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The objective of the review was to determine the effectiveness and safety of pharmacological and surgical interventions used to treat postpartum haemorrhage (PPH). The interventions focused on were those used to treat uterine atony—the most common cause of PPH. The authors planned to compare seven interventions (uterotonics, haemostatics, uterine packing or tamponade, vessel ligation, hysterectomy, uterine compression sutures and radiological embolization); each with other treatments, controls or placebo. Main outcomes defined were maternal mortality, severe maternal morbidity and hysterectomy.

The only study included in the review was conducted in South Africa in 2001 (SA 2001 study) (1). It was a randomized single blind trial that compared rectal misoprostol 800 µg with a “standard regime” for the management of PPH, which consisted of intramuscular syntometrine plus oxytocin infusion (defined as > 500 ml of blood loss). The study was stopped prematurely since, compared with the standard regime, there was a significant benefit in the misoprostol arm of the trial with respect to the cessation of bleeding within 20 minutes (6% vs 34%, RR 0.18, 95% CI 0.04- 0.67). Also, in the misoprostol group, there was a significantly less need for additional medical intervention. No difference was demonstrated on the rates of hysterectomy, vessel ligation, maternal mortality and morbidity. This was largely due to the study being too small. The reviewers indicate that this study was flawed in that it was not blinded for the practitioners who may have been biased in their interpretation of the response to treatment.

Since the publication of the Cochrane review, two randomized controlled trials conducted in South Africa and the Gambia have been reported (2,3). These are double-blind trials comparing misoprostol regimens with placebo for the second line treatment of PPH due to uterine atony. In both studies, management of the third stage of labour included prophylaxis with oxytocin or syntometrine. In women with PPH (defined as > 500 ml of blood loss) in the Gambian study, and “more than usual blood loss” in the South African study, a standard treatment regime of an oxytocin injection with or without ergometrine was initially given. After this women were randomized to the misoprostol or the placebo group, and continuing blood loss measured. Another feature of these studies was that different dosages and routes of misoprostol administration were used: the Gambian study used 200 µg orally plus 400 µg sublingually and the South African study used 200 µg orally, 400 µg sublingually and 400 µg rectally. It was argued that these combinations of different routes administration facilitated rapid and sustained uterotonic action. Both studies showed a trend towards lower blood loss with misoprostol compared with placebo. However, the results were not statistically significant, possibly due to the standard treatment resulting in less blood loss in the placebo group than expected. It would be useful to document how often ergometrine is included in the standard and rescue treatments, since this agent has the potential for severe side-effects. Both studies suggest, but do not conclusively prove, a role for misoprostol as a second line agent for treatment of PPH.

The full RHL commentary also includes sections on: