The Safety of Co-Administered Low-Molecular-Weight Heparin and Continuous Epidural Analgesia after Major Orthopedic Surgery: Assessment of a Standardized Management Protocol.

Background: In patients who have had major orthopedic surgery, low-molecular-weight heparin (LMWH) has established efficacy in preventing venous thromboembolism (VTE) after surgery, and continuous epidural analgesia (CEA) provides better pain control than parenteral analgesia and may reduce the risk of cardiorespiratory complications. However, there is concern about the co-administration of LMWH and CEA after surgery because of an increased risk of epidural hematoma. No study, to our knowledge, has investigated the safety of a standardized treatment regimen that allows co-administered LMWH and CEA after surgery.

Patients and Methods: We assessed the safety of a standardized management protocol in 970 patients who were scheduled to undergo knee or hip replacement surgery and who received post-operative thromboprophylaxis with LMWH and pain control with CEA. All patients received intra-operative spinal (regional) anesthesia, with an indwelling epidural catheter left in place after surgery to administer epidural analgesia with an infusion of fentanyl and bupivacaine. Subcutaneous LMWH (enoxaparin 30 mg twice-daily or dalteparin 5000 IU daily) was started on the morning after surgery and continued for at least 5 days. CEA was administered for 2–3 days after surgery, with the epidural catheter removal occurring during the trough anticoagulant effect of the LMWH, 10 hours and 22 hours after the preceding dose of enoxaparin and dalteparin, respectively. In patients who were to receive warfarin, this treatment was initiated, with a 2.5 mg dose, on the evening prior to the scheduled removal of the epidural catheter. Drugs that are known to affect hemostasis were avoided during CEA, and patients at increased risk for bleeding were not given LMWH. During the period of hospitalization, we calculated the incidence and associated 95% confidence interval (CI) for the following outcomes: epidural hematoma; other bleeding (major and minor); VTE, myocardial infarction, stroke, death.

Results: 970 patients (mean age: 68.2 years; mean weight: 81.4 kg; 63% female) who underwent knee replacement (527 patients) or hip replacement (443 patients) received co-administered LMWH and CEA. The mean duration of LWMH therapy was 7.2±5.3 days. The mean duration (±standard deviation) of CEA was 1.9±0.80 days, respectively. Warfarin was initiated in 758 (78%) patients. There were no episodes of symptomatic epidural hematoma (0%; 95% CI: 0–0.38). During the in-hospital follow-up period, there were 13 episodes of VTE (1.3%; 95% CI: 0.71–2.3), 47 bleeds (4.7%; 95% CI: 3.5–6.3); 4 myocardial infarcts (0.41%; 95% CI: 0.12–1.1), and 4 deaths (0.41%; 95% CI: 0.12–1.1).

Conclusion: Co-administered LMWH and CEA appears safe after major orthopedic surgery when using a standardized management protocol.