Division of Neonatology, Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada; Department of Newborn and Developmental Pediatrics, Sunnybrook Health Sciences Centre, Toronto, Canada.
Department of Paediatrics, University of Toronto, Toronto, Canada; Department of Newborn and Developmental Pediatrics, Sunnybrook Health Sciences Centre, Toronto, Canada.
Semin Perinatol. 2018 Jun;42(4):243-252. doi: 10.1053/j.semperi.2018.05.007. Epub 2018 May 24.
While cyclooxygenase inhibitors have been the most common medications used to facilitate earlier closure of patent ductus arteriosus in preterm infants, adverse effects and variable efficacy have highlighted a need for alternative options. Acetaminophen facilitates ductal closure via an alternate pathway of prostaglandin inhibition. Despite treatment with high doses, toxicity is uncommon in preterm infants, possibly due to immature hepatic metabolism. Pooled data from randomized clinical trials of early treatment demonstrate that acetaminophen has similar efficacy as cyclooxygenase inhibitors for PDA closure with a favorable side effect profile and without any apparent increase in adverse neonatal outcomes. Acetaminophen may therefore be an ideal first-line agent among moderately and extremely preterm infants, though there is a paucity of data from controlled trials regarding its use in infants at the border of viability (gestation age ≤25 weeks). Evidence from clinical studies of limited quality supports acetaminophen treatment as rescue therapy for infants with persistent PDA after unsuccessful cyclooxygenase inhibitor treatment, including those being considered for surgical ligation.
虽然环氧化酶抑制剂一直是用于促进早产儿动脉导管未闭（PDA）更早闭合的最常用药物，但不良反应和疗效的变异性突出表明需要替代选择。对乙酰氨基酚通过前列腺素抑制的替代途径促进导管闭合。尽管使用高剂量，但早产儿中毒并不常见，这可能是由于不成熟的肝脏代谢。来自早期治疗的随机临床试验的汇总数据表明，对乙酰氨基酚在 PDA 闭合方面与环氧化酶抑制剂具有相似的疗效，具有良好的副作用特征，并且新生儿不良结局没有明显增加。因此，对乙酰氨基酚可能是中度和极早产儿的理想一线药物，尽管在临界生存能力（胎龄≤25 周）婴儿中使用的对照试验数据很少。质量有限的临床研究证据支持对乙酰氨基酚治疗作为不成功的环氧化酶抑制剂治疗后持续性 PDA 的婴儿的抢救治疗，包括那些考虑手术结扎的婴儿。
