Methanol Poisoning

[Section Outline]

Description
Etiology

Author:

Kirk L.Cumpston

Description

Colorless, volatile liquid
Absorbed in 30-60 min
Metabolized by liver
Half-life 4-8 hr
Pathophysiology:
- Metabolites formaldehyde and formic acid produce toxic effects
- Inhibits cytochrome oxidase
Formic acid:
- Determines degree of acidosis, visual symptoms, and mortality
- Directly toxic to retinal and optic nerve tissue
Methanol metabolism:
- Step 1: Methanol is converted to formaldehyde by liver enzyme alcohol dehydrogenase
- Step 2: Formaldehyde is then rapidly converted by aldehyde dehydrogenase to formic acid
- Step 3: Formic acid is degraded to carbon dioxide and water by folate-dependent mechanism
- Steps 1 and 3 are rate-limiting steps

Etiology

Common sources of methanol:

Wood alcohol
Windshield washer fluid (>60% cases)
Inhalational abuse of carburetor cleaners
Fuel antifreeze solutions
Formalin
Gasoline
Paint solvents
Household cleaners
Sterno cans
Moonshine
Model airplane fuel
Photocopying fluid
Perfumes

[Section Outline]

Signs and Symptoms
Essential Workup
Diagnostic Tests & Interpretation
Differential Diagnosis

Signs and Symptoms

GI:
- Anorexia
- Nausea/vomiting
- Abdominal pain
CNS:
- Headache
- Dizziness
- Confusion
- Inebriation
- Coma
- Ophthalmologic:
  - Blurry/hazy vision
  - Photophobia
  - “Snowfield vision”
  - Blindness
  - Central scotoma

History

Intentional or unintentional methanol ingestion
No history, but a patient with an unexplained high anion gap metabolic acidosis
Elevated unexplained osmol gap

Physical Exam

Optic disc:
- Hyperemia or pallor
- Papilledema
Afferent pupillary defect
Tachypnea
Altered mental status

Essential Workup

History of all substances ingested
Inquire about visual symptoms
Funduscopic exam
Drawn simultaneously:
- Arterial blood gas
- Serum methanol, ethylene glycol, isopropyl alcohol, and ethanol levels
- Electrolytes, BUN, creatinine, and glucose
- Measured serum osmolality (by freezing-point depression is preferred)

Diagnostic Tests & Interpretation

Lab

Calculate anion gap = (Na⁺) - (Cl⁻ + HCO₃⁻):
- Normal = 8-12
Determine serum osmol gap:
- Osmol gap = measured osmolality - calculated osmolarity
- Calculated osmolarity = 2(Na⁺) + glucose/18 + BUN/2.8 + ethanol (in mg/dL)/4.6
Osmol gap:
- Screens for methanol (methanol is osmotically active, toxic metabolites are not)
- Most sensitive early in poisoning and normalizes as methanol is metabolized or with concurrent ethanol ingestion
- Traditionally an osmol gap >10 is considered indication for ruling out occult methanol ingestion. However, potentially toxic serum concentrations of methanol can be present with osmol gap <10
- A negative osmol gap DOES NOT rule out a methanol exposure
- Ethanol has higher affinity for alcohol dehydrogenase than methanol. With concurrent ethanol ingestion, osmol gap tends to be larger and acidosis tends to be less severe because relatively less methanol has been converted to acid-producing metabolites
Serum methanol concentrations confirm methanol poisoning:
- Late after ingestion, no parent compound (methanol) may be detected and severe high anion gap metabolic acidosis will be present
Ethanol concentration may have clinical implications and is pertinent in interpreting lab tests

Imaging

CT brain

Differential Diagnosis

Increased osmol gap
ME DIE A:
- Methanol
- Ethanol
- Diuretics/diluents (mannitol, glycerin, sorbitol, propylene glycol)
- Isopropyl alcohol
- Ethylene glycol
- Acetone, ammonia
Elevated anion gap metabolic acidosis: A CAT MUDPILES:
- Alcoholic ketoacidosis
- Cyanide, CO, H₂S, others
- Acetaminophen
- Antiretrovirals (NRTI)
- Toluene
- Methanol, metformin
- Uremia
- Diabetic ketoacidosis
- Paraldehyde, phenformin, propylene glycol
- Iron, INH
- Lactic acidosis
- Ethylene glycol
- Salicylate, acetylsalicylic acid (ASA; aspirin), starvation ketosis

[Section Outline]

Prehospital
Initial Stabilization/Therapy
ED Treatment/Procedures
Medication

Prehospital

Transport all possibly ingested substances
Dermal decontamination of a methanol spill by clothing removal, irrigation with soap and water
Monitor airway and CNS depression

Initial Stabilization/Therapy

Airway, breathing, and circulation (ABCs)
Dextrose, naloxone, and thiamine for altered mental status
Prevent further methanol absorption:
- Gastric lavage with nasogastric tube:
  - Likely not helpful because of rapid absorption of methanol and delay in presentation >1 hr
- Activated charcoal:
  - For potential coingestants
  - Poorly adsorbs methanol
  - Aspiration risk for patients with altered mental status

ED Treatment/Procedures

Prevent methanol conversion to toxic metabolites with fomepizole (preferable) or ethanol infusion
Fomepizole (4-MP, Antizol):
- Competitive inhibitor of alcohol dehydrogenase
- Indications:
  - Intentional methanol ingestion OR
  - Accidental methanol ingestion of more than a sip OR
  - Altered mental status or visual symptoms associated with unexplained osmol gap >10 mmol/L and /or elevated anion gap metabolic acidosis, bicarbonate<20 mmol/L, serum pH <7.3
- Initiate before serum methanol level returns if intentional ingestion or more than a sip OR if serum methanol concentration is >20 mg/dL
- Continue until methanol level is <20 mg/dL
- Advantages:
  - No need for continuous infusion
  - No inebriation/CNS depression
  - Ease of dosing
  - No hypoglycemia, no hyponatremia, no hyperosmolality
  - No checking serum concentrations
  - Reduced nursing care and monitoring
  - Occult methanol exposure can often be ruled out before 2nd dose is needed
- Disadvantages:
  - Blurry vision
  - Transient elevation of liver function tests
Ethanol therapy:
- Not FDA approved for treatment of methanol
- Ethanol has greater affinity than methanol for alcohol dehydrogenase:
  - Slows metabolism to formaldehyde and formic acid by competitive inhibition
- Ethanol is the 2nd-choice antidote if fomepizole is not available
- Initiate before methanol level returns if potentially toxic ingestion is highly suspected or confirmed by history:
  - Therapeutic range is 100 mg/dL
- Continue until methanol level is <20 mg/dL
- Indications for ethanol therapy:
  - Intentional methanol ingestion
  - Accidental methanol ingestion of more than a sip OR
  - Altered mental status or visual symptoms associated with unexplained osmol gap > 10 mmol/L and or elevated anion gap metabolic acidosis, bicarbonate <20 mmol/L and serum pH <7.3 OR
  - Serum methanol concentration >20 mg/dL
- Advantages:
  - Easily accessible
  - Oral and IV routes
- Disadvantages:
  - CNS depression especially in children
  - Respiratory depression
  - Hyponatremia or hypernatremia
  - Hypoglycemia
  - Hyperosmolarity
  - Continuous infusion
  - Frequent lab testing
  - Contraindicated in pregnancy
  - Pancreatitis
  - Gastritis
Folic acid and folinic acid (leucovorin):
- Folic acid: Cofactor required for conversion of formic acid to carbon dioxide and water
- Supplemental folate important in malnourished individuals (alcoholics)
Correct acid-base abnormalities:
- Sodium bicarbonate for severe acidosis (pH <7.3)
- The goal of the sodium bicarbonate drip is to maintain a normal serum pH
Hemodialysis:
- Decreases elimination half-life of methanol
- Removes formaldehyde and formic acid
- Indications:
  - Ingestion of >1 mL/kg of 100% methanol OR
  - Ophthalmologic manifestations OR
  - Severe metabolic acidosis, bicarbonate <20 mmol/L and serum pH <7.3 OR
  - Serum methanol level >50 mg/dL alone without above criteria
- Continue hemodialysis until methanol level approaches <20 mg/dL and the metabolic acidosis has resolved

Medication

Activated charcoal: 1 g/kg PO
Dextrose: D₅₀W 1 amp: 50 mL or 25 g (peds: D₂₅W 2-4 mL/kg) IV
Fomepizole:
- Loading dose: 15 mg/kg slow infusion over 30 min
- Maintenance dose: 10 mg/kg q12h for 4 doses, then 15 mg/kg q12h until methanol levels reduced <20 mg/dL
- Dosing related to hemodialysis:
  - Do not administer dose at beginning of dialysis if last dose was <6 hr previously
  - Administer next dose if last dose was >6 hr previously
  - Dose q4h during dialysis
  - If time between last dose and end of dialysis was <1 hr from last dose, do not administer new dose
  - If time between last dose and end of dialysis was 1-3 hr from last dose, administer 1/2 of next scheduled dose
  - If time between last dose and end of dialysis was >3 hr from last dose, administer next scheduled dose
Ethanol:
- Oral: 50% ethanol solution (100-proof liquor) via nasogastric tube:
  - Loading dose 2 mL/kg
  - Maintenance dose 0.5 mL/kg/hr
  - Maintenance dose during hemodialysis 1 mL/kg/hr
- IV: 10% ethanol in D₅W:
  - Loading dose 8 mL/kg over 30-60 min
  - Maintenance infusion 2 mL/kg/hr
  - Maintenance infusion during hemodialysis 4 mL/kg/hr
Folic acid: 50 mg (or 1-2 mg/kg) IV q4h for 24 hr
Sodium bicarbonate: 1-2 mEq/kg in 1 L of D₅W with 40 mEq KCl at 250 mL/hr

[Section Outline]

Disposition
Follow-up Recommendations

Disposition

Admission Criteria

Significant historical methanol ingestion even if initially asymptomatic
ICU admission for patients with unstable vital signs or mental status, or needs hemodialysis
Transfer to another facility if hemodialysis or antidote is indicated but not readily available

Discharge Criteria

Asymptomatic patient with isolated methanol ingestion if serum methanol level is <20 mg/dL; normal acid/base status and electrolytes

Follow-up Recommendations

Psychiatric follow-up for suicidal/depressed patients

An osmol gap <10 mmol/L does not rule out a methanol exposure.
If you have a patient with an elevated anion gap and methanol exposure is in the differential diagnosis, administer fomepizole immediately, initiate hemodialysis and confirm exposure with a serum concentration.
If you cannot confirm a methanol exposure, or do not have hemodialysis capabilities 24/7, or have no antidote, transfer the patient to a facility that has all of these capabilities.
Not all patients will have an elevated osmol and anion gap. Early presenters will have an osmol gap only, because methanol is osmotically active, and there are no toxic metabolites yet. Late presenters may have an anion gap only, because the osmotically active parent compound has metabolized to the toxic acidotic metabolites. Patients who present in between will have a combination of an anion gap and an osmol gap.

DesaiT, SudhalkarA, VyasU, et al. Methanol poisoning predictors of visual outcomes . JAMA Ophthalmol. 2013;131(3):358-364.
KrautJA, MullinsME. Toxic Alcohols . N Engl J Med. 2018;378(3):270-280.
RobertsDM, YateC, MegabarneB, et al. Recommendations for the extracorporeal treatments in the management of acute methanol poisoning: A systematic review and consensus statement . Crit Care Med. 2015;43(2):461-472.

ICD9

980.1 Toxic effect of methyl alcohol

ICD10

T51.1X1A Toxic effect of methanol, accidental (unintentional), initial encounter
T51.1X2A Toxic effect of methanol, intentional self-harm, initial encounter
T51.1X4A Toxic effect of methanol, undetermined, initial encounter

SNOMED

216640006 Accidental poisoning by methyl alcohol
212809004 Methyl alcohol causing toxic effect (disorder)

section name header

Basics ⬇

Diagnosis ⬆ ⬇

History

Physical Exam

Lab

Imaging

Treatment ⬆ ⬇

Follow-Up ⬆ ⬇

Admission Criteria

Discharge Criteria

Pearls and Pitfalls ⬆ ⬇

Additional Reading ⬆ ⬇

Codes ⬆