Routine Uterotonics After Delivery: Is Misoprostol the Best Second Line Agent?

Worldwide, a woman dies every seven minutes from childbirth-related causes. The most common cause of death is postpartum hemorrhage. Anyone who has given birth knows that blood is par for the course, but bleeding more than 500ml for a vaginal delivery and more than 1,000ml for a cesarean delivery is diagnosed as “postpartum hemorrhage.” Fortunately, regions with good access to healthcare have significantly reduced the rates of postpartum hemorrhage with the routine use of uterotonics after delivery, most commonly, oxytocin. But, when routine oxytocin isn’t doing the trick, what is the best second agent to reach for? A new editorial by Dr. Barbieri of Harvard Medical School encourages birth attendants to leave the misoprostol behind.

Uterotonics are a class of drugs that help the uterus clamp down and thus stop bleeding after delivery. (Utero= uterus, tonics= increase tone.)  Doctors and midwives have four choices for uterotonics: oxytocin (aka pitocin), Hemabate, Methergine, and misoprostol. Practitioners routinely give oxytocin after delivery as the first line defense against hemorrhage, and this practice has reduced the incidence of postpartum hemorrhage to about 3%. However, for that 3%, further intervention is needed.

As a second line treatment to prevent or stop postpartum hemorrhage, providers have long turned to misoprostol. Misoprostol is a small tablet, which is commonly given rectally in this scenario. Is misoprostol the best second line choice? One randomized clinical trial compared oxytocin versus misoprostol as the second line agent after routine oxytocin alone did not control bleeding. Both treatments controlled about 90% of bleeding within twenty minutes. 1% of women who received oxytocin lost more than 1,000 ml of blood, while 3% of women who received misoprostol lost more than 1,000 of blood. In another trial, women did not receive the routine oxytocin after delivery, and some of them developed a postpartum hemorrhage. Those who did experience hemorrhage received either oxytocin or oxytocin + misoprostol. The two groups had no difference in amount of blood lost. However, in both of these trials, women who received misoprostol were more likely to develop a fever.

These two studies provide evidence that oxytocin alone works as well if not better than misoprostol, without the increased risk of fever. However, misoprostol still has a place in the uterotonic arsenal. For instance, oxytocin, Hemabate, and Methergine all require refrigeration. Areas with inconsistent refrigeration still benefit from the heat-stable misoprostol. Globally, many women still deliver at home with or without a birth attendant. For these women, misoprostol may be the best defense against hemorrhage. In hospitals with unrestricted access to medications, Dr. Barbieri's editorial promotes the use of oxytocin, Hemabate, and Methergine as second line agents and discourages using misoprostol.

However, these drugs are not without side effects as well. Hemabate cannot be used in patients with asthma and can cause a mild fever, nausea, diarrhea, headache, and numbness/tingling. Methergine cannot be used in patients with high blood pressure and can cause headache, nausea, vomiting, and dizziness. Misoprostol has a similar side effect profile, although may be better tolerated overall.

One very interesting side note: how you give misoprostol matters. Three studies examined the route of administration of misoprostol and its peak circulating concentration in the blood. Rectal administration took longer to reach peak circulation and resulted in lower uterine tone than buccal administration. Rectal administration took longer to take effect, but also had a longer duration of action.

It seems that the jury is still out on the definitive best use of misoprostol. The above clinical trials certainly support using oxytocin over misoprostol alone, and one could argue that they support using oxytocin alone over oxytocin + misoprostol. However, as a quick and easily available drug with a favorable side effect profile, is there still a place for misoprostol when used in conjunction with other uterotonics? We want to hear from you. Do you use misoprostol to prevent or stop postpartum hemorrhage? Do you prefer a different agent?