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PAIN MEDICINE

A Comparison of Depodur^TM, a Novel, Single-Dose Extended-Release Epidural Morphine, with Standard Epidural Morphine for Pain Relief After Lower Abdominal Surgery

David Gambling, MB, BS, FRCPC^*, Thomas Hughes, MD, Gavin Martin, MD, William Horton, MD, Garen Manvelian, MD^|| for the Single-Dose EREM Study Group

*Sharp Mary Birch Hospital for Women, San Diego, California; Woodland Memorial Hospital, Woodland, California; Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; Progressive Research, LLC, Greenville, South Carolina; and ||SkyePharma, Inc., San Diego, California

Address correspondence and reprint requests to David Gambling, MB, BS, FRCPC, Sharp Mary Birch Hospital for Women, Department of Anesthesiology (Second Floor), 3003 Health Center Dr., San Diego, CA 92123. Address e-mail to dgamb{at}san.rr.com.

In this randomized, controlled, dose-ranging study, we evaluated the analgesic efficacy of a novel single-dose extended-release epidural morphine (Depodur^TM) in patients undergoing lower abdominal surgery. Five-hundred-forty-one patients were randomly assigned to one of six epidural treatments administered approximately 30 min before surgery. The 6 treatments were 5 mg of standard epidural morphine sulfate (MS) (active comparator); 5 mg of single-dose extended-release epidural morphine (EREM) (dose control); and 10, 15, 20, and 25 mg of single-dose EREM. The main study objective was to assess the efficacy of single-dose EREM 10, 15, 20, or 25 mg versus single-dose EREM 5 mg for the management of postoperative pain. This was done by plotting a linear dose-response relationship to assess postoperative IV patient-controlled analgesia (PCA) fentanyl consumption for breakthrough pain for 48 h after surgery. Secondary safety and efficacy analyses compared the 10-, 15-, 20-, and 25-mg single-dose EREM groups with the 5-mg single-dose EREM group and compared each single-dose EREM group with 5 mg of MS. As shown by the dose-response relationship, there was a dose-related reduction in the use of postoperative IV fentanyl through 48 h (estimated slope, –22.2; P = 0.0002). Patients treated with 10, 20, and 25 mg of single-dose EREM used significantly less IV fentanyl (mean ± sd: 995 ± 987 µg, P = 0.0446; 972 ± 982 µg, P = 0.0221; and 683 ± 620 µg, P < 0.0001, respectively) through 48 h after surgery compared with the 5-mg single-dose EREM group (1218 ± 894 µg). At 48 h postdose, significantly more single-dose EREM patients (13%) than MS patients (2%) had required no IV fentanyl (P < 0.01). Although all treatment groups had access to PCA fentanyl and there was more frequent PCA fentanyl use in the MS group, patients in the single-dose EREM 15, 20, and 25 mg groups reported significantly lower pain-intensity scores and greater satisfaction with their pain relief. Overall, single-dose EREM was well tolerated, with 97% of adverse events rated as mild to moderate. As expected, the adverse events reported were consistent with those of other epidural opioids (i.e., nausea, vomiting, pruritus, and hypotension). In conclusion, this controlled study demonstrated that single-dose EREM can provide up to 48 h of postoperative analgesia, but supplementation for breakthrough pain is still required in most patients. Within the context of this study, the side effect profile of single-dose EREM was acceptable and predictable.

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