Liabsuetrakul Tippawan, Choobun Thanapan, Peeyananjarassri Krantarat, Islam Q Monir
Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand, 90110.
Cochrane Database Syst Rev. 2018 Jun 7;6(6):CD005456. doi: 10.1002/14651858.CD005456.pub3.
Previous research has shown that the prophylactic use of uterotonic agents in the third stage of labour reduces postpartum blood loss and moderate to severe postpartum haemorrhage (PPH). PPH is defined as a blood loss of 500 mL or more within 24 hours after birth. This is one of a series of systematic reviews assessing the effects of prophylactic use of uterotonic drugs; in this review prophylactic ergot alkaloids as a whole, and different regimens of administration of ergot alkaloids, are compared with no uterotonic agents. This is an update of a Cochrane Review which was first published in 2007 and last updated in 2011.
To determine the effectiveness and safety of prophylactic use of ergot alkaloids in the third stage of labour by any route (intravenous (IV), intramuscular (IM), or oral) compared with no uterotonic agents, for the prevention of PPH.
For this update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (19 September 2017); we also searched reference lists of retrieved studies.
We included all randomised controlled trials or cluster-randomised trials comparing prophylactic ergot alkaloids by any route (IV, IM, or oral) with no uterotonic agents in the third stage of labour among women giving birth vaginally.
Two review authors independently assessed trials for inclusion, extracted data and checked them for accuracy; they also assessed the risk of bias in included studies. Two review authors assessed the quality of the evidence using the GRADE approach.
There were eight included studies: three studies had a low risk of bias and five studies had high risk of bias. The studies compared ergot alkaloids with no uterotonic agents, with a total of 2031 women in the ergot alkaloids group and 1978 women in the placebo or no treatment group. Seven studies used the IV/IM route of administration and one study used the oral route.Ergot alkaloids (any route of administration) versus no uterotonic agentsUse of ergot alkaloids in the third stage of labour decreased mean blood loss (mean difference (MD) -80.52 mL, 95% confidence interval (CI) -96.39 to -64.65 mL; women = 2718; studies = 3; moderate-quality evidence); decreased PPH of at least 500 mL (average risk ratio (RR) 0.52, 95% CI 0.28 to 0.94; women = 3708; studies = 5; I = 83%; low-quality evidence); increased maternal haemoglobin concentration (g/dL) at 24 to 48 hours postpartum (MD 0.50 g/dL, 95% CI 0.38 to 0.62; women = 1429; studies = 1; moderate-quality evidence); and decreased the use of therapeutic uterotonics (average RR 0.37, 95% CI 0.15 to 0.90; women = 2698; studies = 3; I = 89%; low-quality evidence). There were no clear differences between groups in severe PPH of at least 1000 mL (average RR 0.32, 95% CI 0.04 to 2.59; women = 1718; studies = 2; I = 74%; very low-quality evidence). The risk of retained placenta or manual removal of the placenta, or both, were inconsistent with high heterogeneity. Ergot alkaloids increased the risk of elevated blood pressure (average RR 2.60, 95% CI 1.03 to 6.57: women = 2559; studies = 3; low-quality evidence) and pain after birth requiring analgesia (RR 2.53, 95% CI 1.34 to 4.78: women = 1429; studies = 1; moderate-quality evidence) but there were no differences between groups in vomiting, nausea, headache or eclamptic fit.Results for IV/IM ergot alkaloids versus no uterotonic agents were similar to those for the main comparison of ergot alkaloids administered by any route, since most of the studies (seven of eight) used the IV/IM route. Only one small study (289 women) compared oral ergometrine with placebo and it showed no benefit of ergometrine over placebo. No maternal adverse effects were reported.None of the studies reported on any of our prespecified neonatal outcomes AUTHORS' CONCLUSIONS: Prophylactic IM or IV injections of ergot alkaloids may be effective in reducing blood loss, reducing PPH (estimated blood loss of at least 500 mL), and increasing maternal haemoglobin. Ergot alkaloids may also decrease the use of therapeutic uterotonics, but adverse effects may include elevated blood pressure and pain after birth requiring analgesia. There were no differences between groups in terms of other adverse effects (vomiting, nausea, headache or eclamptic fit). There is a lack of evidence on the effects of ergot alkaloids on severe PPH, and retained or manual removal of placenta. There is also a lack of evidence on the oral route of administration of ergot alkaloids.
既往研究表明，在分娩第三阶段预防性使用宫缩剂可减少产后出血及中重度产后出血（PPH）。PPH定义为产后24小时内失血500毫升或更多。这是一系列评估预防性使用宫缩剂效果的系统评价之一；在本评价中，将预防性使用麦角生物碱整体及不同给药方案与不使用宫缩剂进行比较。这是Cochrane系统评价的更新版，该评价首次发表于2007年，上次更新于2011年。
确定与不使用宫缩剂相比，分娩第三阶段通过任何途径（静脉注射（IV）、肌肉注射（IM）或口服）预防性使用麦角生物碱预防PPH的有效性和安全性。
对于本次更新，我们检索了Cochrane妊娠与分娩组试验注册库、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台（ICTRP）（2017年9月19日）；我们还检索了检索到的研究的参考文献列表。
我们纳入了所有将分娩第三阶段通过任何途径（IV、IM或口服）预防性使用麦角生物碱与不使用宫缩剂进行比较的随机对照试验或整群随机试验，这些试验对象为经阴道分娩的女性。
两位综述作者独立评估试验是否纳入、提取数据并检查其准确性；他们还评估了纳入研究的偏倚风险。两位综述作者使用GRADE方法评估证据质量。
纳入八项研究：三项研究偏倚风险低，五项研究偏倚风险高。这些研究将麦角生物碱与不使用宫缩剂进行比较，麦角生物碱组共有2031名女性，安慰剂或未治疗组有1978名女性。七项研究采用IV/IM给药途径，一项研究采用口服途径。
麦角生物碱（任何给药途径）与不使用宫缩剂相比
分娩第三阶段使用麦角生物碱可减少平均失血量（平均差值（MD）-80.52毫升，95%置信区间（CI）-96.39至-64.65毫升；女性=2718；研究=3；中等质量证据）；减少至少500毫升的PPH（平均风险比（RR）0.52，95%CI 0.28至0.94；女性=3708；研究=5；I²=83%；低质量证据）；增加产后24至48小时产妇血红蛋白浓度（克/分升）（MD 0.50克/分升，95%CI 0.38至0.62；女性=1429；研究=1；中等质量证据）；并减少治疗性宫缩剂的使用（平均RR 0.37，95%CI 0.15至0.90；女性=2698；研究=3；I²=89%；低质量证据）。至少1000毫升的严重PPH在两组之间无明显差异（平均RR 0.32，95%CI 0.04至2.59；女性=1718；研究=2；I²=74%；极低质量证据）。胎盘滞留或人工剥离胎盘，或两者兼有的风险存在异质性且结果不一致。麦角生物碱增加了血压升高的风险（平均RR 2.60，95%CI 1.03至6.57：女性=2559；研究=3；低质量证据）以及产后需要镇痛的疼痛风险（RR 2.53，95%CI 1.34至4.78：女性=1429；研究=1；中等质量证据）但两组在呕吐、恶心、头痛或子痫发作方面无差异。
IV/IM麦角生物碱与不使用宫缩剂的结果与麦角生物碱通过任何途径给药的主要比较结果相似，因为大多数研究（八项中的七项）采用IV/IM途径。仅有一项小型研究（289名女性）将口服麦角新碱与安慰剂进行比较，结果显示麦角新碱并不优于安慰剂。未报告产妇不良反应。
没有研究报告我们预先设定的任何新生儿结局。
预防性肌肉注射或静脉注射麦角生物碱可能有效减少失血量、降低PPH（估计失血量至少500毫升）并增加产妇血红蛋白。麦角生物碱也可能减少治疗性宫缩剂的使用，但不良反应可能包括血压升高和产后需要镇痛的疼痛。两组在其他不良反应（呕吐、恶心、头痛或子痫发作）方面无差异。缺乏麦角生物碱对严重PPH以及胎盘滞留或人工剥离胎盘影响的证据。也缺乏麦角生物碱口服给药途径的证据。
