NEW YORK (Reuters Health) – When oxytocin is unavailable, misoprostol appears to be a viable alternative for first-line treatment of primary postpartum hemorrhage, according to two articles published online on January 7 by The Lancet.

In fact, the data show, misoprostol is clinically equivalent to oxytocin when used to stop continued bleeding after oxytocin has been given as prophylaxis.

The risk of death from postpartum bleeding is 100 times higher in resource-poor countries than in developed countries, lead author Dr. Beverly Winikoff, from Gynuity Health Projects, New York, and co-investigators note. One reason is that oxytocin is often unavailable, because it must be refrigerated and given parenterally.

To gather evidence regarding the value of misoprostol as a substitute, Dr. Winikoff and her colleagues conducted a randomized, double-blind trial at four hospitals in Ecuador, Egypt, and Vietnam where oxytocin was not used routinely. Women with postpartum hemorrhage due to suspected uterine atony were assigned to IV oxytocin 40 IU (n = 490) or to sublingual misoprostol 800 ug (n = 488). Median blood loss prior to treatment in both groups was 700 mL.

Active bleeding was controlled within 20 minutes for 90% of women given misoprostol and 96% of those given oxytocin, a nonsignificant difference. Additional median blood loss was 200 mL and 150 mL, respectively (p < 0.0001). Misoprostol was also associated with significantly greater risk of bleeding 300 mL or more.

Moreover, clinicians administered additional uterotonic drugs, blood transfusions, and fluids or plasma expanders more frequently in women given misoprostol.

Compared with oxytocin, misoprostol was associated with higher rates of fever, shivering, and vomiting. However, most instances of high fever occurred in one hospital in Ecuador.

In light of these findings, the authors conclude that “intravenous oxytocin should be used when available, but 800 ug sublingual misoprostol could be an effective first-line treatment alternative when oxytocin is not available.”

The companion study, also done by Dr. Winikoff and her colleagues, was similar except that it involved women who had already received prophylactic oxytocin during the third stage of labor. This trial was conducted at five hospitals in Burkina Faso, Egypt, Turkey and Vietnam. Women with postpartum hemorrhage were randomized to misoprostol (n = 407) or oxytocin (n = 402), at the same doses as in the first report.

There was no significant difference between groups in the time required to control active bleeding, quantity of additional blood loss, or use of extra uterotonic drugs or blood transfusions.

As in the previous trial, misoprostol caused more cases of fever and shivering. There were six hysterectomies (four with misoprostol and two with oxytocin), followed by death in two cases (one in each group).

In both articles, the research team recommends further research to assess the clinical benefits and cost-effectiveness of misoprostol in this setting, and they advise testing lower misoprostol doses to reduce adverse effects while maintaining effectiveness.

Finally, Dr. Winikoff and her group conclude, “Service-delivery guidelines tailored to providers at all levels should be developed to improve management of postpartum hemorrhage with all available methods.”

Reference:
Lancet 2010.