Salicylate overdose causes a high anion gap metabolic acidosis in both children and adults. Adults commonly develop a mixed acid-base disorder as a respiratory alkalosis due to direct respiratory centre stimulation occurs as well. This second disorder is uncommon in children.
Regarding pharmacokinetics of salicylate:
Large overdoses of aspirin can cause a large tablet mass or bezoar in the stomach. This delays absorption and plasma salicylate levels continue to rise over 20 hours or more. For this reason, serial salicylate levels should be measured until the peak has been reached. Repeated oral doses of activated charcoal are indicated in this situation.
High levels of salicylate are toxic because the drug uncouples oxidative phosphorylation as well as inhibiting some enzymes in the cell.
Salicylates directly stimulate the respiratory center to cause hyperventilation (respiratory alkalosis) which is dose-dependent. This stimulation is much more pronounced in adults than in children.
Metabolic acidosis is the most serious acid-base disorder and is due to increased production of endogenous acids rather than the salicylate itself. Plasma salicylate levels rarely exceed a maximum of about 5 mmol/l and the decrement in the [HCO3] is significantly higher than this in these severe cases.
Acidosis is much more pronounced in infants as compared to adults, which is the reverse of the situation with the hyperventilation. In adults, respiratory alkalosis usually predominates. The particular organic acid anions involved in the acidosis of salicylate intoxication have not been identified.
Ketoacidosis may also occur in children who are ill and fasted (ie starvation ketosis).
The combination of metabolic acidosis and respiratory alkalosis can be a difficult situation to diagnose from the blood gases. The problem relates to whether the hyperventilation is primary (ie respiratory alkalosis) or is compensatory for the metabolic acidosis.
Simple urinary alkalinisation with administration of sodium bicarbonate is used to increase urine pH to between 7.5 and 8.5. Hypokalaemia is a risk and potassium should be given at the same time. Hypokalaemia also interferes with the kidney's ability to alkalinise the urine. One recommended regime for an adult is to administer one litre of 1.26% sodium bicarbonate solution (containing 20-40mmols of K+) IV over a 3 hour period
Clinical Presentation
The presentation in severe overdose is a comatose patient with marked hyperventilation and possibly convulsions. Small children usually have a fever. In adults, the diagnosis of overdose or over-ingestion is usually easily made from the history.
Clinicians should have a high index of suspicion in children with a metabolic acidosis particularly if ketoacidosis, lactic acidosis and renal failure have been excluded.
Another clue is that salicylates greatly increase urinary uric acid excretion and plasma urate level is usually very low. If suspicious of overdose it is better to measure salicylate level urgently.
Urine can be screened with a ferric chloride test for salicylates.
Inhalation of toluene (eg by 'glue-sniffing') may cause either a high anion-gap or a normal anion gap acidosis. The high anion gap is probably a consequence of its metabolism to hippuric acid.
Toluene may also cause significant renal damage especially with chronic use. A consequence of this is a toluene-induced renal tubular acidosis in some patients.
Patients with toluene toxicity may initially be suspected of having ethylene glycol toxicity especially as the presentation may be similar (eg a patient with mental obtundation, appearance of intoxication and a metabolic acidosis). These disorders have different treatments and differentiation is important. Toluene toxicity can cause very profound hypokalaemia and often present with muscle weakness and may develop serious arrhythmias (eg ventricular tachycardia).
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Overview of Diagnosis of Toxic Ingestions. | |
As a general rule, the diagnosis of a toxic ingestion should be actively investigated in a patient with a high anion gap acidosis where a diagnosis of ketoacidosis, lactic acidosis or renal failure is not apparent. Treatment can be life-saving if diagnosis is made early. Key Points:
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Guidelines | |
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Important Points in Diagnosing High Anion Gap Acidosis | |
Ketoacidosis |
Can be excluded if normoglycaemia & urine negative for ketones |
Lactic acidosis |
Excluded if lactate level is normal. Suggested if shock or peripheral hypoperfusion. |
Renal failure |
Excluded as cause of acidosis if urea and creatinine normal or only slightly elevated. (In chronic renal failure acidosis is uncommon if creatinine is < 0.30 mmol/l ) |
Methanol |
Suggested if visual impairment and CNS depression or intoxication. Abdominal pain is common. Check the osmolar gap. Do NOT delay therapy until blood level obtained. |
Ethylene glycol |
Suggested if appear intoxicated and no visual disturbance. Check the osmolar gap but it is often normal. |
Salicylate |
Suggested if marked hyperventilation (esp in adults) and mental obtundation. |