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Dosing of enteral acetaminophen in critically ill children: a cohort study
  1. Nadia Roumeliotis1,2,
  2. Helena Frndova3,
  3. Eleanor Pullenayegum4,
  4. Anna Taddio5,6,
  5. Paula Rochon5,7,
  6. Christopher S Parshuram1,5
  1. 1Critical Care Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
  2. 2Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
  3. 3Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada
  4. 4Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
  5. 5Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
  6. 6Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
  7. 7Women's College Hospital, Toronto, Ontario, Canada
  1. Correspondence to Dr Nadia Roumeliotis, Department of Critical Care Medicine, SickKids Research Institute, Toronto, Ontario, Canada; nadia.roumeliotis{at}


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.

  • analgesia
  • epidemiology
  • pharmacology

Data availability statement

Data are available upon reasonable request.

Statistics from

Data availability statement

Data are available upon reasonable request.

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  • Contributors NR conceptualised and designed the study, conducted the statistics, summarised the results, drafted the initial manuscript, and reviewed and revised the manuscript. HF acquired the data, critically reviewed the article. EP contributed to study design, analysis plan, interpretation of results and critical appraisal of intellectual content and approved the final version. AT and PR contributed to study design, critically appraised it for intellectual content, and reviewed and revised the final version of the manuscript. CSP conceptualised and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

  • Funding This study was not funded, but NR received doctoral salary support from the Fonds de Recherche Santé-Québec and the Canadian Critical Care Trials Group.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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