2. Introduction
• Methanol (wood alcohol)
– a common ingredient in many solvents,
windshield-washing solutions, duplicating fluids,
and paint removers
– sometimes is used as an ethanol substitute by
alcoholics
– its metabolic products may cause
• metabolic acidosis, blindness, and death after a
characteristic latent period of 30 hours
3. Mechanism of toxicity
• slowly metabolized by alcohol dehydrogenase
to formaldehyde
• subsequently by aldehyde dehydrogenase to
formic acid (formate)
– systemic acidosis is caused by both formate and
lactate
– blindness is caused primarily by formate
4. Pharmacokinetics
• readily absorbed and quickly distributed to the
body water
• metabolized slowly by alcohol
• "half-life" ranges from 1 to 24 hours
• Only about 3% is excreted unchanged by the
kidneys, and less than 10-20% through the breath
• Formate: half-life ranges from 3-20 hours; during
dialysis the half-life decreases to 1-2.6 hours
5. Toxic dose
• The fatal oral dose of methanol is 30-240 mL
(20-150 g)
• The minimum toxic dose is approximately 100
mg/kg
6. Clinical presentation
• In the first few hours after ingestion
– inebriation and gastritis
– acidosis is not usually present (metabolism to
toxic products has not yet occurred)
7. • After a latent period of up to 30 hours
– severe anion gap metabolic acidosis
– visual disturbances ( may occur within 6 hours ),
blindness, seizures, coma, acute renal failure with
myoglobinuria, and death
– fundoscopic examination - optic disc hyperemia,
venous engorgement, peripapilledema, and retinal
or optic disc edema
– The latent period is longer when ethanol has been
ingested concurrently with methanol
8. Diagnosis
• usually is based on the history, symptoms
• stat methanol levels are rarely available
• Calculation of the osmolar and anion gaps
(see Serum osmolality and osmolar gap)
– A large anion gap not accounted for by elevated
lactate suggests possible methanol (or ethylene
glycol) poisoning, because the anion gap in these
cases is mostly nonlactate
9. • Specific levels
– 1. Serum methanol level
• higher than 20 mg/dL – toxic
• higher than 40 mg/dL - very serious
• After the latent period, a low or nondetectable
methanol level does not rule out serious intoxication in
a symptomatic patient because all the methanol may
already have been metabolized to formate
10. – 2. Elevated serum formate concentrations
• may confirm the diagnosis and are a better measure of
toxicity
• but formate levels are not widely available
11. – 3. Other useful laboratory studies
• include electrolytes (and anion gap), glucose, BUN,
creatinine, serum osmolality and osmolar gap, arterial
blood gases, ethanol level, and lactate level
12. Treatment
• Emergency and supportive measures
– 1. Maintain an open airway and assist ventilation
if necessary
– 2. Treat coma if they occur
– 3. Treat metabolic acidosis with intravenous
sodium bicarbonate
• Correction of acidosis should be guided by arterial
blood gases
13. Specific drugs and antidotes
• 1. Administer fomepizole or ethanol ( to saturate
the enzyme alcohol dehydrogenase and prevent
the formation of methanol's toxic metabolites )
• Indications
– a. A history of significant methanol ingestion when
methanol serum levels are not immediately available
– b. Metabolic acidosis (arterial pH < 7.3, serum
bicarbonate < 20 mEq/L) and an osmolar gap greater
than 10 mOsm/L not accounted for by ethanol
– c. methanol blood concentration greater than 20
mg/dL.
18. • C. Decontamination
– Aspirate gastric contents if this can be performed
within 30-60 minutes of ingestion
– Activated charcoal is not likely to be useful
because the effective dose is very large and
methanol is absorbed rapidly from the GI tract
19. • D. Enhanced elimination
– Hemodialysis rapidly removes both methanol
(half-life reduced to 3-6 hours) and formate
– Indications
• a. Suspected methanol poisoning with significant
metabolic acidosis
• b. Visual abnormalities
• c. Renal failure
• d. An osmolar gap greater than 10 mOsm/L or a
measured serum methanol concentration greater than
50 mg/dL
20. • E. Endpoint of treatment
– Dialysis, fomepizole, or ethanol should be
continued until the methanol concentration is less
than 20 mg/dL
– and the osmolar and anion gaps are normalized