Acute hepatotoxicity associated with therapeutic doses of intravenous acetaminophen

Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists
Steven A SeifertKennon Heard

Abstract

IV acetaminophen at 4 g per day is considered safe, producing no hepatic failure in more than 1400 cases. Oxidation of acetaminophen forms a reactive intermediate that binds to cellular proteins resulting in acetaminophen-protein adducts (APAP-CYS). Serum concentrations of APAP-CYS have been found to correlate with acetaminophen-induced hepatotoxicity. We report a case of hepatotoxicity associated with therapeutic doses of IV acetaminophen, with elevated serum APAP-CYS. The patient was a 92-year-old, 68 kg woman without known hepatic disease or ethanol abuse. On hospital day 3 she underwent laparoscopic reduction of internal hernias under general anesthesia. Surgery was uncomplicated and postoperatively she was treated with subcutaneous heparin and IV acetaminophen, 1 g every 6 h for almost 4 days (total dose = 13 g). At the start of therapy, transaminases were normal. On hospital day 5, she was noted to have marked transaminase elevations (AST: 4698 IU/L; ALT: 3914 IU/L) with increases in INR (1.68), ammonia (60 mcg/dL), and total bilirubin (1.8 mg/dL). Serum acetaminophen concentration was 15.3 mcg/mL 26 h after her last dose. Acetaminophen was discontinued and IV acetylcysteine was given and continued at the second maintenan...Continue Reading

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Citations

Apr 28, 2017·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Anselm Wong, Andis Graudins
Jul 6, 2018·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·R AchterberghJ A Romijn
May 18, 2019·Journal of Clinical Pharmacology·Sibo JiangLaura P James
Jul 12, 2019·Expert Opinion on Drug Metabolism & Toxicology·Yvonne GloorCaroline F Samer
May 11, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Ranjeet Prasad DashNuggehally R Srinivas
Jan 15, 2020·Case Reports in Hepatology·Deanna K BauerleinPreeti R John

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