Aspirin (acetylsalicylic acid, ASA), acetaminophen, and ibuprofen are the principal nonprescription analgesic, antipyretic medications. Aspirin is the least popular, and the association with Reye syndrome decades ago led to a proscription on pediatric use for fever. As a result, both unintentional and intentional salicylate poisoning in children is uncommon, which is fortunate because aspirin has much greater toxicity than its counterparts. The case fatality rate for aspirin poisoning is an order of magnitude greater than that of acetaminophen. Salicylates interfere with energy production, resulting in diffuse cellular toxicity, especially in the central nervous system, that is very difficult to treat. Management is based upon meticulously correcting fluid, electrolyte, and acid–base disturbances, promoting excretion, reducing absorption, and consideration of extracorporeal removal via hemodialysis.

At therapeutic doses, aspirin is rapidly absorbed. When many tablets are ingested, absorption is much slower due to delayed gastric emptying, slow tablet dissolution, mucosal adherence, and occasionally the development of concretions. The result is delayed absorption from the small intestine by many hours, and at times days, particularly following overdose of enteric-coated aspirin.¹ This delay can not only falsely reassure the unwary clinician, but also extend the window of opportunity for gastrointestinal decontamination.

Aspirin is rapidly hydrolyzed to the active metabolite, salicylate. Metabolism and excretion of salicylate becomes saturated (zero order) at higher doses. As a result, a small increase in dose or drug absorbed will result in a large increase in serum salicylate concentration. Renal excretion becomes the dominant route of elimination in overdose when hepatic metabolism is saturated. Acidic urine increases passive reabsorption of the uncharged, protonated salicylic acid from the distal tubule. The volume of distribution of salicylate is also highly variable and dependent on dose ingested. It is therefore impossible to predict the trajectory of serum salicylate concentrations, and frequent measurements are necessary following overdose until the drug is undetectable.

Ingestions of <150 mg/kg are generally nontoxic. With ingestions of 150 to 300 mg/kg, mild-to-moderate toxicity occurs, and overdoses of >300 mg/kg can be lethal. Preparations other than acetylsalicylic acid can cause measurable serum salicylate concentrations (Table 115-1). Oil of wintergreen contains nearly pure methyl salicylate (equivalent to 7000 mg salicylate per 5 mL). Unlike solid tablets of aspirin, oil of wintergreen is rapidly absorbed, and can be lethal in small amounts within a few hours, especially in young children.²

It is best to classify salicylism in terms of mild, moderate, and severe based on clinical assessment and blood gases, rather than relying on the serum salicylate concentration to establish the severity of poisoning (Table 115-2). Young children have a more rapid onset of toxicity and exhibit more severe signs than adults, primarily a consequence of their decreased buffering capacity, more rapid onset of metabolic acidosis, and thus more rapid distribution into the brain. At the upper end of the therapeutic range, patients may complain of tinnitus or, more often, distorted hearing. Direct stimulation of the respiratory center causes tachypnea and acute respiratory alkalosis, the hallmark of mild poisoning. The compensatory excretion of bicarbonate in the urine leads to sodium and potassium losses. At moderate toxicity, uncoupling of oxidative phosphorylation results in increased glucose, oxygen, and lipid consumption, with accumulation of lactic acid, amino acids, and keto acids as well as paradoxical aciduria. An osmotic diuresis contributes to further fluid and electrolyte losses. Thus, the characteristic anion-gap metabolic acidosis is a result of hypovolemia, impaired tissue perfusion, lactate accumulation, circulating salicylate, and other derangements of metabolism. Fluid losses from vomiting, tachypnea, and diaphoresis can be especially severe in young children. They have a more rapid onset of metabolic acidosis than adults, and the early respiratory alkalosis may not be identified.