USE OF MISOPROSTOL FOR LABOR INDUCTION IN PATIENTS WITH SEVERE PRE-ECLAMPSIA

QUESTION
Will use of Cytotec (misoprostol) for induction of a severely pre-eclamptic woman potentially worsen her blood pressure?
O. Sijin, MD

RESPONSE FROM PETER S. BERNSTEIN, MD, MPH, FACOG AND LEV D. KANDINOV, MD
Misoprostol is a synthetic prostaglandin E1 analog. During clinical trials, misoprostol has been shown to induce or augment uterine contractions. Vaginal administration of misoprostol has been used as a cervical ripening agent, for the induction of labor, and for treatment of serious postpartum hemorrhage in the presence of uterine atony. A major adverse effect of the obstetric use of misoprostol is the hyperstimulation of the uterus, which may progress to uterine tetany with marked impairment of uteroplacental blood flow, uterine rupture (requiring surgical repair, hysterectomy, and/or salpingo-oophorectomy), or amniotic fluid embolism. Pelvic pain, retained placenta, severe genital bleeding, shock, fetal bradycardia, and fetal and maternal death have been reported.[1]

Multiple randomized controlled trials demonstrated misoprostol as an effective and economical cervical-ripening and labor-inducing agent. A few studies concluded that 25 to 50 mcg of misoprostol used vaginally every 4 hours is safer and more efficient for cervical ripening and labor induction than oxytocin. The cesarean section rate was significantly lower, and the latent period and the period from induction to vaginal delivery were significantly shorter, for the misoprostol group compared with the oxytocin group. With regard to uterine tonus alterations, tachysystole was significantly more common in the misoprostol group. However, there was no difference in hypoxia and neonatal morbidity between the misoprostol and oxytocin groups.[2,3]

Arachidonic acid metabolites, such as prostaglandins of the E series, have well-documented effects on blood pressure (BP). In one study, researchers hypothesized that misoprostol would exert antihypertensive actions. Therefore, they performed a randomized, placebo-controlled clinical trial in 15 essential hypertensive, nonpregnant patients to characterize the effects of a 400 mcg oral dose of misoprostol on BP and its hemodynamic, autonomic, and biochemical determinants. There was a modest decrease (from 105.3 ± 2.7 to 101.9 ± 2.7 mm Hg, P = 0.006) in mean arterial pressure 20 minutes after the dose was administered, accompanied by a decrease in systemic vascular resistance and a compensatory rise in cardiac output and heart rate. This study concluded that oral misoprostol exerts a modest but transient antihypertensive effect that is unlikely to be of either therapeutic benefit or concern in essential hypertension.[4]

In other studies, misoprostol has been shown to cause transient elevation of BP. A randomized controlled trial looked at the side effects of 600 mcg of oral misoprostol used during the third stage of labor. This study demonstrated an association between postpartum oral misoprostol 600 mcg and shivering, pyrexia, and mild increase in BP. Researchers hypothesized that this increase in BP, as well as the trend toward increased abdominal pain, may be secondary to the uterotonic effect of misoprostol. It is important to differentiate, however, that for labor induction, much lower doses of misoprostol are used, and it is administered vaginally.[5]

In 1996, a case report was published about the use of intravaginal misoprostol for labor induction in 2 patients with severe pre-eclampsia remote from term. Both patients had an uneventful vaginal delivery within 14 hours of the initial application.[6]

A few studies looked at the efficacy and complications of intravaginal misoprostol for induction of labor in patients with and without toxemia of pregnancy. In one trial, 42 patients with toxemia of pregnancy and 59 women at term without toxemia all with Bishop scores of ≤ 6 were treated with 50 mcg intravaginal misoprostol given 4 times at 4-hour intervals. Labor and neonatal outcomes, and any complications, were recorded. This study concluded that intravaginal misoprostol is an equally effective and safe method of induction of labor in patients with toxemia of pregnancy and normal pregnant women.[7]

Another trial compared the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in toxemia of pregnancy with a modified Bishop score of ≤ 4. In this study, 100 pre-eclamptic women with a modified Bishop score of ≤ 4 were randomized into 2 groups of 50 patients; one group received 50 mcg intravaginal misoprostol 4 times at 4-hour intervals, the second group received oxytocin infusion for induction of labor. The results of this study demonstrated that after 12 hours, the median modified Bishop scores of the misoprostol group and oxytocin group were 7 and 4, respectively (P = .027). The rate of patients who were in labor after 12 hours was 94% and 80% in the misoprostol group and the oxycytocin group, respectively (P < .05); the median time from induction to delivery was 14 hours and 16 hours in the misoprostol and oxytocin groups, respectively, with significant difference between the groups (P = .003). The rate of vaginal delivery was significantly higher in the misoprostol group (82%) when compared with the oxytocin group (66%) (P < .05). There were no significant differences between the groups (P = .96, P = .64) with regards to APGAR scores and NICU admissions. Researchers concluded that intravaginal misoprostol is an efficacious, inexpensive, and safe method of induction of labor in toxemia of pregnancy with modified Bishop score of ≤4.[8]

In conclusion, misoprostol seems to be effective for labor induction in cases where expeditious vaginal delivery is necessary (such as severe pre-eclampsia, HELLP syndrome). Currently, there is no evidence in the literature that misoprostol significantly affects a patient’s BP one way or another.

As published here: https://www.medscape.com/viewarticle/484262

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