Learning objectives 

• Diagnose and management of salicylate toxicity

Diagnosis and mechanisms

• 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

Pathophysiology

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

Signs and symptoms

Diagnosis

• Arterial blood gases
• Serum electrolyte panel
• Serum salicylate level
• BUN and creatinine
• ECG
• Head CT scan
• EEG

Management

Suggested reading

• Palmer BF, Clegg DJ. Salicylate Toxicity. N Engl J Med. 2020;382(26):2544-2555.