Toxic Alcohols: Methanol & Ethylene Glycol Poisoning — SAQ

Stem

A 42-year-old man is brought to the emergency department by his wife, 14 hours after a drinking session with friends using illicit 'country liquor'. He complains of severe headache, nausea and abdominal pain, and says his vision is 'blurred, like looking through a snowstorm'. His friends, who drank the same alcohol, have similar but milder symptoms. He is a chronic alcoholic.^[1]

On examination: GCS 13, pulse 110/min, blood pressure 96/60 mmHg, respiratory rate 28/min with deep sighing breaths. Visual acuity is reduced to counting fingers in both eyes; fundoscopy shows bilateral optic disc hyperaemia with retinal oedema; pupils are dilated and react sluggishly. Abdomen is soft but generally tender.^[1]

Investigations: venous blood gas pH 7.15, PaCO2 18 mmHg, bicarbonate 6 mmol/L, base excess -22. Serum sodium 140 mmol/L, chloride 102 mmol/L, potassium 4.6 mmol/L, creatinine 130 micromol/L, glucose 5.2 mmol/L, lactate 2.4 mmol/L. Measured serum osmolality 332 mOsm/kg; calculated osmolality 296 mOsm/kg. Serum ethanol is undetectable.^[1]

Questions

a) What is the diagnosis, and calculate BOTH the anion gap and the osmolal gap. Interpret them. (2 marks)

Diagnosis: methanol poisoning (formic acid toxicity), part of a mass exposure from contaminated illicit alcohol.^[1]

• Anion gap = Na - (Cl + HCO3) = 140 - (102 + 6) = 32 mmol/L — markedly elevated (normal 8-12), confirming a high anion-gap metabolic acidosis.^[5]
• Osmolal gap = Measured - Calculated = 332 - 296 = 36 mOsm/kg — markedly elevated. The osmolal-gap reference value lacks consensus; 20 mOsm/kg or more should prompt suspicion of a toxic alcohol.^[4]
• Interpretation: the dual-gap signature (high anion gap + elevated osmolal gap) plus visual symptoms and optic disc changes localises the parent alcohol to methanol.^[1]

b) Explain the mechanism by which methanol causes BOTH the metabolic acidosis AND the visual loss. (3 marks)

Methanol itself has relatively low toxicity; it is oxidised by hepatic alcohol dehydrogenase (ADH) to formaldehyde, then by formaldehyde dehydrogenase to formic acid (formate), the toxin. Formic acid accumulates and there is a direct correlation between the formic acid concentration and increased morbidity and mortality; the acidosis is caused directly or indirectly by formic acid production. Formate inhibits cytochrome oxidase and is the prime cause of ocular toxicity; acidosis increases toxicity further by enabling greater diffusion of formic acid into cells. Visual function becomes impaired after a latent period of approximately 12-24 hours, ranging from blurred vision and altered visual fields to complete blindness.^[1]

c) Outline the stepwise definitive management, with drug doses. (3 marks)

1. Resuscitation: ABCDE, IV access, isotonic crystalloid, oxygen; continuous monitoring.
2. BLOCK alcohol dehydrogenase immediately — do NOT wait for the methanol concentration. Fomepizole 15 mg/kg loading (intravenously or orally), then 10 mg/kg every 12 hours until alcohol concentrations are under 30 mg/dL. If dialysis is used, give 1 mg/kg/h continuous infusion to compensate for enhanced elimination. Fomepizole is first-line; ethanol is the traditional alternative when fomepizole is unavailable.^[2]
3. Sodium bicarbonate IV for ophthalmologic abnormalities or significant acidosis.^[1]
4. Cofactor: intravenous FOLINIC ACID (leucovorin) to enhance formate metabolism (formic acid is converted by 10-formyl tetrahydrofolate synthetase to carbon dioxide and water). Continue folic/folinic acid during extracorporeal treatment.^[1][3]
5. Haemodialysis — this patient has new vision deficits and a blood pH of 7.15, both EXTRIP extracorporeal indications. Intermittent haemodialysis is the modality of choice. Continue antidotes during extracorporeal treatment; stop when methanol is under 200 mg/L with clinical improvement.^[3]

d) State THREE indications for haemodialysis in toxic alcohol poisoning and ONE treatment that should be AVOIDED, with the reason. (2 marks)

Indications (any three, EXTRIP methanol): coma; seizures; new vision deficits; blood pH of 7.15 or lower; persistent metabolic acidosis despite support and antidotes; anion gap over 24 mmol/L; methanol concentration over 700 mg/L on fomepizole (over 600 mg/L on ethanol; over 500 mg/L with no ADH blocker); impaired kidney function.^[3]

AVOID waiting for a methanol concentration before starting fomepizole — start as soon as possible on history and anion-gap metabolic acidosis while awaiting the alcohol concentration. Every hour of delay converts more parent alcohol into formate.^[2]

References5ShowHide

1. [1]Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning J Toxicol Clin Toxicol, 2002.PMID 12216995
2. [2]Mégarbane B Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole Open Access Emerg Med, 2010.PMID 27147840
3. [3]Roberts DM, Yates C, Megarbane B, et al Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement Crit Care Med, 2015.PMID 25493973
4. [4]Skaaland H, Larstorp ACK, Lindberg M, Jacobsen D Reference values for osmolal gap in healthy subjects and in medical inpatients Scand J Clin Lab Invest, 2020.PMID 31809199
5. [5]Seifter JL Anion-gap metabolic acidemia: case-based analyses Eur J Clin Nutr, 2020.PMID 32873962