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一名儿童意外过量服用液体对乙酰氨基酚后出现肝毒性。

Hepatotoxicity in a child following an accidental overdose of liquid paracetamol.

作者信息

Chiew Angela L, Domingo Genaro, Buckley Nicholas A, Stathakis Paul, Ress Kirsty, Roberts Darren M

机构信息

New South Wales Poisons Information Centre, Children's Hospital at Westmead, Westmead, Australia.

Department of Paediatrics, Tamworth Rural Referral Hospital, Tamworth, Australia.

出版信息

Clin Toxicol (Phila). 2020 Nov;58(11):1063-1066. doi: 10.1080/15563650.2020.1722150. Epub 2020 Feb 18.

DOI:10.1080/15563650.2020.1722150
PMID:32067495
Abstract

Accidental pediatric liquid paracetamol exposure is common. Most children do not require treatment with acetylcysteine and acute liver injury is rare. An otherwise well 3-year-old (15.4 kg) girl with recent vomiting and low-grade fever presented 1 h post-accidental ingestion of up to 150 mL of 24 mg/mL (240 mg/kg) of liquid paracetamol. Paracetamol concentrations 2 and 4 h post-ingestion were 105 and 97 mg/L, respectively, both below the nomogram treatment threshold so acetylcysteine was not administered. The ALT was elevated to 52 U/L 4 h post-ingestion, and then 219 U/L at 17 h, so intravenous acetylcysteine was commenced at 25 h. ALT peaked at 1393 U/L 5d post-ingestion, and INR peaked at 1.5 at 44 h post-ingestion. Acetylcysteine continued for 64 h and she made an uneventful recovery. Paracetamol metabolites were measured including, nontoxic glucuronide and sulphate conjugates and toxic cytochrome P450 (CYP) metabolites (cysteine and mercapturate). The apparent paracetamol half-life was 6.3 h. Her CYP metabolites were higher than usual, 11% of total metabolites. Glucuronide and sulphate conjugates accounted for 71 and 18% of total metabolites, respectively. This uncommon case of hepatotoxicity in a child following accidental liquid paracetamol ingestion may have been due to increased susceptibility from a recent viral illness with decreased oral intake, as evidenced by the higher proportion of CYP metabolites.

摘要

儿童意外摄入液体对乙酰氨基酚很常见。大多数儿童不需要用乙酰半胱氨酸治疗,急性肝损伤也很少见。一名原本健康的3岁(15.4千克)女孩,近期有呕吐和低热症状,在意外摄入多达150毫升24毫克/毫升(240毫克/千克)的液体对乙酰氨基酚后1小时就诊。摄入后2小时和4小时的对乙酰氨基酚浓度分别为105毫克/升和97毫克/升,均低于列线图治疗阈值,因此未给予乙酰半胱氨酸。摄入后4小时谷丙转氨酶(ALT)升至52 U/L,17小时时升至219 U/L,因此在25小时开始静脉注射乙酰半胱氨酸。摄入后5天ALT峰值达到1393 U/L,摄入后44小时国际标准化比值(INR)峰值达到1.5。乙酰半胱氨酸持续使用64小时,她顺利康复。检测了对乙酰氨基酚的代谢产物,包括无毒的葡萄糖醛酸和硫酸盐结合物以及有毒的细胞色素P450(CYP)代谢产物(半胱氨酸和硫醚氨酸)。对乙酰氨基酚的表观半衰期为6.3小时。她的CYP代谢产物高于正常水平,占总代谢产物的11%。葡萄糖醛酸和硫酸盐结合物分别占总代谢产物的71%和18%。这名儿童意外摄入液体对乙酰氨基酚后发生肝毒性的罕见病例,可能是由于近期病毒感染导致易感性增加以及口服摄入量减少,CYP代谢产物比例较高证明了这一点。

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