Double Simultaneous Uterotonic Agents Versus Single Agent Regimen to Prevent Early Postpartum Hemorrhage

Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality in the world, accounting for a quarter of all maternal deaths globally. Most cases of PPH can be attributed to uterine atony, failure of the uterus to contract in the immediate postpartum period. Efforts to prevent uterine atony and thereby PPH have focused on active clinical management of the third stage of labor (the period between delivery of the infant and placenta) and the administration of uterotonic agents (medication that induces uterine contraction). Universal standard of care to prevent postpartum hemorrhage, according to the American College of Obstetrics and Gynecologists and World Health Organization includes various dose infusions of oxytocin. Additional uterotonics are given if necessary, according to noted blood loss and uterine tone. The best uterotonic(s), combination, route, and dose, however, remain actively debated. Randomized controlled trials have not proven that misoprostol is superior to oxytocin or methergine to treat postpartum hemorrhage, but it is a medication that is often used conjunctively or after other agents fail. A Cochrane review of treatment of primary postpartum hemorrhage revealed that oxytocin, ergot alkaloids (i.e., methergine), and combined oxytocin-ergot alkaloid administration were equally effective in preventing PPH in the general obstetric population, whereas prostaglandins alone (i.e., misoprostol) were not. In an effort to determine the benefit of a simultaneous double uterotonic agent regimen in the prevention of PPH, the investigators propose to conduct a controlled trial in which women will be randomly assigned to an intervention group (buccal misoprostol and intravenous oxytocin administered simultaneously) versus a control group (standard of care, intravenous oxytocin alone).