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

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