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DESCRIPTION
- Methanol (methyl alcohol, wood alcohol) is present in windshield wiper fluid, Sterno, industrial solvents, and other products.
- The most common source is windshield wiper fluid, which may contain 95% methanol.
- Methanol is commonly added to ethanol for denaturation and may contaminate bootleg liquor (moonshine).
TOXIC DOSE
Ingestion of just 0.15 ml/kg of 100% methanol may cause toxicity (1.5 ml in a 10-kg child, 10 ml in a 65-kg adult).
PATHOPHYSIOLOGY
- Methanol is metabolized by the enzyme alcohol dehydrogenase to formaldehyde, which is then metabolized to formic acid.
- Retinal toxicity is caused by formic acid accumulation.
- Ethanol is a preferred substrate for alcohol dehydrogenase and will delay formation of formaldehyde and formic acid.
- Folic acid or tetrahydrofolate (Leucovorin) enhances the elimination of formic acid.
EPIDEMIOLOGY
- Poisoning is common.
- Toxic effects are typically severe, if untreated.
- Death may occur in untreated patients.
CAUSES
- Pediatric cases are usually accidental.
- Adult cases usually involve suicidal ingestion or ingestion of methanol as an alcohol substitute.
- The possibility of child abuse should be considered if the patient is under 1 year of age; suicide attempt if the patient is over 6 years of age.
- Inhalation or dermal absorption can produce toxicity under some conditions.
PREGNANCY AND LACTATION
Methanol is a proven teratogen in animals.
WORKPLACE STANDARDS
- ACGIH. TLV TWA is 200 ppm; STEL is 250 ppm.
- OSHA. PEL (ceiling limit) is 200 ppm; PEL TWA is 250 ppm, no ceiling limit.
- NIOSH. IDLH is 6000 ppm.
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DIFFERENTIAL DIAGNOSIS
- Toxic causes of increased anion gap metabolic acidosis include iron, isoniazid, lactic acidosis, ethylene glycol, salicylic acid, and toluene.
- Nontoxic causes of metabolic acidosis are uremia, diabetic ketoacidosis, and alcoholic keto-acidosis.
- Other causes of visual disturbances include ethambutol or quinine poisoning.
SIGNS AND SYMPTOMS
- After ingestion, mild inebriation may be apparent early, followed by worsening metabolic acidosis in untreated patients.
- Development of metabolic acidosis is usually delayed for 8 to 12 hours postingestion.
- Onset may be further delayed by concurrent ethanol intoxication.
Vital Signs
- Hyperpnea usually develops to compensate for metabolic acidosis.
- Hypotension may develop late in severe cases.
HEENT
- Blurred, double, or hazy vision begins several hours after ingestion.
- Constricted visual fields, dilated pupils, hyperemic optic disk and retinal edema, and transient or permanent blindness may develop.
Gastrointestinal
Nausea, vomiting, and abdominal pain may develop.
Renal
Hematuria and acute renal insufficiency have been reported.
Fluids and Electrolytes
Hypokalemia, hypomagnesemia, and elevated anion gap metabolic acidosis are common and may become severe.
Neurologic
- The earliest sign is inebriation, which pro-gresses to ataxia, seizures, and coma in severe cases.
- Parkinsonism may develop as a sequela of severe intoxication.
PROCEDURES AND LABORATORY TESTS
Essential Tests
- Serum electrolytes, BUN, creatinine, and glucose should be measured.
- Elevated anion gap acidosis supports the diagnosis.
- Hypoglycemia may occur during ethanol therapy.
- Arterial blood gases should be measured to assess metabolic acidosis.
- Serum methanol level greater than 50 mg/dl indicates need for hemodialysis; 25 to 50 mg/dl is controversial, and dialysis usually is advised.
Recommended Tests
- Serum ethanol level may be needed to assess intoxication; concurrent ethanol ingestion may delay onset of methanol toxicity for 24 hours or more.
- Serum osmolarity may be measured (by freezing point depression method), if serum methanol level is not readily available.
- An elevated osmolarity gap is consistent with methanol poisoning.
- A normal osmolarity gap cannot exclude methanol poisoning.
- ECG, serum acetaminophen, and aspirin levels may be ordered in an overdose setting to detect occult ingestion.
- Head CT, lumbar puncture, and cultures may be performed as indicated in patients with altered mental status, headache, seizure, or fever.
Not Recommended Tests
Serum osmolarity measurement is not recommended if serum methanol level is available within several hours.
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- Treatment should focus on correction of acid-base abnormality and fomepizole or ethanol administration, followed by hemodialysis in serious cases.
- The dose and time of exposure should be determined for all substances.
- Consultation with a toxicologist and nephrologist should be considered early in symptomatic patients.
DIRECTING PATIENT COURSE
The health-care provider should call the poison control center when:
- Acidosis, visual changes, or other serious effects are present.
- Toxic effects are not consistent with methanol.
- Coingestant, drug interaction, or underlying disease presents an unusual challenge.
The patient should be referred to a health-care facility when:
- Methanol ingestion may have occurred or when any toxic effects are present.
- Attempted suicide or homicide is possible.
- Patient or caregiver seems unreliable.
- Coingestant, drug interaction, or underlying disease presents an unusual challenge.
Admission Considerations
Inpatient treatment is warranted when the patient has methanol levels greater than 20 mg/dl or evidence of organ injury produced by methanol (e.g., elevated anion gap acidosis, visual or mental status changes).
DECONTAMINATION
Out of Hospital
Emesis with ipecac should be considered within 1 hour of ingestion for an alert pediatric or adult patient if health-care evaluation will be delayed.
In Hospital
- Gastric aspiration with nasogastric tube should be considered in pediatric or adult patients presenting within 1 hour of ingestion or if serious effects are present.
- Large-bore tube should be used for gastric aspiration and lavage if coingestion is possible.
- One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if coingestion is possible.
ANTIDOTES
Fomepizole (Antizol)
Fomepizole is the preferred agent for treatment.
Indications
History of possible methanol ingestion and clinical evidence of toxicity (e.g., increased anion gas metabolic acidosis, visual complaints) or increased osmolal gap, and serum methanol level greater than 20 mg/dl indicate the need for fomepizole administration.
Contraindications
Patients with a history of documented allergic reaction to fomepizole should receive a different type of therapy.
Method of Administration
- Loading dose for adult or pediatric patient is 15 mg/kg intravenously.
- Maintenance dose for all age groups is 10 mg/kg every 12 hours for four doses, then 15 mg every 12 hours thereafter until the methanol level is less than 20 mg/dl.
- Each dose is diluted in 100 ml normal saline or D5W and infused over 30 minutes.
- For further details (e.g., dosing during hemodialysis), see SECTION III, Fomepizole chapter.
Ethanol
Ethanol is administered as a 10% solution in D5W.
Indications
Ethanol infusion may be used if fomepizole is not available; indications are the same as for use of fomepizole.
Contraindications
Preexisting ethanol level greater than 125 mg/dl obviates the need for the ethanol loading dose.
Method of Administration
See SECTION III, Ethanol chapter, for details of administration.
- Loading dose is 10 cc/kg of a 10% ethanol solution infused intravenously over 1 hour.
- Maintenance dose is 1.0 to 2.0 ml/kg/h of 10% ethanol solution infused intravenously.
- Target blood ethanol level is 100-125 mg/dl.
- Oral treatment may be used when intravenous formulation is not available.
ADJUNCTIVE TREATMENT
- Folate or tetrahydrofolate (Leucovorin) has been recommended to hasten elimination of formic acid.
- Leucovorin 1 to 2 mg/kg may be administered intravenously every 4 to 6 hours until methanol becomes undetectable.
- Hemodialysis is recommended for serum methanol levels greater than 50 mg/dl (and should be considered for patients with levels in the 25 to 50 mg/dl range) or if signs of end-organ injury are apparent (elevated anion gap acidosis, visual or mental status changes).
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PATIENT MONITORING
- Hourly evaluation of acid-base status and glucose and methanol levels is performed initially to determine whether condition is deteriorating despite therapy.
- Hourly serum ethanol levels are measured to guide ethanol infusion.
EXPECTED COURSE AND PROGNOSIS
- Full recovery is expected if appropriate management is initiated before severe effects develop.
- Permanent visual deficits may develop.
- Renal failure subsequent to myoglobinuria may develop.
- Parkinsonism occurs rarely, associated with basal ganglia infarcts.
- Polyneuropathy occurs rarely.
DISCHARGE CRITERIA/INSTRUCTIONS
- From the emergency department. Asymptomatic patients may be discharged when the following conditions are met:
- Normal electrolytes, BUN, and creatinine
- Serum ethanol and methanol levels of zero
- Eight hours of observation
- Completed psychiatric evaluation, if needed
- From hospital
- An asymptomatic patient with normal or stable laboratory values may be discharged following psychiatric evaluation, if needed.
- Serum methanol and ethanol levels must be zero before discharge.
Section Outline:
ICD-9-CM 980.1Toxic effect of methyl alcohol.
See Also: SECTION II, Anion Gap Metabolic Acidosis (Unexplained) chapter; and SECTION III, Ethanol, Folic Acid/Leucovorin, and Fomepizol (4-Methylpyrazole) chapters.
RECOMMENDED READING
Jacobsen D, McMartin KE. Methanol and ethylene glycol poisonings: mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol 1986;1:309-334.
Author: Luke Yip
Reviewer: Katherine M. Hurlbut