September 2013
•
Volume 117
•
Number 3 www.anesthesia-analgesia.org 677
P
ain control after cesarean delivery presents unique
demands compared with other surgeries, because
women require a rapid recovery to ambulate and
care for their babies. Pain relief must be rapid and effec-
tive, with minimal adverse effects for both the mother and
her baby.
Epidural morphine is an acknowledged standard for
postcesarean delivery pain relief.
1,2
A single dose of epi-
dural morphine provides superior analgesia compared with
parenteral opioids.
1
Nevertheless, the optimal dose of epi-
dural morphine that maximizes analgesia while minimiz-
ing adverse effects is unknown. The side effects of epidural
morphine include pruritus, nausea, sedation, and respira-
tory depression.
1
A recent systematic review
1
recommended 4 mg epidural
morphine for good analgesia after cesarean delivery with
an acceptable side effect profle. The studies included in this
review differed from contemporary practice in that epidural
morphine was not administered as part of a multimodal
The Efficacy of 2 Doses of Epidural Morphine for
Postcesarean Delivery Analgesia: A Randomized
Noninferiority Trial
Sudha I. Singh, MD, FRCPC,* Sarah Rehou, BSc (Hons),† Kristine L. Marmai, MD, FRCPC,‡
and Philip M. Jones, MD, MSc, FRCPC§
Copyright © 2013 International Anesthesia Research Society
DOI: 10.1213/ANE.0b013e31829cfd21
From the Departments of *Anesthesia & Perioperative Medicine, University
Hospital-LHSC, St. Joseph’s Hospital, Schulich School of Medicine & Den-
tistry, †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.
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 conficts 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 (www.anesthesia-analgesia.org).
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
indu.singh@sjhc.london.on.ca.
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 mor-
phine. 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 frst 24 hours. A prespecifed 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 frst 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 dif-
ference 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% confdence interval [CI], 2.5 mg), which was less than
the prespecifed noninferiority margin of 3.33 mg. No signifcant 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
signifcantly 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. (Anesth Analg 2013;117:677–85)
Section Editor: Cynthia A. Wong
Society for Obstetric Anesthesia and Perinatology