Methanol toxicity

Background

• Found in antifreeze, windshield washer fluid, solvents
• Colorless, volatile liquid with distinctive “alcohol” odor
• Parent compound causes only mild inebriation; metabolite (formic acid) causes toxicity
  • Binds to cytochrome oxidase > blockade of oxidative phosphorylation > lactic acidosis
• Most exposures from ingestion; may be systemically absorbed after inhalation or dermal exposure but rarely causes significant clinical toxicity

Clinical Features

1. Symptoms begin 12-24hr after ingestion (may occur even later if ETOH is co-ingested as EtOH competes with alcohol dehydrogenase and has greater affinity for the enzyme than methanol)
   1. CNS depression
      1. Confusion, ataxia, depressed mental status, seizure
      2. Less inebriating than ethanol or ethylene glycol
   2. Visual disturbances (50% of pts)
      1. Development may precede or parallel that of other clinical symptoms
      2. Cloudy or blurry vision ("stepping out into a snowstorm")
   3. Anion-gap acidosis
      1. May be severe (bicarb < 5, pH < 7)
      2. Compensatory tachypnea
   4. CVS
      1. Tachycardia
      2. Hypotension --> can progress to shock
   5. RESP
      1. Tachypnea
      2. SOB (compensating for metabolic acidosis) --> may progress to respiratory depression and/or failure
   6. GI
      1. Abdo pain
      2. N/V
      3. Anorexia
      4. Pancreatitis and gastritis
      5. Transaminitis (mild and transient)

Work-Up

• Chemistry
  • Anion gap acidosis
• Serum Osm
  • Osm gap (measured - calculated)
    • Calculated serum osm = 2Na + BUN/2.8 + glucose/18 + ethanol/4.6
    • Normal is < 10
    • Note: Cannot rule out toxic ingestion with a "normal" osmol gap
      • Only parent alcohol is osmotically active
      • Delayed presentation may mean that much of it is already metabolized
• Toxic alcohol levels - Methanol
  • <20 mg/dL - asymptomatic
  • >20 mg/dL - CNS symptoms may appear
  • >50 mg/dL - ocular problems
  • >150-200 mg/dL - risk of fatality
• Ethanol level
• VBG

Treatment

1. ADH enzyme blockade - both fomepizole and ethanol have greater affinity for ADH than methanol
   1. Fomepizole
      1. Indications:
         1. Ethylene glycol level >20mg/dL
         2. Suspected significant ethylene glycol ingestion w/ ETOH level <100mg/dL
         3. Coma or AMS in pt w/ unclear history and osm gap >10
         4. Coma or AMS in pt w/ unclear history and unexplained met acidosis and ETOH level <100
      2. Dosing
         1. 15mg/kg IV over 30min; follow by 10mg/kg q12hr until level <20 or acidosis resolves
   2. Ethanol
      1. BAL of 100-150 completely saturates alcohol dehydrogenase
      2. IV: load 800mg/kg; then give 100mg/kg/hr
      3. Oral: 3-4 1-oz "shots" of 80-proof liquor); then give 1-2 "shots" per hour
      4. Disadvantages: makes patients inebriated thus requiring close monitoring for CNS and respiratory depression, individual metabolic variations make dosing complicated, frequent serum level monitoring and dosage adjustments are required, administration of the 10% IV ethanol solution requires central venous access
2. Correction of metabolic acidosis with bicarbonate
   1. Bicarbonate 1-2mEq/kg IV bolus to attain pH = 7.45-7.50
      1. Follow by infusion of 150mEq/L in D5 @ 1.5-2x maintenance fluid rate
      2. Monitor for worsening hypocalcemia
3. Dialysis
   1. Indications:
      1. Refractory metabolic acidosis (pH <7.25) w/ AG >30
      2. Renal insufficiency
      3. Visual symptoms
      4. Deteriorating vital signs despite aggressive supportive care
      5. Electrolyte abnormalities refractory to conventional therapy
      6. Methanol level >50mg/dL (controversial)
4. Enchanced formic acid metabolism
   1. Folinic acid 50mg IV q4hr
      1. May facilitate breakdown of formic acid into carbon dioxide and water
5. Consult toxicologist and/or Poison Control Centre

See Also

• Ethylene Glycol Toxicity

Source

• Rosen's
• Tintinalli