Chapter 113

#### High-Yield Facts

• Widely available in both prescription and OTC products, acetaminophen is a common pediatric overdose.

• Acetylcysteine is the antidote for acetaminophen overdose and can be given orally or intravenously.

• Treatment with acetylcysteine is rarely indicated in children less than 6 years of age.

• Acetylcysteine is nearly 100% effective when started within 8 hours of acetaminophen ingestion.

• A child less than 6 years can be safely discharged following an acetaminophen exposure if the maximum ingested dose is less than 200 mg/kg or if acetaminophen is not detected in the serum at any time at least 1 hour after ingestion.

Being ubiquitous, acetaminophen is a leading pharmaceutical taken in overdose, whether accidentally by young children or for self-harm by adolescents and adults. Despite this high incidence of overdose, a large margin of safety and a highly effective antidote ensure that death caused by acute acetaminophen ingestion is unheard of in young children.1 Fatalities are also unlikely when treatment is started within 20 hours of acute overdose, and hepatic injury rare when started within 8 hours. Young children are frequently suspected of ingesting liquid acetaminophen preparations formulated for children. These are absorbed more rapidly than pills but in most instances not enough has been ingested (200 mg/kg)1to warrant concern. Because these patients typically present asymptomatic shortly after the exposure, most of these unintentional exposures in young children do not need empirical therapy with antidote when a serum acetaminophen concentration can be readily measured. Dosing errors with the antidote are not infrequent especially in young children. Therefore, the indications and dosing calculations as well as total fluid volume administered should be verified meticulously. Adolescents often are not aware that acetaminophen ingestion can be lethal, or that many different products contain acetaminophen, and may unknowingly take a life-threatening amount as a suicidal gesture.2

#### Pathophysiology

Acetaminophen (APAP, or paracetamol) is a synthetic analgesic and antipyretic. The therapeutic dose in children is 10 to 15 mg/kg (maximum 650 mg) given every 4 to 6 hours, with a maximum recommended total of five doses per day. Therapeutic serum concentrations are 10 to 20 μg/mL. Acetaminophen is well absorbed after an oral therapeutic dose, with peak levels generally occurring at 30 to 60 minutes. Even after overdose absorption is only minimally delayed in most cases, with peak concentrations seen within 4 hours of acute ingestion. Co-ingested opioids and antimuscarinic agents, solids, and sustained-release formulations of acetaminophen have only a minor effect on this absorption. Absorption of liquid formulations is more rapid than that of tablets or caplets. Following gastrointestinal absorption, APAP is taken up and metabolized by the liver, which is the primary target organ of toxicity. The normal serum elimination half-life is 2 to 3 hours but may be prolonged significantly following massive overdose or if liver injury has occurred. Indeed, an elimination half-life greater than 4 hours is one of the first manifestations of serious liver injury.

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