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Drug-associated harm is common but difficult to detect in the hospital setting. In critically ill children, we sought to evaluate drug-associated hepatic injury following enteral acetaminophen error, defined as acetaminophen dosing that exceeds daily maximum recommendations. This retrospective cohort study took place in two pediatric intensive care units within a pediatric hospital center. The included patients are children (< 18 years of age) admitted to the pediatric and cardiac intensive care unit between January 2008 and January 2018, and receiving enteral acetaminophen. We defined acetaminophen dosing error as exceeding daily acetaminophen dosing by > 10% the upper limit of maximum recommended dose for weight and age (> 82.5 mg/kg/day or > 4400 mg/day). We included 14,146 admissions, who received 147,485 doses of acetaminophen. Acetaminophen dosing errors occurred 1 in every 9.5 patient-days on acetaminophen. ALT and AST decreased significantly over the course of ICU admission (p < 0.0001). In patients with acetaminophen errors, ALT and AST measured in the 24 to 96 h post error were not significantly different than when measured outside this window. A sensitivity analysis using > 100 mg/kg/day as the upper daily acetaminophen error cut-off did not reveal any subsequent significant increase in ALT or ALT in the 24 to 96-h post-error window, compared to measurements taken outside the window., Conclusion: Although the administration of acetaminophen in critically ill children frequently exceeds the daily recommended limit and vigilance is needed, we did not find any associated increase in liver transaminases following acetaminophen errors., What Is Known: • Acetaminophen dosing errors are common in pediatric outpatients. • Excessive acetaminophen dosing can be associated with harm, including hepatic injury., What Is New: • Exceeding daily acetaminophen dosing limit occurs 1 in every 9.5 patient-days in children admitted to the critical care unit. • In patients with daily dose excess of acetaminophen, we did not find a significant increase in the measured liver enzymes in the 24 to 96 h following the overdosing., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Acetaminophen is the most common medication prescribed in children's hospitals. The aim of the study was to estimate the frequency and risk factors for acetaminophen underdosing and overdosing in the paediatric intensive care unit (PICU)., Design: Retrospective cohort of drug administrations in a large tertiary care PICU., Patients: All PICU admissions, less than 18 years of age, admitted between 1 January 2008 and 1 January 2018, having received at least one dose of enteral acetaminophen., Methods: The primary outcome was acetaminophen underdosing and overdosing, defined as doses exceeding the 10% upper and lower limits of the standard reference range (10-15 mg/kg) and 10% above daily maximum dose (75 mg/kg). A generalised estimating equation regression assessed patient risk factors for single underdosing, single overdosing and cumulative daily overdosing of acetaminophen., Results: Of the 147 485 doses of enteral acetaminophen administered, 7814 (5.3%) were single underdoses (1 in every 19 doses) and 4640 (3.1%) were single overdoses (1 in every 32 doses). There were 6813 cumulative overdose days (1 in every 9 patient-days). Risk factors for both underdosing and overdosing included older age and cardiac admission, whereas risk factors for cumulative overdosing were young age and cardiac admission. Electronic prescribing increased the risk of underdosing and overdosing, but decreased cumulative acetaminophen overdosing (relative risk 0.51, p=0.001)., Conclusion: Acetaminophen underdosing and overdosing are common in the PICU and can be detected with pharmacoepidemiology. Electronic prescribing increased the risk of single underdosing and overdosing, although it reduced the risk of cumulative overdosing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)