Lee Zon-Min, Yang Yao-Hsu, Chang Ling-Sai, Chen Chih-Cheng, Yu Hong-Ren, Kuo Kuang-Che
Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan.
Children (Basel). 2022 Aug 7;9(8):1184. doi: 10.3390/children9081184.
Backgrounds: Drugs with the ability to displace bilirubin from albumin-binding sites subsequently leading to an increased bilirubin level may cause hyperbilirubinemia in neonates. Ibuprofen is commonly used to treat patent ductus arteriosus (PDA) in neonates, yet the use of ibuprofen has drawn mixed conclusions. We performed a retrospective study to determine how ibuprofen use influences the total serum bilirubin (TSB) level in neonates of differing birth weight (BW). Materials and methods: Neonates (including premature infants) born at Chang Gung Memorial Hospital, Taiwan during January 2004 to July 2020 were entered into this study. We recorded the phototherapy duration, including the initial day and end day, and determined the average influence of one-day phototherapy on TSB level. The highest monitored TSB level post-ibuprofen use minus the one measured prior to ibuprofen use was considered the TSB change following ibuprofen administration in this study, and the above-mentioned influence of daily phototherapy on the TSB level was used to correlate the results. Neonates with any of the following conditions were excluded: those who received ceftriaxone, those with intraventricular hemorrhage, and those infected with TORCH. Results: The average daily influence of phototherapy on the TSB level of neonates was −0.20 (−0.570.05) mg/dL, −0.28 (−0.840.13) mg/dL, −0.75 (−1.770.10) mg/dL, and −1.60 (−2.70−0.50) mg/dL in neonates with BWs of <1 kg, 1−1.49 kg, 1.5−2.49 kg, and ≥2.5 kg, respectively, indicating that neonates with a BW ≥ 1.5 kg experienced a greater reduction in TSB level following phototherapy as compared with those with a BW < 1.5 kg. The average TSB increase following ibuprofen use in neonates was 3.38 ± 2.77 mg/dL, 2.04 ± 2.53 mg/dL, and 1.34 ± 2.24 mg/dL in neonates with BWs of <1 kg, 1−1.49 kg, and ≥1.5 kg, respectively, i.e., an elevated TSB change with a decreased neonate BW was noted post-ibuprofen use (p = 0.026, one-way analysis of variance (ANOVA)). Conclusions: As ibuprofen use is correlated with an apparent increase in TSB level in neonates with a lower BW, especially in those with a BW < 1 kg, iv acetaminophen can be an appropriate alternative to ibuprofen for ELBW neonates for the treatment of PDA if they are experiencing severe unconjugated hyperbilirubinemia.
能够从白蛋白结合位点置换胆红素从而导致胆红素水平升高的药物可能会引起新生儿高胆红素血症。布洛芬常用于治疗新生儿动脉导管未闭（PDA），但其使用结论不一。我们进行了一项回顾性研究，以确定布洛芬的使用如何影响不同出生体重（BW）的新生儿的总血清胆红素（TSB）水平。
纳入2004年1月至2020年7月在台湾长庚纪念医院出生的新生儿（包括早产儿）。我们记录了光疗持续时间，包括开始日期和结束日期，并确定了一天光疗对TSB水平的平均影响。本研究中，布洛芬使用后监测到的最高TSB水平减去使用布洛芬之前测量的水平被视为布洛芬给药后TSB的变化，并使用上述每日光疗对TSB水平的影响来关联结果。排除患有以下任何一种情况的新生儿：接受头孢曲松治疗的新生儿、患有脑室内出血的新生儿以及感染TORCH的新生儿。
体重<1kg、1 - 1.49kg、1.5 - 2.49kg和≥2.5kg的新生儿，光疗对其TSB水平的每日平均影响分别为−0.20（−0.570.05）mg/dL、−0.28（−0.840.13）mg/dL、−0.75（−1.770.10）mg/dL和−1.60（−2.70−0.50）mg/dL，这表明与体重<1.5kg的新生儿相比，体重≥1.5kg的新生儿在光疗后TSB水平降低幅度更大。体重<1kg、1 - 1.49kg和≥1.5kg的新生儿在使用布洛芬后TSB的平均升高分别为3.38±2.77mg/dL、2.04±2.53mg/dL和1.34±2.24mg/dL，即使用布洛芬后，TSB变化升高且新生儿体重降低（p = 0.026，单因素方差分析（ANOVA））。
由于布洛芬的使用与低体重新生儿尤其是体重<1kg的新生儿的TSB水平明显升高相关，如果超低出生体重（ELBW）新生儿患有严重的非结合性高胆红素血症且正在接受PDA治疗，静脉注射对乙酰氨基酚可能是布洛芬的合适替代药物。
