PURPOSE:

• Active management of the 3^rd 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.

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?