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The Effect of Intrathecal Morphine Dose on Outcomes After Elective Cesarean Delivery: A Meta-Analysis

Sultan, Pervez MBChB, FRCA; Halpern, Stephen H. MD; Pushpanathan, Ellile MBBS, BMedSci, FRCA; Patel, Selina MBBS, FRCA; Carvalho, Brendan MBBCh, FRCA

doi: 10.1213/ANE.0000000000001255
Obstetric Anesthesiology: Meta-Analysis

BACKGROUND: The intrathecal morphine dose achieving optimal analgesia for cesarean delivery while minimizing side effects has not yet been deduced. In this meta-analysis, our objective was to determine whether low- or high-dose intrathecal morphine provides acceptable duration and intensity of analgesia with fewer side effects.

METHODS: A literature search (PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and CINAHL) was performed to identify randomized controlled trials involving patients undergoing elective cesarean delivery under spinal anesthesia comparing low-dose (LD; 50–100 μg) morphine with higher dose (HD; >100–250 μg). The primary outcome was the time for first request for supplemental analgesia. The secondary outcomes included pain scores, morphine use, maternal side effects (vomiting and pruritus), and Apgar scores. Mean differences (MDs) and odds ratios (ORs) were calculated using random effects modeling with 95% confidence intervals (CIs).

RESULTS: Eleven articles met our inclusion criteria. Four hundred eighty patients were recruited in all study groups (233 patients in the HD and 247 in the LD groups). The mean time to first analgesic request was longer (MD, 4.49 hours [95% CI, 1.85–7.13]; P = 0.0008) in the HD group compared with the LD group. Pain scores (0–100 scale) at 12 hours (MD, 2.54 [95% CI, −2.55 to 7.63]; P = 0.33) as well as morphine consumption at 24 hours (MD, 1.31 mg [95% CI, −3.06 to 7.31]; P = 0.42) were not significantly different. The incidence of nausea or vomiting (OR, 0.44 [95% CI, 0.27–0.73]; P = 0.002) and pruritus (OR, 0.34 [95% CI, 0.20–0.59]; P = 0.0001) was lower in the LD group. The incidence of Apgar scores <7 at 1 minute was not different between groups (OR, 1.11 [95% CI, 0.06–20.49]; P = 0.94).

CONCLUSIONS: This meta-analysis shows that HDs of intrathecal morphine prolong analgesia after cesarean delivery compared with lower doses. The MD of 4.5 hours (95% CI, 1.9–7.1 and 99% CI, 1.0–8.2 hours) of pain relief must be balanced against the increased risk of maternal pruritus and vomiting. Results from this study can be used by clinicians to weigh the benefits and potential side effects of using HDs of intrathecal morphine for cesarean delivery.

Supplemental Digital Content is available in the text.Published ahead of print April 13, 2016

From the *Department of Anaesthesia, University College London Hospital, London, United Kingdom; Department of Anesthesia, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Anaesthesia, St. Thomas’ Hospital, London, United Kingdom; and §Department of Anesthesia, Stanford University School of Medicine, Stanford, California.

Accepted for publication February 8, 2016.

Published ahead of print April 13, 2016

Funding: Dr. Sultan has received research capability funding from the National Institute for Health Research (reference RCF146/PS/2014).

The authors declare no conflicts of interest.

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Address correspondence to Pervez Sultan, Department of Anaesthesia, University College London Hospital, 235 Euston Rd., London, NW1 2BU, United Kingdom. Address e-mail to

© 2016 International Anesthesia Research Society