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宫缩剂：一项随机对照试验。


目的 评价两种最常用的二线宫缩剂——马来酸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期中心进行了一项双盲随机试验，受试者为接受非紧急剖宫产且子宫收缩乏力难治性子宫收缩乏力的患者，由手术产科医生诊断。干预包括在诊断时术中肌内注射单剂量甲基麦角新碱或卡前列素。主要结果，即研究药物给药后 10 分钟在 0-10 数字评定量表上的子宫张力，由对所给药药物不知情的手术产科医生进行评分。次要结局包括 5 分钟子宫张力评分、额外宫缩剂的给药、子宫收缩乏力或出血的其他干预措施、定量失血、尿量、产后血清血细胞比容变化、输血、住院时间、药物或输血不良反应以及产后出血并发症。计划每组 50 名参与者的样本量，以检测平均主要结局的 1 分差异（估计组内 SD 为 1.5），在双侧 α 水平为 0.05 时，80% 的功效，同时考虑潜在的协议违规行为。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。甲基麦角新碱后 ±SD 10 分钟子宫张力评分为 7.3±1.7，卡前列素后为 7.6±2.1，校正后均值差异为 -0.1 （95% CI，-0.8 至 0.6，P =.76）。甲基麦角新碱组 30.0% 和卡前列素组 34.0% 需要额外的二线宫缩剂 （校正比值比 0.72,95% CI，0.27-1.89，P =.505），几何平均定量失血量分别为 756 mL （95% CI， 636-898） 和 708 mL （95% CI， 619-810） （调整后的几何平均值比率 1.06,95% CI，0.86-1.31，P =.588）。未发现子宫收缩乏力或产后出血的其他干预措施的发生率存在差异。结论 服用甲基麦角新碱或卡波前列素治疗难治性子宫收缩乏力后 10 分钟子宫张力评分未见差异，表明任何一种药物都是可以接受的。临床试验注册 ClinicalTrials.gov ， NCT03584854.