Two articles published Online First and in The Lancet consider the use of misoprostol in tablet form for treatment of post-birth bleeding. They compare it with oxytocin and aim to define the potential roles of both drugs in treating excess bleeding after childbirth in different health care settings. Currently, Oxytocin is the gold-standard treatment for post-birth bleeding, but it requires refrigeration, intravenous infusion, and skilled health-care workers for optimum use.
The two articles are the work of a team of authors at Gynuity Health Projects, New York, USA and their international colleagues. They describe two large randomized controlled trials that compare the efficacy and acceptability of 800 mcg of oral misoprostol to 40 IU intravenous oxytocin to control postpartum bleeding. In both studies primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment.
Researchers examined whether sublingual misoprostol is non-inferior to intravenous oxytocin for treatment of post-partum haemorrhage in women who had not received any oxytocin to prevent post-partum bleeding (first article, Winikoff, et. al). This situation portrays that of the majority developing world locations where use of oxytocin is not feasible. In the second article (Blum et. al), researchers compared the same two treatments in women who had received prophylactic oxytocin but haemorrhaged despite this prophylaxis. The results of the two trials supply evidence about the possible role of misoprostol in treating haemorrhage in different health service environments.
The first article describes a study that included 9,348 women. They were not exposed to prophylactic oxytocin and had blood loss measured after vaginal delivery at four hospitals in Ecuador, Egypt, and Vietnam. These comprised of one secondary-level and three tertiary-level facilities. A total of 978 (10 percent) women were diagnosed with primary post-partum haemorrhage and were randomly assigned to receive 800 μg misoprostol (n=488) or 40 IU intravenous oxytocin (n=490).
Results indicated that active bleeding was controlled within 20 min in a similar proportion of women in both groups. It was 90 percent in the misoprostol group versus 96 percent in the oxytocin group. However, additional blood loss of 300 mL or more was considerably more frequent in the misoprostol group (30 percent) than the oxytocin group (17 percent). Shivering (47 percent compared to 17 percent) and fever (44 percent compared to 6 percent) were also significantly more common with misoprostol than with oxytocin. There were no reports of women having hysterectomies or dying.
The second article describes a trial that included 31,055 women. They were exposed to prophylactic oxytocin and had blood loss measured after vaginal delivery at five hospitals in Burkina Faso, Egypt, Turkey, and Vietnam. These comprised of two secondary-level and three tertiary-level facilities. A total of 809 (3 percent) women were diagnosed with post-partum haemorrhage and were randomly assigned to receive 800 μg misoprostol (n=407) or 40 IU intravenous oxytocin (n=402).
Results indicated that active bleeding was controlled equally well within 20 min after initial treatment for both regimens. It was the case for 89 percent of women given misoprostol and 90 percent of those given oxytocin. Additional blood loss of 300 mL or greater after treatment was similar for the two groups and occurred for 34 percent of women receiving misoprostol and 31 percent receiving oxytocin. Shivering (37 percent compared to 15 percent) and fever (22 percent compared to15 percent) were significantly more common with misoprostol than with oxytocin. There were report of six women having hysterectomies and two women dying.
Researchers note: “Intravenous oxytocin should be used when available, but 800 μg sublingual misoprostol could be an effective first-line treatment alternative when oxytocin is not available. Since many women in developing countries deliver at home or at low-level facilities, misoprostol provides a potential for immediate treatment of post-partum haemorrhage.”
The authors also remark that while there was a lack of evidence to support a particular regimen, “These findings provide evidence that 800 μg sublingual misoprostol is a viable alternative to 40 IU intravenous oxytocin for treatment of primary post-partum haemorrhage after oxytocin prophylaxis during the third stage of labour. Misoprostol stopped bleeding as rapidly as did oxytocin and with a similar quantity of additional blood loss [among women receiving prophylaxis].”
They comment: “Building on the efficacy and safety shown…future research is needed to assess the clinical benefits and cost-effectiveness of introducing misoprostol as an alternative to universal referral for treatment in settings that do not have access to intravenous oxytocin.”
They say in conclusion: “Future research should investigate the effectiveness of treatment for post-partum haemorrhage with misoprostol when introduced widely into clinical practice at secondary and primary health-care facilities and, importantly, after misoprostol prophylaxis has been administered. Clinical research examining whether a lower treatment dose shows similar effectiveness with fewer undesirable side-effects would also be useful.”
“Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial”
Beverly Winikoff, Rasha Dabash, Jill Durocher, Emad Darwish, Nguyen Thi Nhu Ngoc, Wilfrido León, Sheila Raghavan, Ibrahim Medhat, Huynh Thi Kim Chi, Gustavo Barrera, Jennifer Blum
DOI: 10.1016/S0140-6736(09)61924-3
The Lancet
Written by Stephanie Brunner (B.A.)