Evaluation of a single-dose, extended-release epidural morphine formulation for pain after knee arthroplasty.
BACKGROUND: DepoDur is a single-dose, extended-release epidural morphine formulation designed to provide forty-eight hours of pain relief. The drug offers potential advantages over continuous epidural infusions, particularly in patients being treated with anticoagulation therapy. The purpose of this study was to evaluate the efficacy and safety of single-dose epidural DepoDur for pain control following knee arthroplasty. METHODS: In this multicenter, randomized, double-blind, parallel-group study, patients were randomized to receive a single-dose of DepoDur (20 or 30 mg) or a sham epidural injection thirty minutes before administration of general or regional anesthesia for knee arthroplasty. At their first request for postoperative analgesia, patients who had received DepoDur were given an intravenous bolus of hydromorphone followed by placebo patient-controlled analgesia. Patients who had received the sham epidural were given an intravenous bolus of morphine followed by patient-controlled analgesia with morphine. Patient ratings of pain intensity at rest and with activity, their rating of overall pain control, and postoperative opioid use were recorded. The ability to tolerate physical therapy, the range of motion of the knee, and the need for physical support were assessed as well. Adverse events and vital signs were recorded. RESULTS: Of 168 patients randomized to receive the 20-mg injection of DepoDur, the 30-mg injection of DepoDur, or the sham epidural injection, fifty-one, fifty-eight, and fifty-five patients, respectively, were included in the efficacy analysis. Compared with the patients treated with intravenous patient-controlled analgesia with morphine, the patients treated with DepoDur had significantly reduced mean pain-intensity-recall scores during the four to eight, four to twelve, four to twenty-four, and four to thirty-hour postdose intervals (p < 0.05 for all comparisons). The patients treated with DepoDur used approximately a threefold lower amount of postoperative opioids in total, with a significant percentage requiring no supplemental opioids. Adverse events common to all groups were nausea (78%), pyrexia (46%), vomiting (43%), pruritus (43%), and hypotension (36%). Respiratory depression was the most common serious adverse event, with serious respiratory depression observed in four DepoDur-treated patients, who were more than sixty-five years of age. CONCLUSIONS: With appropriate patient selection and monitoring, perioperative single-dose epidural DepoDur was a safe and effective analgesic alternative to postoperative intravenous patient-controlled analgesia following knee arthroplasty, with younger patients benefiting from the 20-mg dose. Additional studies of 10 to 15-mg doses for older patients are warranted.
Hartrick, CT; Martin, G; Kantor, G; Koncelik, J; Manvelian, G
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