Salicylate poisoning

Salicylate poisoning is a serious complication of aspirin overdose and is characterized by mixed respiratory alkalosis and increased anion gap metabolic acidosis.

Pathophysiology

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• Occurs with acute ingestion of >150 mg/kg. Doses >300 mg/kg are associated with severe toxicity, and >500 mg/kg are potentially lethal.
• Dual mechanism of acid-base disturbance:
  • Respiratory Alkalosis (Early): Salicylates directly stimulate the medullary respiratory center, leading to hyperventilation and a primary respiratory alkalosis. This is the initial disturbance.
  • Anion Gap Metabolic Acidosis (Later): Salicylates uncouple oxidative phosphorylation in the mitochondria. This shifts cells to anaerobic metabolism, leading to the accumulation of lactate and ketoacids, causing a primary metabolic acidosis.
• The classic picture is a mixed respiratory alkalosis and metabolic acidosis.
• In young children, metabolic acidosis may be the dominant or only initial finding.

Clinical features

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• Early Symptoms: Nausea, vomiting, abdominal pain, and lethargy are common. Tinnitus (ringing in the ears) is a classic and early symptom.
• Systemic Symptoms:
  • Hyperthermia/Fever: Due to uncoupling of oxidative phosphorylation, which generates heat. This is particularly common in children.
  • Tachypnea: Caused by direct stimulation of the respiratory center.
• Severe Toxicity:
  • Altered Mental Status: Confusion, agitation, delirium, seizures, or coma can occur, often due to low glucose levels in the brain and cerebral edema.
  • Pulmonary Edema: Non-cardiogenic pulmonary edema can develop from direct lung toxicity.
  • Hypoglycemia: Can occur despite normal serum glucose due to low CNS glucose levels.

Diagnostics

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Differential diagnostics

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Feature	Salicylate (ASA) Poisoning	Acetaminophen (APAP) Poisoning	Reye Syndrome
Classic Hx	Overdose (intentional/accidental)	Intentional OD; chronic EtOH use	Child after viral illness + ASA use
Pathophysiology	Uncouples ox-phos; Resp center stim; Direct ototoxicity	Glutathione depletion → toxic metabolite (NAPQI) → liver necrosis	Mitochondrial dysfunction → fatty liver & encephalopathy
Presentation	Tinnitus, fever, hyperventilation, AMS	Asymptomatic initially → RUQ pain → fulminant liver failure	Profuse vomiting, delirium/coma, NO jaundice
Key Lab Finding	Mixed resp. alkalosis + metabolic acidosis	Massive AST/ALT elevation (>1000s)	Hyperammonemia, elevated LFTs, hypoglycemia
Antidote / Tx	IV Sodium Bicarbonate, Hemodialysis	N-acetylcysteine (NAC)	Supportive care (manage ICP, hypoglycemia)
Buzzword	”Mixed acid-base disorder"	"Rumack-Matthew nomogram"	"Child + virus + aspirin”

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Treatment

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• 1. Supportive Care (ABCDE Approach): Stabilize airway, breathing, and circulation.
  • Intravenous fluids are given for dehydration.
  • Glucose (Dextrose) should be administered, even if serum glucose is normal, to address potential CNS hypoglycemia.
  • Avoid intubation if possible. If necessary, hyperventilation must be maintained on the ventilator to prevent worsening acidosis, as a sudden rise in PaCO2 can be fatal.
• 2. GI Decontamination:
  • Activated Charcoal: Can be given if the patient presents within 1-2 hours of ingestion to decrease absorption. Multiple doses may be considered for large or sustained-release ingestions.
• 3. Enhanced Elimination:
  • IV Sodium Bicarbonate: This is the mainstay of treatment. It serves two purposes:
    • Alkalinizes the urine (to a pH of 7.5-8.0), which traps the ionized form of salicylic acid in the renal tubules, enhancing its excretion.
    • Alkalinizes the serum, which helps shift salicylate out of the central nervous system and into the plasma.
  • Potassium supplementation is often required, as hypokalemia can prevent effective urinary alkalinization.
• 4. Hemodialysis:
  • Indications: Used for severe cases and is life-saving.
  • Criteria include: very high salicylate levels (>90-100 mg/dL), end-organ damage (e.g., seizures, cerebral edema, renal failure, pulmonary edema), severe acidosis (pH < 7.2), or failure of standard therapy.