General Principles

Mechanism: Toxicity is not from the parent alcohol but from its metabolites, which are produced by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).
Diagnosis: Suspect in any pt with altered mental status and an unexplained ↑ anion gap metabolic acidosis.
- ↑ Osmolar Gap: All toxic alcohols are osmotically active and will initially cause an increased osmolar gap.
- ↑ Anion Gap Metabolic Acidosis: Occurs as the alcohols are metabolized to acidic compounds. Anion gap increases as the osmolar gap decreases.
- Exception: Isopropyl alcohol causes an ↑ osmolar gap but no significant anion gap acidosis.
Treatment: The primary goal is to inhibit alcohol dehydrogenase.
- Fomepizole: Competitive inhibitor of ADH. Preferred treatment.
- Ethanol: Competitive substrate for ADH with a higher affinity than toxic alcohols. Used if fomepizole is unavailable.
- Hemodialysis: Used to remove the parent alcohol and toxic metabolites, especially in severe acidosis or end-organ damage.

Methanol Poisoning

Sources: Windshield washer fluid, “moonshine” (improperly distilled homemade alcohol), solvents, cooking fuel.
Pathophysiology:
- Methanol ---(ADH)⇒ Formaldehyde ---(ALDH)⇒ Formic Acid
- Formic acid is the primary toxic metabolite. It inhibits mitochondrial cytochrome c oxidase, leading to cellular hypoxia and severe metabolic acidosis.
Clinical Features:
- Latent period of 12-24 hours before Sx appear.
- CNS depression (similar to ethanol intoxication).
- Visual disturbances: Classic finding. Described as “snowstorm vision,” blurry vision, or central scotoma. Fundoscopy may show optic disc hyperemia. Can lead to permanent blindness.
- Abdominal pain, pancreatitis.
Diagnostics:
- ↑ Osmolar gap
- Severe high anion gap metabolic acidosis
Treatment:
- Fomepizole or Ethanol
- Hemodialysis for severe acidosis (pH < 7.25-7.30), visual changes, or high methanol levels.
- Folinic acid (leucovorin) may enhance the metabolism of formic acid.

Sources: Antifreeze, engine coolants. Often ingested intentionally due to its sweet taste.
Pathophysiology:
- Ethylene Glycol ---(ADH)⇒ Glycoaldehyde ---(ALDH)⇒ Glycolic Acid ⇒ Oxalic Acid
- Glycolic acid: Causes severe metabolic acidosis.
- Oxalic acid: Combines with calcium to form calcium oxalate crystals.
Clinical Features:
- Stage 1 (30 min - 12 hr): CNS depression, intoxication (“drunk” pt without the smell of alcohol).
- Stage 2 (12 - 24 hr): Cardiopulmonary toxicity (tachycardia, tachypnea, ARDS).
- Stage 3 (24 - 72 hr): Acute Kidney Injury (AKI). Flank pain, hematuria, oliguria. Caused by deposition of calcium oxalate crystals in renal tubules.
Diagnostics:
- ↑ Osmolar gap
- Severe high anion gap metabolic acidosis
- Hypocalcemia (due to precipitation with oxalate), which can cause a prolonged QT interval.
- Urine microscopy: Envelope-shaped or dumbbell-shaped calcium oxalate crystals.
- Urine fluorescence may be positive (fluorescein is added to antifreeze).
Treatment:
- Fomepizole or Ethanol
- Hemodialysis for severe acidosis or renal failure.
- Thiamine and Pyridoxine (B6) can help divert metabolites to non-toxic products.

Sources: Rubbing alcohol, hand sanitizers.
Pathophysiology:
- Isopropyl Alcohol ---(ADH)⇒ Acetone
- Acetone is a ketone but not a ketoacid. It does not cause a significant anion gap acidosis.
Clinical Features:
- Predominantly CNS depression (more potent than ethanol), disequilibrium, coma.
- Hemorrhagic gastritis → abdominal pain, vomiting, hematemesis.
- Fruity or acetone-like odor on breath.
Diagnostics:
- Large ↑ Osmolar Gap
- No or minimal anion gap metabolic acidosis. This is the key differentiating feature.
- Positive serum and urine ketones.
Treatment:
- Supportive care is the mainstay of treatment.
- Fomepizole/Ethanol are NOT indicated, as the metabolite (acetone) is less toxic than the parent compound. Inhibiting ADH would prolong the intoxicating effects of isopropyl alcohol.
- Hemodialysis only in cases of severe, refractory hypotension or coma.