Source of Methanol Exposure

  • Antifreeze Ingestion
  • Copy Machine Fluid Ingestion
  • Denaturant Ingestion: used to make ethanol unfit for consumption
  • Illicit Ethanol Distillation (Illicit Production of *Moonshine”): may result in toxicity to multiple individuals
  • Organic Solvent Exposure/Ingestion
  • Paint Remover/Shellac/Varnish Ingestion
  • Sterno Ingestion
  • Windshield Washer Fluid Ingestion



  • Gastrointestinal Absorption: methanol is rapidly absorbed following ingestion
    • Toxicity: as little as 30 mL may result in significant toxicity
    • Peak Levels: occur within 1-2 hrs after ingestion (with negligible protein binding)
  • Dermal Absorption: may occur through normal skin
    • Toxicity: however, dermal exposure rarely results in toxicity
  • Respiratory Absorption: methanol is rapidly absorbed following inhalation
    • Toxicity: however, inhalational exposure rarely results in toxicity

Background on Alcohols and Their Metabolism

Ethylene Glycol (see Ethylene Glycol, [[Ethylene Glycol]])

  • Ethylene Glycol is a Primary Alcohol Which is Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase to Carboxylic Acids (Namely, Glycolic Acid, Glyoxylic Acid, and Oxalic Acid): these carboxylic acids cause most of the toxic effects


  • Methanol is a Primary Alcohol Which is Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase to Carboxylic Acids (Namely, Formic Acid): these carboxylic acids cause most of the toxic effects

Isopropanol (see Isopropanol, [[Isopropanol]])

  • Isopropanol is a Secondary Alcohol Which is Metabolized by Alcohol Dehydrogenase Only to a Ketone (Namely, Acetone), Rather than to an Aldehyde: ketones cannot be oxidized to an aldehyde and therefore, only limited acidosis can result

Methanol Metabolism

  • Methanol is (Predominantly) Hepatically Metabolized by Alcohol Dehydrogenase to Formaldehyde, Then By Aldehyde Dehydrogenase to Formic Acid
    • Approximately 10% of methanol is renally excreted unchanged
  • Kinetics
    • Absence of Treatment: methanol elimination follows zero-order kinetics
      • Rate of Elimination: 8.5 mg/dL per hr
    • Treatment with Alcohol Dehydrogenase Inhibitor (Ethanol, Fomepizole): methanol elimination changes to first-order kinetics
      • Rate of Elimination: decreases (half-life increases to 48-54 hrs)
      • Elimination via renal and pulmonary routes increases

End-Organ Toxicity

  • General Comments
    • The metabolites which cause most of the toxicity associated with methanol are distributed in body water
    • Acidemia increases the central nervous system cellular penetration by formic acid
    • Formic acid is a highly-specific neurotoxin (often leaving other organs spared)
  • Central Nervous Depression Depression
  • Cerebral Edema
  • Retinal and Basal Gangliar Damage: due to formic acid
    • Believed to be mediated via disruption of mitochondrial function


Arterial Blood Gas (ABG) (see Arterial Blood Gas, [[Arterial Blood Gas]])

  • Elevated Anion Gap Metabolic Acidosis (see Metabolic Acidosis-Elevated Anion Gap, [[Metabolic Acidosis-Elevated Anion Gap]]): anion gap is usually >20 (due to lactic acid and formic acid, therefore, may not be seen early in all cases)

Serum Osmolality (see Serum Osmolality, [[Serum Osmolality]])

  • Elevated Osmolal Gap: >10 mOsm/kg
    • Note: the serum osmolal gap estimates the molar quantity of uncharged molecules and consequently, increases only in the presence of the parent alcohol methanol
      • The toxic methanol metabolite (formic acid), exist primarily in a dissociated/charged form at physiologic pH: as these anions are accompanied by a cation (mostly sodium), they do not contribute to the serum osmolal gap since they are accounted for in the serum sodium term in the formula for the serum osmolal gap

Serum Amylase (see Hyperamylasemia, [[Hyperamylasemia]])

  • Elevated

Methanol Level

  • Elevated early) usually >6 mmol/L (20 mg/dL), measured 12-48 hrs after ingestion
  • Severe: >60 mmol/L

Formic Acid Level

  • Increased (later)

Clinical Manifestations

General Comments

  • Onset of Symptoms: variable and may be delayed
  • May mimic manifestations of ethanol intoxication

Early Stage (Due to Methanol)

Central Nervous System Manifestations

  • Altered Mental Status
  • Headache (see Headache, [[Headache]])
  • Seizures (see Seizures, [[Seizures]])
  • Vertigo (see Vertigo, [[Vertigo]])

Gastrointestinal Manifestations

Late Stage (Due to Formic Acid)

Cardiovascular Manifestations

  • Hypotension/Shock (see Hypotension, [[Hypotension]]): due to myocardial depression

Central Nervous System Manifestations

Ophthalmologic Manifestations

  • Retinal Damage: usually occurs >15-19 hrs after ingestion (potentially reversible if therapy is given early)
    • Decreased Visual Acuity
    • Spots
    • Visual Field Defects
    • Blindness (“Snow Blindness'”)
  • Mydriasis or Miosis (see Mydriasis, [[Mydriasis]] or Miosis, [[Miosis]]))
  • Papilledema

Renal Manifestations

  • Anion Gap Metabolic Acidosis (AGMA) (see Metabolic Acidosis-Elevated Anion Gap, [[Metabolic Acidosis-Elevated Anion Gap]])
    • Clinical: may occur with/without osmolal gap
  • Elevated Osmolal Gap (see Serum Osmolality, [[Serum Osmolality]])
    • Physiology: due to presence of the osmotically-active solute, methanol
      • Importantly, the serum osmolal gap estimates the molar quantity of uncharged molecules -> consequently, the osmolal gap is increased due to the presence of methanol itself
      • The toxic methanol metabolite, formic acid, exists primarily in a dissociated (charged) form at physiologic pH -> as this anion is accompanied by a cation (mostly sodium), it does not contribute to the serum osmolal gap since it is accounted for in the serum sodium term in the serum osmolal gap formula
    • Clinical: may produce a large osmolal gap (>20 mOsm/L)
      • Osmolal gap may occur with/without an anion gap metabolic acidosis
      • The absence of an osmolal gap does not exclude the presence of methanol
      • There are often discrepancies between the degree of osmolal gap and the severity of clinical manifestations


Supportive Care

Gastrointestinal Decontamination

  • Gastric Empyting: effective only if done early (due to rapid gastrointestinal absorption)
  • Activated Charcoal (see Activated Charcoal, [[Activated Charcoal]]): ineffective

Alcohol Dehydrogenase Inhibition

Ethanol (see Ethanol, [[Ethanol]])

  • Mechanism: competes with both methanol and ethylene glycol for alcohol dehydrogenase (alcohol dehydrogenase enzyme has higher affinity for ethanol and becomes saturated at an ethanol level between 13-30 mg/dL), preventing formation of toxic metabolites
  • Administration: load with 10% ethanol at 10 mL/kg IV, then infuse 10% ethanol at 1.5 mL/kg/hr IV drip -> titrate to keep ethanol level between 100-200 mg/dl
    • Concomitant Hemodialysis and Ethanol Infusion: when hemodialysis is used with ethanol infusion, increase the ethanol drip rate to account for its loss with hemodialysis -> administer 3 mL/kg/hr IV drip instead
    • Monitor: monitor ethanol and methanol levels during therapy
      • Continue until methanol level is <6 mmol/L (20 mg/dL) and symptoms have resolved
  • Adverse Effects
    • Inebriation
    • Hepatotoxicity (see xxxx, [[xxxx]])
    • Hypoglycemia (see Hypoglycemia, [[Hypoglycemia]])
  • Disadvantages: kinetics are unpredictable

Fomepizole (see Fomepizole, [[Fomepizole]])

  • May be useful (but is currently only approved for ethylene glycol intoxication)


  • Decreases renal and optho toxicity in MeOH intoxication (possibly by decreasing the relative concentration of formic acid in central nervous system in presence of systemic acidosis)
  • Alkalinization of urine also facilitates formic acid excretion

Hemodialysis (see Hemodialysis, [[Hemodialysis]])

  • Method of choice to accelerate MeOH removal (also corrects acidosis by clearing formic acid)/ improves prognosis in MeOH intoxication
  • Indications
    • MeOH level >15 mmol/L (>50 mg/dL)
    • MeOH ingestion of >30 mL
    • Significant metabolic acidosis
    • Visual symptoms
  • Continue HD until MeOH level is <25 mg/dL (due to rebound increase in levels after cessation of HD due to redistribution)
  • HD removes ETOH also: add ETOH to dialysate or increase ETOH infusion rate


  • Folate (see Folate, [[Folate]]): increases formic acid clearance
    • Folate administration increases tetrahydrofolate, which is required to metabolize formic acid

Inffective Treatments

  • Diuresis


  • Poorer prognosis in presence of seizures, severe acidosis, anuria
  • Serum MeOH levels correlate with prognosis


  • Zimmerman J. Poisonings and overdoses in the intensive care unit: general and specific management issues. Crit Care Med 2003; 31:2794-2801