Methanol toxicity

Background

• Found in antifreeze, windshield washer fluid
• Parent compound causes only mild inebriation; metabolite (formic acid) causes toxicity
  • Binds to cytochrome oxidase > blockade of oxidative phosphorylation > lactic acidosis

Clinical Features

1. Symptoms begin 12-24hr after ingestion (may occur even later if ETOH is co-ingested)
   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

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
• Ethanol level
• VBG

Treatment

1. ADH enzyme blockade
   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
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

Source

• Rosen's
• Tintinalli