Salicylate Overdose

Aka: Salicylate Overdose, Salicylate Toxicity, Aspirin Overdose, Aspirin Toxicity, Salicylism, Salicylate Poisoning, Chronic Salicylate Poisoning

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II. Causes: Salicylate sources

  1. Aspirin
  2. Pepto Bismol
  3. Topical Salicylates
    1. Ben Gay
    2. Salicylic Acid
    3. Methyl Salicylate (oil of wintergreen)
      1. One teaspoon contains 7000 mg of Salicylate

III. Precautions

  1. Consider intentional Overdose (Suicidality) in the elderly
  2. Salicylate Poisoning (especially chronic Poisoning) has a high mortality and is easily mis-diagnosed
  3. Chronic Salicylate Toxicity is frequently missed
    1. Symptoms and signs occur at lower Salicylate levels
    2. Patients may present with encephalopathy, Coagulopathy (INR increased), and Non-Cardiogenic Pulmonary Edema

IV. Pathophysiology

  1. Salicylates directly act at the cerebral Medulla, increasing Respiratory Rate (with a Respiratory Alkalosis)
  2. Salicylate Toxicity uncouples Oxidative Phosphorylation (ATP generation in mitochondria from NADH and FADH2)
    1. Results in shift to anaerobic metabolism, resulting in a Lactic Acidosis (and Metabolic Acidosis with Anion Gap)
    2. Compensatory Hyperventilation (triggered by Metabolic Acidosis) further increases Tachypnea

V. Symptoms

  1. Nausea and Vomiting
  2. Epigastric Pain
  3. Tinnitus

VI. Signs

  1. Tachypnea or Hyperventilation (key clinical clue in Salicylate Overdose)
  2. Diaphoresis
  3. Disorientation or Coma
  4. Seizures
  5. Deafness
  6. Tachycardia (related to volume depletion)
  7. Low grade fever may be present
  8. Non-Cardiogenic Pulmonary Edema (chronic Salicylate Toxicity)

VII. Differential Diagnosis

  1. See Metabolic Acidosis with increased Anion Gap
  2. Sepsis
  3. Myocardial Infarction
  4. Diabetic Ketoacidosis
  5. Alcoholic Ketoacidosis
  6. Reye's Syndrome
  7. Methylxanthine toxicity (e.g. Theophylline, Caffeine)
  8. Beta-Agonist Overdose

VIII. Labs: General

  1. Tests
    1. See Unknown Ingestion
    2. Complete Blood Count
    3. Comprehensive metabolic panel
    4. Venous Blood Gas
    5. INR
    6. Salicylate Level (see below)
    7. Acetaminophen Level
    8. Urine Drug Screen
    9. Blood Alcohol Level
  2. Findings
    1. Alkalosis or acidosis
      1. Initial: Respiratory Alkalosis (related to Tachypnea)
      2. Later: Metabolic Acidosis with increased Anion Gap
    2. Hyponatremia
    3. Hypokalemia
    4. Hyperglycemia or Hypoglycemia
    5. Acute Renal Failure
    6. Coagulopathy (INR increases after 15 years from ingestion)

IX. Lab: Plasma Salicylate level (Dose related Aspirin effect)

  1. Precautions
    1. Interpret Salicylate level based on Salicylate nomogram in the context of time since ingestion
      1. Done Nomogram (formulated in 1961) is only valid in a single acute Salicylate ingestion
      2. Done Nomogram is not typically used clinically
        1. Not predictive of serious Salicylate Toxicity
        2. Contrast with Rumack-Matthew Nomogram used in Acetaminophen Overdose
    2. Manage Salicylate level based on local lab protocols and poison control
    3. Be aware of Units of Measure (local lab may use a measurement other than mg/dl)
  2. Serious toxicity occurs with ingestion >150 mg/kg
  3. Therapeutic Levels
    1. Plasma Salicylate level <10 mg/dl: Analgesic effect
    2. Plasma Salicylate level 10-20 mg/dl: Anti-inflammatory
  4. Overdosage levels (based on 6 hour Salicylate levels in acute toxicity)
    1. Plasma Salicylate level 20-45 mg/dl: Asymptomatic mild toxicity
    2. Plasma Salicylate level 45-65 mg/dl: Mild symptomatic toxicity
      1. Tinnitus (especially children) or Decreased Hearing (especially adults)
      2. Hyperventilation
    3. Plasma Salicylate level 65-90 mg/dl: Moderate toxicity
      1. Fever
      2. Metabolic Acidosis
    4. Plasma Salicylate level 90-110 mg/dl: Severe toxicity
      1. Coma
      2. Cardiovascular instability
    5. Plasma Salicylate level >110 mg/dl: Lethal toxicity
      1. Renal Failure
      2. Respiratory Failure

X. Management: Salicylate Overdose

  1. General measures
    1. Start management prior to serum level available if high level of suspicion and symptomatic patient
    2. Consider Gastric Decontamination (e.g. Activated Charcoal, Gastric Lavage) in presentation <1 hour or large ingestion
    3. Consult poison control
    4. Supplemental Oxygen
    5. Protect airway
  2. Load crystalloid to maintain Urine Output (critical to maximize urine Salicylate excretion)
    1. Patients are typically volume depleted at presentation (2 L deficit on average for adults, with variable Hypotension)
    2. Adult: Start with NS 1-2 Liter bolus
    3. Child: Start with NS 10-20 cc/kg bolus
  3. Alkalinizing serum and urine increases Salicylate excretion
    1. Alkalinization keeps Salicylates from crossing blood brain barrier and aids in renal excretion
    2. Solution
      1. Start with 3 Sodium Bicarbonate ampules (100 meq/50 ml each) in 850 ml D5W (8.4% solution)
      2. Add 40 meq KCl (if not hyperkalemic)
    3. Adult: Infuse above solution at 150-200 ml/hour (or 2-3 ml/kg/hour)
      1. Consider preceding infusion with 1-2 amps of Sodium Bicarbonate
    4. Child: Infuse above solution at 1.5 to 2 times maintenance
      1. Consider preceding infusion with 1-2 meq/kg of Sodium Bicarbonate
  4. Monitoring
    1. Serum pH
      1. Maintain pH at no higher than 7.4 to 7.5 (by VBG)
    2. Urine Output
      1. Goal Urine Output 1 to 1.5 ml/kg/h
    3. Urine pH
      1. Confirm Urine pH 7.5 to 8.5 at 1-2 hours after starting Sodium Bicarbonate infusion
      2. Adjust alkalinization protocol if urine not adequately alkalinized
    4. Serum Potassium
      1. Correct Hypokalemia to aid alkalinization of the urine
      2. Target Serum Potassium at mid to high end of the normal range
      3. In Hypokalemia, renal reabsorption of Potassium results in Hydrogen Ion excretion (acidification)
    5. Mental Status
      1. Salicylates cross the blood brain barrier in Metabolic Acidosis
      2. Mental status may paradoxically worsen despite a decreasing serum Salicylate level
    6. Intracranial Hypoglycemia
      1. Intracranial Hypoglycemia may occur despite normal Serum Glucose
      2. Consider dextrose administration
  5. Hemodialysis Indications
    1. Acute toxicity: Salicylate level >100 mg/dl in adults (>80 mg/dl in children)
    2. Chronic toxicity: Salicylate level >60 mg/dl in adults
    3. Worsening mental status (encephalopathy) or other end organ damage
    4. Large volume fluid administration contraindicated
    5. Patient requiring intubation
  6. Intubated patients
    1. Match Ventilatory rate to respiratory prior to intubation (Respiratory Rate often 30-40 in Salicylate Toxicity)
    2. Risk of rapidly progressive, catastrophic Metabolic Acidosis if hypoventilated

XI. References

  1. Claudius, Grock and Levine in Herbert (2020) EM:Rap 20(1):12-4
  2. Claudius and Levine in Herbert (2012) EM:Rap 12(5): 7
  3. Done (1960) Pediatrics 26:800 [PubMed]
  4. O'Malley (2007) Emerg Med Clin North Am 25(2): 333-46 [PubMed]
  5. Vega (2024) Am Fam Physician 109(2): 143-53 [PubMed]

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