Oxytocin agonists for preventing postpartum haemorrhage
Abstract
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 methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 2), MEDLINE (1966 to June 2006) and EMBASE (1974 to June 2006). We checked references of articles and communicated with authors and pharmaceutical industry.
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 extracted data and assessed trial quality.
Main results
Four studies (1037 women) were included in the review (three studies on caesarean delivery and one on vaginal delivery). The risk of PPH was similar in both oxytocin and carbetocin arms for participants who underwent caesarean delivery as well as participants, with risk factor(s) for PPH, who underwent vaginal delivery. Use of carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonic agent (relative risk (RR) 0.44, 95% confidence interval (CI) 0.25 to 0.78) compared to oxytocin for those who underwent caesarean section, but not for vaginal delivery. Carbetocin is also associated with a reduced need for uterine massage in both caesarean and vaginal deliveries (RR 0.38, 95% CI 0.18 to 0.80; RR 0.70, 95% CI 0.51 to 0.94) respectively. However, this outcome measure was only documented in one study on caesarean delivery and in the only study on vaginal delivery. Pooled data from the trials did not reveal any statistically significant differences in terms of the adverse effects between carbetocin and oxytocin.
Authors' conclusions
There is insufficient evidence that 100 micrograms of intravenous carbetocin is as effective as oxytocin to prevent PPH. In comparison to oxytocin, carbetocin was associated with reduced need for additional uterotonic agents, and uterine massage. There was limited comparative evidence on adverse events.
PICOs
Plain language summary
Oxytocin agonists for preventing postpartum haemorrhage
Oxytocin agonists for reducing postpartum haemorrhage.
In low/middle income countries, postpartum haemorrhage is a major cause of maternal mortality and morbidity. 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, has three interrelated components: a drug that helps the uterus to contract, early cord clamping and controlled cord traction. Different drugs have been tried, and generally either intramuscular oxytocin or intramuscular syntometrine are given. Oxytocin agonists are a group of drugs that mimic oxytocin action, oxytocin being the hormone that helps to reduce blood loss at birth. The review of trials found four studies, involving 966 participants. Most trials compared carbetocin (oxytocin agonist) against oxytocin, mostly given intravenously, either in women giving birth vaginally who were at increased risk, or by elective caesarean deliveries. Limited evidence suggests that there is little difference in the effectiveness between carbetocin and oxytocin, and adverse effects like headache, nausea and vomiting were also similar. No outcomes were assessed on the baby, and three studies were known to be supported by grants from a pharmaceutical company. Further larger studies are needed.
