Preventing Postpartum Hemorrhage After Cesarean Delivery: A Network Meta-Analysis of Available Pharmacologic Agents.

Abstract Background Postpartum hemorrhage causes a quarter of global maternal deaths. WHO recommends oxytocin as the first line agent to prevent hemorrhage at cesarean delivery. However, some randomized controlled trials suggest other uterotonics are superior. Objective We conducted a network meta-analysis comparing pharmacological agents in reducing blood loss and minimizing need for additional uterotonics at cesarean delivery. Study design We searched the CENTRAL, Embase, and Medline databases, from inception to May 2020, for randomized controlled trials that compared oxytocin, carbetocin, misoprostol, ergometrine, carboprost or combinations of these. Quality of evidence was assessed with the “Confidence in Network Meta-Analysis” approach and GRADE tool within the summary of findings table. Our primary outcomes were estimated blood loss and need for additional uterotonics. Secondary outcomes included nausea and postpartum hemorrhage of > 1000 ml. We performed sensitivity analyses to explore the influence of surgical context and oxytocin administration strategy. Results 46 studies with 7368 participants were included. 21 trials (6 agents and 3665 participants) formed the “estimated blood loss” network, and considering treatment effects, certainty in the evidence and SUCRA scores, carbetocin was assessed to be probably superior to oxytocin but only to reduce estimated blood loss by a clinically insignificant volume (54.83 [95% CI: 26.48 more to 143.78 less] ml). Misoprostol, ergometrine and the combination of oxytocin + ergometrine were assessed as probably inferior whilst the combination of oxytocin + misoprostol was assessed as definitely inferior to oxytocin. 37 trials (8 agents and 6193 participants) formed the “additional uterotonic” network and, again, carbetocin was assessed as probably superior to oxytocin, requiring additional uterotonics 185 (95% CI: 130 to 218) fewer times per 1000. Oxytocin + misoprostol, oxytocin + ergometrine and misoprostol were assessed to be probably inferior whilst carboprost, ergometrine and placebo were definitely inferior to oxytocin. For both primary outcomes, oxytocin administration strategies had a higher probability of being the best uterotonic if they were initiated with a bolus. Conclusions Carbetocin is probably the most effective agent in reducing blood loss and the need for additional uterotonics. Oxytocin appears to be more effective when initiated with a bolus.