A 3-year-old, previously healthy boy is brought to the emergency department due to accidental drug ingestion. His mother found him playing with his grandfather's pill bottles earlier today, and later, he developed nausea and vomited twice. The patient also began breathing rapidly and appeared ill. His grandfather recently had a myocardial infarction and takes multiple medications. On physical examination, the patient is mildly lethargic, tachypneic, and tachycardic. The abdomen is soft and nontender. The extremities are warm and capillary refill time is normal. Laboratory studies reveal high anion gap metabolic acidosis. Treatment with intravenous sodium bicarbonate infusion is begun. This therapy is most likely to provide a beneficial effect via which of the following mechanisms?
Acute salicylate poisoning | |
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*Often presenting as mixed primary respiratory alkalosis-primary metabolic acidosis. | |
This patient with tachypnea and anion gap metabolic acidosis following ingestion of an unknown substance most likely has acute salicylate toxicity. Salicylate is the active ingredient in aspirin, and it causes toxicity via stimulation of central respiratory drive and interference with cellular metabolism. Toxicity commonly presents with tinnitus, nausea, vomiting, and alteration in mental status ranging from irritability to lethargy or even coma. Patients classically have primary respiratory alkalosis and primary anion gap metabolic acidosis, a mixed disturbance that often presents with blood pH near or within the normal range.
The toxicity of salicylate is caused mostly by its protonated, salicylic acid form (Sal-H), which is lipophilic and readily passes into the tissues. Therefore, sodium bicarbonate helps treat salicylate toxicity in 2 ways:
The bicarbonate acts as a base to bind free hydrogen ions in the blood. This facilitates the conversion of lipophilic salicylic acid to a lipophobic salicylate ion (Sal−), trapping much of the compound within the bloodstream.
The bicarbonate also alkalinizes the urine to facilitate the conversion of salicylate and its metabolites to their lipophobic, ionized form, which reduces renal tubular reabsorption of the compounds and increases urinary excretion.
Notably, acetazolamide is contraindicated in acute salicylate toxicity because it alkalinizes the urine at the expense of acidifying the blood (sodium bicarbonate alkalinizes both the blood and urine), which facilitates additional tissue absorption of salicylic acid.
(Choice A) Sodium bicarbonate is used to reduce the cardiotoxic effects of tricyclic antidepressant (TCA) overdose by decreasing the binding of TCAs to cardiac sodium channels and lowering the risk of arrhythmia.
(Choice B) Sodium bicarbonate facilitates conversion to the salicylate ion (Sal−), increasing, not decreasing, the amount of charged compound in the blood.
(Choice C) Activated charcoal is commonly given orally to patients with acute salicylate toxicity because it binds to salicylate in the gastric lumen and prevents absorption of the drug. Sodium bicarbonate is given intravenously and acts within the bloodstream and urine.
(Choice E) Salicylate is metabolized mostly via hepatic glucuronidation; however, the induction of hepatic glucuronidation is not used to treat toxicity.
Educational objective:
Salicylate toxicity typically presents with mixed primary respiratory alkalosis and anion gap metabolic acidosis. Sodium bicarbonate facilitates conversion to the lipophobic, ionized form of salicylate (Sal−), which traps much of the compound in the bloodstream and increases its urinary excretion.