WESTPORT, CT (Reuters Health) Oct 09 - Titrated administration reduces the risk that oral misoprostol will cause uterine hyperstimulation in pregnant women undergoing induction of labor.

Dr. G. J. Hofmeyr, of the University of Witwatersrand, South Africa, and colleagues conducted a randomized clinical trial comparing the effects of titrated oral misoprostol solution and vaginal dinoprostone. At hospitals in South Africa and Liverpool, UK, 695 women undergoing labor induction after 34 weeks of pregnancy were randomized to receive oral misoprostol solution or two doses of vaginal dinoprostone (2 mg) given 6 hours apart.

"The smallest preparation of misoprostol available in trial countries was a 200 µg tablet," the team explains in the September issue of the British Journal of Obstetrics and Gynecology. "For induction of labour a starting dose of 20 µg was required. To overcome the problem...we dissolved the tablet in 200 mL water."

After two or three doses, depending on the site, the dose was increased to 40 µg. The solution was administered every 2 hours until adequate contractions occurred.

The investigators observed no significant difference between the groups in failure to deliver vaginally within 24 hours. Sixteen percent and 20% of misoprostol patients and dinoprostone patients, respectively, required cesarean section (relative risk 0.80). Four percent of misoprostol patients and 3% of dinoprostone patients experienced hyperstimulation with fetal heart rate changes (RR 1.32).

Women with intact membranes and unfavorable cervices who were treated with misoprostol had a slower response to induction of labor than those treated with dinoprostone. The response was slower in patients treated with dinoprostone when membranes were ruptured. The team observed no significant differences in neonatal outcomes between the groups.

"A possible solution to the problem of hyperstimulation [with misoprostol]," Dr. Hofmeyr and colleagues suggest, "is the use of a single, small vaginal dose to achieve the local effect in women with unfavourable cervices, followed by frequent, small titrated oral doses to 'fine-tune' the uterine response."

Br J Obstet Gynecol 2001;108:952-959.