The efficacy of 2 doses of epidural morphine for postcesarean delivery analgesia: a randomized noninferiority trial.
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.


CONCLUSIONS
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.
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.
Sudha I
SI
Singh
Sarah
S
Rehou
Kristine L
KL
Marmai
And Philip M
APM
Jones
D000293:Adolescent; D000328:Adult; D016362:Analgesia, Obstetrical / Q000379:methods*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002585:Cesarean Section; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020910:Ketorolac / Q000627:therapeutic use; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D017060:Patient Satisfaction; D011247:Pregnancy; D011537:Pruritus / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009020:Morphine; D020910:Ketorolac