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.

 

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.

 

摘要

背景

用於預防產後出血的催產素(oxytocin)促效劑

產後出血(PPH)在全球上是造成母體死亡與罹病的主要原因之一。對於分娩的第3階段進行積極處理，已被證實可以有效地預防產後出血。跟oxytocin比較起來，syntometrine的效力更強，但是卻會帶來較多的副作用。屬於一種長效型oxytocin促效劑的carbetocin，對於預防產後出血而言，顯然會是一種有希望的藥物。

目標

針對預防產後出血而言，要確認使用oxytocin促效劑是否會跟傳統的子宮收縮劑(uterotonic agent)一樣有效，並評估給藥的最佳途徑以及oxytocin促效劑的最佳劑量。

搜尋策略

我們搜尋了the Cochrane Pregnancy and Childbirth Group's Trials Register(2006年九月)、the Cochrane Central Register of Controlled Trials(CENTRAL) (The Cochrane Library 2006，Issue 2)、MEDLINE(1966年到2006年六月)以及EMBASE(1974年到2006年六月)。我們檢查了這些文章的參考書目，並與作者和製藥工業方面聯繫。

選擇標準

針對預防產後出血，隨機的對照試驗將oxytocin促效劑(carbetocin)與其他的子宮收縮劑，或是跟安慰劑或是不採取治療等方式進行比較。

資料收集與分析

有2位回顧的作者獨立擷取了資料並評估過試驗的品質。

主要結論

本篇回顧中共包含了4份研究(1037名婦女3份剖腹、1份陰道產)。對於接受過剖腹產的參與者來說，在oxytocin與carbetocin這兩個部分中，產後出血的風險是類似的，這跟接受陰道產而且帶有產後出血之風險因子的參與者一樣。跟用於那些接受剖腹產的婦女身上之oxytocin相比，在統計學上，使用carbetocin會導致對於治療用的子宮收縮劑之需求明顯下降(relative risk (RR) 0.44, 95% confidence interval (CI) 0.25 to 0.78)，但是卻不適用於陰道產的情況。在剖腹產與陰道產兩者之中，carbetocin也會分別造成對於子宮按摩的需求下降(RR 0.38, 95% CI 0.18 to 0.80; RR 0.70, 95% CI 0.51 to 0.94)。然而，這項結果的測量方法僅在1份針對剖腹產的研究中有記錄起來，而且也僅出現在唯一1份針對陰道產的研究中。若是提到在carbetocin與oxytocin之間的不良反應，從這些試驗中取得的混合資料並沒有在統計學上顯示出任何的顯著差異。

作者結論

並沒有充足的證據顯示，靜脈注射100微克的carbetocin能夠跟oxytocin一樣有效地預防產後出血。跟oxytocin比較起來，carbetocin會伴隨著對於額外的子宮收縮劑以及子宮按摩之需求降低。就不良反應而言，比較性的證據還是有限的。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

針對降低產後出血所用的oxytocin促效劑。在低/中收入的國家中，產後出血是造成母體死亡與罹病的主要原因。在高收入的國家中，這樣的問題就少得多了，但是對於生產完的婦女來說，仍然在主要的出血問題中具有小型的風險。在分娩的第3階段進行的積極處理通常是用來減少生產時的血液流失，這種積極處理，包含3種互相牽連的成分：某種能夠幫助子宮收縮的藥物、早點剪斷臍帶，以及讓臍帶收縮受到控制。已經有人嘗試過不同的藥物，而且通常是選用肌肉注射型的oxytocin或是肌肉注射型的syntometrine。在模擬oxytocin作用的藥物當中，oxytocin促效劑是其中的1種，而oxytocin是幫助降低生產時血液流失的荷爾蒙。本篇試驗的回顧發現了4份研究，共包含966名參與者。大多數的試驗都是將carbetocin(oxytocin 促效劑)相對於oxytocin拿來比較，而且大部分是以靜脈注射給藥，對象則為處於較高風險的陰道產婦女，或是選擇性剖腹產的婦女。有限的證據顯示，在carbetocin與oxytocin之間，效力上並沒有太大的差異而且像是頭痛、噁心與嘔吐之類的不良反應都是類似的。沒有任何結果是針對嬰兒來進行評估，而我們知道當中又有3份研究是由製藥公司的資金所支持。還需要有更深入、更大型的研究。