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

---

• 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

---

• 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

---

Differential diagnostics

---

t

Feature	Salicylate (ASA)	Acetaminophen (APAP)	Reye Syndrome
Path	Uncouple oxidative phosphorylation (leads to hyperthermia); Direct stimulation of resp center.	Glutathione depletion $\to$ NAPQI $\to$ centrilobular hepatic necrosis.	Mito dysfunction ($\downarrow$ $\beta$-oxidation) $\to$ Microvesicular fatty change in liver
Hx/Trigger	OD; Wintergreen oil	OD (esp. w/ CYP inducers/EtOH)	Child + Virus + ASA
Key Sx	Tinnitus, Hyperthermia, Tachypnea	RUQ pain, Fulminant liver failure	Encephalopathy, Vomiting
Labs/Path	Mixed Resp Alk + Met Acidosis	Zone 3 Necrosis, $\uparrow \uparrow$ AST/ALT	Microvesicular fatty liver, $\downarrow$ Glucose, $\uparrow$ Ammonia
Tx	NaHCO3 (Alkalinize urine), Dialysis	N-acetylcysteine (restore glutathione)	Supportive

Link to original

Treatment

---

• 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.