Postpartum haemorrhage (PPH) is one of the major contributors to maternal mortality and morbidity worldwide. Active management of the third stage of labour has been proven to be effective in the prevention of PPH.
Syntometrine is more effective than
oxytocin but is associated with more side effects.
Carbetocin, a long-acting
oxytocin agonist, appears to be a promising agent for the prevention of PPH.
OBJECTIVES: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 March 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1 of 4), MEDLINE (1966 to 1 March 2011) and EMBASE (1974 to 1 March 2011). We checked references of articles and communicated with authors and pharmaceutical industry contacts.
SELECTION CRITERIA: Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data.
MAIN RESULTS: We included 11 studies (2635 women) in the review. Six trials compared
carbetocin with
oxytocin; four of these were conducted for women undergoing caesarean deliveries, one was for women following vaginal deliveries and one did not state the mode of delivery clearly. The
carbetocin was administered as 100 µg intravenous dosage across the trials, while
oxytocin was administered intravenously but at varied dosages. Four trials compared intramuscular
carbetocin and intramuscular
syntometrine for women undergoing vaginal deliveries. Three of the trials were on women with no risk factor for PPH, while one trial was on women with risk factors for PPH. One trial compared the use of intravenous
carbetocin with placebo. Use of
carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonics (risk ratio (RR) 0.62; 95% confidence interval (CI) 0.44 to 0.88; four trials, 1173 women) compared to
oxytocin for those who underwent
caesarean section, but not for vaginal delivery. Compared to
oxytocin,
carbetocin was associated with a reduced need for uterine
massage following both caesarean delivery (RR 0.54; 95% CI 0.37 to 0.79; two trials, 739 women) and vaginal delivery (RR 0.70; 95% CI 0.51 to 0.94; one trial, 160 women). Pooled data also showed that
carbetocin resulted in a lower risk of PPH compared to
oxytocin in women who underwent caesarean delivery (RR 0.55; 95% CI 0.31 to 0.95; three trials, 820 women). This is, however, limited by the number of studies and risk of bias in the studies. Comparison between
carbetocin and
syntometrine showed a lower mean blood loss in women who received
carbetocin compared to
syntometrine (mean difference (MD) -48.84 ml; 95% CI -94.82 to -2.85; four trials, 1030 women). There was no statistically significant difference in terms of the need for therapeutic uterotonic agents, but the risk of adverse effects such as
nausea and
vomiting were significantly lower in the
carbetocin group:
nausea (RR 0.24; 95% CI 0.15 to 0.40; four trials, 1030 women);
vomiting (RR 0.21; 95% CI 0.11 to 0.39; four trials, 1030 women). The incidence of postpartum
hypertension was also significantly lower in women who received
carbetocin compared to those who received
syntometrine. Cost-effectiveness of
carbetocin was investigated by one study published as an abstract, with limited data.
AUTHORS' CONCLUSIONS: There is evidence to suggest that 100 µg of intravenous
carbetocin is more effective than
oxytocin for preventing PPH in women undergoing caesarean deliveries, but more studies are needed to validate this finding.
Carbetocin is associated with less blood loss compared to
syntometrine in the prevention of PPH for women who have vaginal deliveries and is associated with significantly fewer adverse effects. Further research is needed to analyse the cost-effectiveness of
carbetocin as a uterotonic agent.