Salicylates are used widely for their analgesic and anti-inflammatory properties. They are found in a variety of prescription and over-the-counter analgesics, cold preparations, topical keratolytic products (methyl salicylate), and even Pepto-Bismol (bismuth subsalicylate). Before the introduction of child-resistant containers, aspirin (acetylsalicylic acid) overdose was one of the leading causes of accidental death in children. Two distinct syndromes of intoxication may occur, depending on whether the exposure is acute or chronic.
Mechanism of toxicity. Salicylates have a variety of toxic effects.
Central stimulation of the respiratory center results in hyperventilation, leading to respiratory alkalosis. Secondary consequences from hyperventilation include dehydration and compensatory metabolic acidosis.
Intracellular effects include uncoupling of oxidative phosphorylation and interruption of glucose and fatty acid metabolism, which contribute to metabolic acidosis.
The mechanism by which cerebral and pulmonary edema occurs is not known but may be related to an alteration in capillary integrity.
Salicylates alter platelet function and may also prolong the prothrombin time.
Pharmacokinetics. Salicylates are well absorbed from the stomach and small intestine. Large tablet masses and enteric-coated products may dramatically delay absorption (hours to days). The volume of distribution of salicylate is about 0.1–0.3 L/kg, but this can be increased by acidemia, which enhances movement of the drug into cells. Elimination is mostly by hepatic metabolism at therapeutic doses, but renal excretion becomes important with overdose. The elimination half-life is normally 2–4.5 hours but can be as long as 18–36 hours after overdose. Renal elimination is dependent on urine pH (see also Table II–61).
Toxic dose. The average therapeutic single dose of aspirin is 10 mg/kg, and the usual daily therapeutic dose is 40–60 mg/kg/d. Each tablet of aspirin contains 325–650 mg of acetylsalicylic acid. One teaspoon of concentrated oil of wintergreen contains 5 g of methyl salicylate, equivalent to about 7.5 g of aspirin.
Acute ingestion of 150–200 mg/kg of aspirin will produce mild intoxication; severe intoxication is likely after acute ingestion of 300–500 mg/kg. Fatalities have been reported in children with ingestion of 5 mL or less of oil of wintergreen.
Chronic intoxication with aspirin may occur with ingestion of more than 100 mg/kg/d for 2 days or more.
Clinical presentation. Patients may become intoxicated after an acute accidental or suicidal overdose or as a result of chronic repeated overmedication for several days.
Acute ingestion. Vomiting occurs shortly after ingestion, followed by hyperpnea, tinnitus, and lethargy. Mixed respiratory alkalemia and metabolic acidosis are apparent when arterial blood gases are determined. With severe intoxication, coma, seizures, hypoglycemia, hyperthermia, and pulmonary edema may occur. Death is caused by CNS failure and cardiovascular collapse.
Chronic intoxication. Victims are usually confused elderly persons who are taking salicylates therapeutically. The diagnosis is often overlooked because the presentation is nonspecific; confusion, dehydration, and metabolic acidosis are often attributed to sepsis, pneumonia, or gastroenteritis. However, morbidity and mortality rates are much higher than after an acute overdose. Cerebral and pulmonary edema is more common than with acute intoxication, and severe poisoning occurs at ...