Leathersich Sebastian J, Vogel Joshua P, Tran Thach Son, Hofmeyr G Justus
King Edward Memorial Hospital for Women, 374 Bagot Road, Subiaco, WA, Australia, 6008.
Cochrane Database Syst Rev. 2018 Jul 4;7(7):CD009770. doi: 10.1002/14651858.CD009770.pub2.
Uterine tachysystole (more than 5 contractions per 10 minutes in 2 consecutive intervals) is common during labour, particularly with use of labour-stimulating agents. Tachysystole may reduce fetal oxygenation by interrupting maternal blood flow to the placenta during contractions. Reducing uterine contractions may improve placental blood flow, improving fetal oxygenation. This review aimed to evaluate the use of tocolytics to reduce or stop uterine contractions for improvement of the condition of the fetus in utero. This new review supersedes an earlier Cochrane Review on the same topic.
To assess the effects of the use of acute tocolysis during labour for uterine tachysystole or suspected fetal distress, or both, on fetal, maternal and neonatal outcomes.
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (2 February 2018), and reference lists of retrieved studies.
Randomised controlled trials (RCTs) evaluating acute tocolysis for uterine tachysystole, intrapartum fetal distress, or both.
We used standard methods expected by Cochrane.
We included eight studies (734 women), conducted in hospital settings, predominantly in high-income countries (USA, Austria, Uruguay). Two trials were conducted in upper and lower middle-income countries (South Africa, Sri Lanka). The hospital facilities all had the capacity to perform caesarean section. Overall, the studies had a low risk of bias, except for methods to maintain blinding. All of the trials used a selective beta (ß)-adrenergic agonist in one arm, however the drug used varied, as did the comparator. Limited information was available on maternal outcomes.Selective ß-adrenergic agonist versus no tocolytic agent, whilst awaiting emergency deliveryThere were two stillbirths, both in the no tocolytic control group (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.01 to 4.55; 2 studies, 57 women; low-quality evidence). One had gross hydrocephalus and the second occurred with vaginal delivery after waiting 55 minutes for caesarean section. The decision for caesarean section delivery was an inclusion criterion in both studies so we could not assess this as an outcome under this comparison. Abnormal fetal heart trace is probably lower with tocolytic treatment (RR 0.28, 95% CI 0.08 to 0.95; 2 studies, 43 women; moderate-quality evidence). The effects on the number of babies with Apgar score below seven were uncertain (low-quality evidence).Intravenous (IV) atosiban versus IV hexoprenaline (1 study, 26 women) One infant in the hexoprenaline group required > 24 hours in the neonatal intensive care unit (NICU) following a forceps delivery (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence). There were no fetal or neonatal mortalities and no Apgar scores below seven. There was one caesarean delivery in the IV hexoprenaline group (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence), and one case of abnormal fetal heart score in the atosiban group (RR 3.00, 95% CI 0.13 to 67.51; very low-quality evidence).IV fenoterol bromhydrate versus emergency delivery (1 study, 390 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. IV fenoterol probably increases the risk of caesarean delivery (RR 1.12, 95% CI 1.04 to 1.22; moderate-quality evidence). Fenoterol may have little or no effect on the risk of Apgar scores below seven (RR 1.28, 95% CI 0.35 to 4.68; low-quality evidence).IV hexoprenaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 37 women) No data were reported for perinatal death or severe morbidity. There were two fetal deaths in the no tocolytic control group (RR 0.23, 95% CI 0.01 to 4.55; low-quality evidence). The rate of caesarean delivery was not reported. There were two babies with Apgar scores below seven in the control group and none in the hexoprenaline group (RR 0.24, 95% CI 0.01 to 4.57; 35 women; low-quality evidence).Subcutaneous terbutaline versus IV magnesium sulphate (1 study, 46 women)No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. The decision for caesarean section was an inclusion criterion, so we could not assess this. The effects on abnormal fetal heart trace are uncertain (very low-quality evidence).Subcutaneous terbutaline with continuation of oxytocic infusion versus cessation of oxytocic infusion without tocolytic agent (1 study, 28 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery in the subcutaneous terbutaline (8/15) and control groups (4/13) (RR 1.73, 95% CI 0.68 to 4.45; low-quality evidence). There were no cases of Apgar scores below seven or abnormal fetal heart trace.Subcutaneous terbutaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 20 women) No data were reported for perinatal death or severe morbidity. There were no fetal or neonatal mortalities. The decision for caesarean section was an inclusion criterion, so we could not assess this. There were two babies with Apgar scores below seven in the control group and none in the terbutaline group (RR 0.17, 95% CI 0.01 to 3.08; low-quality evidence).IV terbutaline versus IV nitroglycerin (1 study, 110 women)No data were reported for perinatal death or severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery between the IV terbutaline (30/57) and control groups (29/53) (RR 0.96, 95% CI 0.68 to 1.36; low-quality evidence). There were no cases of Apgar scores below seven.
AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effects of tocolytics for uterine tachysystole or suspected fetal distress during labour. The clinical significance for some of the improvements in measures of fetal well-being with tocolytics is unclear. The sample sizes were too small to detect effects on neonatal morbidity, mortality or serious adverse effects. The majority of studies are from high-income countries in facilities with access to caesarean section, which may limit the generalisability of the results to lower-resource settings, or settings where caesarean section is not available.Further well-designed and adequately powered RCTs are required to evaluate clinically relevant indicators of maternal and neonatal morbidity and mortality.
子宫收缩过速（连续两个间期内每10分钟宫缩超过5次）在分娩期间很常见，尤其是在使用引产药物时。宫缩过速可能会在宫缩期间中断母体流向胎盘的血流，从而减少胎儿的氧合作用。减少子宫收缩可能会改善胎盘血流，提高胎儿氧合作用。本综述旨在评估使用宫缩抑制剂减少或停止子宫收缩以改善子宫内胎儿状况的效果。这篇新综述取代了之前Cochrane协作网关于同一主题的综述。
评估分娩期间使用急性宫缩抑制药物治疗子宫收缩过速或疑似胎儿窘迫或两者兼有的情况对胎儿、母体和新生儿结局的影响。
我们检索了Cochrane妊娠与分娩试验注册库、ClinicalTrials.gov和世界卫生组织国际临床试验注册平台（ICTRP）（2018年2月2日），并检索了所获研究的参考文献列表。
评估急性宫缩抑制药物治疗子宫收缩过速、产时胎儿窘迫或两者兼有的随机对照试验（RCT）。
我们采用了Cochrane协作网期望的标准方法。
我们纳入了八项研究（734名女性），这些研究均在医院环境中进行，主要来自高收入国家（美国、奥地利、乌拉圭）。两项试验在中低收入国家（南非、斯里兰卡）进行。所有医院设施均具备实施剖宫产的能力。总体而言，除维持盲法的方法外，这些研究的偏倚风险较低。所有试验均在一组中使用了选择性β-肾上腺素能激动剂，但使用的药物不同，对照药物也不同。关于母体结局的信息有限。
选择性β-肾上腺素能激动剂与不使用宫缩抑制药物对比，同时等待紧急分娩
有两例死产，均发生在不使用宫缩抑制药物的对照组（风险比（RR）0.23，95%置信区间（CI）0.01至4.55；2项研究，57名女性；低质量证据）。一例患有严重脑积水，另一例在等待剖宫产55分钟后经阴道分娩。两项研究均将剖宫产分娩的决定作为纳入标准，因此我们无法将此作为该对比下的一个结局进行评估。宫缩抑制药物治疗可能会降低异常胎儿心率的发生率（RR 0.28，95%CI 0.08至0.95；2项研究，43名女性；中等质量证据）。对Apgar评分低于7分的婴儿数量的影响尚不确定（低质量证据）。
静脉注射阿托西班与静脉注射海索那林对比（1项研究，26名女性）
海索那林组有一名婴儿在产钳分娩后需要在新生儿重症监护病房（NICU）住院超过24小时（RR 0.33，95%CI 0.01至7.50；低质量证据）。没有胎儿或新生儿死亡，且没有Apgar评分低于7分的情况。静脉注射海索那林组有一例剖宫产（RR 0.33，95%CI 0.01至7.50；低质量证据），阿托西班组有一例异常胎儿心率评分（RR 3.00，95%CI 0.13至67.51；极低质量证据）。
静脉注射溴化非诺特罗与紧急分娩对比（1项研究，390名女性）
未报告围产期死亡、严重发病情况或胎儿或新生儿死亡的数据。静脉注射溴化非诺特罗可能会增加剖宫产的风险（RR 1.12，95%CI 1.04至1.22；中等质量证据）。溴化非诺特罗对Apgar评分低于7分的风险可能几乎没有影响（RR 1.28，95%CI 0.35至4.68；低质量证据）。
静脉注射海索那林与不使用宫缩抑制药物对比，同时等待紧急分娩（1项研究，37名女性）
未报告围产期死亡或严重发病情况的数据。不使用宫缩抑制药物的对照组有两例胎儿死亡（RR 0.23，95%CI 0.01至4.55；低质量证据）。未报告剖宫产率。对照组有两名婴儿Apgar评分低于7分，海索那林组无（RR 0.24，95%CI 0.01至4.57；35名女性；低质量证据）。
皮下注射特布他林与静脉注射硫酸镁对比（1项研究，46名女性）
未报告围产期死亡、严重发病情况或胎儿或新生儿死亡的数据。剖宫产的决定是纳入标准，因此我们无法对此进行评估。对异常胎儿心率的影响尚不确定（极低质量证据）。
皮下注射特布他林并继续输注缩宫素与停止输注缩宫素且不使用宫缩抑制药物对比（1项研究，28名女性）
未报告围产期死亡、严重发病情况或胎儿或新生儿死亡的数据。皮下注射特布他林组（8/15）和对照组（4/13）的剖宫产率可能几乎没有差异（RR 1.73，95%CI 0.68至4.45；低质量证据）。没有Apgar评分低于7分或异常胎儿心率的情况。
皮下注射特布他林与不使用宫缩抑制药物对比，同时等待紧急分娩（1项研究，20名女性）
未报告围产期死亡或严重发病情况的数据。没有胎儿或新生儿死亡。剖宫产的决定是纳入标准，因此我们无法对此进行评估。对照组有两名婴儿Apgar评分低于7分，特布他林组无（RR 0.17，95%CI 0.01至3.08；低质量证据）。
静脉注射特布他林与静脉注射硝酸甘油对比（1项研究，110名女性）
未报告围产期死亡、严重发病情况或胎儿或新生儿死亡的数据。静脉注射特布他林组（30/57）和对照组（29/53）的剖宫产率可能几乎没有差异（RR 0.96，95%CI 0.68至1.36；低质量证据）。没有Apgar评分低于7分的情况。
尚无足够证据确定宫缩抑制药物对分娩期间子宫收缩过速或疑似胎儿窘迫的影响。宫缩抑制药物对一些胎儿健康指标改善的临床意义尚不清楚。样本量过小，无法检测对新生儿发病率、死亡率或严重不良反应的影响。大多数研究来自有剖宫产条件的高收入国家的医疗机构，这可能会限制研究结果在资源较少地区或无法进行剖宫产地区的推广。需要进一步开展设计良好且样本量充足的随机对照试验，以评估与母体和新生儿发病率及死亡率相关的临床指标。
