Salicylate Toxicity

Salicylate (aspirin) toxicity causes a complex metabolic disturbance through multiple mechanisms. Salicylates stimulate the medullary respiratory center, causing hyperventilation and primary respiratory alkalosis (early finding). Simultaneously, salicylates uncouple oxidative phosphorylation in mitochondria, impairing aerobic metabolism and increasing anaerobic glycolysis, leading to lactic acidosis and primary metabolic acidosis (late finding). The result is a characteristic mixed acid-base disturbance: respiratory alkalosis with metabolic acidosis (the 'classic' salicylate ABG). Salicylates also inhibit the Krebs cycle enzymes, increase oxygen consumption, cause hyperthermia from uncoupled oxidative phosphorylation, stimulate lipid metabolism producing ketoacids, and cause fluid and electrolyte disturbances (dehydration, hypokalemia). At toxic levels, salicylates cross the blood-brain barrier more readily in acidic conditions (ion trapping — unionized salicylate penetrates membranes more easily), causing neurotoxicity: tinnitus, hearing loss, confusion, agitation, seizures, cerebral edema, and coma. The therapeutic range is 15-30 mg/dL; toxicity begins at 40-50 mg/dL; severe toxicity occurs >70 mg/dL. Treatment focuses on GI decontamination (activated charcoal if within 1-2 hours), urinary alkalinization with sodium bicarbonate (ion trapping: alkaline urine keeps salicylate ionized in the renal tubule, preventing reabsorption and enhancing excretion), and hemodialysis for...