Lin-Lin Su1, Yap-Seng Chong, Miny Samuel. 1. Department ofObstetrics andGynaecology, Yong Loo Lin School ofMedicine,NationalUniversity of Singapore, Singapore, Singapore. obgsll@nus.edu.sg.
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 (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). 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.
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 (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). 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.
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