ACOG’s 2009 Induction Guidelines: Spin Doctoring Misoprostol (Cytotec)
Ahh, the new ACOG induction guidelines, so much to dislike, so little time. Still, others are also commenting, so I will focus on debunking ACOG’s portrayal of misoprostol.
ACOG STATEMENT: “There is . . . a large body of published reports supporting (misoprostol’s) safety and efficacy when used appropriately” (p. 387).
FACT: None of the studies have been big enough either alone or in the aggregate to detect differences in rare, catastrophic events, a point acknowledged by a Cochrane systematic review, and it is those rare, catastrophic events that are the issue with “miso.” And while more disasters will occur with higher doses and in women with prior cesareans, there is no “appropriate” use of misoprostol in terms of safety.
ACOG STATEMENT: “No studies indicate that intrapartum exposure . . . has any long-term adverse health consequences to the fetus in the absence of fetal distress [emphasis mine]. . . .” (p. 387).
FACT: Well, that’s the catch, isn’t it? The long-term adverse health consequences to the fetus occur in the presence of fetal distress subsequent to uterine rupture—including in unscarred uteruses and with moderate doses of misoprostol—and amniotic fluid embolism. In some cases, of course, the fetus doesn’t survive to experience long-term consequences.
ACOG STATEMENT: “Although misoprostol currently is approved by the U.S. Food and Drug Administration (FDA) for the prevention of peptic ulcers, the FDA in 2002 approved a new label on the use of misoprostol during pregnancy for cervical ripening and for the induction of labor. This labeling does not contain claims regarding the efficacy or safety of misoprostol” (p. 387).
FACT: A reader can be forgiven for assuming from this convoluted phrasing that the FDA now approves of using misoprostol to induce labor. The reader would be wrong. The FDA removed the “black box” designation prohibiting use in pregnant women, but it takes a much dimmer view of “miso” than merely not claiming it is safe. Here is an excerpt from the FDA’s 2002 statement (PDF):
A major adverse effect of the obstetrical use of Cytotec is hyperstimulation of the uterus which may progress to uterine tetany [uterus contracts and doesn’t let go] with marked impairment of uteroplacental blood flow, uterine rupture (requiring surgical repair, hysterectomy, and/or salpingo-oophorectomy [removal of the ovaries and Fallopian tubes]), or amniotic fluid embolism [maternal and infant mortality is very high from this]. Pelvic pain, retained placenta, severe genital bleeding, shock, fetal bradycardia [profound slowing of the fetal heart], and fetal and maternal death have been reported.
There may be an increased risk of uterine tachysystole [contractions coming too fast], uterine rupture, meconium passage, meconium staining of amniotic fluid, and Cesarean delivery due to uterine hyperstimulation with the use of higher doses of Cytotec; including the manufactured 100 mcg tablet. The risk of uterine rupture increases with advancing gestational ages and with prior uterine surgery, including Cesarean delivery. Grand multiparity [usually defined as more than four births] also appears to be a risk factor for uterine rupture.
What actually happened was this: ACOG held that “misoprostol is one of the most important medications in obstetrical practice. . . . The real victims in this scenario [i.e., prohibition in pregnancy] are pregnant women who receive treatment in hospitals that will not allow the use of misoprostol” (Hale 2001, p. 59). Lobbied by ACOG, the FDA rescinded the black box designation on the grounds that obstetricians were using it to induce labor, a rationale that amounts to “but all the kids are doing it.”
ACOG STATEMENT: “The majority of adverse maternal and fetal outcomes associated with misoprostol therapy resulted from the use of doses greater than 25 mcg” (p. 387).
FACT: The “majority” of adverse outcomes is hardly reassuring. What about the minority? Not to mention that obstetricians may ignore recommended dosages, and even the guidelines say “Misoprostol in higher doses (50 mcg every 6 hours) may be appropriate in some situations” (p. 390). In any case, misoprostol is formulated in 100 mcg tablets for use as an oral ulcer medication. Getting a 25 mcg dose means cutting an unscored tablet in quarters. It’s anybody’s guess what dosage is really delivered.
The real kicker is that according to the Cochrane systematic review, misoprostol is no more effective than the FDA approved medication, PGE2 (a.k.a dinoprostone, trade names Cervidil and Prepidil). More vaginal deliveries happened within 24 hours after administration, but cesarean rates overall did not differ between groups. Cesarean rates in trials comparing misoprostol with with intravenous oxytocin (trade names Pitocin or “Pit” and “Syntocinon”) were more variable, but not all of them found reductions in cesarean rates with misoprostol. Meanwhile, misoprostol results in higher rates of uterine hyperstimulation and uterine hyperstimulation with adverse changes in the fetal heart rate than other agents. And misoprostol has yet another major disadvantage: Oxytocin has a short half-life. If contractions get too strong or too close together, turn the I.V. drip down or off, and within a little while, contractions fade. If misoprostol hyperstimulates the uterus, you are stuck. Moreover, lurking in the “miso works faster” benefit is a problem not captured in the trials because they only measure major morbidity: some women are thrown into violent labors. These labors should have given researchers pause, though, if for no other reason than they are the precursor, the shark fin in the water, of misoprostol’s potential for severe fetal distress, massive hemorrhage, uterine rupture, and amniotic fluid embolism.
Why, then, are obstetricians so enamored of misoprostol? The answer is summed up by this obstetrician enthusiast:
The best part about it is that you can block-schedule your nurses so that you have enough on hand. . . [I]f we start our inductions at 7 a.m., we know that we’re going to have X number of patients in labor being admitted by 4 p.m. That’s helped our hospital tremendously, . . . [Cytotec is] a great agent. It works very, very efficiently. . . . And it’s ungodly inexpensive: 27 cents per tablet.
In other words, Cytotec’s real benefits are convenience for obstetricians and helping the hospital’s bottom line. For women and babies, though, it’s a roll of the dice. Most times things go fine, but sometimes the dice come up snake eyes.
Hale, R. W., & Zinberg, S. (2001). Use of misoprostol in pregnancy. N Engl J Med, 344(1), 59-60.