Chen Lori, Zhang Monica, Yung Jason, Chen Jennifer, McNair Carol, Lee Kyong-Soon
RPh, BScPhm, ACPR, is with the Department of Pharmacy, The Hospital for Sick Children, Toronto, Ontario.
PharmD, is with the Department of Pharmacy, Joseph Brant Hospital, Burlington, Ontario.
Can J Hosp Pharm. 2018 Nov-Dec;71(6):364-369. Epub 2018 Dec 31.
On the basis of pharmacokinetic modelling, high-dose acetaminophen by rectal administration has been recommended for neonates needing antipyretic or analgesic therapy, but the safety and efficacy of this approach have not been established in vivo.
The primary objective was to assess the safety of rectal acetaminophen administration for neonates, as indicated by changes in the results of hepatic and renal function tests. The secondary objective was to assess the efficacy of rectal acetaminophen administration in terms of the Premature Infant Pain Profile-Revised (PIPP-R) score.
This single-centre retrospective chart analysis was conducted in the neonatal intensive care unit at a quaternary care children's hospital. Neonates who received all prescribed doses of acetaminophen by continu - ous rectal administration for 24 h or more, from January 1, 2011, to December 31, 2012, were included. For the primary objective, hepatotoxicity was assessed in terms of changes in liver enzyme levels, and nephrotoxicity was assessed in terms of changes from baseline serum creatinine values.
Twenty-five patients, who received a total of 27 courses of acetaminophen by rectal administration, met the inclusion criteria. Median gestational age at initiation of acetaminophen was 37.0 weeks (interquartile range 35.0-39.8 weeks). Values of alanine aminotransferase remained within normal limits during acetaminophen therapy for all but 3 patients, for whom the changes were attributable to confounding factors. Renal function remained unchanged. The secondary outcome of efficacy (based on PIPP-R score) could not be evaluated because of concurrent use of opioids for most patients.
Continuous rectal administration of acetaminophen over a short period (< 48 h) appeared to be well tolerated. The conclusions that can be drawn from these results are limited because of small sample size, the prescribing of doses lower than those recommended by the hospital's formulary, and limited blood sampling. Further studies are required.
基于药代动力学模型，已建议对需要退热或镇痛治疗的新生儿采用直肠给予高剂量对乙酰氨基酚，但该方法的安全性和有效性尚未在体内得到证实。
主要目的是通过肝肾功能检查结果的变化来评估直肠给予对乙酰氨基酚对新生儿的安全性。次要目的是根据修订的早产儿疼痛量表（PIPP-R）评分评估直肠给予对乙酰氨基酚的有效性。
在一家四级护理儿童医院的新生儿重症监护病房进行了这项单中心回顾性病历分析。纳入2011年1月1日至2012年12月31日期间通过连续直肠给药接受所有规定剂量对乙酰氨基酚达24小时或更长时间的新生儿。对于主要目的，根据肝酶水平变化评估肝毒性，根据血清肌酐值与基线的变化评估肾毒性。
25例患者共接受了27个疗程的直肠给予对乙酰氨基酚治疗，符合纳入标准。开始使用对乙酰氨基酚时的中位胎龄为37.0周（四分位间距35.0 - 39.8周）。除3例患者外，所有患者在对乙酰氨基酚治疗期间丙氨酸氨基转移酶值均保持在正常范围内，这3例患者的变化归因于混杂因素。肾功能保持不变。由于大多数患者同时使用阿片类药物，无法评估有效性的次要结果（基于PIPP-R评分）。
短期内（< 48小时）连续直肠给予对乙酰氨基酚似乎耐受性良好。由于样本量小、所开剂量低于医院处方集推荐剂量以及采血有限，从这些结果中得出的结论有限。需要进一步研究。
