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The Efficacy of 2 Doses of Epidural Morphine for Postcesarean Delivery Analgesia: A Randomized Noninferiority Trial

Singh, Sudha I. MD, FRCPC*; Rehou, Sarah BSc (Hons); Marmai, Kristine L. MD, FRCPC; Jones, and Philip M. MD, MSc, FRCPC§

doi: 10.1213/ANE.0b013e31829cfd21
Obstetric Anesthesiology: Research Report

BACKGROUND: A single dose of epidural morphine is effective in reducing pain after cesarean delivery but is associated with adverse effects. In this study, we sought to establish whether half the traditional dose of epidural morphine, when administered as part of a multimodal analgesia regimen after cesarean delivery, was associated with noninferior analgesia and fewer adverse effects.

METHODS: Ninety term parturients undergoing cesarean delivery under epidural anesthesia were enrolled in this randomized, double-blinded, noninferiority study. Patients were randomly allocated to receive either 3 mg epidural morphine or, half this dose, 1.5 mg epidural morphine. In addition, subjects received regular systemic ketorolac and acetaminophen. Rescue analgesia (oral oxycodone) was administered for breakthrough pain. The primary outcome was the difference between groups in total opioid consumption (measured in median IV morphine equivalents) within the first 24 hours. A prespecified noninferiority margin of 3.33 mg was used. Secondary outcomes included total opioid consumption from 24 to 48 hours, numerical rating scale pain scores, time to first request for analgesics, overall pain relief, maternal satisfaction, quality of recovery, and adverse effects.

RESULTS: Data were analyzed for 87 participants. Noninferiority was demonstrated as the difference in median 24-hour opioid consumption between the 1.5 mg epidural morphine (EM) and 3 mg EM groups was 0 mg (1-sided 95% confidence interval [CI], 2.5 mg), which was less than the prespecified noninferiority margin of 3.33 mg. No significant differences were found between groups in the median 24- to 48-hour opioid consumption or the median total opioid consumption within 48 hours. Pain scores, overall pain relief, and satisfaction at 24 and 48 hours were not significantly different between groups. The 1.5 mg EM group had a lower incidence of moderate and severe pruritus at 6 and 12 hours (relative risk [RR] 0.44, 95% CI, 0.2–0.9 and RR 0.41, 95% CI, 0.2–0.8, respectively) and had less nausea and vomiting at 6 hours (RR 0.22, 95% CI, 0.05–0.9). There was no difference in average pain scores at 12 weeks between the 2 groups.

CONCLUSION: When used as part of a multimodal analgesia regimen, 1.5 mg epidural morphine provided noninferior postcesarean analgesia and caused fewer adverse effects compared with 3 mg epidural morphine.

Supplemental Digital Content is available in the text.Published ahead of print August 6, 2013

From the Departments of *Anesthesia & Perioperative Medicine, University Hospital-LHSC, St. Joseph’s Hospital, Schulich School of Medicine & Dentistry, Anesthesia & Perioperative Medicine, Schulich School of Medicine & Dentistry, St. Joseph’s Hospital, Anesthesia & Perioperative Medicine, Victoria Hospital-LHSC, and §Anesthesia & Perioperative Medicine and Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.

Accepted for publication April 15, 2013.

Published ahead of print August 6, 2013

Funding: Supported by a Departmental Internal Fund from the Department of Anesthesia & Perioperative Medicine at the Schulich School of Medicine & Dentistry, The University of Western Ontario.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site.

Reprints will not be available from the authors.

Address correspondence to Sudha I. Singh, MD, FRCPC, Department of Anesthesia & Perioperative Medicine, St. Joseph’s Hospital, Schulich School of Medicine & Dentistry, The University of Western Ontario, Room A1-609, 268 Grosvenor St., London, ON N6A 2V2, Canada. Address e-mail to

© 2013 International Anesthesia Research Society