07. Salicylate Overdose

Mechanism and Pharmacokinetics

Uncouples oxidative phosphorylation and is a respiratory stimulant. Plasma half-life 2-3 hours, 20-36 hours following OD. Toxicity:

  • Acute: <150 mg/kg = mild, 150-300 mg/kg = moderate, >300 mg/kg = severe. Determine if enteric-coated or regular. Must check serial levels (every 2 hours) especially with enteric-coated or massive ingestion.
  • Chronic: >100 mg/kg/day over several days is associated with approximately 25% mortality. Use pH and bicarbonate levels to predict severity of chronic OD. Levels correlate poorly with symptoms.

Signs and Symptoms

Hyperventilation with primary respiratory alkalosis, anion-gap metabolic acidosis, tinnitus, nausea, vomiting, tachycardia, hyperthermia, lethargy, confusion, seizures, cerebral and pulmonary edema (non-cardiac), thrombocytopenia.

Evaluation

Check salicylate level; check CBC, electrolytes, BUN, creatinine, glucose, PT/PTT, and q2h ABG. Evaluate for co-ingestions (such as acetaminophen).

Management

  • ABCDE’s (see section Toxicology Basics), largely supportive. Intubation is very risky because it may interfere, even transiently, with the patient’s need to maintain pH with hyperventilation. If necessary, pretreat with IV bicarbonate, ensure high minute ventilation, try to maintain pH 7.5-7.9. Consider ICU for all symptomatic patients and massive ingestions.
  • Call Poison Control (800-222-1222) or Medical Toxicology consult service (415-443-0122) for assistance.
  • Activated charcoal, 1 g/kg per NGT (consult Poison Control regarding the use of multiple doses of activated charcoal). May repeat every 4 hours if concern for ongoing absorption. Consider whole bowel irrigation for massive ingestions (e.g., more than 100 tablets).
  • Alkalinize plasma/urine: bolus 1-2 amps of NaHCO3, then start 2 amps NaHCO3 (100meq) per 1L D5-1/4NS, run at ~4 ml/kg/h and titrate to urine pH 7.5-8. Do NOT use acetazolamide. Caution in elderly and renal failure as ASA can cause pulmonary edema.
  • Replete K+ to maintain normal serum levels, as alkalinization will be difficult to achieve otherwise.
  • Treat hypoglycemia and coagulopathy if present. Studies show brain glucose depletion even with euglycemia, so goal BG 80-120 mg/dL.
  • External cooling if hyperthermic (no acetaminophen as it is ineffective). If patient is hyperthermic due to ASA, patient will likely be sick enough to require HD, which will also help in cooling.
  • Call Nephrology early, especially if level >100 mg/dL in a patient with normal renal function or an elderly patient (>60 years old) with a level of >60mg/dL, AMS, pulmonary/cerebral edema, fluid overload, refractory acidosis, or renal failure.
  • Follow salicylate level every 2-4 hours until falling. If not falling, think sustained release preparation, ASA bezoar (ASA can cause pyloric spasm with resultant tablet bezoar).

Key Points

  • Consider ASA in the differential of anion gap acidosis.
  • Use alkalinization to promote elimination. Watch for delayed absorption of enteric coated formulations. Supplement glucose if AMS or evidence of hypoglycemia.
  • Low threshold to initiate dialysis, especially if level >100 mg/dl or systemic toxicity.
  • Intubate only if absolutely necessary and be sure to set high minute ventilation.

 

Mokhlesi B, Leikin JB, Murray P, etc. Adult toxicology in critical care: Part II: specific poisonings. Chest 2003:123;897-922.

O’Malley GF. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am 2007;25:333-346. Poisoning & Drug Overdose. 6th ed. 2012.