Oxytocin is currently the gold-standard treatment for post-birth bleeding, but it needs refrigeration, intravenous infusion, and skilled health-care workers for optimum use. Two Articles published Online First (www.thelancet.com) look at the use of misoprostol in tablet form compared with oxytocin and help to define the potential roles of both drugs in treating excess bleeding after childbirth in different health care settings.
The two Articles were written by a team of authors at Gynuity Health Projects, New York, USA and their international colleagues. The Articles describe two large randomised controlled trials comparing the efficacy and acceptability of 800 mcg of oral misoprostol to 40 IU intravenous oxytocin to control postpartum bleeding. Primary endpoints in both studies were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment.
In the first Article (Winikoff, et. al), 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. This situation mimics that of most 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 provide evidence about the potential role of misoprostol in treating haemorrhage in differing health service environments.
The study in the first Article included 9348 women not exposed to prophylactic oxytocin who had blood loss measured after vaginal delivery at four hospitals in Ecuador, Egypt, and Vietnam (one secondary-level and three tertiary-level facilities). 978 (10%) 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).
The researchers found that active bleeding was controlled within 20 min in a similar proportion of women in both groups (90% misoprostol versus 96% oxytocin). However, additional blood loss of 300 mL or more was significantly more frequent in the misoprostol group (30%) than the oxytocin group (17%). Shivering (47% vs 17%) and fever (44% vs 6%) were also significantly more common with misoprostol than with oxytocin. No women had hysterectomies or died.
In the trial in the second Article, 31 055 women exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at five hospitals in Burkina Faso, Egypt, Turkey, and Vietnam (two secondary-level and three tertiary-level facilities). 809 (3%) 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).
The researchers found that active bleeding was controlled equally well within 20 min after initial treatment for both regimens (89% of women given misoprostol and 90% of those given oxytocin). Additional blood loss of 300 mL or greater after treatment was similar for the two groups and occurred for 34% of women receiving misoprostol and 31% receiving oxytocin. Shivering (37% vs 15%) and fever (22% vs 15%) were significantly more common with misoprostol than with oxytocin. Six women had hysterectomies and two women died.
The authors say: "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."
They also note that while evidence to support a particular regimen has been lacking, "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 say: "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 conclude: "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."
Gynuity Health Projects, New York, USA. T) +1-212-448-1230
For both Articles see: http://press.
Note to editors: An accompanying Comment is not available at this time, but will be published when the Articles appear in the Jan 16 weekly issue of The Lancet