Misoprostol in the treatment of postpartum haemorrhage in addition to routine management: a placebo randomised controlled trial. A randomized study comparing rectally administered misoprostol versus Syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage.
Postpartum haemorrhage remains a leading cause of maternal mortality, despite treatment with conventional methods. In this randomised controlled trial, we compared misoprostol 600 microg (200 microg orally and 400 microg sublingually) with placebo in the treatment of postpartum haemorrhage in addition to routine treatment. One hundred and sixty consenting women who delivered vaginally with measured blood loss > or =500 mL and for whom inadequate uterine contraction was thought to be a possible factor were given either misoprostol or placebo in addition to normal treatment and after routine active management with uterotonics. Blood loss was measured by collection in a special plastic bedpan and side effects of treatment were recorded. Measured average additional blood loss was 325 mL (95% confidence interval [CI] 265 to 384 mL) with misoprostol and 410 mL (95% CI 323 to 498 mL) with placebo. No severe side effects were noted in the use of misoprostol. Post partum hemorrhage is a major cause of maternal death, particularly in developing countries, and most cases are due to an atonic uterus. Hemorrhage can occur despite active management of the third stage of labor. Presently, misoprostol (Cytotec, Searle Pharmaceuticals) is the only thermostable uterotonic agent potentially available which would be economically beneficial for developing countries where refrigeration of drugs poses a problem. The objective of the study was to compare intra-muscular Syntometrine (Sandoz Pharmaceuticals) (ampoule=5 iu oxytocin and 500 mcg ergometrine maleate) plus Syntocinon (Sandoz Pharmceuticals) (10 iu oxytocin diluted in 500 ml normal saline) intravenous infusion versus 800 mcg misoprostol per rectum for treatment of primary post partum hemorrhage in a developing country.
                Randomized single blinded two-center study, set in both a township and teaching hospital in South Africa. Sixty-four women with primary post partum hemorrhage due to an atonic uterus were recruited. The primary outcome measure was whether the hemorrhage ceased within 20 minutes of administering the first line treatment, once hemorrhage was clinically recognized.
                There was a 28.1% difference between the misoprostol arm and the Syntometrine and Syntocinon arm (p=0.01). This result had a greater than 80% power. Misoprostol performed better.
                800 mcg misoprostol per rectum is effective at treating primary post partum hemorrhage.
There is insufficient evidence to show that the addition of misoprostol is superior to the combination of oxytocin and ergometrine alone for the treatment of primary PPH. Large multi-centre, double-blind, randomised controlled trials are required to identify the best drug combinations, route, and dose of uterotonics for the treatment of primary PPH. Further work is required to assess the best way of managing women who fail to respond to uterotonics therapy.