Background

Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during cesarean delivery. However, some randomized controlled trials suggest that other uterotonics are superior.

Objective

We conducted a network meta-analysis comparing the ability of pharmacologic agents to reduce blood loss and minimize the need for additional uterotonics during cesarean delivery.

Data Sources

We searched the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE databases from inception to May 2020.

Study Eligibility Criteria

We included randomized controlled trials that compared oxytocin, carbetocin, misoprostol, ergometrine, carboprost, or combinations of these in the prevention of postpartum hemorrhage during cesarean delivery.

Methods

We performed a systematic review followed by an NMA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quality of the evidence was assessed with the Confidence in Network Meta-Analysis approach and Grading of Recommendations, Assessment, Development and Evaluations tool within the summary of findings table. Our primary outcomes were the estimated blood loss and need for additional uterotonics. Secondary outcomes included nausea and postpartum hemorrhage of >1000 mL. We performed sensitivity analyses to explore the influence of surgical context and oxytocin administration strategy.

Results

A total of 46 studies with 7368 participants were included. Of those, 21 trials (6 agents and 3665 participants) formed the “estimated blood loss” network and, considering the treatment effects, certainty in the evidence, and surface under the cumulative ranking curve scores, carbetocin was assessed to probably be superior to oxytocin, but only in reducing the estimated blood loss by a clinically insignificant volume (54.83 mL; 95% confidence interval, 26.48–143.78). Misoprostol, ergometrine, and the combination of oxytocin and ergometrine were assessed to probably be inferior, whereas the combination of oxytocin and misoprostol was assessed to definitely be inferior to oxytocin. A total of 37 trials (8 agents and 6193 participants) formed the “additional uterotonic” network and, again, carbetocin was assessed to probably be superior to oxytocin, requiring additional uterotonics 185 (95% confidence interval, 130–218) fewer times per 1000 cases. Oxytocin plus misoprostol, oxytocin plus ergometrine, and misoprostol were assessed to probably be inferior, whereas carboprost, ergometrine, and the placebo were definitely inferior to oxytocin. For both primary outcomes, oxytocin administration strategies had a higher probability of being the best uterotonic, if initiated as a bolus.

Conclusion

Carbetocin is probably the most effective agent in reducing blood loss and the need for additional uterotonics. Oxytocin appears to be more effective when initiated as a bolus.

中文翻译：

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预防剖宫产后产后出血：现有药物的网络荟萃分析

背景

产后出血导致全球四分之一的孕产妇死亡。世界卫生组织建议将催产素作为预防剖宫产时出血的一线药物。然而，一些随机对照试验表明，其他子宫收缩剂更胜一筹。

客观的

我们进行了一项网络荟萃分析，比较了药物在剖宫产期间减少失血和最大限度减少额外宫缩剂需求的能力。

数据源

我们检索了 Cochrane Central Register of Controlled Trials、Embase 和 MEDLINE 数据库从开始到 2020 年 5 月。

学习资格标准

我们纳入了比较催产素、卡贝缩宫素、米索前列醇、麦角新碱、卡前列素或这些组合在预防剖宫产期间产后出血方面的随机对照试验。

方法

我们根据系统评价和元分析指南的首选报告项目进行了系统评价，然后进行了 NMA。证据的质量是使用网络元分析方法的置信度和结果摘要表中的建议、评估、开发和评估工具分级来评估的。我们的主要结果是估计失血量和额外宫缩剂的需求。次要结局包括恶心和产后出血 > 1000 mL。我们进行了敏感性分析，以探索手术环境和催产素给药策略的影响。

结果

共纳入 46 项研究，共有 7368 名参与者。其中，21 项试验（6 名药物和 3665 名参与者）形成了“估计失血量”网络，考虑到治疗效果、证据的确定性和累积排名曲线得分下的表面，卡贝缩宫素被评估为可能优于催产素，但仅能将估计的失血量减少临床上微不足道的体积（54.83 mL；95% 置信区间，26.48–143.78）。米索前列醇、麦角新碱以及催产素和麦角新碱的组合被评估为可能较差，而催产素和米索前列醇的组合被评估为肯定不如催产素。总共 37 项试验（8 名药物和 6193 名参与者）形成了“额外的子宫收缩”网络，并且再次评估卡贝缩宫素可能优于催产素，每 1000 例需要额外的宫缩剂 185（95% 置信区间，130-218）次。催产素加米索前列醇、催产素加麦角新碱和米索前列醇被评估为可能较差，而卡前列素、麦角新碱和安慰剂肯定不如催产素。对于这两个主要结果，如果以推注方式启动，催产素给药策略更有可能成为最佳子宫收缩剂。

结论

卡贝缩宫素可能是减少失血和减少额外宫缩剂需求的最有效药物。催产素在以推注形式开始时似乎更有效。