Salicylate toxicity

Learning objectives

Salicylate toxicity is the result of ingestion of, or (rarely) topical exposure to, chemicals metabolized to salicylate
Poisoning may occur due to acute or chronic salicylate exposure
- Uncouple oxidative phosphorylation
- Interfere with the Krebs cycle
- Lead to accumulation of lactic acid & ketoacids
Characterized by acid-base disturbances, electrolyte abnormalities, and central nervous system effects
Unintentional salicylate toxicity is more common than intentional intoxication
The most common source of salicylate poisoning is aspirin itself (acetylsalicylic acid) which is rapidly hydrolyzed to salicylate in the gastrointestinal tract, liver, and bloodstream
- Acute toxicity may occur after ingestion of a single dose of aspirin or the equivalent of >150 mg/kg or >6.5 g
- Chronic poisoning tends to occur as a result of repeated exposure to high-dose aspirin or equivalent (150 mg/kg/day), particularly in the setting of renal insufficiency
- Beware that many over-the-counter medications contain salicylates such as Pepto-Bismol, etheric oils, vapors, or analgesic ointments
Herbs and spices such as ginger or mint also contain salicylates which can add to the drug burden
Initially, symptoms such as tachypnea, lung crackles, and fever, often mimic a viral infection
The classic triad of mild toxicity:
- Nausea
- Vomiting
- Tinnitus

Therapeutic levels of salicylates

Irreversibly block COX-1 and modify COX-2 leading to a decrease in inflammation and platelet aggregation

Toxic levels of salicylates

Stimulate the respiratory center causing hyperpnea
Shift in metabolism to glycolysis for energy production → ↑ oxygen consumption and heat production → lactic acidosis

Nervous system	Tinnitus Listlessness Vertigo and incoordination Hallucinations Muscle rigidity Seizures Cerebral edema Coma
Gastro-intestinal	Nausea Vomiting
Respiratory	Hyperpnea Noncardiogenic pulmonary edema
Cardiac	Cardiovascular collapse
Metabolic	Fever Respiratory alkalosis Increased anion-gap metabolic acidosis (late sign) Hypernatremia due to fluid deficit Hypokalemia