Question
A 27-year-old woman presents 6 hours after deliberately ingesting a large quantity of aspirin. She complains of nausea, vomiting, ringing in her ears and reduced hearing. She is sweating, agitated and breathing rapidly.
Investigations show:
- pH: 7.46
- PaCO₂: 3.0 kPa
- HCO₃⁻: 17 mmol/L
- Serum salicylate: 580 mg/L
- Creatinine: normal
She has no pulmonary oedema, altered consciousness or other neurological abnormalities.
What is the most appropriate treatment?
A. Intravenous calcium gluconate
B. Intravenous sodium bicarbonate with urinary alkalinisation
C. Intravenous N-acetylcysteine
D. Immediate haemodialysis
E. Intravenous flumazenil
Answer
B. Intravenous sodium bicarbonate with urinary alkalinisation
Explanation
Salicylate poisoning classically produces tinnitus, deafness, nausea, vomiting, sweating, agitation and hyperventilation. Severe poisoning may progress to confusion, seizures, pulmonary oedema, coma and cardiovascular instability.
A particularly important clue is the characteristic acid–base disturbance.
Initially, salicylates directly stimulate the medullary respiratory centre, causing hyperventilation and therefore:
Respiratory alkalosis → ↓ PaCO₂
As toxicity progresses, salicylates uncouple oxidative phosphorylation and generate organic acids, producing:
Metabolic acidosis → ↓ HCO₃⁻
Therefore, established salicylate poisoning commonly produces a mixed respiratory alkalosis + metabolic acidosis. The pH may appear relatively normal or even mildly alkalotic despite significant poisoning because these two abnormalities partially offset each other.
Why sodium bicarbonate?
Salicylic acid is a weak acid. Increasing blood and urinary pH converts more salicylate into its ionised form.
Salicylic acid ⇌ H⁺ + salicylate⁻
The ionised salicylate crosses cell membranes, including the blood–brain barrier, less readily and is excreted more efficiently by the kidneys.
Intravenous sodium bicarbonate therefore:
- alkalinises the serum
- alkalinises the urine
- decreases penetration of salicylate into tissues and the CNS
- increases renal salicylate elimination by “ion trapping”
A commonly used target urine pH is approximately 7.5–8.0, sometimes quoted as up to 8.5.
Potassium must be monitored and corrected because hypokalaemia makes urinary alkalinisation difficult: the kidney retains potassium in exchange for hydrogen secretion, making the urine more acidic.
Salicylate levels
Serum salicylate concentrations should be measured serially rather than relying on a single level. Absorption may be delayed, particularly after large overdoses or enteric-coated preparations, so levels may continue to rise for several hours.
The clinical condition and acid–base status are at least as important as the numerical salicylate concentration.
When is haemodialysis required?
Haemodialysis rapidly removes salicylate and corrects severe acid–base and electrolyte abnormalities. Important indications include severe CNS toxicity, severe or refractory metabolic acidosis, pulmonary oedema, significant renal failure, clinical deterioration despite bicarbonate therapy, or a very high salicylate concentration. A serum concentration around ≥700 mg/L after an acute overdose is a traditional examination threshold suggesting severe toxicity and the need to consider haemodialysis, but treatment should not be based on the concentration alone.
Activated charcoal
Activated charcoal is most useful when the patient presents early after a significant ingestion and the airway is protected. Classically it is given within approximately 1 hour, although toxicology advice may support later administration when absorption is expected to be delayed.
Key pattern
Aspirin overdose → tinnitus + sweating + vomiting + tachypnoea → early respiratory alkalosis → later metabolic acidosis → mixed acid–base disorder → IV sodium bicarbonate/urinary alkalinisation → haemodialysis if severe.
Summary for quick exam revision
Salicylate poisoning should be suspected in a patient with tinnitus, deafness, nausea, vomiting, sweating and marked hyperventilation. Early toxicity causes respiratory alkalosis because salicylates directly stimulate the respiratory centre. As toxicity progresses, uncoupling of oxidative phosphorylation and accumulation of organic acids produce metabolic acidosis. The classic acid–base pattern is therefore a mixed respiratory alkalosis and metabolic acidosis, and the blood pH may appear deceptively normal. Severe poisoning can cause agitation, confusion, seizures, pulmonary oedema, coma and cardiovascular instability. Measure serum salicylate concentrations serially because absorption may be delayed and the level can continue to rise. Clinical severity, renal function and acid–base status are more important than interpreting a single salicylate concentration in isolation. The principal treatment for significant poisoning without immediate indications for dialysis is intravenous sodium bicarbonate. Sodium bicarbonate alkalinises both blood and urine, ionising salicylate and reducing its movement into the brain and other tissues. Urinary alkalinisation also increases renal elimination through ion trapping, with a target urine pH of roughly 7.5–8.0, sometimes quoted up to 8.5. Potassium must be monitored and corrected because hypokalaemia prevents effective urinary alkalinisation. Activated charcoal is useful after a significant recent ingestion when the airway is protected, especially when given early. Haemodialysis should be considered for severe acidosis, renal failure, pulmonary oedema, significant CNS manifestations or clinical deterioration despite appropriate treatment. A very high serum salicylate concentration, classically around ≥700 mg/L in acute poisoning, is another important reason to consider dialysis, although the patient’s clinical state remains paramount. The key examination association is tinnitus plus hyperventilation plus a mixed respiratory alkalosis and metabolic acidosis, followed by treatment with IV sodium bicarbonate and escalation to haemodialysis when toxicity is severe.