Vogel Joshua P, West Helen M, Dowswell Therese
UNDP/UNFPA/UNICEF/WHO/Word Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research, World Health Organization, Avenue Appia 20, Geneva, Switzerland, CH-1211.
Cochrane Database Syst Rev. 2013 Sep 23;2013(9):CD010648. doi: 10.1002/14651858.CD010648.pub2.
Labour dystocia is associated with a number of adverse maternal and neonatal outcomes. Augmentation of labour is a commonly used intervention in cases of labour dystocia. Misoprostol is an inexpensive and stable prostaglandin E1 analogue that can be administered orally, vaginally, sublingually or rectally. Misoprostol has proven to be effective at stimulating uterine contractions although it can have serious, and even life-threatening side-effects. Titration refers to the process of adjusting the dose, frequency, or both, of a medication on the basis of frequent review to achieve optimal outcomes. Studies have reported on a range of misoprostol titration regimens used for labour induction and titrated misoprostol may potentially be effective and safe for augmentation of labour.
To examine the effects and safety of titrated oral misoprostol compared with placebo, oxytocin, other interventions, or no active treatment, in women with labour dystocia.
The Trials Search Co-ordinator of the Cochrane Pregnancy and Childbirth Group searched the Cochrane Pregnancy and Childbirth Group's Trials Register; date of search: 29 May 2013. We also searched the reference lists of retrieved studies
Randomised trials (including quasi-randomised and cluster-randomised trials) comparing titrated oral misoprostol with placebo, other interventions (e.g. oxytocin, other prostaglandins), or no treatment in women requiring augmentation of labour were eligible for inclusion.
Two review authors independently assessed eligibility for inclusion, carried out data extraction and assessed risk of bias in included studies. Data were entered by one author and checked for accuracy.
We included two randomised trials with a total of 581 women each comparing different regimens of titrated oral misoprostol with intravenous oxytocin. One study compared 20 mcg doses of misoprostol dissolved in water (repeated every hour up to four hours, after which the dose was increased to 40 mcg per hour up to a maximum total dose of 1600 mcg), while the second study gave women 75 mcg doses (repeated after four hours provided there were no adverse effects observed).Neither trial reported maternal death, severe maternal morbidity, or fetal/neonatal mortality outcomes, and only a few fetal/neonatal morbidity outcomes were considered, none of which were significantly different between groups. For several outcomes (such as maternal side-effects, instrumental birth, maternal blood transfusion for hypovolaemia and epidural analgesia), the number of events was generally too low for sufficient statistical power to be achieved. Maternal satisfaction was not reported in either trial. One trial reported a slight reduction in the median duration of labour from the start of augmentation to vaginal delivery in the oxytocin group.Neither trial reported significantly higher rates of caesarean section (CS) in the oral misoprostol group. Rates of vaginal delivery within 12 and 24 hours of commencing augmentation were not significantly different in the trial using a 20 mcg misoprostol dose. Neither trial had significantly higher rates of uterine hyperstimulation with fetal heart rate changes in the titrated oral misoprostol group. However, the rates of this outcome varied so greatly between the two studies as to suggest that other factors were at play. The only significant differences between groups related to uterine hyperstimulation (without fetal heart rate changes), and results were not consistent in the two trials. In the trial examining the higher dose of misoprostol, more women in the misoprostol group experienced hyperstimulation of labour measured over a 10-minute period compared with those receiving oxytocin (risk ratio (RR) 1.17, 95% confidence interval (CI) 1.02 to 1.35, 350 women). In the study examining the lower titrated dose of misoprostol, there was a lower incidence of tachysystole when labour was augmented with titrated oral misoprostol than with oxytocin (RR 0.39, 95% CI 0.17 to 0.91, 231 women) with no occurrences of hypertonus in either group of women.
AUTHORS' CONCLUSIONS: Important uncertainties still exist on the safety and acceptability of titrated oral misoprostol compared with intravenous oxytocin regimens in women with dystocia following spontaneous onset of labour. Although in facilities where electronic oxytocin infusion is not available, low-dose titrated misoprostol may offer a better alternative to an uncontrolled oxytocin infusion to avoid hyperstimulation. Further research is needed in both high- and low-resource settings More trials should be conducted to evaluate the effect of a standard titration oral misoprostol regimen, both following spontaneous labour and labour induction. Comparisons with other augmentation methods are also warranted, as are any effects on women's birth experiences.
产程延长与多种不良母儿结局相关。引产是产程延长病例中常用的干预措施。米索前列醇是一种廉价且稳定的前列腺素E1类似物,可口服、经阴道、舌下或直肠给药。米索前列醇已被证明能有效刺激子宫收缩,尽管它可能有严重甚至危及生命的副作用。滴定是指根据频繁评估来调整药物剂量、给药频率或两者,以实现最佳效果的过程。已有研究报道了一系列用于引产的米索前列醇滴定方案,滴定米索前列醇可能对产程延长有效且安全。
比较滴定口服米索前列醇与安慰剂、缩宫素、其他干预措施或无积极治疗,对产程延长女性的效果和安全性。
Cochrane妊娠与分娩组的试验检索协调员检索了Cochrane妊娠与分娩组的试验注册库;检索日期:2013年5月29日。我们还检索了检索到的研究的参考文献列表。
比较滴定口服米索前列醇与安慰剂、其他干预措施(如缩宫素、其他前列腺素)或对需要引产的女性不进行治疗的随机试验(包括半随机试验和整群随机试验)符合纳入标准。
两位综述作者独立评估纳入资格、进行数据提取并评估纳入研究的偏倚风险。数据由一位作者录入并检查准确性。
我们纳入了两项随机试验,共581名女性,分别比较了不同方案的滴定口服米索前列醇与静脉滴注缩宫素。一项研究比较了溶解于水中的20微克米索前列醇剂量(每小时重复给药,最多4小时,之后剂量增至每小时40微克,最大总剂量为1600微克),另一项研究给予女性75微克剂量(4小时后若无不良反应则重复给药)。两项试验均未报告产妇死亡、严重产妇发病率或胎儿/新生儿死亡率结局,仅考虑了少数胎儿/新生儿发病率结局,两组之间均无显著差异。对于一些结局(如产妇副作用、器械助产、因低血容量进行的产妇输血和硬膜外镇痛),事件数量通常过少,无法获得足够的统计效力。两项试验均未报告产妇满意度。一项试验报告缩宫素组从引产开始到阴道分娩的产程中位数略有缩短。两项试验均未报告口服米索前列醇组剖宫产率显著更高。在使用20微克米索前列醇剂量的试验中,开始引产后12小时和24小时内的阴道分娩率无显著差异。滴定口服米索前列醇组胎儿心率改变的子宫过度刺激率均无显著更高。然而,两项研究中该结局的发生率差异极大,表明还有其他因素在起作用。两组之间唯一的显著差异与子宫过度刺激(无胎儿心率改变)有关,且两项试验结果不一致。在研究较高剂量米索前列醇的试验中,与接受缩宫素的女性相比,米索前列醇组更多女性在10分钟内经历了产程过度刺激(风险比(RR)1.17,95%置信区间(CI)1.02至1.35,350名女性)。在研究较低滴定剂量米索前列醇的试验中,滴定口服米索前列醇引产时的子宫收缩过速发生率低于缩宫素(RR 0.39,95%CI 0.17至0.91,231名女性),两组女性均未发生子宫强直收缩。
与静脉滴注缩宫素方案相比,滴定口服米索前列醇在自然发动分娩后产程延长女性中的安全性和可接受性仍存在重要的不确定性。尽管在没有电子缩宫素输注设备的机构中,低剂量滴定米索前列醇可能是避免过度刺激的无控制缩宫素输注的更好替代方法。在高资源和低资源环境中都需要进一步研究。应进行更多试验来评估标准滴定口服米索前列醇方案在自然分娩和引产中的效果。与其他引产方法的比较以及对女性分娩体验的任何影响也值得研究。