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宫缩抑制剂治疗中的争议

Controversies in tocolytic therapy.

作者信息

Katz V L, Farmer R M

机构信息

Center for Genetics and Maternal-Fetal Medicine, Sacred Heart Medical Center, Eugene, Oregon 97401, USA.

出版信息

Clin Obstet Gynecol. 1999 Dec;42(4):802-19. doi: 10.1097/00003081-199912000-00008.

Abstract

In general, tocolytic agents are effective in stopping uterine contractions and in temporarily delaying delivery. The benefit of stopping uterine contractions is dependent on the fetal status and gestational age. The rationale for stopping preterm labor is to improve neonatal outcome. At this time, the best way to improve neonatal outcome would be to assure delivery in a center capable of caring for a preterm infant and prescription of glucocorticoids to decrease the risk of respiratory distress syndrome and other neonatal complications. Intravenous tocolysis for premature labor has found a prominent place in the obstetrician's armamentarium. We recommend the use of magnesium sulfate as first-line therapy. When comparing maternal and fetal risks, side effects, and the safety profile, magnesium sulfate is superior to beta-mimetics; however, there are still significant problems with potential morbidity and mortality for both mother and fetus with any tocolytics. Adjunctive use of indomethacin with magnesium sulfate may be used through 32 weeks for up to 48 hours at a time. Most tocolytics are effective in stopping labor for 48-72 hours. None have been shown to decrease the rate of preterm delivery. Once the uterus is quiescent and intravenous tocolytics are stopped, prolonged use of tocolytics has not been shown to be effective in preventing preterm birth. Tocolytics have significant long-term side effects to the mother's cardiovascular system, carbohydrate metabolism, and the fetal cardiovascular system. Thus, the prolonged use of prophylactic tocolytics after cessation of intravenous medications is not recommended. Tocolytics may be an appropriate therapy during preterm labor vaginal bleeding, ruptured membranes, multiple gestation, or advanced cervical dilatation. In all situations, however, careful guidelines must be observed. These guidelines include: (1) maternal and fetal well-being must be established before tocolytic therapy; (2) causes of preterm labor should be evaluated and treated when possible; (3) the risk/benefit ratio for both the mother and fetus must be re-evaluated on an ongoing basis; (4) when tocolytics are given before pulmonary maturity, then antenatal corticosteroids also should be considered in every case; (5) long-term use of tocolytics is difficult to justify at this time; (6) the safest tocolytic should be used for the shortest amount of time possible. It is doubtful, because of the nature of tocolytics, that newer tocolytics will be developed that will eliminate the problems of preterm delivery. Preterm delivery is an end-stage symptom of a multifactorial disease. Preterm labor is one of the last symptoms in a cascade of biochemical events that lead to preterm delivery. The most appropriate way to end preterm delivery would be to prevent the causes that initiate the cascade that ends in preterm labor. Authors' Note: Literally hundreds of papers have been written in the last 30 years on tocoloysis. For the purposes of space, when studies are summarized in peer-reviewed articles, we have referenced the reviews instead of the individual studies.

摘要

一般来说,宫缩抑制剂可有效抑制子宫收缩并暂时延迟分娩。抑制子宫收缩的益处取决于胎儿状况和孕周。抑制早产的目的是改善新生儿结局。目前,改善新生儿结局的最佳方法是确保在有能力护理早产婴儿的中心分娩,并使用糖皮质激素以降低呼吸窘迫综合征和其他新生儿并发症的风险。静脉使用宫缩抑制剂治疗早产在产科医生的治疗手段中占据重要地位。我们推荐使用硫酸镁作为一线治疗药物。在比较母体和胎儿风险、副作用及安全性时,硫酸镁优于β-拟交感神经药;然而,任何宫缩抑制剂对母亲和胎儿都仍存在潜在发病和死亡的重大问题。吲哚美辛与硫酸镁联合使用可在孕32周前每次使用长达48小时。大多数宫缩抑制剂能有效抑制宫缩48 - 72小时。尚无证据表明其能降低早产发生率。一旦子宫静止且停止静脉使用宫缩抑制剂,长期使用宫缩抑制剂并不能有效预防早产。宫缩抑制剂对母亲的心血管系统、碳水化合物代谢以及胎儿的心血管系统均有显著的长期副作用。因此,不建议在停止静脉用药后长期预防性使用宫缩抑制剂。宫缩抑制剂可能是早产伴阴道出血、胎膜破裂、多胎妊娠或宫颈扩张进展时的合适治疗方法。然而,在所有情况下都必须遵循仔细的指导原则。这些原则包括:(1)在进行宫缩抑制治疗前必须确定母体和胎儿的健康状况;(2)应评估并尽可能治疗早产的原因;(3)必须持续重新评估母亲和胎儿的风险/获益比;(4)当在肺成熟前使用宫缩抑制剂时,每种情况都应考虑使用产前糖皮质激素;(5)目前难以证明长期使用宫缩抑制剂的合理性;(6)应使用最安全的宫缩抑制剂并尽可能缩短使用时间。鉴于宫缩抑制剂的性质,开发出能消除早产问题的新型宫缩抑制剂令人怀疑。早产是一种多因素疾病的终末期症状。早产宫缩是导致早产的一系列生化事件中的最后症状之一。终止早产的最合适方法是预防引发导致早产宫缩的级联反应的原因。作者注:在过去30年里, literally有成百上千篇关于宫缩抑制的论文。为节省篇幅,当研究在同行评审文章中被总结时,我们引用了综述而非个别研究。

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