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Grand Rounds

Meta-Analysis: Comparison of Medications for PPH Prevention During Cesarean Delivery

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BACKGROUND AND PURPOSE:

  • WHO recommends oxytocin for PPH prophylaxis based on Cochrane network meta-analysis
    • Limited focus on cesarean delivery
  • Jaffer et al. (AJOG, 2021) conducted a network meta-analysis of pharmacologic agents to reduce blood loss and minimize uterotonics during cesarean delivery

METHODS:

  • Systematic review and network meta-analysis
  • Inclusion criteria
    • RCTs
    • Studies that compared
      • Oxytocin | Carbetocin | Misoprostol | Ergometrine | Carboprost | Combinations of these medications
      • Medications used to prevent PPH during cesarean delivery
  • Study design
    • Quality of the evidence was assessed with GRADE criteria
    • Additional analyses were used to explore the influence of surgical context and oxytocin administration strategy
  • Primary outcomes
    • Estimated blood loss
    • Need for additional uterotonics
  • Secondary outcomes
    • Nausea
    • PPH >1000 mL

RESULTS:

  • 46 studies | 7368 participants

Estimated Blood Loss: 21 trials | 3665 participants

  • Carbetocin was assessed to probably be superior to oxytocin, but only in reducing the estimated blood loss by a clinically insignificant volume
    • Mean difference in blood loss with carbetocin: –54.83 mL (95% CI, 26.48 to 143.78)
  • The following were assessed to probably be inferior to oxytocin
    • Misoprostol
    • Ergometrine
    • Combination of oxytocin and ergometrine
  • The combination of oxytocin and misoprostol was assessed to definitely be inferior to oxytocin

Additional Uterotonics: 37 trials | 6193 participants

  • Carbetocin was assessed to probably be superior to oxytocin
    • Difference in need for additional uterotonics with carbetocin: 185 fewer times per 1000 cases (95% CI, 130 to 218)
  • The following were assessed to probably be inferior to oxytocin
    • Oxytocin plus misoprostol
    • Oxytocin plus ergometrine
    • Misoprostol
  • The following were assessed to be definitely inferior to oxytocin
    • Carboprost
    • Ergometrine
    • Placebo
  • For both primary outcomes, oxytocin had a higher probability of being the best preventative medication if initiated as a bolus

CONCLUSION:

  • Carbetocin is probably a superior first line uterotonic, compared to oxytocin, for preventing PPH after cesarean
    • However, the difference in blood loss with carbetocin was clinically insignificant, compared to oxytocin
    • Oxytocin may have a higher probability of superior medication performance if given as a bolus
  • There was a reduced need for addition uterotonics with carbetocin
  • Limitations of the study: Heterogeneity | Unable to examine modifiers such as BMI or baseline risk for PPH
  • The authors state

…carbetocin may be the most effective, but larger high-quality randomized controlled trials are required to confirm this, and further research is also warranted to confirm the optimal administration strategy for oxytocin

Learn More – Primary Sources:

Preventing postpartum hemorrhage after cesarean delivery: a network meta-analysis of available pharmacologic agents

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Related ObG Topics:

RCT Results: Does the Addition of Uterotonics to Prophylactic Oxytocin Reduce PPH following Cesarean for Arrest of Labor
What are the Possible Causes of a PPH that is Unresponsive to First Line Uterotonics?
Cochrane Review 2018: Uterotonic Agents for PPH Prophylaxis
Cochrane Review: Oxytocin to Prevent Postpartum Hemorrhage in Third Stage of Labor
Meta-Analysis: Is There an Optimal IV Oxytocin Dosing Regimen for PPH Prevention Post-Cesarean? A Meta-Analysis

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