OBJECTIVE To evaluate the comparative efficacy of two of the most commonly used second-line uterotonics-methylergonovine maleate and carboprost tromethamine. METHODS We conducted a double-blind randomized trial at two large academic perinatal centers in patients undergoing nonemergency cesarean delivery with uterine atony refractory to oxytocin, as diagnosed by the operating obstetrician. The intervention included administration of a single dose of intramuscular methylergonovine or carboprost intraoperatively at diagnosis. The primary outcome, uterine tone on a 0-10 numeric rating scale 10 minutes after study drug administration, was rated by operating obstetricians blinded to the drug administered. Secondary outcomes included uterine tone score at 5 minutes, administration of additional uterotonic agents, other interventions for uterine atony or hemorrhage, quantitative blood loss, urine output, postpartum change in serum hematocrit, transfusion, length of hospital stay, adverse drug or transfusion reactions, and postpartum hemorrhage complications. A sample size of 50 participants per group was planned to detect a 1-point difference (with estimated within-group SD of 1.5) in the mean primary outcome with 80% power at a two-sided α level of 0.05 while accounting for potential protocol violations. RESULTS A total of 1,040 participants were enrolled, with 100 randomized to receive one of the study interventions. Mean±SD 10-minute uterine tone scores were 7.3±1.7 after methylergonovine and 7.6±2.1 after carboprost, with an adjusted difference in means of -0.1 (95% CI, -0.8 to 0.6, P=.76). Additional second-line uterotonics were required in 30.0% of the methylergonovine arm and 34.0% in the carboprost arm (adjusted odds ratio 0.72, 95% CI, 0.27-1.89, P=.505), and geometric mean quantitative blood loss was 756 mL (95% CI, 636-898) and 708 mL (95% CI, 619-810) (adjusted ratio of geometric means 1.06, 95% CI, 0.86-1.31, P=.588), respectively. No differences were detected in the occurrence of other interventions for uterine atony or postpartum hemorrhage. CONCLUSION No difference was detected in uterine tone scores 10 minutes after administration of either methylergonovine or carboprost for refractory uterine atony, indicating that either agent is acceptable. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03584854.

中文翻译：

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子宫收缩乏力的二线子宫收缩剂：随机对照试验。


目的 评价两种最常用的二线宫缩剂——马来酸甲基麦角新碱和卡前列素氨丁三醇的疗效比较。方法 我们在两个大型学术围产中心对接受非紧急剖腹产的患者进行了一项双盲随机试验，这些患者经主刀产科医生诊断，子宫收缩乏力，对催产素无效。干预措施包括在诊断时在术中肌注单剂量甲基麦角新碱或卡前列素。主要结果是研究药物给药后 10 分钟按 0-10 数字评分量表对子宫张力进行评分，由对所给药药物不知情的产科医生进行评分。次要结局包括 5 分钟子宫张力评分、给予额外的子宫收缩剂、针对子宫收缩乏力或出血的其他干预措施、定量失血量、尿量、产后血清红细胞比容变化、输血、住院时间、药物不良或输血反应、以及产后出血并发症。计划每组 50 名参与者的样本量，以检测平均主要结果的 1 点差异（估计组内 SD 为 1.5），在考虑到潜在方案的情况下，两侧 α 水平为 0.05 时的功效为 80%违规行为。结果 共有 1,040 名参与者入组，其中 100 名随机接受其中一项研究干预措施。甲基麦角新碱治疗后 10 分钟子宫张力评分的平均值±标准差为 7.3±1.7，卡前列素治疗后为 7.6±2.1，调整后的平均值差异为 -0.1（95% CI，-0.8 至 0.6，P=.76）。甲基麦角新碱组中 30.0% 需要额外的二线宫缩剂，卡前列素组中 34.0% 需要额外二线宫缩剂（调整后优势比 0.72，95% CI，0.27-1.89，P=.505），几何平均定量失血量为 756 mL（95% CI，636-898）和 708 mL（95% CI，619-810）（几何平均值调整比 1.06，95% CI，0.86-1.31，P =.588），分别。对于子宫收缩乏力或产后出血的其他干预措施的发生率没有发现差异。结论 对于难治性子宫收缩乏力，使用甲基麦角新碱或卡前列素治疗 10 分钟后，子宫张力评分没有检测到差异，表明这两种药物都是可以接受的。临床试验注册 ClinicalTrials.gov，NCT03584854。