Carbetocin untuk mencegah pendarahan selepas bersalin
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). 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.
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.
PICO
Plain language summary
Carbetocin untuk mencegah pendarahan selepas bersalin
Di negara berpendapatan rendah dan sederhana, pendarahan selepas bersalin adalah punca utama kematian ibu serta kesihatan yang kurang baik. Di negara‐negara berpendapatan tinggi, masalah ini adalah kurang tetapi masih terdapat risiko kecil masalah pendarahan berat dalam wanita selepas melahirkan anak. Pengendalian aktif bersalin pada fasa ketiga, yang secara umumnya untuk mengurangkan kehilangan darah semasa kelahiran, terdiri daripada pemberian ubat yang membantu pengecutan rahim ibu, mengikat tali pusat dengan segera dan menarik tali pusat secara terkawal untuk mengeluarkan plasenta. Pelbagai ubat dicuba dan kebiasaannya oxytocin intramuskular atau syntometrine intramuskular diberikan. Carbetocin adalah agonis oxytocin. Agonis oxytocin adalah sekumpulan ubat‐ubatan yang menyamai tindakan oxytocin, oxytocin sebagai hormon semulajadi yang membantu mengurangkan kehilangan darah semasa bersalin. Ulasan ini merangkumi 11 kajian rawak terkawal yang melibatkan 2635 wanita. Kajian tersebut telah membandingkan carbetocin dengan oxytocin atau syntometrine yang diberikan selepas kelahiran bayi, melalui vagina atau pembedahan. Perbandingan antara carbetocin intramuskular dan oxytocin menunjukkan bahawa tidak ada perbezaan pada risiko pendarahan berat, tetapi wanita yang menerima carbetocin kurang memerlukan ubat lain untuk mengecutkan uterus selepas pembedahan. Perbandingan antara carbetocin dan syntometrine menunjukkan bahawa wanita yang menerima carbetocin kurang kehilangan darah berbanding wanita yang menerima syntometrine selepas kelahiran melalui vagina, serta kurang mengalami kesan sampingan seperti mual dan muntah. Kejadian tekanan darah tinggi pada 30 dan 60 minit selepas bersalin juga secara signifikan lebih rendah dalam wanita yang menerima carbetocin berbanding mereka yang menerima syntometrine. Lima daripada 11 kajian termaklum disokong oleh sebuah syarikat farmaseutikal.
