II. Causes: Salicylate sources
- Aspirin
- Pepto Bismol
- Topical Salicylates
- Ben Gay
- Salicylic Acid
- Methyl Salicylate (oil of wintergreen)
- One teaspoon contains 7000 mg of Salicylate
III. Precautions
- Consider intentional Overdose (Suicidality) in the elderly
- Salicylate Poisoning (especially chronic Poisoning) has a high mortality and is easily mis-diagnosed
- Chronic Salicylate Toxicity is frequently missed
- Symptoms and signs occur at lower Salicylate levels
- Patients may present with encephalopathy, Coagulopathy (INR increased), and Non-Cardiogenic Pulmonary Edema
IV. Pathophysiology
- Salicylates directly act at the cerebral Medulla, increasing Respiratory Rate (with a Respiratory Alkalosis)
- Salicylate Toxicity uncouples Oxidative Phosphorylation (ATP generation in mitochondria from NADH and FADH2)
- Results in shift to anaerobic metabolism, resulting in a Lactic Acidosis (and Metabolic Acidosis with Anion Gap)
- Compensatory Hyperventilation (triggered by Metabolic Acidosis) further increases Tachypnea
V. Symptoms
VI. Signs
- Tachypnea or Hyperventilation (key clinical clue in Salicylate Overdose)
- Diaphoresis
- Disorientation or Coma
- Seizures
- Deafness
- Tachycardia (related to volume depletion)
- Low grade fever may be present
- Non-Cardiogenic Pulmonary Edema (chronic Salicylate Toxicity)
VII. Differential Diagnosis
- See Metabolic Acidosis with increased Anion Gap
- Sepsis
- Myocardial Infarction
- Diabetic Ketoacidosis
- Alcoholic Ketoacidosis
- Reye's Syndrome
- Methylxanthine toxicity (e.g. Theophylline, Caffeine)
- Beta-Agonist Overdose
VIII. Labs: General
- Tests
- See Unknown Ingestion
- Complete Blood Count
- Comprehensive metabolic panel
- Venous Blood Gas
- INR
- Salicylate Level (see below)
- Acetaminophen Level
- Urine Drug Screen
- Blood Alcohol Level
- Findings
- Alkalosis or acidosis
- Initial: Respiratory Alkalosis (related to Tachypnea)
- Later: Metabolic Acidosis with increased Anion Gap
- Hyponatremia
- Hypokalemia
- Hyperglycemia or Hypoglycemia
- Acute Renal Failure
- Coagulopathy (INR increases after 15 years from ingestion)
- Alkalosis or acidosis
IX. Lab: Plasma Salicylate level (Dose related Aspirin effect)
- Precautions
- Interpret Salicylate level based on Salicylate nomogram in the context of time since ingestion
- Done Nomogram (formulated in 1961) is only valid in a single acute Salicylate ingestion
- Done Nomogram is not typically used clinically
- Not predictive of serious Salicylate Toxicity
- Contrast with Rumack-Matthew Nomogram used in Acetaminophen Overdose
- Manage Salicylate level based on local lab protocols and poison control
- Be aware of Units of Measure (local lab may use a measurement other than mg/dl)
- Interpret Salicylate level based on Salicylate nomogram in the context of time since ingestion
- Serious toxicity occurs with ingestion >150 mg/kg
- Therapeutic Levels
- Plasma Salicylate level <10 mg/dl: Analgesic effect
- Plasma Salicylate level 10-20 mg/dl: Anti-inflammatory
- Overdosage levels (based on 6 hour Salicylate levels in acute toxicity)
- Plasma Salicylate level 20-45 mg/dl: Asymptomatic mild toxicity
- Plasma Salicylate level 45-65 mg/dl: Mild symptomatic toxicity
- Tinnitus (especially children) or Decreased Hearing (especially adults)
- Hyperventilation
- Plasma Salicylate level 65-90 mg/dl: Moderate toxicity
- Plasma Salicylate level 90-110 mg/dl: Severe toxicity
- Coma
- Cardiovascular instability
- Plasma Salicylate level >110 mg/dl: Lethal toxicity
X. Management: Salicylate Overdose
-
General measures
- Start management prior to serum level available if high level of suspicion and symptomatic patient
- Consider Gastric Decontamination (e.g. Activated Charcoal, Gastric Lavage) in presentation <1 hour or large ingestion
- Consult poison control
- Supplemental Oxygen
- Protect airway
- Load crystalloid to maintain Urine Output (critical to maximize urine Salicylate excretion)
- Patients are typically volume depleted at presentation (2 L deficit on average for adults, with variable Hypotension)
- Adult: Start with NS 1-2 Liter bolus
- Child: Start with NS 10-20 cc/kg bolus
- Alkalinizing serum and urine increases Salicylate excretion
- Alkalinization keeps Salicylates from crossing blood brain barrier and aids in renal excretion
- Solution
- Start with 3 Sodium Bicarbonate ampules (100 meq/50 ml each) in 850 ml D5W (8.4% solution)
- Add 40 meq KCl (if not hyperkalemic)
- Adult: Infuse above solution at 150-200 ml/hour (or 2-3 ml/kg/hour)
- Consider preceding infusion with 1-2 amps of Sodium Bicarbonate
- Child: Infuse above solution at 1.5 to 2 times maintenance
- Consider preceding infusion with 1-2 meq/kg of Sodium Bicarbonate
- Monitoring
- Serum pH
- Maintain pH at no higher than 7.4 to 7.5 (by VBG)
- Urine Output
- Goal Urine Output 1 to 1.5 ml/kg/h
- Urine pH
- Confirm Urine pH 7.5 to 8.5 at 1-2 hours after starting Sodium Bicarbonate infusion
- Adjust alkalinization protocol if urine not adequately alkalinized
- Serum Potassium
- Correct Hypokalemia to aid alkalinization of the urine
- Target Serum Potassium at mid to high end of the normal range
- In Hypokalemia, renal reabsorption of Potassium results in Hydrogen Ion excretion (acidification)
- Mental Status
- Salicylates cross the blood brain barrier in Metabolic Acidosis
- Mental status may paradoxically worsen despite a decreasing serum Salicylate level
- Intracranial Hypoglycemia
- Intracranial Hypoglycemia may occur despite normal Serum Glucose
- Consider dextrose administration
- Serum pH
-
Hemodialysis Indications
- Acute toxicity: Salicylate level >100 mg/dl in adults (>80 mg/dl in children)
- Chronic toxicity: Salicylate level >60 mg/dl in adults
- Worsening mental status (encephalopathy) or other end organ damage
- Large volume fluid administration contraindicated
- Patient requiring intubation
- Intubated patients
- Match Ventilatory rate to respiratory prior to intubation (Respiratory Rate often 30-40 in Salicylate Toxicity)
- Risk of rapidly progressive, catastrophic Metabolic Acidosis if hypoventilated
XI. References
- Claudius, Grock and Levine in Herbert (2020) EM:Rap 20(1):12-4
- Claudius and Levine in Herbert (2012) EM:Rap 12(5): 7
- Done (1960) Pediatrics 26:800 [PubMed]
- O'Malley (2007) Emerg Med Clin North Am 25(2): 333-46 [PubMed]
- Vega (2024) Am Fam Physician 109(2): 143-53 [PubMed]