Salicylate toxicity

Background

• Chronic toxicity can produce severe neuro changes that do not correlate w/ ASA levels
• Fatal dose:
  • ~10-30g by adult
  • ~3g by child
• Levels:
  • Therapeutic: 10-30mg/dL
  • Intoxication: >40-50 mg/dL
  • Peak occurs ~6hr after absorption (up to 60hr if enteric-coated or extended release)

Pathophysiology

• As level rises, switches from hepatic to renal clearance (slower)
• N/V
  • Stimulates chemoreceptor trigger zone
• Respiratory alkalosis
  • Activates respiratory center of medulla
  • If have resp acidosis consider pulm edema, resp depressing co-ingestant, or fatigue
• Anion gap metabolic acidosis
  • Interferes w/ cellular metabolism
• Hyperthermia
  • Uncouples oxidative phosphorylation
  • As pH drops more ASA is uncharged; able to cross BBB
• Altered mental status
  • 1. Direct toxicity of salicylate species in the CNS
  • 2. Cerebral edema
  • 3. Neuroglycopenia
    • May occur despite normal serum glucose levels
• Pulmonary Edema
  • Usually occurs in elderly
  • Due to increased pulmonary vascular permeability

Clinical Features

1. Mild (<150mg/kg)
   1. Tinnitus
   2. Hearing loss
   3. Dizziness
   4. N/V
2. Moderate (150-300mg/kg)
   1. Tachypnea
   2. Hyperpyrexia
   3. Diaphoresis
   4. Ataxia
   5. Anxiety
3. Severe (>300mg/kg)
   1. AMS
   2. Seizure
   3. Acute lung injury
   4. N/V
   5. Renal failure
   6. Cardiac arrhythmias
   7. Shock

Work-Up

• ASA level
  • Check q2hr until two consecutive levels show a decrease
• APAP level
• ETOH level
• Utox
• UA
  • Proteinuria
• VBG
• CBC
• Chem
  • Renal failure prevents ASA clearance
  • Hypokalemia requires aggressive repletion
    • K+/H+ pump in distal tubule > decr urinary alkalinization
• LFT
• Coags
  • Rarely may cause hepatotoxicity
• hCG
• ECG

Treatment

Airway

• Avoid intubation unless absolutely necessary!
  • Very difficult to achieve adequate minute ventilation on vent
    • Leads to resp acidosis > incr ASA crossing BBB
  • Sedation/paralysis > incr ASA crossing BBB
• Indications = Hypoxemia or hypoventilation
• If intubate maintain pH 7.50 - 7.59, hyperventilate

Breathing

• Acute lung injury may lead to high O2 requirements

Circulation

• Hypotension is common due to systemic vasodilation
  • Give fluids if no cerebral edema, no pulmonary edema
    • If these are present consider pressors

Decontamination

• Charcoal 1g/kg up to 50g PO
  • Effectively absorbs ASA
  • Give multiple doses if tolerated
    • 25g PO q2hr x 3 doses OR 50g q4hr x 2 doses after initial dose

Glucose

• Give D50 to altered pts regardless of serum glucose concentration
  • ASA toxicity impairs glucose metabolism

Alkalinization of plasma and urine

• Traps ASA in blood and in rental tubules
  • Increases elimination, prevents diffusion across BBB
• Alkalemia from resp alkalosis is NOT a contraindication to NaHCO3 tx
  • Blood pH goal = >7.5, <7.6
  • Urine pH goal = 7.5-8
• Consider bicarb if ASA>35 or suspect serious toxicity
  • NaHCO3 1-2mEq/kg IV bolus then D5W w/ 3amps bicarb/L @ 2x maintenance for goal ur pH>7.5

Dialysis

Indicated for:

• AMS
• Coma
• Seizure
• Refractory acidosis
• Pulmonary edema
• Acute/chronic Renal Failure
  • Will not be able to clear ASA
• 6hr level > 100

See Also

• General Psych Workup
• Acetaminophen (Tylenol)
• Antidotes

Source

• UpToDate
• Tintinalli