Free salicylate is then able to penetrate tissues and exert toxic effects. Acidemia increases the volume of distribution by facilitating salicylate tissue penetration. In small doses, most salicylate is metabolized in the liver by conjugation with small amounts being hydroxylated. These pathways become saturated at higher doses prolonging salicylate elimination. Conjugated and hydroxylated metabolites are readily excreted by the kidney.
Renal elimination is responsible for the majority of salicylate elimination in overdose.
An alkaline urine will promote salicylate elimination by decreasing renal tubular reabsorption while an acid urine will retard excretion by promoting reabsorption of salicylate by the kidney tubules. For acute ingestions, salicylate levels should NOT be plotted on the Done nomogram. Follow-up studies of salicylate poisoned patients have shown that the nomogram failed to adequately predict serious salicylate toxicity. Because of possible delays in absorption, serial salicylate levels must be obtained and the levels used with clinical assessment of the patient. An initial salicylate level should be obtained following gastric decontamination procedures and a second level should be drawn approximately two hours after the initial level to assure that peak levels have occurred and that elimination has begun.