Raknoo Thitinun, Janjindamai Waricha, Sitaruno Sirima, Dissaneevate Supaporn, Ratanajamit Chaveewan
B.Pharm. College of Pharmacotherapy Thailand, Nontaburi, Thailand and department of Pharmacy, Suratthani Hospital , Suratthani, Thailand .
M.D. Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University , Hat Yai, Songkhla, Thailand .
Pharm Pract (Granada). 2021 Oct-Dec;19(4):2409. doi: 10.18549/PharmPract.2021.4.2409. Epub 2021 Nov 29.
Intravenous indomethacin has been used in infants for many years as the pharmacological closure of ductus arteriosus, but the incidence, risk, and risk factors of acute kidney injury (AKI) among infants treated with indomethacin, were still scarce.
To determine the incidence, risk, and risk factors of AKI among infants treated with indomethacin (exposed group) for patent ductus arteriosus (PDA) closure compared with the matched non-exposed infants.
A matched retrospective cohort study of infants admitted to the neonatal intensive care unit of Songklanagarind Hospital from January 2003 to December 2018 was performed. All data were collected from computerized medical records. A non-exposed infant was matched (1:1) by gestational age and birth weight to each exposed infant. AKI, the outcome of interest, was diagnosed according to neonatal AKI definitions. The incidence (95% CI) of AKI was estimated for each group. Conditional logistic regression was used to estimate the odds ratio (OR) of developing AKI among those who received indomethacin compared with those who did not, adjusted for potential confounders (concomitantly used nephrotoxic potential medications including aminoglycosides, amphotericin B, vancomycin, furosemide, systemic corticosteroids, and systemic vasopressors and inotropes). Kaplan-Meier estimate was performed to examine probability of recovery from AKI after AKI events.
The matching resulted in 193 pairs of exposed and non-exposed infants. The incidences [95% CI] of AKI in the exposed and the non-exposed group, were 33.7% [27.0%:40.4%] and 15.5% [10.4%:20.7%], respectively. Indomethacin statistically increased the risk for developing AKI, crude OR 2.94[95%CI 1.77:4.90], McNemar's chi square p<0.001, and adjusted OR 2.73 [95%CI 1.55:4.80], p=0.001. The risk of AKI associated with potentially nephrotoxic medications were inconclusive. Time to recovery from AKI was relatively rapid, median recovery time was 3 days in both groups and all infants who developed AKI recovered within 6 days.
The incidence of AKI among infants treated with indomethacin for PDA closure were doubled that in the indomethacin-nonexposed infants. Indomethacin significantly increased the risk of AKI, while the risk associated with other concomitant nephrotoxic medications were inconclusive. Transient nephrotoxicity associated with indomethacin should be balanced with the risk associated with delayed PDA closure. All infants receiving indomethacin should be routinely monitored for serum creatinine and/or urine output, throughout the treatment and one to two weeks after treatment cessation. Alternatives with better renal safety profiles should be considered in the population with higher risk of AKI.
静脉注射吲哚美辛多年来一直用于婴儿动脉导管未闭的药物性闭合，但在接受吲哚美辛治疗的婴儿中，急性肾损伤（AKI）的发生率、风险及风险因素仍缺乏相关研究。
确定与匹配的未暴露婴儿相比，接受吲哚美辛（暴露组）治疗动脉导管未闭（PDA）的婴儿中AKI的发生率、风险及风险因素。
对2003年1月至2018年12月在宋卡纳加拉林医院新生儿重症监护病房住院的婴儿进行匹配回顾性队列研究。所有数据均从计算机化医疗记录中收集。按胎龄和出生体重将一名未暴露婴儿与每名暴露婴儿进行1:1匹配。根据新生儿AKI定义诊断感兴趣的结局AKI。估计每组AKI的发生率（95%可信区间）。采用条件逻辑回归估计接受吲哚美辛治疗的婴儿与未接受治疗的婴儿相比发生AKI的比值比（OR），并对潜在混杂因素（同时使用的具有肾毒性的潜在药物，包括氨基糖苷类、两性霉素B、万古霉素、呋塞米、全身性皮质类固醇以及全身性血管加压药和正性肌力药）进行校正。采用Kaplan-Meier估计法检查AKI事件后从AKI恢复的概率。
匹配后得到193对暴露和未暴露婴儿。暴露组和未暴露组AKI的发生率[95%可信区间]分别为33.7%[27.0%:40.4%]和15.5%[10.4%:20.7%]。吲哚美辛在统计学上增加了发生AKI的风险，粗OR为2.94[95%可信区间1.77:4.90]，McNemar卡方检验p<0.001，校正后OR为2.73[95%可信区间1.55:4.80]，p = 0.001。与潜在肾毒性药物相关的AKI风险尚无定论。从AKI恢复的时间相对较快，两组的中位恢复时间均为3天，所有发生AKI的婴儿均在6天内恢复。
接受吲哚美辛治疗PDA闭合的婴儿中AKI的发生率是未接受吲哚美辛治疗婴儿的两倍。吲哚美辛显著增加了AKI的风险，而与其他同时使用的肾毒性药物相关的风险尚无定论。应权衡与吲哚美辛相关的短暂肾毒性与延迟PDA闭合相关的风险。在整个治疗过程中以及治疗停止后1至2周，所有接受吲哚美辛治疗的婴儿都应常规监测血清肌酐和/或尿量。对于AKI风险较高的人群，应考虑使用肾安全性更好的替代药物。
