Sridharan Kannan, Al Jufairi Muna, Al Ansari Eman, Al Marzooq Reem, Hubail Zakariya, Hasan Sadeq Jaafar Radhi, Al Madhoob Abdulraoof
Department of Pharmacology & Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
Neonatology Intensive Care Unit, Department of Pediatrics, Salmaniya Medical Complex, Manama, Kingdom of Bahrain.
J Clin Pharm Ther. 2021 Aug;46(4):1010-1019. doi: 10.1111/jcpt.13384. Epub 2021 Feb 27.
Acetaminophen has been increasingly used in treating patent ductus arteriosus (PDA) in preterm neonates. Variations were observed in the dosing regimen of acetaminophen across the studies. There is hardly any data available for a relatively higher dose of intravenous acetaminophen (15 mg/kg/dose every 6 hours) in the preterm population. We present here the results of a prospective study with this dose of intravenous acetaminophen for treating PDA in critically ill preterm neonates.
Preterm neonates (≤37 weeks of gestational age) with haemodynamically significant PDA were enrolled. Intravenous acetaminophen at 15 mg/kg/dose every 6 hours was administered. Echocardiographic monitoring, liver and renal function tests were carried out. Standard definitions were adhered for defining acute kidney injury (AKI) and hepatotoxicity.
Fifty-five neonates were recruited. Following the first dose, less than half had their serum acetaminophen concentrations in the therapeutic range. Extreme preterm neonates were less likely to have a sustained therapeutic acetaminophen concentration after the first dose. Following multiple doses and at steady state, 97.2% and 98.8% respectively were in the therapeutic range. Forty-three (78.2%) neonates had successful closure of the ductus arteriosus of which 22 were extreme preterm, 17 were very preterm and 4 were late preterm neonates; and considering their birthweights, 21 were extremely low, 16 were very low and 6 were low birthweight categories. Ten neonates had elevated alanine aminotransferase levels with three in the low-to-moderate risk of hepatotoxicity category. Eight neonates had altered renal function tests indicating AKI.
Intravenous acetaminophen at 15 mg/kg/dose every 6 hours was efficacious in 78.2% of the preterm neonates with PDA. We observed a lower incidence of hepatotoxicity, and AKI in the study population. No association was observed between the serum acetaminophen concentrations and PDA closure.
对乙酰氨基酚在治疗早产儿动脉导管未闭（PDA）中的应用日益增多。各项研究中对乙酰氨基酚的给药方案存在差异。对于早产儿群体中相对较高剂量的静脉注射对乙酰氨基酚（每6小时15mg/kg/剂量），几乎没有可用数据。我们在此呈现一项前瞻性研究的结果，该研究使用此剂量的静脉注射对乙酰氨基酚治疗危重新生儿PDA。
纳入有血流动力学意义的PDA的早产儿（胎龄≤37周）。每6小时静脉注射15mg/kg/剂量的对乙酰氨基酚。进行超声心动图监测、肝肾功能检查。采用标准定义来界定急性肾损伤（AKI）和肝毒性。
招募了55名新生儿。首次给药后，不到一半的新生儿血清对乙酰氨基酚浓度处于治疗范围内。极早产儿首次给药后维持治疗性对乙酰氨基酚浓度的可能性较小。多次给药并达到稳态后，分别有97.2%和98.8%处于治疗范围内。43名（78.2%）新生儿动脉导管成功闭合，其中22名是极早产儿，17名是非常早产儿，4名是晚期早产儿；考虑到他们的出生体重，21名是极低出生体重儿，16名是超低出生体重儿，6名是低出生体重儿。10名新生儿丙氨酸转氨酶水平升高，其中3名处于肝毒性低至中度风险类别。8名新生儿肾功能检查结果异常，提示存在AKI。
每6小时静脉注射15mg/kg/剂量的对乙酰氨基酚对78.2%的PDA早产儿有效。我们观察到研究人群中肝毒性和AKI的发生率较低。未观察到血清对乙酰氨基酚浓度与PDA闭合之间存在关联。
