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#Grand Rounds

Cochrane Review 2018: Uterotonic Agents for PPH Prophylaxis

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PURPOSE:

  • Active management of the 3rd stage of labor
    • Uterotonics for PPH prophylaxis administered immediately prior to or after placental delivery
    • Controlled cord traction until delivery of the placenta
  • Gallos et al. (Cochrane Reviews, 2018) sought to determine the effectiveness and safety profile of uterotonic agents used for PPH prophylaxis

METHODS:

  • Systematic Review and meta-analysis
    • RCTs and cluster-randomized trials that assessed effectiveness and side-effects of uterotonics for PPH prophylaxis
  • 7 uterotonics were compared
    • Against each other
    • Against women receiving no uterotonic agents

RESULTS:

  • 196 trials included | 135,559 women
    • 7 uterotonics
    • 53 countries (high-, middle- and low-income countries)
    • 95.4% in a hospital setting
    • 71.5% vaginal delivery
  • Highest ranked uterotonics (PPH ≥ 500 mL) that were more effective compared to oxytocin
    • Ergometrine plus oxytocin combination: RR 0.70 (95% CI 0.59 to 0.84, moderate certainty)
    • Misoprostol plus oxytocin combination: RR 0.70 (95% CI 0.59 to 0.84, moderate certainty)
    • Carbetocin: RR 0.72 (95% CI 0.56 to 0.93, moderate certainty)
    • Misoprostol alone, injectable prostaglandins, and ergometrine did not perform better than oxytocin
  • Misoprostol plus oxytocin when compared to oxytocin
    • Reduced the use of additional uterotonics: RR 0.56 (95% CI 0.42 to 0.73, high certainty)
    • Reduced the risk of blood transfusion: RR 0.51 (95% CI 0.37 to 0.70, moderate certainty)
  • Maternal deaths or severe morbidity
    • Due to rarity of outcomes, differences for these outcomes could not be detected between the different uterotonic agents
  • Combination uterotonics had greater risk for significant side effects
    • Misoprostol and oxytocin combination: Increased risk of vomiting and fever
    • Ergometrine plus oxytocin: Increased risk of vomiting
  • Subgroup analysis
    • No difference between vaginal and cesarean delivery
    • Hospital vs community setting
    • High vs low risk for PPH
    • Misoprostol: ≥600 mcg vs <600 mcg
    • Oxytocin: bolus only vs bolus and infusion vs infusion only

CONCLUSION:

  • All drugs were effective in the prevention of PPH ≥500 mL
  • The authors state

We found that oxytocin has substantial desirable effects compared with placebo or no treatment and trivial side effects. As a result, the balance of effects is expected to favour oxytocin.

  • While combination protocols may be more effective than oxytocin alone, their use is associated with higher risk of complications
  • Carbetocin may be more effective than oxytocin without additional adverse effects

Learn More – Primary Sources:

Cochrane Review: Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis.

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Related ObG Topics:

Postpartum Hemorrhage Prophylaxis: The World Health Organization Recommendations
Postpartum Hemorrhage – Medications to Treat Uterine Atony 
How Effective is Intrauterine Balloon Tamponade for Severe Postpartum Hemorrhage
Heat Stable Carbetocin: A Heat-Stable Alternative to Oxytocin?
Intramuscular or Intravenous Oxytocin to Prevent Postpartum Hemorrhage?

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