Salicylate poisoning

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Salicylate poisoning is a serious complication of aspirin overdose and is characterized by mixed respiratory alkalosis and increased anion gap metabolic acidosis. Early symptoms include tinnitus, nausea, vomiting, and tachypnea. Late symptoms include altered mental status, seizures, and hyperthermia. Fluid resuscitation, oral activated charcoal, and alkalinization of the serum and urine are the most important aspects of treatment. In severe cases, hemodialysis may be indicated. Intubation should be avoided, as it can precipitate clinical decompensation if ventilation needs are not met. For other side effects related to aspirin use, see antiplatelet agents.

Overview

• Early mixed respiratory alkalosis → ↑ anion gap metabolic acidosis
  1. Salicylates directly stimulate the respiratory center of the brain → hyperventilation → CO₂ washout → primary respiratory alkalosis
  2. Disruption of mitochondrial oxidative phosphorylation → inhibition of TCA cycle and ATP production → accumulation of lactic acid and ketones → ↑ anion gap metabolic acidosis ^[2]
  3. Fatigue impairs the ability to compensate for acidosis (via hyperventilation) → hemodynamic instability and end-organ damage
• ↑ Pulmonary capillary permeability → ARDS with pulmonary edema.
• For more information on adverse effects (e.g., tinnitus), see “Irreversible cyclooxygenase inhibitors” in “Antiplatelet agents.”

Pharmacokinetics of poisoning

• Salicylates cause pyloric sphincter spasm → ↑ time spent in stomach → ↑ absorption
• At high concentrations, metabolic pathways become saturated → zero order elimination

• Early symptoms: tinnitus, nausea, vomiting, tachypnea, hyperpnea
• Late symptoms: hyperthermia, agitation, delirium, seizures, noncardiogenic pulmonary edema

• ABG: mixed respiratory alkalosis and increased anion gap metabolic acidosis ^[2]
• Serum salicylate level: > 40 mg/dL ^[3]
• BMP: hypokalemia, ↑ BUN, ↑ creatinine
• Toxicology screen: evaluate for concurrent ingestion

Because salicylate levels may be falsely low within 4 hours of ingestion and do not necessarily correlate with clinical presentation, a high index of suspicion should be maintained when caring for a patient with symptoms of salicylate poisoning. Rapid treatment is essential.

General principles ^[2][3]

• Stabilization of vitals
• Oral/orogastric activated charcoal
• IV sodium bicarbonate
• Hemodialysis

Initial assessment and airway management

• Stabilize the patient.
• Assess the severity of salicylate poisoning (see salicylate poisoning severity above).
• For symptomatic patients: Consult ICU, nephrology, and toxicology.
• Evaluate the need for intubation but avoid intubation, if possible.
  • If intubation is necessary
    • Administer bicarbonate prior to intubation
    • Maximize minute ventilation (e.g., at least 8–10 mL/kg/breath)

Indications for intubation in salicylate poisoning

• Deteriorating mental state
• Seizures
• ARDS
• Hypoventilation (e.g., hypercarbia)

Indications for hemodialysis in salicylate poisoning ^[4]

• Serum salicylates > 100 mg/dL (> 90 mg/dL if renal function impaired)
• Serum salicylates > 90 mg/dL (> 80 mg/dL if renal function impaired) or arterial pH ≤ 7.2 despite supportive care
• Altered mental status
• Hypoxemia requiring supplemental O₂

Intubating patients with salicylate poisoning is dangerous! If intubation is required, extra care should be taken to maximize minute ventilation, as there is a high risk of worsening acidosis and death.

Salicylate combinations with other substances (like opioids) can lead to mixed intoxications that require specific management (e.g., naloxone).

Gastric decontamination ^[3][5]

• Considerations for gastric lavage
  • The ingested aspirin dose is known to be > 500 mg/kg.
  • Ingestion occurred < 1 hour prior to presentation.
• Considerations for oral activated charcoal
  • The patient must have a secure airway (i.e., is awake and alert or is intubated with an orogastric tube).
  • Timing of ingestion: There are no specific recommendations. ^[5]
    • 2–4 hours of known ingestion: Giving at least one dose is most likely beneficial.
    • Within 4–24 hours of known ingestion: may be beneficial in some patients (e.g., ingestion of a large amount, severe poisoning)

Fluid and acid-base management ^[3]

• Fluid resuscitation
  • Preferred fluids: LR and/or 5% dextrose
  • Isotonic bicarbonate solutions, if alkalinization is required (see below)
  • Avoid normal saline, as it can aggravate acidosis.
  • Add IV dextrose even if blood glucose is normal to prevent cerebral hypoglycemia.
• Alkalinization of serum and urine with IV sodium bicarbonate ^[2][3]
  • Indications: any symptomatic patient, or if serum salicylates > 60 mg/dL
  • Bicarbonate dosage
    • Consider bicarbonate loading dose , especially if arterial pH < 7.3 or patient requires intubation.
    • Continuous bicarbonate [dosage:2770] in 150 mL D5W to achieve and maintain urine alkalization ^[2][3]
    • Targets ^[3]
      • Serum pH 7.5–7.55
      • Urine pH 7.5–8.5
      • Urine output: 2–3 mL/kg/hour ^[2]
      • Serum potassium: 4–4.5 mEq/L

Monitoring and additional concerns

• Repeat labs every 2 hours.
  • Blood glucose, BMP, ABG
  • Serum salicylates (until consistently < 40 mg/dL)
• ICU level of care
• Continuous cardiac monitoring, continuous pulse oximetry, frequent neurological checks
• Evaluate and treat suicidal ideation.

• Establish IV access.
• Fluid resuscitation with LR and/or D5W (avoid normal saline)
• Assess the severity of intoxication (see salicylate poisoning severity).
• Consult ICU, nephrology, and toxicology.
• Avoid intubation if possible, but secure the airway if necessary (see indications for intubation in salicylate poisoning).
• Assess the need for hemodialysis (see indications for hemodialysis in salicylate poisoning).
• Start alkalization of serum and urine (see fluid and acid-base management in “Treatment”).
• Avoid and correct hypoglycemia and hypokalemia.
• Check toxicology screen for concurrent ingestions.
• Evaluate for suicidal ideation.
• Order repeat labs (BMP, glucose, salicylate levels) every 2 hours.
• Admit to the ICU.