Carbetocin for preventing postpartum haemorrhage

In low- and middle-income countries, postpartum haemorrhage is a major cause of maternal deaths and ill health. In high-income countries, the problems are much less but there is still a small risk of major bleeding problems for women after giving birth. Active management of the third stage of labour, which is generally used to reduce blood loss at birth, consists of giving the mother a drug that helps the uterus to contract, early cord clamping and controlled cord traction to deliver the placenta. Different drugs have been tried and generally either intramuscular oxytocin or intramuscular syntometrine is given. Carbetocin is an oxytocin agonist. Oxytocin agonists are a group of drugs that mimic the oxytocin action, oxytocin being the natural hormone that helps to reduce blood loss at birth. This review includes 11 randomised controlled trials involving 2635 women. The trials compared carbetocin against either oxytocin or syntometrine given after delivery, vaginally or by caesarean section. The comparison between intramuscular carbetocin and oxytocin showed that there was no difference in the risk of heavy bleeding, but that women who received carbetocin were less likely to require other medications to produce uterine contractions following caesarean sections. Comparisons between carbetocin and syntometrine showed that women who received carbetocin had less blood loss compared to women who received syntometrine after vaginal delivery, and were much less likely to experience side effects such as nausea and vomiting. The incidence of hypertension at 30 and 60 minutes post delivery was also significantly lower in women who received carbetocin compared to those who received syntometrine. Five of the 11 studies were known to be supported by a pharmaceutical company.

Authors' conclusions: 

For women who undergo caesarean section, carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonics compared to oxytocin, but there is no difference in the incidence of postpartum haemorrhage. 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.

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Background: 

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: 

To determine if the use of oxytocin agonist is as effective as conventional uterotonic agents for the prevention of PPH, and assess the best routes of administration and optimal doses of oxytocin agonist.

Search strategy: 

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: 

Randomised controlled trials which compared oxytocin agonist (carbetocin) with other uterotonic agents or with placebo or no treatment for the prevention of PPH.

Data collection and analysis: 

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). There were no statistically significant differences between carbetocin and oxytocin in terms of risk of any PPH (blood loss greater than 500 ml) or in risk of severe PPH (blood loss greater than 1000 ml). 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.

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