INDEX

    Salicylate (ASA) Overdose

    Toxicology

    Last Updated Jun 18, 2020
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    Context

    • Salicylates are derivatives of salicylic acid. Many over-the-counter products contain salicylates, including:
      • Acetylsalicylic acid (ASA).
      • Methyl salicylates in topical pain-relief ointments and mouthwash products.
      • Salicylic acid in topical wart treatment products.
      • Oil of wintergreen: extremely high level of methyl salicylate (1.4g/mL). Ingestion of < 5 mL of oil of wintergreen can kill a young child.
    •  Salicylate toxicity can be life-threatening. Early diagnosis and treatment are critical.

    Pathophysiology

    • Salicylates disrupt aerobic metabolism by uncoupling oxidative phosphorylation, leading to lactate and ketone accumulation.
    • At lower serum pH, more salicylic acid exists in an uncharged state, allowing more distribution into tissues.
    • Neurotoxicity:
      • Metabolic disruption causes neuroglycopenia (depletion of glucose in CNS).
      • Direct stimulation of medulla leads to tachypnea.
      • Severe toxicity causes neuronal injury and cerebral edema.
    • GI: direct irritant effects causing nausea, vomiting and abdominal pain.
    • Respiratory: increased alveolar capillary membrane permeability and non-cardiogenic pulmonary edema.
    • Renal: direct nephrotoxicity.
    • Chronic toxicity is more likely in elderly patients with dehydration and/or renal injury.

    Toxic Dose

    • Mild toxicity is seen after ingestions > 150mg/kg.
    • The LD50 (dose that is lethal to 50% of the population) is 500mg/kg.
    • Chronic toxicity can result from therapeutic dosing if dehydration or renal injury is present.

    Signs and Symptoms

    • Acute toxicity:
      • Early symptoms: nausea, vomiting, abdominal pain, tinnitus, and tachypnea.
      • Late symptoms: altered level of consciousness, respiratory failure, seizures, hyperthermia, and coma.
    • Chronic toxicity:
      • Altered level of consciousness, tinnitus, tachypnea, hallucinations, hyperthermia, seizures, and coma.
      • GI symptoms are uncommon.

    Diagnostic Process

    • Initial work-up should include electrolytes, creatinine, glucose, magnesium, venous blood gas (VBG) and ASA level.
    • Always check for co-ingestants in deliberate self-harm ingestions: ethanol level, acetaminophen level, serum osmolality and urea/blood urea nitrogen (to calculate osmolar gap).
    • ASA level should always be interpreted with a blood gas. Patients can have severe toxicity with a low ASA level, suggested by concurrent metabolic acidosis.
    • Salicylates can have erratic and prolonged absorption. ASA level and venous blood gas should be repeated every 2 hours until a peak level is seen.
    • Chest X-ray to evaluate for pulmonary edema.
    • Enteric coated pills can form bezoar: consider flat plate abdomen if rising ASA level despite alkalinization.
    • ECG: usually sinus tachycardia. Ventricular dysrhythmias and AV block are reported but rare.

    Recommended Treatment

    Resuscitation:

    • Aggressive fluid resuscitation if no evidence of pulmonary or cerebral edema.
    • If any neurologic symptoms present, try 1 amp of D50W IV to treat potential neuroglycopenia.
    • Treat seizures with 1 amp of D50W IV (regardless of blood glucose) and benzodiazepines.
    • Exercise extreme caution when intubating a patient with salicylate poisoning. If unavoidable, anticipate a physiologically difficult airway due to severe acidosis. Maintain hyperventilation during induction and after intubation. Consider pre-treatment with 1-2 amps of sodium bicarbonate IV bolus immediately before induction.

    Decontamination: activated charcoal within 6 hours of ingestion is indicated in patients at low risk of aspiration.

    • The window for charcoal administration is extended as absorption is frequently prolonged in salicylate toxicity due to salicylate-induced pylorospasm and bezoar formation.

    Urinary alkalinization: initiate in consultation with the poison centre.

    • Mechanism: increases renal elimination of salicylic acid.
    • Indications:
      • Moderate to severe symptoms regardless of ASA level.
      • Serum pH < 7.45 and/or HCO3 < 20 mmol/L.
      • ASA level > 2.17 mmol/L (30 mg/dL).
      • Suspected salicylate toxicity and symptomatic before laboratory investigations available.
    • Goals:
      • Serum pH 7.45-7.55.
      • Urine pH 7.5-8.
      • Serum potassium 3.5-5.0 mmol/L.
    • Contra-indications
      • Serum pH > 7.55.
      • Pulmonary edema or cerebral edema.
      • Renal failure or congestive heart failure.

    Dialysis indications: decision should be made in consultation with the poison centre and nephrology.

    • If ASA level > 7.2 mmol/L.
    • If ASA level > 6.5 mmol/L in the presence of impaired kidney function.
    • In the presence of altered mental status.
    • In the presence of new hypoxemia requiring supplemental oxygen.
    • Failure to tolerate or respond to urinary alkalinization.

    Chronic ASA toxicity can be difficult to diagnose and treat.

    • Deciding whether and how to treat may require serial ASA levels + VBGs, ruling out other causes of altered LOC, and consideration of other comorbidities (renal function, lung comorbidities). Questions about diagnostic uncertainty and treatment should be discussed with a toxicologist.

    Clinical Pitfalls

    • Failure to replete potassium and magnesium – urine will not alkalinize if hypokalemia is present. Hypomagnesemia is a common cause of refractory hypokalemia in these patients.
    • Failure to recognize worsening toxicity – salicylate concentrations decline not only because of elimination but also due to increasing distribution into tissues. A falling ASA level with worsening acidosis is concerning for severe toxicity.
    • Failure to consider chronic salicylate poisoning in the delirious and febrile elderly patient.
    • Intubation and ventilation can be associated with rapid worsening of salicylate toxicity and death unless hyperventilation is maintained.

    Consult

    BC Drug and Poison Information Centre 604-682-5050, or 1-800-567-8911.

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