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 24hr if enteric-coated or extended release

Pathophysiology

• As level rises, hepatic detox is saturated, switches to renal clearance (slower)
• As pH drops more ASA is uncharged > crosses BBB
• AMS
  • Causes:
    • 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

• Anion gap metabolic acidosis (interferes w/ cellular metabolism)
• Nausea/vomiting (stimulates chemoreceptor trigger zone)
• Respiratory alkalosis (activates respiratory center of medulla)
  • If have resp acidosis consider pulm edema, resp depressing co-ingestant, or fatigue

2. fluid loss, lytes off: emesis, tachypnea, kidneys excrete bicarb/K,nonolig RF vs oligur (SIADH)

3. abnml gluc metabolism

4. non-cards pulm & cerebral edema

5. plt dysfxn, anemia (chronic tox)

6. n/v/gastritis/decr gastric motility

Signs/Symptoms

• Tinnitus
  • May occur within therapeutic range
• Fever
• Vertigo
• N/V
• Diarrhea
• AMS
• Coma
• Noncardiac pulmonary edema
• Death
  • Correlated with CNS salicylate levels

Vital signs

• Tachypnea
• Increase body temperature
  • Lack of hyperthermia does not rule out toxicity!
• Tachycardia (due to hypovolemia, agitation, or general distress)

Work-Up

• ASA level
  • Check q2hr until two consec levels show a decrease
• Tylenol level
• ETOH level
• Utox
• UA
• VBG
• CBC
• Chem
  • If renal failure unable to clear ASA
  • Hypokalemia requires aggressive repletion
    • K+/H+ pump in distal tubule > decr ur. alkalinization
• LFT
• Coags
  • Rarely may cause hepatotoxicity
• hCG
• ekg
  • level >30mg/dL s/s of tox or >35 at any time

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 pts with AMS regardless of serum glucose concentration

Alkalinization of plasma and urine

• Alkalemia from resp alkalosis is NOT a contraindication to NaHCO3 tx
  • Blood pH goal = >7.5, <7.6
  • Urine pH goal = 7.5-8

• lytes: consider 40mEq KCl/L, hypoK will prevent urine alkaliniz
• Alkalinization
  • Traps ASA in blood and in rental tubules (so can't diffuse across BBB)
  • fxn of flow & pH
    • consider bicarb if ASA>35 or suspect serious toxicity
    • 1-2mEq/kg IV bolus then D5W c 3amps bicarb/L @1.5-2x maintenance for goal urine pH>7.5

Dialysis

• Indicated for:
  • AMS
  • Coma
  • Seizure
  • Refractory acidosis
  • Pulmonary edema
  • Acute/chronic renal failure
    • Pts will not be able to clear ASA
  • 6hr level > 100

Source

UpToDate