What are the clinical manifestations and management of aspirin (acetylsalicylic acid) induced high anion gap metabolic acidosis?

Clinical Presentation of Aspirin-Induced High Anion Gap Metabolic Acidosis

Aspirin (salicylate) poisoning classically presents with a mixed acid-base disturbance featuring both high anion gap metabolic acidosis and respiratory alkalosis, though the metabolic acidosis is typically mild and the respiratory component often dominates the clinical picture. 1

Key Clinical Manifestations

Acid-Base Disturbances

• The metabolic acidosis is usually mild despite potentially severe toxicity, with the high anion gap resulting from accumulation of salicylate ions and lactate 1
• Respiratory alkalosis frequently coexists and may be the predominant acid-base abnormality, caused by direct stimulation of the respiratory center by salicylates 1
• The mixed picture can mask the severity of poisoning, as the respiratory alkalosis may partially compensate for or even override the metabolic acidosis 1

Diagnostic Pitfall: Normal Anion Gap Presentation

• Salicylate intoxication can paradoxically present with a normal anion gap metabolic acidosis due to laboratory interference, where salicylate ions are misread as chloride ions by direct ion-selective electrodes (ISE), falsely elevating the measured chloride concentration 2, 3
• This aberrant reading occurs with commonly used analyzers (such as ABL90-flex direct ISE), leading to a falsely normal or even negative anion gap that can delay diagnosis 2, 3
• Maintain high clinical suspicion for salicylate poisoning even when the anion gap is normal, as this laboratory artifact can cause significant avoidable morbidity and mortality 3
• If salicylate toxicity is suspected despite normal anion gap, request chloride measurement using an indirect ISE method (such as Roche Cobas 8000), which does not exhibit this interference 2

Clinical Symptoms to Identify

• Tachypnea is a cardinal feature, reflecting the respiratory alkalosis component and direct respiratory center stimulation 1
• Tinnitus may be present and is reversible, potentially indicating high salicylate blood levels 4
• Altered mental status can develop, ranging from confusion to psychosis, particularly in older patients 4
• Nausea, vomiting, and nonspecific gastrointestinal symptoms are common 4
• Fever may be present due to uncoupling of oxidative phosphorylation 1

Initial Laboratory Assessment

Essential Testing

• Obtain serum salicylate level immediately when suspicion exists, as therapeutic range is 50-300 mg/L and severe toxicity occurs at levels >500 mg/L 2
• Measure arterial blood gas to assess both metabolic acidosis and respiratory alkalosis components 1
• Calculate anion gap using: Na+ + K+ - Cl- - HCO3-, but recognize that a normal result does not exclude salicylate toxicity 5, 2
• Check serum osmolality to calculate osmolar gap, though this is typically normal in pure salicylate toxicity (unlike methanol or ethylene glycol) 1
• Obtain comprehensive metabolic panel including electrolytes, glucose, BUN, creatinine 6

Monitoring Parameters

• Recheck salicylate levels serially as absorption may be delayed with enteric-coated preparations or bezoar formation 2
• Monitor blood gases, pH, and electrolytes every 2-4 hours until stabilized 6
• Follow anion gap trends if initially elevated, though recognize laboratory interference may persist 2

Management Approach

Severity Assessment

• The American Association of Poison Control Centers recommends considering extracorporeal treatment (hemodialysis) if blood pH is ≤7.20 in patients with salicylate poisoning 5
• Hemodialysis should also be considered for severe acidosis, altered mental status, pulmonary edema, renal failure, or salicylate levels >100 mg/dL (7.2 mmol/L) in acute ingestion 1

Supportive Care

• Begin fluid resuscitation with isotonic saline to maintain urine output and enhance renal elimination 5
• **Avoid aggressive bicarbonate therapy unless pH <7.0**, as bicarbonate is generally not indicated for pH >7.0 5
• For severe acidosis with pH <7.0, consider 1-2 mEq/kg sodium bicarbonate over 1 hour 5
• Alkalinization of urine (target pH 7.5-8.0) enhances salicylate excretion by ion trapping, though this is distinct from treating the acidosis itself 1

Specific Treatment

• Hemodialysis is the definitive treatment for severe salicylate poisoning and effectively removes both the toxin and corrects acid-base abnormalities 2
• Continue monitoring for rebound toxicity after hemodialysis, as salicylate can redistribute from tissues 2
• Administer activated charcoal if presentation is within 1-2 hours of ingestion and airway is protected 1

Critical Pitfalls to Avoid

• Do not rule out salicylate poisoning based on normal anion gap alone, as laboratory interference can mask the expected high anion gap 2, 3
• Do not delay treatment while waiting for complete diagnostic workup in severe acidosis 6
• Avoid relying solely on a single salicylate level, as delayed absorption can occur 2
• Do not assume the acid-base picture will be purely metabolic acidosis—expect mixed disturbances with respiratory alkalosis 1
• Be aware that the respiratory alkalosis may initially mask the severity of metabolic acidosis 1