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Practice

Treating acetaminophen overdose

Marco L.A. Sivilotti, Mark C. Yarema and David N. Juurlink
CMAJ April 19, 2022 194 (15) E554; DOI: https://doi.org/10.1503/cmaj.210703
Marco L.A. Sivilotti
Departments of Emergency Medicine, and of Biomedical and Molecular Sciences (Sivilotti), Queen’s University, Kingston, Ont.; Department of Emergency Medicine (Yarema), University of Calgary, Calgary, Alta.; Poison and Drug Information Service, Section of Clinical Pharmacology and Toxicology (Yarema), Alberta Health Services, Calgary, Alta.; Departments of Medicine, of Pediatrics and of Health Policy, Management, and Evaluation (Juurlink), University of Toronto; Ontario Poison Centre (Sivilotti, Juurlink), Hospital for Sick Children, Toronto, Ont.
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Mark C. Yarema
Departments of Emergency Medicine, and of Biomedical and Molecular Sciences (Sivilotti), Queen’s University, Kingston, Ont.; Department of Emergency Medicine (Yarema), University of Calgary, Calgary, Alta.; Poison and Drug Information Service, Section of Clinical Pharmacology and Toxicology (Yarema), Alberta Health Services, Calgary, Alta.; Departments of Medicine, of Pediatrics and of Health Policy, Management, and Evaluation (Juurlink), University of Toronto; Ontario Poison Centre (Sivilotti, Juurlink), Hospital for Sick Children, Toronto, Ont.
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David N. Juurlink
Departments of Emergency Medicine, and of Biomedical and Molecular Sciences (Sivilotti), Queen’s University, Kingston, Ont.; Department of Emergency Medicine (Yarema), University of Calgary, Calgary, Alta.; Poison and Drug Information Service, Section of Clinical Pharmacology and Toxicology (Yarema), Alberta Health Services, Calgary, Alta.; Departments of Medicine, of Pediatrics and of Health Policy, Management, and Evaluation (Juurlink), University of Toronto; Ontario Poison Centre (Sivilotti, Juurlink), Hospital for Sick Children, Toronto, Ont.
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Acetaminophen overdose remains common

A billion doses of acetaminophen are taken safely each year, but 10000 people in Canada overdose on this medication annually. About one-third are hospitalized for treatment with the antidote, acetylcysteine, and 1%–2% die.1 Most fatalities result from delayed presentation after deliberate overdose, or from excessive dosing for fever or pain over several days.

Clinicians should treat overdoses empirically with acetylcysteine, unless clearly unnecessary

Because the efficacy of acetylcysteine is highly time-dependent, it can be started for any acetaminophen overdose.2 For acute overdoses that occurred at a reliably known time, acetylcysteine is not needed provided that the patient’s peak acetaminophen concentration is below the Rumack–Matthew nomogram treatment line. Death from acetaminophen-induced liver failure is rare if acetylcysteine is started promptly. Dosed correctly, adverse reactions are rarely life-threatening.3

Acetylcysteine should be continued until the patient meets stopping criteria based on individualized serial testing

Although original treatment protocols stipulated a fixed treatment duration (e.g., 20 h), medical toxicologists now recommend a patient-tailored approach to reduce both over- and undertreatment.2,4 Serial testing permits more accurate risk stratification and often shortens treatment. Acetylcysteine can be safely stopped when the patient’s acetaminophen concentration is undetectable, liver function tests are improving, and the patient is not encephalopathic (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.210703/tab-related-content).2,4,6 Acetaminophen concentrations should fall tenfold every 12 hours if absorption is complete and liver function is normal.

Massive overdose with early-onset coma and lactic acidosis requires more intense treatment

Acetaminophen directly affects mitochondrial function. Within hours of massive ingestion (i.e., > 600 mg/kg, serum acetaminophen several-fold higher than the treatment threshold), it causes coma, acidosis and hypothermia. Hemodialysis and higher doses of acetylcysteine may be warranted in this context.5

A medical toxicologist should be consulted for the most current recommendations

Some poison centres, including those in Ontario and Alberta, now recommend a standardized 1- or 2-bag (i.e., admixture) acetylcysteine infusion protocol. In contrast, the original protocol involved preparing 3 distinct, weight-based bags, which contributed to dosing interruptions and errors.6 Furthermore, higher acetylcysteine dosing is now recommended for persistently elevated acetaminophen concentrations, and adjunctive fomepizole can be used for the highest-risk patients.

CMAJ invites submissions to “Five things to know about …” Submit manuscripts online at http://mc.manuscriptcentral.com/cmaj

Footnotes

  • Competing interests: None declared.

  • This article has been peer reviewed.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/

References

  1. ↵
    1. Sivilotti MLA,
    2. Eisen JS,
    3. Lee JS,
    4. et al
    . Can emergency departments not afford to carry essential antidotes? CJEM 2002;4:23–33.
    OpenUrlPubMed
  2. ↵
    1. Rumack BH,
    2. Bateman DN
    . Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Phila) 2012;50:91–8.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Yarema M,
    2. Chopra P,
    3. Sivilotti MLA,
    4. et al
    . Anaphylactoid reactions to intravenous N-acetylcysteine during treatment for acetaminophen poisoning. J Med Toxicol 2018;14:120–7.
    OpenUrl
  4. ↵
    1. Bateman DN,
    2. Dear JW,
    3. Thanacoody HK,
    4. et al
    . Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet 2014;383:697–704.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Sivilotti ML,
    2. Juurlink DN,
    3. Garland JS,
    4. et al
    . Antidote removal during haemodialysis for massive acetaminophen overdose. Clin Toxicol (Phila) 2013;51:855–63.
    OpenUrl
  6. ↵
    1. Mullins ME,
    2. Yarema MC,
    3. Sivilotti MLA,
    4. et al
    . Comment on “Acetylcysteine in paracetamol poisoning: a perspective of 45 years of use”. Toxicol Res 2019;8:1057–8.
    OpenUrl
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Canadian Medical Association Journal: 194 (15)
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Vol. 194, Issue 15
19 Apr 2022
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Treating acetaminophen overdose
Marco L.A. Sivilotti, Mark C. Yarema, David N. Juurlink
CMAJ Apr 2022, 194 (15) E554; DOI: 10.1503/cmaj.210703

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Treating acetaminophen overdose
Marco L.A. Sivilotti, Mark C. Yarema, David N. Juurlink
CMAJ Apr 2022, 194 (15) E554; DOI: 10.1503/cmaj.210703
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    • Acetaminophen overdose remains common
    • Clinicians should treat overdoses empirically with acetylcysteine, unless clearly unnecessary
    • Acetylcysteine should be continued until the patient meets stopping criteria based on individualized serial testing
    • Massive overdose with early-onset coma and lactic acidosis requires more intense treatment
    • A medical toxicologist should be consulted for the most current recommendations
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