• Ingestion of 30-60 mL is potentially lethal to an adult. The onset of anion gap metabolic acidosis and visual impairment are delayed and death can occur within hours to days, usually due to respiratory failure or cardiovascular collapse. Survivors of severe poisoning may suffer permanent blindness and/or neurologic impairment.

General

• Initial symptoms (onset about 2 hours) may resemble ethanol intoxication.
• Latent period of 4-12 hours prior to onset of metabolic acidosis and associated symptoms. Massive exposure results in early onset of acidosis;
• Co-ingestion of ethanol will delay onset of toxicity.
• Contact the BC Drug and Poison Information Centre 604-682-5050, 1-800-567-8911 early.

HEENT (Head, Eyes, Ears, Nose, Throat)

• Ocular effects begin 8-36 hours after exposure.
• Early symptoms include blurred vision, decreased visual acuity, sensation of “being in a snowstorm”.
• Findings range from normal to decreased pupillary light reactions, hyperemia or pallor of optic disc, retinal edema.
• Bilateral blindness may develop.
• Retinal and optic nerve damage can be permanent; partially or fully reversible in some cases.

CVS

• Cardiovascular effects may be seen in severely poisoned, moribund patients.
• Sinus bradycardia indicates a poor prognosis.

Respiratory

• Tachypnea or Kussmaul respirations secondary to metabolic acidosis are common.
• Respiratory arrest may occur.

Neurologic

• Early symptoms may resemble ethanol intoxication; may be of short duration.
• Progressively worsening headache, vertigo, weakness, apprehension, confusion develop within hours, and can progress to, seizures and coma.
• Late symptoms (> 12-24 hours) include cerebral edema, cerebral hemorrhage and/or necrosis; basal ganglia infarcts.
• Necrosis of the putamen is characteristic of severe methanol poisoning.

Gastrointestinal

• Nausea, vomiting, abdominal pain (may be severe).

Genitourinary

• Renal failure is uncommon; may be secondary to rhabdomyolysis.

Metabolic

• Progressive metabolic acidosis with elevated anion gap is characteristic. Onset usually within 12 hours; may be delayed with ethanol co-ingestion. May be rapid following massive exposure.

Musculoskeletal

• Rhabdomyolysis may occur.

Other

• Elevation of serum amylase with or without pancreatitis has been reported.

Late Sequelae

• Partial or complete visual impairment, Parkinsonian-like symptoms, pseudobulbar palsy, cognitive defects

• 30-60 mL is potentially lethal to an adult;
• 2.5-5 mL could produce serious toxicity in a young child.

• Laboratory testing must be used to make the diagnosis because clinical symptoms are delayed and it is better to provide treatment before symptoms develop.
• However, only three hospitals, the Royal Columbian Hospital, the Royal Jubilee Hospital and Vancouver General Hospital can perform definitive testing using gas chromatography and the approval of the clinical chemist on call must be obtained.
• Therefore, surrogate testing must be used. The osmolar gap, the anion gap and the serum bicarbonate from an arterial blood gas are commonly used surrogate tests.
• In hospitals where surrogate testing is not available, the patient will need to be transferred to complete this testing. Contact the Poison Control Centre.

Calculate Anion and Osmolar Gaps 

Anion Gap (AG):

Elevated AG indicates accumulation of toxic acid metabolite. AG may remain normal for several hours after exposure, or with ethanol co-ingestion.

AG = Na+ – (Cl- + HCO3-)

Reference range ~6-12

Osmole Gap (OG):

OG gives an imprecise estimate of serum methanol concentration, has poor sensitivity for detecting low methanol levels and may be within normal limits in late presentation cases. Serum osmolality (Om), sodium, urea, glucose and ethanol must be measured simultaneously.

OG = Om–([2 x Na+]+ urea+ glucose+ ethanol); all values in mmol/L

Reference range -10 to +10

Onset of anion gap metabolic acidosis and visual impairment are delayed.

Qualitative (colorimetric) methanol assay is prone to false positive results.

Recommended treatment includes:

• supportive care,
• aggressive treatment of acidosis,
• the use of the antidotes fomepizole and folate and
• hemodialysis.

a)  Gastrointestinal decontamination

• Charcoal, laxatives and enemas are not effective and have no role in pure methanol overdoses.
• If co-ingestants are possible, consider if a large quantity of toxin consumed and < 1 hour post ingestion.

b)  Treat metabolic acidosis aggressively.

• Prompt correction of acidosis reduces tissue penetration of formate and improves outcome. Monitor serum sodium and potassium closely. Maintain fluid and electrolyte balance.
• Administer IV sodium bicarbonate for arterial pH < 7.25-7.

c)  Antidote therapy: Begin fomepizole (preferred) or ethanol therapy if:

• Serum methanol level ³ 6 mmol/L, OR
• Osmole gap > 10 (corrected for ethanol) with history of methanol exposure, OR
• History or strong clinical suspicion of methanol poisoning with at least two of the following criteria:
  • Serum bicarbonate < 20 mmol/L
  • AG > 16
  • arterial pH < 7.3
  • Osmole gap > 10

d)  Monitor vital signs and electrolytes. Monitor blood gases in symptomatic patients.

e)  Fomepizole Administration:

• Administration WITHOUT dialysis: Initial loading dose 15 mg/kg to a maximum of 1500 mg (one vial), subsequent doses 10 mg/kg every 12 hours, dosage adjustment may be required after 48 hours of treatment because fomepizole induces its own metabolism.
• Administration WITH dialysis: Initial loading dose 15 mg/kg to a maximum of 1500 mg (one vial), the second dose 10 mg/kg should be given 4 hours after the start of dialysis, the third dose should be given at the end of dialysis.
• Treatment Endpoint: Continue treatment until metabolic acidosis has resolve and methanol level is < 6mmol/L.f.

f)  Folate therapy:

• Administer either folic acid or leucovorin to enhance detoxification of formic acid. Indicated for all high risk patients.
• 50 mg of folate should be given every 4 hours.

g)  Hemodialysis

Indications for hemodialysis include:

• Arterial pH < 7.25 that fails to rapidly normalize with treatment, OR
• Visual defects, OR
• Other serious clinical effects (e.g. coma, seizures, severe electrolyte imbalance, renal impairment), OR

Clinical condition deteriorates during antidote treatment, OR

• Initial measured or estimated methanol serum level > 15 mmol/L. Methanol is eliminated slowly during antidote therapy (serum level of 15 mmol/L would require ~ 3 days of treatment with antidote alone to reach sub-toxic levels).
• Continuous renal replacement therapy such as CVVHD clears the toxins more slowly than conventional hemodialysis (limited data). Conventional hemodialysis is preferred for rapid detoxification, if the patient can tolerate the procedure.

Any patient who may have ingested methanol who has:

• any symptoms
• acidosis
• an elevated anion gap or
• an elevated osmolar gap

• If patient requires ICU care or dialysis not available locally

• BC Drug and Poison Information Centre 604-682-5050, 1-800-567-8911

• Patients may be discharged after observation periods have been met and the patient’s psychiatric condition has been treated if the overdose was intentional.

1. EM Cases podcast Feb 2018 “Toxic alcohols – minding the gaps.”

   
   

1. Poison Management Manual (PMM), BC Drug and Poison Information Centre, 2015
2. Kruse JA. Methanol poisoning. Intensive Care Medicine. 1992;18(7): 391-7.
3. Hovda, K.E., et al., Methanol outbreak in Norway 2002-2005: epidemiology, clinical features and prognostic signs. Journal of Internal Medicine, 2005. 258: p. 181-190.
4. Megarbane B, Borron SW, Baud F. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Medicine. 2005;31:189-195
5. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. Journal of Toxicology – Clinical Toxicology. 2002;40(4):415-446.