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Paracetamol toxicity: what would be the implications of a change in UK treatment guidelines?

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Treatment of single-time-point ingestion acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is guided by plotting a timed plasma paracetamol concentration on established nomograms. Guidelines in the UK differ from those in the U.S. and Australasia by having two treatment lines on the nomogram. Patients deemed to be at ‘normal’ risk of hepatotoxicity are treated using the treatment line starting at 200 mg/L at 4 h post-ingestion; those at higher risk are treated using the ‘high risk’ treatment line starting at 100 mg/L at 4 h post-ingestion.

Aim

To examine the effect on treatment numbers if UK guidelines were to adopt a single treatment line nomogram or lower, risk-stratified treatment lines.

Methods

We undertook a retrospective analysis of a series of acute single-time-point paracetamol poisonings presenting to our inner city emergency department. Treatment numbers and effect on treatment costs were modelled for three alternative scenarios: a 150 line—a combined single treatment line starting at a 4 h concentration of 150 mg/L, a 100 line—a combined single treatment line starting at a 4 h concentration of 100 mg/L, and a 150/75 line—a double treatment line at the lower concentrations of 150 mg/L for normal risk and 75 mg/L for high risk patients.

Results

A total of 1,214 cases were identified. Under current UK guidance, 133 (11.0%) high risk cases and 98 (8.1%) normal risk cases needed treatment (total 231, 19.0%). A 150 line would result in 87 (7.2%) high risk cases and 155 (12.8%) normal risk cases needing treatment (total 242, 19.9%). A 100 line would result in 133 (11.0%) high risk and 251 (20.7%) normal risk cases needing treatment (total 384, 31.6%). A 150/75 line would result in 153 (12.6%) high risk and 155 (12.8%) normal risk cases needing treatment (total 308, 25.4%).

Conclusions

Both a 100 line and a 150/75 line would result in a large increase in the number of patients being treated and an associated increase in the costs of treatment. A single 150 mg/L treatment line would simplify treatment algorithms and lead to a similar number of patients being treated with NAC overall. A potential concern however is whether any of the high risk cases that would no longer be treated might develop significant hepatotoxicity. After consideration of the evidence for dual treatment lines, we feel that these risks are small and that it is worth reconsidering a change of treatment recommendations to a single 150 line.

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Conflict of interest

D.W. and P.D. have received a research grant from McNeill Pharmaceuticals for research into the home storage of paracetamol in the UK. P.D. has acted as an expert adviser to the U.S. Food and Drug Administration on paracetamol poisoning. J.K. is an advisor as part of the College of Emergency Medicine Clinical Effectiveness Committee to a panel at the UK Medicines and Healthcare Regulatory Authority on an ongoing review of paracetamol management.

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Authors and Affiliations

  1. Emergency Department, Guy’s and St Thomas’ NHS Foundation Trust and King’s Health Partners, London, UK

    David J. McQuade

  2. Clinical Toxicology, Guy’s and St Thomas’ NHS Foundation Trust and King’s Health Partners, London, UK

    David J. McQuade, Paul I. Dargan & David M. Wood

  3. King’s College London, London, UK

    Paul I. Dargan & David M. Wood

  4. Emergency Medicine Department, King’s College Hospital NHS Foundation Trust and King’s Health Partners, London, UK

    Jeff Keep

  5. Medical Toxicology Office, Guy’s Hospital, 2nd Floor, Bermondsey Wing, Great Maze Pond, London, SE1 9RT, UK

    David M. Wood

Authors
  1. David J. McQuade
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  2. Paul I. Dargan
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  3. Jeff Keep
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  4. David M. Wood
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Correspondence to David M. Wood.

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McQuade, D.J., Dargan, P.I., Keep, J. et al. Paracetamol toxicity: what would be the implications of a change in UK treatment guidelines?. Eur J Clin Pharmacol 68, 1541–1547 (2012). https://doi.org/10.1007/s00228-012-1285-7

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  • DOI: https://doi.org/10.1007/s00228-012-1285-7

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