Acute hepatotoxicity associated with therapeutic doses of intravenous acetaminophen

  • Seifert S
  • Kovnat D
  • Anderson V
 et al. 
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AbstractBackground: 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. Case details: 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 maintenance dose rate for a second 16-hour infusion, at which time transaminases, INR, ammonia and total bilirubin were all improving. The patient was discharged 2 days later. Serum APAP-CYS concentrations in serum samples obtained during her hospitalization were elevated (peak?=?4.81??M on hospital day 5; expected range for therapeutic dosing

Author-supplied keywords

  • Acetaminophen
  • IV acetaminophen
  • acetaminophen-protein adducts
  • hepatotoxicity

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