Acetaminophen: The 150 mg/kg Myth

Acetaminophen is a very common drug overdose inyoung children. For the year 2001, the AmericanAssociation of Poison Control Centers reported over25,000 telephone enquiries regarding children under theage of six who were thought to have ingested anoverdose of this drug (1). Management is based upon thereported dose that has been ingested. Recommendationsfor interventions such as activated charcoal and themeasurement of the serum acetaminophen concentrationare made once a threshold dose has been exceeded. Forover a quarter of a century, the recommended thresholdhas been 150 mg/kg. The earliest literature citation thatI could find supporting this dose was from 1984 (2). Avalid threshold is required to assist poison centers inreferring to hospitals only those patients who trulyrequire the services of such facilities and to helpphysicians identify those patients who truly requireinterventions. The goal of this commentary is to assessthe validity of 150 mg/kg of acetaminophen as athreshold for interventions in a young child.MORBIDITY AND MORTALITY INYOUNG CHILDRENIt is logical to assume that this threshold is basedupon morbidity and mortality data. Although morbidityand mortality are well described after repeated dosingin young childen (3,4), the so-called ‘‘therapeuticmisadventure,’’ it is negligible after a single dose. Infact, there are no well-described deaths of childrenunder the age of six due to a single ingestion ofacetaminophen. Indeed, there are only two reports ofsevere toxicity in this age group. In 1978, Arena et al.(5) described a 14.2 kg, 40-month-old girl whoingested 11.4 g (800 mg/kg) of acetaminophen. Theserum concentration was 94 mg/L at 24h, a value thatwould be expected to produce significant hepatotoxic-ity. This occurred with her AST being 20,376 I.U. onday 3. She received supportive care and had a fullrecovery. In 1984, Lieh-Lai et al. (6) described a 12-month-old male who ingested 10.0 g of acetaminophen.Assuming a weight of 10 kg, this would amount to1000 mg/kg, a dose expected to produce significanthepatotoxicity. Despite treatment with N-acetylcys-teine, significant hepatotoxicity ensued with his ASTrising to 5,520 on day 3. He had a full recovery.Therefore this threshold dose of 150 mg/kg wasnot derived from pediatric data, as they do not exist. Alogical assumption is that it was taken from adult data.The dose of concern in an adult is 7.5–15.0 g (2).Assuming an adult body weight of 70 kg, and a dose ofconcern of 10.0 g, this amounts to 143 mg/kg. Thiswould seem to be the likely explanation, and Jacksonet al. commented that this figure was ‘‘extrapolated’’from adult data (2).

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