Gynuity Health Projects, New York, NY, USA.
Lancet. 2010 Jan 16;375(9710):210-6. doi: 10.1016/S0140-6736(09)61924-3. Epub 2010 Jan 6.
Oxytocin, the standard of care for treatment of post-partum haemorrhage, is not available in all settings because of refrigeration requirements and the need for intravenous administration. Misoprostol, an effective uterotonic agent with several advantages for resource-poor settings, has been investigated as an alternative. This trial established whether sublingual misoprostol was similarly efficacious to intravenous oxytocin for treatment of post-partum haemorrhage in women not exposed to oxytocin during labour.
In this double-blind, non-inferiority trial, 9348 women not exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at four hospitals in Ecuador, Egypt, and Vietnam (one secondary-level and three tertiary-level facilities). 978 (10%) women were diagnosed with primary post-partum haemorrhage and were randomly assigned to receive 800 microg misoprostol (n=488) or 40 IU intravenous oxytocin (n=490). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350.
All randomly assigned participants were analysed. Active bleeding was controlled within 20 min with study treatment alone for 440 (90%) women given misoprostol and 468 (96%) given oxytocin (relative risk [RR] 0.94, 95% CI 0.91-0.98; crude difference 5.3%, 95% CI 2.6-8.6). Additional blood loss of 300 mL or greater after treatment occurred for 147 (30%) of women receiving misoprostol and 83 (17%) receiving oxytocin (RR 1.78, 95% CI 1.40-2.26). Shivering (229 [47%] vs 82 [17%]; RR 2.80, 95% CI 2.25-3.49) and fever (217 [44%] vs 27 [6%]; 8.07, 5.52-11.8) were significantly more common with misoprostol than with oxytocin. No women had hysterectomies or died.
In settings in which use of oxytocin is not feasible, misoprostol might be a suitable first-line treatment alternative for post-partum haemorrhage.
缩宫素是产后出血治疗的标准药物，但由于需要冷藏和静脉给药，并非所有环境都能使用。米索前列醇是一种有效的宫缩剂，在资源匮乏的环境中有多种优势，已被研究作为替代药物。本试验旨在确定舌下给予米索前列醇是否与静脉给予催产素治疗分娩时未使用催产素的产妇产后出血同样有效。
在这项双盲、非劣效性试验中，厄瓜多尔、埃及和越南的 4 家医院（1 家二级医院和 3 家三级医院）共纳入了 9348 名未接受预防性催产素治疗的阴道分娩产妇，测量产后出血量。978 名（10%）产妇诊断为原发性产后出血，并随机分配接受 800μg 米索前列醇（n=488）或 40IU 静脉催产素（n=490）治疗。提供者和产妇对治疗分配均不知情。主要终点为治疗后 20 分钟内出血停止和治疗后出血量增加 300mL 或以上。如果 97.5%CI 的上限低于预先设定的 6%非劣效性边界，则接受米索前列醇的临床等效性。所有结局均从初始治疗开始时进行评估。本研究在 ClinicalTrials.gov 注册，编号为 NCT00116350。
所有随机分配的参与者均被纳入分析。单独使用研究药物，440 名（90%）接受米索前列醇治疗的产妇和 468 名（96%）接受催产素治疗的产妇在 20 分钟内出血停止（相对风险 [RR] 0.94，95%CI 0.91-0.98；粗差 5.3%，95%CI 2.6-8.6）。治疗后出血量增加 300mL 或以上的产妇有 147 名（30%）接受米索前列醇治疗，83 名（17%）接受催产素治疗（RR 1.78，95%CI 1.40-2.26）。接受米索前列醇治疗的产妇中，出现寒战（229 名[47%]）和发热（217 名[44%]）的比例显著高于接受催产素治疗的产妇（分别为 82 名[17%]和 27 名[6%]；RR 2.80，95%CI 2.25-3.49）。没有产妇接受子宫切除术或死亡。
在无法使用催产素的环境中，米索前列醇可能是产后出血的一种合适的一线治疗替代药物。
