Misoprostol to prevent and treat postpartum haemorrhage: a systematic review and meta-analysis of maternal deaths and dose-related effects

Abstract

Objective To review maternal deaths and the dose-related effects of misoprostol on blood loss and pyrexia in randomized trials of misoprostol use for the prevention or treatment of postpartum haemorrhage. Methods We searched the Cochrane Controlled Trials Register and Pubmed, without language restrictions, for "(misoprostol AND postpartum) OR (misoprostol AND haemorrhage) OR (misoprostol AND hemorrhage)", and we evaluated reports identified through the Cochrane Pregnancy and Childbirth Group search strategy. Randomized trials comparing misoprostol with either placebo or another uterotonic to prevent or treat postpartum haemorrhage were checked for eligibility. Data were extracted, tabulated and analysed with Reviewer Manager (RevMan) 4.3 software. Findings We included 46 trials with more than 40 000 participants in the final analysis. Of 11 deaths reported in 5 trials, 8 occurred in women receiving ³ 600 µg of misoprostol (Peto odds ratio, OR: 2.49; 95% confidence interval, CI: 0.76-8.13). Severe morbidity, defined as the need for major surgery, admission to intensive care, organ failure or body temperature ³ 40 °C, was relatively infrequent. In prevention trials, severe morbidity was experienced by 16 of 10 281 women on misoprostol and by 16 of 10 292 women on conventional uterotonics; in treatment trials, it was experienced by 1 of 32 women on misoprostol and by 1 of 32 women on conventional uterotonics. Misoprostol recipients experienced more adverse events than placebo recipients: 8 of 2070 versus 5 of 2032, respectively, in prevention trials, and 5 of 196 versus 2 of 202, respectively, in treatment trials. Meta-analysis of direct and adjusted indirect comparisons of the results of randomized trials showed no evidence that 600 µg are more effective than 400 µg for preventing blood loss ³ 1000 ml (relative risk, RR: 1.02; 95% CI: 0.71-1.48). Pyrexia was more than twice as common among women who received ³ 600 µg rather than 400 µg of misoprostol (RR: 2.53; 95% CI: 1.78-3.60). Conclusion Further research is needed to more accurately assess the potential beneficial and harmful effects of misoprostol and to determine the smallest dose that is effective and safe. In this review, 400 µg of misoprostol were found to be safer than ³ 600 µg and just as effective.Une traduction en français de ce résumé figure à la fin de l'article. Al final del artículo se facilita una traducción al español. ‫املقالة.‬ ‫لهذه‬ ‫الكامل‬ ‫النص‬ ‫نهاية‬ ‫يف‬ ‫الخالصة‬ ‫لهذه‬ ‫العربية‬ ‫الرتجمة‬

Sublingual Misoprostol to Reduce Blood Loss at Cesarean Delivery

“…As the side effects are dose related, a dose of 400 mcg was chosen in the present study to minimize maternal adverse effects with optimal therapeutic benefit. In a recent review, 400 mcg of misoprostol was found to be safer than 600 mcg and just as effective [11].…”

Rethinking WHO guidance: review of evidence for misoprostol use in the prevention of postpartum haemorrhage

“…The database search revealed two systematic reviews 10,16 and further studies were also identified from the sources. Studies were excluded if duplicate, considering injectable prostaglandins, non-RCTs, not reported in English, in high-income and hospital settings.…”

The Effect of Combined Oxytocin–Misoprostol Versus Oxytocin and Misoprostol Alone in Reducing Blood Loss at Cesarean Delivery: A Prospective Randomized Double-Blind Study

“…Hofmeyr et al presented no more efficacy for higher dose of misoprostol in preventing hemorrhage more than 1,000 cc through a meta-analysis [24]. However, synergistic effects of two agents would allow a reduction in dose for both agents and therefore limit the side effects while improving efficacy.…”