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Meta-analysis of the effect of extended-release epidural morphine versus intravenous patient-controlled analgesia on respiratory depression

Shawn Sumida, MD, Maggie R. Lesley, BS, Marie N. Hanna, MD, Jamie D. Murphy, MD, Kanupriya Kumar, MD, Christopher L. Wu, MD


Objective: Extended-release epidural morphine (EREM) is a single-dose, extended-release epidural morphine formulation intended to provide postoperative pain relief over a 48-hour period. There have been a few randomized controlled trials investigating the use and safety of EREM versus intravenous patient-controlled analgesia with opioids (IV-PCA); however, the adverse event of respiratory depression of this treatment is unclear. The authors have undertaken a meta-analysis to examine this issue.
Methods: A systematic literature search of the National Library of Medicine’s PubMed database was conducted for terms related to EREM. Only randomized controlled trials, in the English language, assessing the rates of respiratory depression of EREM to IV-PCA were included for analysis. Data on pertinent study characteristics and relevant outcomes were extracted from accepted articles. Meta-analysis was performed using the Review Manager 4.2.7 (The Cochrane Collaboration, 2004). A random effects model was used.
Results: The authors’ literature search yielded three articles which met all inclusion criteria. All studied doses of EREM were evaluated. Pooled estimates (odds ratio) were made for rates of adverse events of respiratory depression. Use of EREM was associated with significantly higher odds of respiratory depression compared to IV-PCA (odds ratio = 5.74; 95% confidence interval: 1.08, 30.54, p = 0.04). Even when examining only Food and Drug Administration approved dosages for EREM, the use of EREM was associated with significantly higher odds of respiratory depression when compared with IV-PCA (odds ratio = 5.80; 95% confidence interval: 1.05, 31.93, p = 0.04).
Conclusions: Although perioperative single-dose epidural EREM (versus IV-PCA) was effective for postoperative pain relief for up to 48 hours, it is associated with significantly higher odds of respiratory depression. Further examination of the issue of respiratory depression of epidural EREM may be warranted.


meta-analysis, respiratory depression, extended-release epidural morphine

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