Salicylates act directly on the respiratory center in the brainstem, causing hyperventilation and respiratory alkalosis.
In addition, salicylates interfere with the citric acid cycle limiting adenosine triphosphate (ATP) production and generating lactate. Due to increased catecholamines and an increased utilization of glucose, fatty acid metabolism increases leading to ketoacidosis.
Finally, salicylates are weak acids and contribute to the acidosis through direct proton donation. These factors contribute to increased ventilation through compensation but would not be expected to cause alkalemia (overcompensation).
Although the metabolic acidosis begins in the earliest stages of salicylate toxicity, the respiratory alkalosis predominates initially, leaving the patient with a respiratory alkalosis, metabolic acidosis, and alkalemia.
Adolescents or adults presenting with respiratory acidosis early after a salicylate overdose likely have a coingested CNS depressants, experience salicylate-induced acute lung injury, or have underlying respiratory disease.
The combination of acute respiratory alkalosis, metabolic acidosis, and acidemia is an ominous finding, indicating a life-threatening salicylate overdose.
Reference: Tintinalli
