Predicting concentrations in children presenting with acetaminophen overdose.
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.


CONCLUSIONS
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.
Anderson
B J
BJ
Department of PICU, Auckland Children's Hospital, Park Road, Grafton, Auckland, New Zealand.
Holford
N H
NH
Armishaw
J C
JC
Aicken
R
R
D000082:Acetaminophen / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning*; D000328:Adult; D000367:Age Factors; D018712:Analgesics, Non-Narcotic / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning*; D000931:Antidotes / Q000627:therapeutic use; D001835:Body Weight; D002606:Charcoal / Q000627:therapeutic use; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods*; D062787:Drug Overdose / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D004638:Emergency Treatment; D006801:Humans; D007223:Infant; D007408:Intestinal Absorption; D008657:Metabolic Clearance Rate; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D002606:Charcoal; D000082:Acetaminophen