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Am Fam Physician. 2023;107(5):539-540

Author disclosure: No relevant financial relationships.

Clinical Question

What is the most effective medical therapy for preventing postpartum hemorrhage after vaginal delivery?

Evidence-Based Answer

Oxytocin plus misoprostol is more effective than oxytocin alone in reducing postpartum hemorrhage after vaginal delivery. (Strength of Recommendation [SOR]: A, network meta-analysis of a randomized controlled trial [RCT] and subsequent large RCT.) However, this combination causes more nausea and vomiting than oxytocin alone. Tranexamic acid plus oxytocin does not significantly reduce the rate of postpartum hemorrhage compared with oxytocin alone. (SOR: B, large RCT.) Overall, oxytocin is the medication of choice for the prevention of postpartum hemorrhage because of the balance of high effectiveness and low incidence of adverse effects. (SOR: C, expert opinion.)

Evidence Summary

A systematic review and network meta-analysis involving 137 RCTs (many multinational) and 87,466 women examined uterotonic medications for the prevention of postpartum hemorrhage and ranked their effectiveness.1 Trials examined oxytocin, ergometrine (not available in the United States; similar to methylergonovine), misoprostol, and carbetocin (not available in the United States; similar to oxytocin) as single agents and the combinations of oxytocin plus misoprostol and oxytocin plus ergometrine. Patients delivered by vaginal birth or cesarean section. The medication was administered prophylactically by a systemic route: sublingually, subcutaneously, intramuscularly, rectally, orally, via intravenous bolus, or intravenous infusion; the timing of administration varied. These interventions were compared with other uterotonics, placebo, or no treatment. Two medication combinations—misoprostol plus oxytocin and ergometrine plus oxytocin—were more effective than standard oxytocin but had higher rates of nausea and vomiting (Table 1).1 A subanalysis of data from vaginal deliveries only (85 trials, N not provided) yielded similar reductions in hemorrhages of 500 mL or greater compared with oxytocin alone (relative risk [RR] of oxytocin plus misoprostol = 0.74; 95% CI, 0.56 to 0.99; and RR of oxytocin plus ergometrine = 0.69; 95% CI, 0.56 to 0.84). Most trials (71%) had a high risk or unclear risk of bias.

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Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (

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