Biomedical subjects
Publications and source records attributed to N Rosencher.
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PURPOSE OF THE STUDY: Peri-prosthetic ossifications are a frequent complication of total hip arthroplasty, which, if effective preventive measures are not taken, occur in 60% of patients. Numerous classic antiinflammatory agents have shown their preventive efficacy. New selective Cox-2 inhibitors offer the possibility of reducing the adverse effects of antiinflammatory drugs but remain to be proven effective in this indication. The purpose of this pilot study was to compare the efficacy of celecoxib versus ketoprofen. MATERIAL AND METHODS: In order to obtain sufficient statistical power to have a 70% chance of detecting a 25% difference between the two treatments with a 5% risk of error, we evaluated the incidence of peri-prosthetic ossifications of the hip in a prospective monocentric series of 52 patients receiving 400 mg celecoxib a day during a week. It was compared with the incidence in a control series of 52 matched patients (same age, gender, diagnosis, operator experience) given 200 mg ketoprofen iv for 48 hr then 300 mg po for 5 days as preventive treatment. Ossifications were studied on the plain AP view of the pelvis at a mean follow-up of more than 11 months (11.4 vs 11.9). The Brooker classification was determined. RESULTS: The percent of patients presenting peri-prosthetic ossifications was equivalent. For the celecoxib group, 60% of the patients were free of ossifications; 28.9% presented stage 1 ossification and 11.1% stage 2 ossification; none of the hip exhibited a higher stage. In the ketoprofen control group, 53.2% of patients were free of ossification, 38.2% had stage 1 ossification, 6.4% stage 2, and 2.1% stage 3; there was no patient with stage 4. Fisher's exact test did not demonstrate a significant difference between the groups (p<0.51). Compared with an older series of patients who were not given preventive treatment, there was a significant reduction in incidence of peri-prosthetic ossification (p=0.014). DISCUSSION: The two study groups were not significantly different for age, gender, or underlying disease. There were an equivalent number of cases of intolerance to treatment in the two groups. CONCLUSION: These findings appear to indicate an equivalent efficacy for celecoxib and ketoprofen for the reduction of peri-prosthetic ossifications. Based on these results, a randomized prospective comparative study can be undertaken without risk of losing effective prevention in one group. This prospective study should enable a more precise evaluation of treatment equivalence and quantify any potential gain in morbidity obtained with celecoxib.
BACKGROUND: Dabigatran etexilate is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolism (VTE) following orthopedic surgery. METHODS: In a multicenter, parallel-group, double-blind study, 1973 patients undergoing total hip or knee replacement were randomized to 6-10 days of oral dabigatran etexilate (50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily), starting 1-4 h after surgery, or subcutaneous enoxaparin (40 mg once daily) starting 12 h prior to surgery. The primary efficacy outcome was the incidence of VTE (detected by bilateral venography or symptomatic events) during treatment. RESULTS: Of the 1949 treated patients, 1464 (75%) patients were evaluable for the efficacy analysis. VTE occurred in 28.5%, 17.4%, 16.6%, 13.1% and 24% of patients assigned to dabigatran etexilate 50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily and enoxaparin, respectively. A significant dose-dependent decrease in VTE occurred with increasing doses of dabigatran etexilate (P < 0.0001). Compared with enoxaparin, VTE was significantly lower in patients receiving 150 mg twice daily [odds ratio (OR) 0.65, P = 0.04], 300 mg once daily (OR 0.61, P = 0.02) and 225 mg twice daily (OR 0.47, P = 0.0007). Compared with enoxaparin, major bleeding was significantly lower with 50 mg twice daily (0.3% vs. 2.0%, P = 0.047) but elevated with higher doses, nearly reaching statistical significance with the 300 mg once-daily dose (4.7%, P = 0.051). CONCLUSIONS: Oral administration of dabigatran etexilate, commenced early in the postoperative period, was effective and safe across a range of doses. Further optimization of the efficacy/safety balance will be addressed in future studies.
BACKGROUND: Recent changes in the management of hip fracture surgery patients may have modified the epidemiology of postoperative complications. OBJECTIVES: We performed an observational study of a cohort of patients undergoing hip fracture surgery to update the epidemiological data on this population. The primary study outcome was the incidence of confirmed symptomatic venous thromboembolism (VTE) [defined as deep vein thrombosis, pulmonary embolism (PE), or both] at 3 months. Overall mortality at 1, 3 and 6 months was also evaluated. PATIENTS/METHODS: Consecutive patients aged at least 18 years hospitalized in French public or private hospitals (531 centers) undergoing hip fracture surgery were recruited prospectively during 2 months in 2002 and a follow-up at 6 months. Predictive factors for VTE at 3 months and for death at 6 months were also analyzed. RESULTS: Data from 6860 (97.3%) of the 7019 recruited patients were included in the analysis. The median age was 82 years. Low molecular weight heparins were administered perioperatively in 97.6% of patients; 69.5% received this treatment for at least 4 weeks. The actuarial rate of confirmed symptomatic VTE at 3 months was 1.34% (85 events, 95% CI: 1.04-1.64). There were 16 PEs (actuarial rate: 0.25%), three of which were fatal. Overall, 1006 (14.7%) patients were dead at 6 months. Cardiovascular disease was the most frequent cause of death (270 patients; 26.8%). CONCLUSIONS: The current rate of postoperative VTE is low, but overall mortality remains high. Indeed, hip fracture patients belong to a vulnerable group of old people with comorbid diseases and a high risk of postoperative morbidity and mortality. An interdisciplinary approach could be the challenge to improve short and long-term outcome.
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The oral direct thrombin inhibitor ximelagatran shows great promise for prevention of venous thromboembolic events following major elective orthopaedic surgery. Its consistent and predictable pharmacokinetics and pharmacodynamics across a wide range of patient populations allow administration with fixed dosing and with no coagulation monitoring. In orthopaedic surgery clinical trials, ximelagatran was effective and well tolerated compared with standard therapy, with dose and timing relative to surgery important factors in determining its optimal profile. In European trials, an initial 3-mg postoperative dose of subcutaneous melagatran, the active form of ximelagatran, followed by oral ximelagatran 24 mg twice daily achieved similar efficacy and safety to enoxaparin. Although the risk of spinal haematoma following neuraxial anaesthesia is rare, it is increased by the concomitant use of anticoagulants. In orthopaedic surgery trials with ximelagatran to date, complications such as spinal haematoma have not been reported. The pharmacokinetic profile of ximelagatran suggests that concurrent use with neuraxial anaesthesia should require no further precautions than those currently necessary with low-molecular-weight heparin.
In moderately anaemic patients, Autologous Blood Donation is much less effective than Erythropoïetin (EPO) at constituting a pre-operative RBC reserve. Indeed, the ability to give blood is limited or even impossible for anaemic individuals. EPO lowers the risks associated with autologous and allogeneic transfusions, while improving probably the quality of life of the patients. EPO therapy is efficient, in moderate anaemic patients, to reduce allogeneic transfusion when iron supplementation is associated. All blood conservation techniques carry their own efficiency limits, constraints and risks that, in addition to institutional considerations and individual patient characteristics, are determinant to settle a blood conservation strategy. But to optimise benefit/cost/effectiveness of this technique, it is important to take into account the delay before surgery, the anticipated blood loss for the procedure that varies among institutions and the tolerable blood loss without transfusion for the patient. To reduce the cost, a strategy according to baseline haematocrit and to blood loss has to be adapted at each patient. Furthermore, when the delay between the first EPO injection and the surgical procedure is sufficient, the number of injections can be easily reduced to obtain the same Ht the day prior to surgery.
BACKGROUND: Ximelagatran and its subcutaneous (s.c.) form melagatran are novel direct thrombin inhibitors for the prevention and treatment of thromboembolic disease. METHODS: In a double-blind study, 2835 consecutive patients undergoing total hip or knee replacement were randomized to either melagatran/ximelagatran or enoxaparin. Melagatran 2 mg was started immediately before surgery; 3 mg was then administered postoperatively, followed by 24 mg of oral ximelagatran b.i.d. beginning the next day. Enoxaparin 40 mg, administered subcutaneously o.d., was started 12 h before surgery. Both treatments were continued for 8-11 days. The main efficacy outcome measures were major venous thromboembolism (VTE); [proximal deep vein thrombosis (DVT), non-fatal and/or fatal pulmonary embolism (PE), death where PE could not be ruled out], and total VTE (proximal and distal DVT; PE; death from all causes). DVT was detected by mandatory bilateral ascending venography at the end of the treatment period or earlier if clinically suspected. The main safety outcome was bleeding. RESULTS: The rates of major and total VTE were significantly lower in the melagatran/ximelagatran group compared with the enoxaparin group (2.3% vs. 6.3%, P = 0.0000018; and 20.3% vs. 26.6%, P < 0.0004, respectively). Fatal bleeding, critical site bleeding and bleeding requiring reoperation did not differ between the two groups. 'Excessive bleeding as judged by the investigator' was more frequent with melagatran/ximelagatran than with enoxaparin. CONCLUSIONS: In patients undergoing total hip or knee replacement, preoperatively initiated s.c. melagatran followed by oral ximelagatran was significantly more effective in preventing VTE than preoperatively initiated s.c. enoxaparin.
Autologous blood transfusion techniques are the principal means of reducing allogeneic blood exposure. Those techniques were developed in order to prevent the risk of contamination by viruses, mainly HVB, HCV and HIV. However that risk has become so small that all studies show an exorbitant cost/efficiency ratio. Autologous blood transfusion would therefore be of no interest in terms of public health but a recent experimental study suggested a possible transmission of the BSE agent through blood. Until the matter is settled, the precaution principle means we should prefer alternative techniques to allogeneic blood whenever possible, hence a renewed interest in autologous transfusion.
We studied the perioperative blood loss in 100 total hip arthroplasties performed for rapidly destructive coxarthrosis and compared it with the blood loss in 100 total hip arthroplasties for regular coxarthrosis. The treatment protocol was identical in both groups. Total blood loss was calculated as the compensated blood loss (volume transfused during and immediately after surgery) and the non-compensated blood loss using Nadler and Mercuriali formula. The mean blood loss calculated in milliliters of red blood cells (100% haematocrit) was 578 ml in regular coxarthrosis and 945 ml in rapidly destructive coxarthrosis. The blood loss after total hip arthroplasty is greater when surgery is performed for rapidly destructive coxarthrosis than for regular coxarthrosis (P < 0.001).
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The amount of transfused blood is related to blood loss calculated for the specific type of surgical procedure, transfusion hematocrit trigger and patient's red blood cell mass on the day before surgery. To optimise the benefit/cost and benefit/risk ratios of blood transfusion, a correct prescription must be done in accordance with the patient's red blood cell mass and surgical blood loss. Indeed, there is a clear need to define the appropriate uses of blood management methods and to seek new methods of improving perioperative blood management. The number of moderately anaemic patients undergoing surgery is currently thought to be 20%. Where transfusion requirements are estimated at two to three blood units, as for instance in the most common types of orthopaedic surgery, preoperative haemoglobin is the key factor governing transfusion needs. In this case, the simplest approach is to prescribe Epoetin Alfa subcutaneous at a dose of 600 IU/kg/week starting three weeks before the surgery. In addition, it is important in all cases to give concomitant iron supplements. Concomitant use of other methods to decrease allogeneic blood requirements is of no value. Obviously, the higher the haematocrit the day prior to surgery, the higher the patient's RBC mass and the greater the patient's permitted blood loss, decreasing the transfusion trigger. In this way, allogeneic blood loss is reduced, but without the need for the patient to attend the blood transfusion center and to undergo laboratory screening and testing of donated blood, and without the risk of inducing preoperative anaemia compared with sequential autologous blood donation. But, to optimise the benefit/cost ratio, we try to define precisely the patient populations likely to benefit from preoperative erythropoietin. Using different examples, management is proposed with algorithms.
BACKGROUND: Patients who undergo total hip replacement have a high risk of thromboembolic complications. Recombinant hirudin (desirudin), a specific inhibitor of thrombin, represents a new development in antithrombotic therapy. We compared the efficacy and safety of desirudin with those of a low-molecular-weight heparin (enoxaparin) for the prevention of thromboembolic complications in patients undergoing primary total hip replacement. METHODS: Both treatments, which were assigned in a randomized, double-blind manner, were started preoperatively: enoxaparin on the evening before surgery, and desirudin within 30 minutes before the start of surgery. The dose of desirudin was 15 mg subcutaneously twice daily, and the dose of enoxaparin was 40 mg subcutaneously once daily. The duration of treatment was 8 to 12 days. Deep-vein thrombosis was verified by bilateral venography performed at the end of the treatment period or earlier, if there were clinical signs of deep-vein thrombosis. RESULTS: At 31 centers in 10 European countries, 2079 eligible patients were randomly assigned to receive desirudin or enoxaparin. A total of 1587 patients were included in the primary analysis of efficacy. In the desirudin group, as compared with the enoxaparin group, there was a significantly lower rate of proximal deep-vein thrombosis (4.5 vs. 7.5 percent, P=0.01; relative reduction in risk, 40.3 percent) and a lower overall rate of deep-vein thrombosis (18.4 vs. 25.5 percent, P=0.001; relative reduction in risk, 28.0 percent). The safety profiles were similar in the two treatment groups. CONCLUSIONS: When administered 30 minutes before total hip replacement surgery, desirudin is more effective than enoxaparin in preventing deep-vein thrombosis.
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Total hip replacement is an extremely frequent operation for the treatment of degenerative joint disease. Indication for surgery must take into account the patient's general status, associated diseases, multiple joint involvement, and the efficacy and tolerance to medical treatments. The decision to operate is taken together by the physician and the patient. The degree of functional impairment and the patient's age are important factors. The patient must be informed that the period of hospitalization will be approximately 15 days and that good results are obtained in approximately 98% of the cases. Preoperative consultation with the anesthesist will focus on associated diseases with special attention to possible infectious foyers. Early post operative care includes a 48 hour antibiotic reginien, thromboprophylaxy with low molecular weight heparin for 3 days followed by anti-vitamin K for 6 weeks, and non-steroid antiinflammatory drugs for 5 days of up to 6 weeks in case of suspected risk of ossification. At mid-term, complications may include hematomas, infection and luxation. The fixation may also fail in certain cases where transtrochanter access was used. Long-term follow-up monitors for possible late onset infection and late luxations which usually result from prosthesis wear and more rarely from muscular causes.
OBJECTIVES: To compare three techniques for decreasing homologous blood requirements in total hip arthroplasty (THA), including preoperative autologous donation (PAD), preoperative acute normovolaemic haemodilution with erythrocytapheresis (erythro) and intraoperative normovolaemic haemodilution (haemo). STUDY DESIGN: Prospective clinical trial. PATIENTS: The study included 45 patients scheduled for THA, under general anaesthesia and operated on by the same surgeon. The patients were allocated into three groups of 15 each. METHODS: Blood loss was assessed, during surgical procedure, by the weight of sponges and, the amount of blood collected in the suction bottles during and after surgery. The haemoglobin concentration was measured at the time of preoperative assessement (d-30), just prior to surgery (d-1), in the recovery room (d+3h), and 1, 3, and 8 days later (d8). The transfusion end-point in the three groups was to obtain a haemoglobin concentration of 100 g.L-1 from d+3h until d8. Every pack of red blood cells transfused was weighed and its haematocrit assessed to determine the accurate volume of red blood cells. RESULTS: In the three groups haemoglobin concentration was similar from d+3h until d8. In the PAD group, no patient required homologous blood transfusion. There was no significant difference between the two other groups in the mean volume of homologous red blood cells required (308 +/- 197 mL in erythro group and 331 +/- 202 mL in the haemo group, respectively). The intraoperative blood loss was significantly higher (P = 0.001) in the erythro group: 914 +/- 305 mL vs 665 +/- 263 in the PAD group and 512 +/- 146 mL in the haemo group, respectively. There was an inverse correlation between haematocrit at d-1 and intraoperative bleeding (r = -0.7) (P = 0.0001). The distribution of the points was fitted as an exponential curve. CONCLUSIONS: In THA, PAD is obviously the best technique to avoid homologous blood transfusion. However, when PAD is not feasible, removal of blood prior to surgery does not decrease requirements of homologous blood, as intraoperative blood loss is higher. Our results strongly question the use of major haemodilution during a surgical procedure exposing a major blood loss.