or total knee surgery. All consecutive patients having total hip or total knee surgery were entered into this study and evaluated with preoperative and postoperative ventilation perfusion scans and a postoperative venogram. The aspirin and warfarin treatment groups were compared by size and location of venographically revealed clots and changes in ventilation perfusion scans. The results showed that there was no difference in the size or location of deep venous thrombosis in the aspirin or warfarin treatment groups. The venogram was negative in 44.5% of patients; 28.8% had small ++calf clots, 16% had large calf clots, 3.9% had popliteal clots, and 6.7% had femoral clots. Patients with total knee replacement had a 2.6 times greater incidence of calf deep venous thrombosis than patients with total hip replacement. There was no difference between the aspirin and warfarin groups in the incidence of changes in ventilation perfusion scans (18.9%). There was no difference between the 2 groups in bleeding complications. The results suggest that aspirin and warfarin are equivalent in prophylaxis against thromboembolic disease, as determined by prevention of venographic changes or changes in ventilation perfusion scans.

Long-term changes in bone mineral density following total knee replacement.

Bone density was measured using dual photon absorptiometry and dual xray absorptiometry below the tibial component under the medial and lateral plateaus, under the central peg, and distal to the central peg. Measurements of bone density were taken at 1 week, 6 weeks, 6 months, and 1 year after surgery in 31 patients. Seven of these patients also had measurements taken 8 years after surgery. The average age of the patients at surgery was 69 years old. One week after surgery, the mean bone density from all regions was 0.77 g/cm2 in women compared with 1.14 g/cm2 in men. Between 6 weeks and 6 months, the bone density below the tibial component declined inconsistently in most patients, but by 1 year the bone mineral density was statistically equal to the initial bone density at 1 week after surgery. Eight years after total knee arthroplasty, there was a 36.4% decrease in bone mineral density between men and women was not statistically significant. Medial plateau, lateral plateau, under the peg, and distal to the peg bone density changes tended to be the same. Maximum rates of bone resorption in patients with osteoporosis of the same age group have been reported to be between 1% and 2% per year. In this study, after an initial stable period, the bone density of the proximal tibia beneath the tibial component consistently decreased at a rate of 5% per year. Surgeons must consider this relatively large decrease in bone density if they are relying on bone for long-term stable fixation of the prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteonecrosis of the knee following laser-assisted arthroscopic surgery: a report of six cases.

We report six cases where significant postoperative pain persisted in individuals following arthroscopic surgery augmented with the use of lasers. Subsequent magnetic resonance images showed lesions with signal changes compatible with the diagnosis of osteonecrosis in areas directly addressed with laser energy.