Department of Pediatrics, Division of Neonatology, University of Florida College of Medicine, Jacksonville, Florida.
Department of Pediatrics, Division of Neonatology, Johns Hopkins Children's Center, John Hopkins University, Baltimore, Maryland.
Am J Perinatol. 2022 Sep;39(12):1326-1333. doi: 10.1055/s-0040-1722329. Epub 2021 Jan 17.
The study aimed to evaluate the efficacy of dual medication therapy (DMT) with oral acetaminophen and oral ibuprofen for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA).
In a prospective case-control cohort study (July 2017-May 2019), infants <29 weeks' gestational age and birth weight <1,000 g at ≤14 postnatal days with hsPDA and ratio of the smallest ductal diameter to the ostium of the left pulmonary artery diameter >0.5 were eligible. Infants received 10 mg/kg oral ibuprofen followed by two additional doses of 5 mg/kg at 24 and 48 hours after the initial ibuprofen dose and concomitant treatment with 15 mg/kg oral acetaminophen every 6 hours for 3 days (12 doses). Success of PDA treatment was defined as a small or absent PDA as ascertained by echocardiographic measurements. The -values of comparisons were adjusted for multiple comparisons to preserve an error rate of 5%.
Overall, 20 infants received oral DMT and 11 infants received intravenous single medication therapy (SMT) with ibuprofen. The rates of successful PDA treatment following the first treatment in DMT and SMT groups were not statistically different (11/20 [55%] vs. 4/11 [36%], = 0.46). However, DMT significantly decreased PDA size (mean difference = 0.54 mm, 95% confidence interval [CI]: 0.21-0.96, adjusted -value = 0.0002) and PDA/LPA ratio (mean difference = 0.27, 95% CI: 0.10-0.47, adjusted -value = 0.0004). We observed no evidence of hematologic, hepatic, or renal impairment.
DMT achieved a greater degree of PDA closure than SMT and did not result in abnormalities in hepatic and renal profile.
· No consensus on optimal medication for PDA treatment is available.. · Dual oral medication therapy (ibuprofen and acetaminophen) could be an effective alternative treatment for PDA.. · Dual oral medication therapy (ibuprofen and acetaminophen) may have a better safety profile than currently approved medications such as intravenous indomethacin and intravenous ibuprofen..
本研究旨在评估口服对乙酰氨基酚和布洛芬联合用药（DMT）治疗早产儿动脉导管未闭（hsPDA）的疗效。
这是一项前瞻性病例对照队列研究（2017 年 7 月至 2019 年 5 月），纳入胎龄<29 周、出生体重<1000g、生后≤14 天、hsPDA 且动脉导管直径与左肺动脉直径比值>0.5 的早产儿。所有患儿接受 10mg/kg 口服布洛芬，首次用药后 24 小时和 48 小时各追加 5mg/kg，同时给予 15mg/kg 口服对乙酰氨基酚，每 6 小时 1 次，连用 3 天（共 12 剂）。成功治疗的定义为超声心动图检查提示动脉导管较小或完全关闭。比较的 P 值经多重比较校正，以保持错误率为 5%。
共有 20 例患儿接受 DMT，11 例患儿接受静脉单药治疗（SMT），静脉单药治疗使用布洛芬。DMT 组首次治疗后 PDA 关闭成功率（11/20[55%]）与 SMT 组（4/11[36%]）相比无统计学差异（=0.46）。然而，DMT 显著降低了 PDA 直径（平均差值=0.54mm，95%可信区间：0.21-0.96，校正 P 值=0.0002）和 PDA/LPA 比值（平均差值=0.27，95%可信区间：0.10-0.47，校正 P 值=0.0004）。未观察到血液学、肝肾功能损害的证据。
DMT 比 SMT 更能有效关闭 PDA，且未导致肝肾功能异常。
· 目前尚无关于 PDA 治疗最佳药物的共识。· 口服双药治疗（布洛芬和对乙酰氨基酚）可能是治疗 PDA 的有效替代方法。· 与目前批准的药物（如静脉用吲哚美辛和静脉用布洛芬）相比，口服双药治疗（布洛芬和对乙酰氨基酚）可能具有更好的安全性。
