Salati Jennifer A, Leathersich Sebastian J, Williams Myfanwy J, Cuthbert Anna, Tolosa Jorge E
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, USA, 97239.
Cochrane Database Syst Rev. 2019 Apr 29;4(4):CD001808. doi: 10.1002/14651858.CD001808.pub3.
Active management of the third stage of labour reduces the risk of postpartum blood loss (postpartum haemorrhage (PPH)), and is defined as administration of a prophylactic uterotonic, early umbilical cord clamping and controlled cord traction to facilitate placental delivery. The choice of uterotonic varies across the globe and may have an impact on maternal outcomes. This is an update of a review first published in 2001 and last updated in 2013.
To determine the effectiveness of prophylactic oxytocin to prevent PPH and other adverse maternal outcomes in the third stage of labour.
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (6 March 2019) and reference lists of retrieved studies.
Randomised, quasi- or cluster-randomised trials including women undergoing vaginal delivery who received prophylactic oxytocin during management of the third stage of labour. Primary outcomes were blood loss 500 mL or more after delivery, need for additional uterotonics, and maternal all-cause mortality.
Two review authors independently assessed trials for inclusion, extracted data, and assessed trial quality. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach.
This review includes 24 trials, with 23 trials involving 10,018 women contributing data. Due to many trials assessed at high risk of bias, evidence grade ranged from very low to moderate quality.Prophylactic oxytocin versus no uterotonics or placebo (nine trials)Prophylactic oxytocin compared with no uterotonics or placebo may reduce the risk of blood loss of 500 mL after delivery (average risk ratio (RR) 0.51, 95% confidence interval (C) 0.37 to 0.72; 4162 women; 6 studies; Tau² = 0.10, I² = 75%; low-quality evidence), and blood loss 1000 mL after delivery (RR 0.59, 95% CI 0.42 to 0.83; 4123 women; 5 studies; low-quality evidence). Prophylactic oxytocin probably reduces the need for additional uterotonics (average RR 0.54, 95% CI 0.36 to 0.80; 3135 women; 4 studies; Tau² = 0.07, I² = 44%; moderate-quality evidence). There may be no difference in the risk of needing a blood transfusion in women receiving oxytocin compared to no uterotonics or placebo (RR 0.88, 95% CI 0.44 to 1.78; 3081 women; 3 studies; low-quality evidence). Oxytocin may be associated with an increased risk of a third stage greater than 30 minutes (RR 2.55, 95% CI 0.88 to 7.44; 1947 women; 1 study; moderate-quality evidence), however the confidence interval is wide and includes 1.0, indicating that there may be little or no difference.Prophylactic oxytocin versus ergot alkaloids (15 trials)It is uncertain whether oxytocin reduces the likelihood of blood loss 500 mL (average RR 0.84, 95% CI 0.56 to 1.25; 3082 women; 10 studies; Tau² = 0.14, I² = 49%; very low-quality evidence) or the need for additional uterotonics compared to ergot alkaloids (average RR 0.89, 95% CI 0.43 to 1.81; 2178 women; 8 studies; Tau² = 0.76, I² = 79%; very low-quality evidence), because the quality of this evidence is very low. The quality of evidence was very low for blood loss of 1000 mL (RR 1.13, 95% CI 0.63 to 2.01; 1577 women; 3 studies; very low-quality evidence), and need for blood transfusion (average RR 1.37, 95% CI 0.34 to 5.51; 1578 women; 7 studies; Tau² = 1.34, I² = 45%; very low-quality evidence), making benefit of oxytocin over ergot alkaloids uncertain. Oxytocin probably increases the risk of a prolonged third stage greater than 30 minutes (RR 4.69, 95% CI 1.63 to 13.45; 450 women; 2 studies; moderate-quality evidence), although it is uncertain if this translates into increased risk of manual placental removal (average RR 1.10, 95% CI 0.39 to 3.10; 3127 women; 8 studies; Tau² = 1.07, I² = 76%; very low-quality evidence). Oxytocin may make little or no difference to risk of diastolic blood pressure > 100 mm Hg (average RR 0.28, 95% CI 0.04 to 2.05; 960 women; 3 studies; Tau² = 1.23, I² = 50%; low-quality evidence), and is probably associated with a lower risk of vomiting (RR 0.09, 95% CI 0.05 to 0.14; 1991 women; 7 studies; moderate-quality evidence), although the impact of oxytocin on headaches is uncertain (average RR 0.19, 95% CI 0.03 to 1.02; 1543 women; 5 studies; Tau² = 2.54, I² = 72%; very low-quality evidence).Prophylactic oxytocin-ergometrine versus ergot alkaloids (four trials)Oxytocin-ergometrine may slightly reduce the risk of blood loss greater than 500 mL after delivery compared to ergot alkaloids (RR 0.44, 95% CI 0.20 to 0.94; 1168 women; 3 studies; low-quality evidence), based on outcomes from quasi-randomised trials with a high risk of bias. There were no maternal deaths reported in either treatment group in the one trial that reported this outcome (RR not estimable; 1 trial, 807 women; moderate-quality evidence). Need for additional uterotonics was not reported.No subgroup differences were observed between active or expectant management, or different routes or doses of oxytocin for any of our comparisons.
AUTHORS' CONCLUSIONS: Prophylactic oxytocin compared with no uterotonics may reduce blood loss and the need for additional uterotonics. The effect of oxytocin compared to ergot alkaloids is uncertain with regards to blood loss, need for additional uterotonics, and blood transfusion. Oxytocin may increase the risk of a prolonged third stage compared to ergot alkaloids, although whether this translates into increased risk of manual placental removal is uncertain. This potential risk must be weighed against the possible increased risk of side effects associated with ergot alkaloids. Oxytocin-ergometrine may reduce blood loss compared to ergot alkaloids, however the certainty of this conclusion is low. More high-quality trials are needed to assess optimal dosing and route of oxytocin administration, with inclusion of important outcomes such as maternal mortality, shock, and transfer to a higher level of care. A network meta-analysis of uterotonics for PPH prevention plans to address issues around optimal dosing and routes of oxytocin and other uterotonics.
积极处理第三产程可降低产后出血风险，其定义为预防性使用宫缩剂、早期脐带结扎及控制脐带牵拉以促进胎盘娩出。全球宫缩剂的选择各异，这可能会对产妇结局产生影响。本综述首次发表于2001年，上次更新于2013年，此次为更新版。
确定预防性使用缩宫素预防第三产程产后出血及其他不良产妇结局的有效性。
为进行此次更新，我们检索了Cochrane妊娠与分娩试验注册库、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台（ICTRP，2019年3月6日）以及检索到的研究的参考文献列表。
随机、半随机或整群随机试验，纳入在第三产程管理期间接受预防性缩宫素的阴道分娩女性。主要结局包括产后失血500毫升或更多、需要额外使用宫缩剂以及产妇全因死亡率。
两位综述作者独立评估试验是否纳入、提取数据并评估试验质量。对数据进行准确性检查。我们使用GRADE方法评估证据质量。
本综述纳入24项试验，其中23项试验涉及10,018名女性并提供了数据。由于许多试验被评估为存在高偏倚风险，证据等级从极低到中等质量不等。
预防性缩宫素与不使用宫缩剂或安慰剂（9项试验）
预防性缩宫素与不使用宫缩剂或安慰剂相比，可能降低产后失血500毫升的风险（平均风险比（RR）0.51，95%置信区间（CI）0.37至0.72；4162名女性；6项研究；Tau² = 0.10，I² = 75%；低质量证据），以及产后失血1000毫升的风险（RR 0.59，95% CI 0.42至0.83；4123名女性；5项研究；低质量证据）。预防性缩宫素可能降低额外使用宫缩剂的需求（平均RR 0.54，95% CI 0.36至0.80；3135名女性；4项研究；Tau² = 0.07，I² = 44%；中等质量证据）。与不使用宫缩剂或安慰剂相比，接受缩宫素治疗的女性输血风险可能无差异（RR 0.88，95% CI 0.44至1.78；3081名女性；3项研究；低质量证据）。缩宫素可能与第三产程超过30分钟的风险增加相关（RR 2.55，95% CI 0.88至7.44；1947名女性；1项研究；中等质量证据），然而置信区间较宽且包含1.0，表明可能差异不大或无差异。
预防性缩宫素与麦角生物碱（15项试验）
与麦角生物碱相比，缩宫素是否能降低失血500毫升的可能性（平均RR 0.84，95% CI 0.56至1.25；3082名女性；10项研究；Tau² = 0.14，I² = 49%；极低质量证据）或额外使用宫缩剂的需求尚不确定（平均RR 0.89，95% CI 0.43至1.81；2178名女性；8项研究；Tau² = 0.76，I² = 79%；极低质量证据），因为此证据质量极低。对于失血1000毫升的证据质量极低（RR 1.13，95% CI 0.63至2.01；1577名女性；3项研究；极低质量证据），以及输血需求（平均RR 1.37，95% CI 0.34至5.51；1578名女性；7项研究；Tau² = 1.34，I² = 45%；极低质量证据），使得缩宫素优于麦角生物碱的益处尚不确定。缩宫素可能增加第三产程延长超过30分钟的风险（RR 4.69，95% CI 1.63至13.45；450名女性；2项研究；中等质量证据），尽管不确定这是否会转化为人工剥离胎盘风险增加（平均RR 1.10，95% CI 0.39至3.10；3127名女性；8项研究；Tau² = 1.07，I² = 76%；极低质量证据）。缩宫素对舒张压>100 mmHg的风险可能影响不大或无差异（平均RR 0.28，95% CI 0.04至2.05；960名女性；3项研究；Tau² = 1.23，I² = 50%；低质量证据），且可能与较低的呕吐风险相关（RR 0.09，95% CI 0.05至0.14；1991名女性；7项研究；中等质量证据），尽管缩宫素对头痛的影响尚不确定（平均RR 0.19，95% CI 0.03至1.02；1543名女性；5项研究；Tau² = 2.54，I² = 72%；极低质量证据）。
预防性缩宫素 - 麦角新碱与麦角生物碱（4项试验）
基于存在高偏倚风险的半随机试验结果，与麦角生物碱相比，缩宫素 - 麦角新碱可能会略微降低产后失血超过500毫升的风险（RR 0.44，95% CI 0.20至0.94；1168名女性；3项研究；低质量证据）。在报告该结局的一项试验中，两个治疗组均未报告产妇死亡（RR无法估计；1项试验，807名女性；中等质量证据）。未报告额外使用宫缩剂的需求。
在我们的任何比较中，未观察到积极管理或期待管理之间，或缩宫素的不同给药途径或剂量之间存在亚组差异。
与不使用宫缩剂相比，预防性使用缩宫素可能减少失血和额外使用宫缩剂的需求。在失血、额外使用宫缩剂的需求和输血方面，缩宫素与麦角生物碱相比的效果尚不确定。与麦角生物碱相比，缩宫素可能增加第三产程延长的风险，尽管这是否会转化为人工剥离胎盘风险增加尚不确定。这种潜在风险必须与麦角生物碱可能增加的副作用风险相权衡。与麦角生物碱相比，缩宫素 - 麦角新碱可能减少失血，然而这一结论的确定性较低。需要更多高质量试验来评估缩宫素给药的最佳剂量和途径，并纳入重要结局，如产妇死亡率、休克以及转至更高护理水平。一项关于预防产后出血宫缩剂的网状Meta分析计划解决缩宫素及其他宫缩剂的最佳剂量和途径相关问题。
