Salicylate toxicity

(Redirected from Aspirin 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)[1]
    • 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[2]:
    • 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

References

  1. ↑ Palmer BF, Clegg DJ. Salicylate Toxicity. N Engl J Med. 2020;382(26):2544-2555. PMID 32579814
  2. ↑ Juurlink DN, et al. Extracorporeal treatment for salicylate poisoning: systematic review and recommendations from the EXTRIP workgroup. Ann Emerg Med. 2015;66(2):165-181. PMID 25986310
  • 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
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