Salicylate-ASA toxicity

Mechanism of Toxicity

1. Stimulation of the respiratory center of the brain, leading to hyperventilation and respiratory alkalosis.
2. Uncoupling of oxidative phosphorylation, leading to increased oxygen utilization and glucose demand, increased oxygen and glucose demand, increased glyconeogenesis, and increased heat production.
3. Inhibition of Krebs cycle enzymes, leading to decreased glucose availability and increased organic acids.
4. Alterations in lipid metabolism and amino acid metabolism, increasing metabolic acidosis.
5. Increased fluid and electrolyte losses, leading to dehydration, sodium and potassium depletion,, and loss of buffer capacity.

Clinical Manifestations

Blood Gas

• Starts with a respiratory alkalosis from activation of the respiratory centre causing hyperventilation
• Followed by an anion gap metabolic acidosis due to inhibition of cellular metabolism and accumulation of organic acids, including lactic acid and ketoacids

Management

• Try to avoid intubation
• Volume resuscitation +/- vasopressors
• Decontamination: If presented within 2 hours of ingestion, activated charcoal 1 g/kg PO once (maximum 50 g)
• Neuroglycopenia: If altered mental status, should get supplemental glucose as ASA can cause neuroglycopenia with normoglycemia
• Urinary alkalinization: sodium bicarbinate 1 to 2 mEq/kg IV bolus followed by bicarb infusion (3 amps in 1L D5W) to target a urine pH of 7.5 to 8
  • Usually requires a rate of 1.5 to 2 times their maintenance fluids
• Dialysis: Indicated for the usual things in the setting of aspirin toxicity

Urinary alkalinization

• Aspirin is a weak acid: H^+^ + Sal^-^ <—> H Sal
• As pH increases (becomes more basic), more of the salicylate is in the Sal^-^ form, and the H Sal can diffuse out of the CNS

Further Reading

• Temple AR. Pathophysiology of aspirin overdosage toxicity, with implications for management. Pediatrics. 1978;62(5 Pt 2 Suppl):873–876.