Salicylate toxicity

Background

• 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
  • Normal AG does not exclude ASA toxicity in pt w/ an unknown ingestion (mixed picture)
• 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

Diagnosis

• Triple-mixed acid-base disturbance
  • AG metabolic acidosis, metabolic alkalosis (contraction), respiratory alkalosis
  • Only other entity that produces this pattern is sepsis
• Elevated ASA level
  • Obtain levels q1-2hr until levels decline and pt's clinical status stabilizes
  • May be deceptively low early after ingestion and with chronic toxicity

Work-Up

• ASA level
• Chem
  • Renal failure prevents ASA clearance
  • Hypokalemia requires aggressive repletion
    • Urinary alkalinization inhibited by excretion of H+ in order to reabsorb K+
• Utox
• UA
  • Proteinuria
• VBG
• CBC
• ECG

Treatment

Airway

• Avoid intubation unless absolutely necessary!
  • Very difficult to achieve adequate minute ventilation on vent
    • Sedation/paralysis -> decreased RR -> resp acidosis -> incr ASA crossing BBB
• Indications: hypoxemia or hypoventilation
• If mechnically ventilate must set increased RR to to maintain pH 7.50 - 7.59

Breathing

• Acute lung injury may lead to high O2 requirements

Circulation

• Hypotension is common due to systemic vasodilation
• IVF +/- K+ (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
• Whole-bowel irrigation
  • Consider for ingestion of large amount of enteric-coated or extended-release forms

Glucose

• Give D50 to altered pts regardless of serum glucose concentration
• Except for fluids used for initial resuscitation, all IVF should be D5W
  • ASA toxicity impairs glucose metabolism

Alkalinization of plasma and urine

• Not a substitute for dialysis in severe salicylism
• Alkalemia from resp alkalosis is NOT a contraindication to NaHCO3 tx
• Mechanism
  • Traps ASA in blood and in renal tubules
    • Increases elimination; prevents diffusion across BBB
• Indications
  • ASA>35 or suspect serious toxicity
• Goals
  • Blood pH goal: = >7.5, <7.6
  • Urine pH goal: 7.5-8
• Dosing
  • NaHCO3 1-2mEq/kg IV bolus; then 3amp bicarb in 1L D5W @ 2-3mL/kg/hr
    • Maintain urine pH >7.5

Dialysis

Indicated for:

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

Disposition

• Admit all pts who have ingested enteric-coated or extended-release preprarations

See Also

• General Psych Workup
• Acetaminophen (Tylenol)
• Antidotes

Source

• UpToDate
• Tintinalli