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Liver enzymes after short-term acetaminophen error in critically ill children: a cohort study

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Abstract

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.

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Availability of data

Data may be available upon request.

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Coding availability in SAS may be available upon request.

Abbreviations

ADE:

Adverse drug events

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CICU:

Cardiac intensive care unit

GGT:

Gamma-glutamyl transferase

ICU:

Intensive care unit

IQR:

Interquartile range

PICU:

Pediatric intensive care unit

PRISM:

Pediatric risk of mortality

SD:

Standard deviation

References

  1. Mort JR, Shiyanbola OO, Ndehi LN, Xu Y, Stacy JN (2011) Opioid-paracetamol prescription patterns and liver dysfunction: a retrospective cohort study in a population served by a US health benefits organization. Drug Saf 34(11):1079–1088

    Article  Google Scholar 

  2. Brune K, Renner B, Tiegs G (2015) Acetaminophen/paracetamol: a history of errors, failures and false decisions. Eur J Pain 19(7):953–965

    Article  CAS  Google Scholar 

  3. Locci C, Cuzzolin L, Capobianco G, Antonucci R (2021) Paracetamol overdose in the newborn and infant: a life-threatening event. Eur J Clin Pharmacol 77(6):809–815

    Article  CAS  Google Scholar 

  4. Bonafide CP, Miller JM, Localio AR, Khan A, Dziorny AC, Mai M, Stemler S, Chen W, Holmes JH, Nadkarni VM et al (2020) Association between mobile telephone interruptions and medication administration errors in a pediatric intensive care unit. JAMA Pediatr 174(2):162–169

    Article  Google Scholar 

  5. Gaetani M, Frndova H, Seto W, Parshuram C (2017) Concurrent intravenous drug administration to critically ill children: Evaluation of frequency and compatibility. J Crit Care 41:198–203

    Article  Google Scholar 

  6. Sharek PJ, Classen D (2006) The incidence of adverse events and medical error in pediatrics. Pediatr Clin North Am 53(6):1067–1077

    Article  Google Scholar 

  7. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet (London, England) 370(9596):1453–1457

    Article  Google Scholar 

  8. Roumeliotis N, Pullenayegum E, Rochon P, Taddio A, Parshuram C (2020) A modified Delphi to define drug dosing errors in pediatric critical care. BMC Pediatr 20(1):488

    Article  Google Scholar 

  9. Lau E (2017) The Hospital for Sick Children’s Drug Formulary and Handbook: Wolters Kluwer Clinical Drug Information 2017

  10. Dlugosz CK, Chater RW, Engle JP (2006) Appropriate use of nonprescription analgesics in pediatric patients. J Pediatr Health Care 20(5):316–325; quiz 326–318

  11. Temple AR, Temple BR, Kuffner EK (2013) Dosing and antipyretic efficacy of oral acetaminophen in children. Clin Ther 35(9):1361–1375.e1361–1345

  12. Acetaminophen (2012) LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]

  13. Roumeliotis N, Frndova H, Pullenayegum E, Taddio A, Rochon P, Parshuram CS (2022) Dosing of enteral acetaminophen in critically ill children: a cohort study. Arch Dis Child 107(4):388–393

    Article  Google Scholar 

  14. Camire E, Moyen E, Stelfox HT (2009) Medication errors in critical care: risk factors, prevention and disclosure. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 180(9):936–943

  15. Dart RC, Erdman AR, Olson KR, Christianson G, Manoguerra AS, Chyka PA, Caravati EM, Wax PM, Keyes DC, Woolf AD et al (2006) Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 44(1):1–18

    Article  CAS  Google Scholar 

  16. Dart RC, Green JL, Kuffner EK, Heard K, Sproule B, Brands B (2010) The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol – a randomized study. Aliment Pharmacol Ther 32(3):478–486

    Article  CAS  Google Scholar 

  17. Temple AR, Zimmerman B, Gelotte C, Kuffner EK (2017) Comparison of the efficacy and safety of 2 acetaminophen dosing regimens in febrile infants and children: a report on 3 legacy studies. J Pediatr Pharmacol Ther 22(1):22–32

    Article  Google Scholar 

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Acknowledgements

Special thanks to local pharmacists Winnie Seto and Angela Trope for their help with dosing practice in the unit over time. Thanks to Melanie Gaetani for coding support with medication identification.

Funding

This study was not funded, but N. Roumeliotis received doctoral salary support from the Fonds de Recherche Santé- Québec, and the Canadian Critical Care Trials Group (CCCTG).

Author information

Authors and Affiliations

  1. Department of Critical Care Medicine, The Hospital for Sick Children, Toronto, ON, Canada

    Nadia Roumeliotis & Chris Parshuram

  2. Child Health Evaluative Sciences, and Center for Safety Research, SickKids Research Institute, Toronto, ON, USA

    Nadia Roumeliotis, Eleanor Pullenayegum, Anna Taddio & Chris Parshuram

  3. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, USA

    Nadia Roumeliotis, Paula Rochon & Chris Parshuram

  4. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, USA

    Anna Taddio

  5. Women’s College Research Institute, Women’s College Hospital, Toronto, ON, USA

    Paula Rochon

  6. Department of Medicine, University of Toronto, Toronto, ON, USA

    Paula Rochon

  7. Department of Pediatrics, CHU Sainte-Justine, 3175 chemin de la Cote-Sainte-Catherine, Montreal, Qc, H3T 1C5, Canada

    Nadia Roumeliotis

Authors
  1. Nadia Roumeliotis
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  2. Eleanor Pullenayegum
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  3. Anna Taddio
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  4. Paula Rochon
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  5. Chris Parshuram
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Contributions

Dr Roumeliotis conceptualized and designed the study, conducted the statistics, summarized results, drafted the initial manuscript, and reviewed and revised the manuscript. Dr Pullenayegum contributed to study design, analysis plan, interpretation of results, critical appraisal of intellectual content, and approved final version. Drs Taddio and Rochon contributed to study design, critically appraised it for intellectual content, and reviewed and revised the final version of manuscript. Dr Parshuram conceptualized 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 agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Nadia Roumeliotis.

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Ethics approval

Ethics approval was obtained from The Hospital for Sick Children (#1000059340) and the University of Toronto (# 00037936) approved this study.

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Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Piet Leroy

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Roumeliotis, N., Pullenayegum, E., Taddio, A. et al. Liver enzymes after short-term acetaminophen error in critically ill children: a cohort study. Eur J Pediatr 181, 2943–2951 (2022). https://doi.org/10.1007/s00431-022-04502-y

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  • DOI: https://doi.org/10.1007/s00431-022-04502-y

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