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 (AMS), 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.

Salicylate poisoning is caused by acute or chronic supratherapeutic ingestion of salicylate-containing products. ^[2]

Salicylate-containing products ^[2]

• Aspirin (most common)
• Topical salicylates
• Bismuth subsalicylate
• Wintergreen oil (i.e., methyl salicylate)
• Willow bark

Even a lick or taste of wintergreen oil can be toxic in children < 6 years of age. ^[3]

Risk factors for severe salicylate toxicity ^[4][5]

• Exposure to multiple salicylate-containing products
• Advanced age
• Kidney disease (CKD or AKI)
• Coingestions (e.g., acetaminophen, opioids, benzodiazepines, alcohol)

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 ^[6]
  3. Fatigue impairs the ability to compensate for acidosis (via hyperventilation) → hemodynamic instability and end-organ damage
• ↓ pH → ↑ permeability of salicylates across cell membranes → ↑ toxic effects ^[3]
• ↑ Blood-brain barrier permeability → cerebral edema, seizures, and/or coma ^[7]
• ↑ 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 stage: tinnitus, nausea, vomiting, tachypnea, hyperpnea ^[2]
• Late stage: hyperthermia, agitation, delirium, seizures, noncardiogenic pulmonary edema ^[2]

Typical clinical features may be subtle or absent in patients with chronic supratherapeutic ingestions. ^[4]

Tachypnea at clinical presentation is a red flag feature. ^[5]

The degree of tachypnea and signs of organ failure (e.g., kidney failure, neurological dysfunction, respiratory failure) correlate with poor outcomes in patients with salicylate poisoning. ^[9]

Approach

• Establish diagnosis based on a combination of clinical evaluation, serum salicylate levels, and additional laboratory studies (e.g., blood gas).
• Perform a toxicological risk assessment based on the severity of salicylate poisoning.
• See “Diagnostics for the poisoned patient” for additional studies in patients with suspected poisoning.

Clinical evaluation of poisoning ^[4]

• Identify clinical features of salicylate poisoning.
• Determine type of exposure (e.g., acute ingestion vs. chronic supratherapeutic ingestion).
• Identify the source and potency of salicylate-containing products.
• Identify risk factors for severe salicylate toxicity.

Toxic dose ^[10]

• Aspirin (or equivalent): > 150 mg/kg or > 6.5 g (whichever amount is lower)
• Wintergreen oil
  • Children < 6 years: any oral exposure (even minimal)
  • Children ≥ 6 years: > 4 mL

Serum salicylate level ^[2][3][4]

• Interpretation ^[4][6]
  • Salicylate levels only correlate loosely with clinical features, time of ingestion, and severity of salicylate poisoning.
  • Maintain a high index of suspicion for patients with symptoms of salicylate poisoning, regardless of levels, and use overall clinical condition to guide management.
• Therapeutic levels: 15–30 mg/dL ^[4]
• Toxic levels: typically defined as > 30 mg/dL ^[3]
• Timing ^[6]
  • Obtain as soon as possible.
  • Consider repeat levels in patients with:
    • Acute ingestion within the last 4 hours ^[8]
    • Suspected chronic supratherapeutic ingestion ^[4]
    • Enteric-coated or extended-release formulations ^[4]
  • Continue serial measurements until the level is reliably declining and symptoms have resolved. ^[6]

Salicylate levels can be falsely low within 4 hours of acute ingestion or with large ingestions that form bezoars and/or delay gastric emptying. ^[2][8]

Pediatric patients and those with chronic supratherapeutic ingestions may experience toxicity at the upper end of therapeutic levels. ^[4][8]

Additional laboratory studies ^[2][3]

• ABG or VBG: mixed respiratory alkalosis and increased anion gap metabolic acidosis ^[6]
• BMP: hypokalemia, ↑ BUN, ↑ creatinine
• ↑ Lactate
• Liver function tests
• Coagulation studies
• Screening for coingestion (e.g., acetaminophen level, urine drug screen)

• Sepsis
• CNS infection (e.g., meningitis, encephalitis)
• Substance withdrawal
• Diabetic ketoacidosis (see “Etiology of high anion gap metabolic acidosis”)
• Other causes of AMS and coma

The differential diagnoses listed here are not exhaustive.

Initial management ^[2][3][4]

• Stabilization
  • Follow the ABCDE approach for poisoning.
  • Provide IV fluid resuscitation and electrolyte repletion as needed.
  • Administer supplemental glucose for AMS. ^[3]
  • Perform airway management for salicylate poisoning with caution.
• GI decontamination: : Consider single-dose activated charcoal (AC) or multidose activated charcoal (MDAC); see “GI decontamination in salicylate poisoning.” ^[3]
• Enhanced elimination
  • Initiate serum and urine alkalinization with IV sodium bicarbonate.
  • Evaluate need for hemodialysis; see “Indications for hemodialysis in salicylate poisoning.”
• Urgent consults
  • Call the local poison control center: In the US, the Poison Help line is 1-800-222-1222.
  • Consult psychiatry for all intentional overdoses.
  • Consult nephrology for dialysis, if indicated.

Airway management in salicylate poisoning ^[2][3]

• Avoid early intubation and mechanical ventilation if possible.
• Consider intubation with caution in patients with: ^[6]
  • Worsening AMS causing airway compromise
  • Salicylate-induced acute lung injury
  • Refractory severe agitation
• If intubation is unavoidable:
  • Administer pre-intubation sodium bicarbonate. ^[3]
  • Consider awake intubation with ketamine to minimize respiratory depression.
• Follow ventilation strategies for severe acidosis and hyperventilate to maintain preintubation pCO₂ levels.

Avoid intubation and mechanical ventilation unless absolutely necessary, as patients may decompensate rapidly if respiratory acidosis develops.

GI decontamination in salicylate poisoning ^[3][4][6]

• Consider single-dose AC even > 2–4 hours after acute ingestion.
• Consider MDAC in consultation with a toxicologist. ^[3][4]
• Discuss risks and benefits of other GI decontamination methods (e.g., WBI) with a specialist. ^[11]

Avoid activated charcoal in patients without a secure airway. ^[12]

Serum and urine alkalinization ^[2][3][6]

• Indications ^[3]
  • All symptomatic patients with serum salicylate levels > 30 mg/dL
  • Suspected salicylate poisoning before obtaining serum salicylate level
• Dosing: See “Urine alkalinization.”
• Goals ^[3]
  • Serum pH 7.45–7.55
  • Urine pH 7.5–8.0

Replete potassium because hypokalemia prevents urinary alkalinization. ^[3]

Indications for hemodialysis in salicylate poisoning ^[13]

• Hemodialysis is recommended for any of the following:
  • Serum salicylate level > 100 mg/dL (> 90 mg/dL if renal function is impaired)
  • AMS
  • New hypoxemia requiring supplemental oxygen
• Hemodialysis is suggested if standard therapy fails and any of the following are present:
  • Serum salicylate level > 90 mg/dL (> 80 mg/dL if renal function is impaired)
  • Serum pH ≤ 7.2

Monitoring ^[3]

• Repeat laboratory studies every 2–4 hours. ^[2][3]
  • ABG or VBG, BMP ^[3]
  • Serum salicylate level
  • See “Urinary alkalization” for monitoring specific to this therapy.
• Endpoints for monitoring
  • Clinical improvement
  • Sustained decrease in salicylate level ^[2]
  • Normalized or increased serum pH

Disposition ^[2]

• Most patients require ICU admission, e.g., for: ^[2]
  • Pulmonary edema
  • AMS
  • Seizures
  • Serum pH < 7.3
  • Electrolyte abnormalities
  • Dehydration
  • Renal insufficiency
  • Increasing salicylate levels
• Consult toxicology to determine if discharge is appropriate for asymptomatic patients with low-risk features.
• Consult psychiatry and admit patients with high suicidal risk to hospital even if medically stable; involuntary commitment may be necessary.

• Follow the ABCDE approach.
• Consult poison control.
• Order diagnostics for salicylate poisoning.
• Consider GI decontamination, e.g., single-dose AC or MDAC.
• Provide IV fluid resuscitation and electrolyte repletion.
• Administer supplemental glucose for altered mental status.
• Initiate serum and urine alkalinization with IV sodium bicarbonate.
• Evaluate for indications for hemodialysis in salicylate poisoning.
• Monitor serial salicylate levels and blood gas analyses.
• Consult psychiatry for intentional overdose.
• Consider ICU admission for severe toxicity.