Elsevier

The Journal of Pediatrics

Volume 135, Issue 3, September 1999, Pages 290-295
The Journal of Pediatrics

Predicting concentrations in children presenting with acetaminophen overdose,☆☆,

https://doi.org/10.1016/S0022-3476(99)70122-8Get rights and content

Abstract

Objective: To predict serum concentrations to evaluate and improve guidelines for the treatment of children (1 to 5 years) with accidental ingestion of acetaminophen elixir. Methods: Acetaminophen concentrations for 1000 children were simulated with pharmacokinetic parameters and their expected variability. The distribution of concentrations arising from a 300 mg/kg dose at different age groups was predicted. These predictions were validated by comparison with concentrations obtained at 4 hours from 121 children with accidental ingestion of acetaminophen elixir. Results: No child who presented with overdose had a concentration in the probable risk area of the Rumack-Matthew toxicity nomogram. Enteral charcoal administered 98 minutes (SD 44) after ingestion had no effect on serum concentrations. The simulation predicted that an acetaminophen dose of 300 mg/kg would result in concentrations of 32 to 208 mg/L (95% CI) at 4 hours after ingestion. The maximum concentration occurred before 2 hours in 95% of simulated children. Conclusion: Children (1 to 5 years) with reported ingestion of >250 mg/kg acetaminophen elixir should have serum concentrations measured at 2 hours after ingestion rather than at the 4-hour time point recommended in adults. This can be expected to speed discharge and reduce anxiety. The use of enteral charcoal is unlikely to enhance acetaminophen elimination, unless it is given within an hour of acetaminophen ingestion. (J Pediatr 1999;135:290-5)

Section snippets

METHODS

A retrospective review of children (1 to 5 years) who presented to a children’s emergency department with accidental acetaminophen elixir ingestion from January 1995 to June 1997 was performed. The records of patients who had reported ingestions >50 mg/kg and who had serum acetaminophen concentrations >1.5 mg/L (minimum quantifiable concentration) at 4 hours were identified. These concentrations were compared with concentrations predicted by a 1-compartment, first order input, first order

RESULTS

A total of 218 children presented with accidental acetaminophen elixir ingestion, and of these 121 children (Table II) met the study criteria.

. Demographic data of children presenting with accidental acetaminophen ingestion (n = 121)

Mean age (SD)33 (9) months
Mean weight (SD)14.6 (2.8) kg
Median dose (range)165 (50-822) mg/kg
Median concentration (range)30 (5.5-181) mg/L at 4 h
The accuracy of the 4-hour sampling time is limited by the interpretation of retrospective chart reviews. The dose

DISCUSSION

The Rumack-Matthew2 nomogram, widely used to guide management of acetaminophen overdose in adults and children, was derived from a study of 30 adult patients who ingested an overdose of acetaminophen.10 The half-life was <4 hours in all patients without liver damage. The Rumack-Matthew nomogram is simply a line drawn on a time-log concentration plot from 200 mg/L at 4 hours with a half-life of 4 hours. An ad hoc “possible toxicity” line 25% below the standard nomogram (150 mg/L at 4 hours and 5

References (26)

  • NHG. Holford

    A size standard for pharmacokinetics

    Clin Pharmacokinet

    (1996)
  • HP. Peters

    The ecological implications of body size

  • LB Sheiner et al.

    Some suggestions for measuring predictive performance

    J Pharmacokinet Biopharm

    (1981)
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    Supported in part by grants from “The Children’s Pain Trust” and “SmithKline Beecham Pharmaceuticals” (New Zealand). Dr Holford is a member of the Scientific Advisory Board for Pharsight and is a stockholder in the company.

    ☆☆

    Reprint requests: B.J. Anderson, MD, Paediatric Intensive Care Unit, Auckland Children’s Hospital, Park Road, Grafton, Auckland, New Zealand.

    0022-3476/99/$8.00 + 0  9/21/99435

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