Salicylate toxicity

Background

• Aspirin (acetylsalicylic acid) is the most common salicylate
• Other salicylate sources: bismuth subsalicylate (Pepto-Bismol), oil of wintergreen (most concentrated — 1 teaspoon = ~7g aspirin), topical agents (Ben-Gay)
• Therapeutic level: 10-30 mg/dL
• Toxic ingestion: >150 mg/kg
• Lethal dose: ~500 mg/kg
• Mechanism of toxicity:
  • Uncouples oxidative phosphorylation → impaired aerobic metabolism, heat generation
  • Direct CNS stimulation of respiratory center → respiratory alkalosis (early)
  • Accumulation of organic acids → anion gap metabolic acidosis (late)
  • Inhibits Krebs cycle, disrupts lipid and amino acid metabolism
• Pharmacokinetics change in overdose:
  • Zero-order kinetics at toxic levels (saturable metabolism)
  • Delayed absorption with enteric-coated or sustained-release formulations
  • Bezoar formation possible with massive ingestion

Clinical Features

Acute Toxicity

• Early: tinnitus, nausea, vomiting, tachypnea (respiratory alkalosis)
• Moderate: diaphoresis, tachycardia, hyperthermia, agitation, confusion
• Severe: altered mental status, seizures, pulmonary edema (noncardiogenic), cerebral edema, coma
• Classic acid-base pattern:
  • Adults: mixed respiratory alkalosis + metabolic acidosis
  • Children: metabolic acidosis predominates (may not have initial respiratory alkalosis phase)

Chronic Toxicity

• More insidious and often misdiagnosed (especially in elderly)
• Presents with confusion, tinnitus, dehydration, metabolic acidosis
• May be diagnosed as sepsis, altered mental status workup

Differential Diagnosis

• Sepsis (similar presentation with tachypnea, metabolic acidosis, AMS)
• Other causes of anion gap metabolic acidosis (MUDPILES: methanol, uremia, DKA, propylene glycol, INH/iron, lactic acidosis, ethylene glycol, salicylates)
• Theophylline toxicity (similar features)
• Acetaminophen toxicity (common coingestion)
• Iron toxicity

Evaluation

• Salicylate level:
  • Therapeutic: 10-30 mg/dL
  • Toxic: > 30 mg/dL
  • Severe: >90 mg/dL
  • Repeat level every 2 hours until declining (delayed absorption, bezoar)
  • Done nomogram (not well validated for chronic or enteric-coated ingestions)
• ABG/VBG: assess pH (acidemia dramatically worsens toxicity by driving salicylate into CNS)
• BMP: anion gap, glucose (CNS hypoglycemia may occur despite normal serum glucose), potassium, bicarbonate, creatinine
• Acetaminophen level (common coingestion)
• LFTs, coagulation studies (hepatotoxicity, coagulopathy)
• Lactate
• Urine pH: target alkalinization to pH 7.5-8.0
• CXR if concern for pulmonary edema

Management

GI Decontamination

• Activated charcoal 1 g/kg (max 50g): effective if within 1-2 hours of ingestion
  • May benefit later with large ingestions, enteric-coated tablets, or bezoar
  • Multiple doses may be considered
• Whole bowel irrigation for massive ingestions or sustained-release/enteric-coated tablets

Alkalinization (Cornerstone of Treatment)

• IV sodium bicarbonate
• Goal: urine pH 7.5-8.0 and serum pH 7.50-7.55
  • Alkaline urine traps ionized salicylate in renal tubules → enhanced elimination
  • Alkaline serum prevents salicylate from crossing blood-brain barrier
• Protocol:
  • Bolus: 1-2 mEq/kg IV NaHCO3
  • Infusion: 150 mEq NaHCO3 in 1L D5W at 150-250 mL/hr
  • Add 20-40 mEq KCl per liter (hypokalemia impairs urinary alkalinization)
• CRITICAL: alkalinization will NOT work without adequate potassium replacement
• Monitor serum pH, urine pH, and potassium every 1-2 hours

Dextrose

• Give D50W (50 mL IV) empirically if any CNS symptoms (altered mental status, seizures)
• CNS glucose may be low even with normal serum glucose (salicylate impairs CNS glucose transport)
• Add dextrose to maintenance fluids

Hemodialysis

• Most effective method of salicylate removal
• EXTRIP Workgroup Indications:
  • Recommended: salicylate level > 90 mg/dL (acute) or > 80 mg/dL (chronic)
  • Recommended: altered mental status, new hypoxemia requiring supplemental O2
  • Recommended: pH ≤ 7.20 despite bicarbonate therapy
  • Suggested: salicylate level > 80 mg/dL (acute), renal failure limiting salicylate clearance, clinical deterioration despite treatment
• Also dialyzes out the metabolic acidosis
• Consult nephrology early

What to Avoid

• Do NOT intubate unless absolutely necessary
  • Salicylate patients compensate with profound hyperventilation
  • Loss of respiratory compensation (even brief during intubation) causes rapid acidemia → CNS salicylate accumulation → cardiac arrest
  • If intubation required: maximize bicarb, match minute ventilation to pre-intubation rate
• Avoid acetazolamide (causes metabolic acidosis)
• Avoid excessive IV fluids without bicarb (dilutes serum alkalinity)

Disposition

• ICU admission for: level >50 mg/dL, acidemia, AMS, pulmonary edema, renal failure
• Monitored bed for moderate toxicity with improving levels
• Serial salicylate levels every 2 hours until clearly declining
• Poison control: 1-800-222-1222
• Psychiatric evaluation for intentional ingestions

See Also

• Toxicology
• Acetaminophen toxicity
• Metabolic acidosis
• Anion gap

References

• Palmer BF, Clegg DJ. Salicylate toxicity. N Engl J Med. 2020;382(26):2544-2555. PMID 32579815
• O'Malley GF. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. 2007;25(2):333-346. PMID 17482022
• Pearlman BL, Gambhir R. Salicylate intoxication: a clinical review. Postgrad Med. 2009;121(4):162-168. PMID 19641282