Onset and Symptoms of Acute Salicylate (Aspirin) Toxicity
After a potentially lethal dose of aspirin, symptoms typically begin within 3-6 hours and include tinnitus, nausea, vomiting, hyperpnea, tachypnea, and altered mental status.
Initial Presentation and Early Symptoms
Acute salicylate toxicity follows a predictable progression:
Early Phase (30 minutes - 3 hours)
- Nausea and vomiting (earliest symptoms)
- Epigastric pain/discomfort
- Tinnitus (ringing in ears) - a hallmark early symptom
- Hearing loss or decreased auditory acuity
- Dizziness
Intermediate Phase (3-6 hours)
- Hyperpnea (deep, rapid breathing)
- Tachypnea (increased respiratory rate)
- Respiratory alkalosis (due to direct stimulation of respiratory center)
- Diaphoresis (excessive sweating)
- Dehydration
- Electrolyte disturbances (particularly hypokalemia)
Severe Phase (6-12 hours)
- Altered mental status (confusion, lethargy)
- Metabolic acidosis (develops as toxicity progresses)
- Hyperthermia
- Pulmonary edema
- Seizures
- Coma
Severity Assessment
The severity of aspirin toxicity correlates with plasma salicylate concentrations:
- Mild toxicity: 30-50 mg/dL
- Moderate toxicity: 50-70 mg/dL
- Severe toxicity: >70 mg/dL
- Potentially lethal: >100 mg/dL
However, chronic toxicity can occur at lower levels, particularly in elderly patients or those with renal impairment 1.
Special Considerations
Enteric-Coated Formulations
With enteric-coated aspirin, symptom onset may be delayed by 8-12 hours due to delayed absorption 2. This can lead to a false sense of security in the early post-ingestion period.
Risk Factors for Severe Toxicity
- Age extremes (very young or elderly)
- Pre-existing renal impairment
- Dehydration
- Concurrent use of other medications (especially anticoagulants or NSAIDs)
- Acidemia (worsens toxicity by increasing CNS penetration)
Warning Signs of Life-Threatening Toxicity
Immediate medical attention is required for:
- Hematemesis (vomiting blood)
- Dyspnea (difficulty breathing)
- Seizures
- Unexplained lethargy or confusion
- Tachypnea with altered mental status 1
Pathophysiology of Symptoms
The constellation of symptoms results from:
- Direct stimulation of respiratory center in the medulla
- Uncoupling of oxidative phosphorylation
- Inhibition of Krebs cycle enzymes
- Alteration of platelet function
- Direct gastric irritation
Pulmonary edema, a particularly concerning complication, results from increased capillary permeability and can develop rapidly in severe cases 3.
Management Considerations
Early recognition is critical. The presence of an unexplained anion gap metabolic acidosis with respiratory alkalosis should raise suspicion for salicylate toxicity. Patients with suspected lethal ingestions require immediate medical attention, and treatment should not be delayed 1.
For severe cases with altered mental status, respiratory distress, or high salicylate levels, urinary alkalinization and consideration of hemodialysis are often necessary 4, 5.
Remember that the clinical presentation may mimic other conditions such as sepsis ("pseudosepsis"), diabetic ketoacidosis, or other toxic ingestions, potentially delaying diagnosis and appropriate treatment 3.