ICU · toxicology

Acute Methanol and Ethylene Glycol Poisoning — Comprehensive ICU Management

Also known as Methanol poisoning · Ethylene glycol poisoning · Toxic alcohols · Fomepizole · 4-methylpyrazole · Formic acid toxicity · Calcium oxalate crystals · Osmolar gap · Anion gap acidosis · Wood alcohol · Antifreeze poisoning

Toxic alcohol poisoning = methanol and ethylene glycol (the 'toxic alcohols') — both are metabolised by ALCOHOL DEHYDROGENASE (ADH) to highly toxic organic acids → SEVERE HIGH ANION GAP METABOLIC ACIDOSIS + end-organ injury. Methanol (CH3OH) → formaldehyde → FORMIC ACID → inhibits mitochondrial cytochrome c oxidase → RETINAL/optic nerve toxicity → BLINDNESS + basal ganglia injury. Ethylene glycol (HOCH2CH2OH) → glycoaldehyde → GLYCOLIC ACID (main acidosis driver) → glyoxylic acid → OXALIC ACID → precipitates with calcium → CALCIUM OXALATE CRYSTALS in renal tubules → ACUTE KIDNEY INJURY + hypocalcaemia. Both cause CNS depression, nausea, abdominal pain. DIAGNOSTIC CLUE: HIGH anion gap metabolic acidosis + HIGH osmolar gap EARLY (parent alcohol present — small osmotically active molecules). The osmolar gap FALLS as the anion gap RISES (parent alcohol is metabolised into organic acids) — so a LATE presenter may have a NORMAL osmolar gap. Latent period 12–24 h (metabolism required) — patient looks 'drunk' then deteriorates. Management PILLARS: (1) FOMEPIZOLE 15 mg/kg IV LOAD (blocks ADH → stops toxic metabolite formation — PREFERRED over ethanol — far safer, no CNS depression/hypoglycaemia) then 10 mg/kg q12h; (2) HAEMODIALYSIS (removes parent alcohol + metabolites — indicated for severe acidosis pH <7.3, AKI, visual symptoms, high levels >50 mg/dL, deterioration); (3) COFACTORS — FOLINIC ACID (methanol — folate-dependent oxidation of formate → CO2 + H2O) + THIAMINE + PYRIDOXINE (ethylene glycol — shunt glyoxylate to non-toxic glycine, AWAY from oxalate); (4) sodium bicarbonate for acidosis (also ion-traps formate/glycolate → enhances elimination). Ethanol is the ALTERNATIVE ADH inhibitor if fomepizole unavailable (target 100–150 mg/dL). Activated charcoal is USELESS (alcohols are small, rapidly absorbed, poorly bound). Outbreaks from illicit/counterfeit alcohol common. Mortality methanol 10–40% (up to 50% in outbreaks); ethylene glycol ~1–2% with early fomepizole + dialysis.

high6 referencesUpdated 2 July 2026

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HIGH anion gap metabolic acidosis + HIGH osmolar gap = TOXIC ALCOHOL until proven otherwise — start fomepizole immediately; do NOT wait for methanol/ethylene glycol levels (often unavailable for hours)Visual symptoms (blurred vision, 'snowstorm' vision, photophobia, optic disc hyperaemia) = METHANOL → start fomepizole + folinic acid + arrange haemodialysis NOW — delay = permanent BLINDNESSA NORMAL osmolar gap does NOT exclude toxic alcohol — the parent alcohol is metabolised over 12–24 h, so a LATE presenter has a HIGH anion gap with a NORMAL osmolar gap (parent alcohol gone, organic acids remain)Ethylene glycol + hypocalcaemia + AKI + calcium oxalate crystalluria — give thiamine + pyridoxine (shunt glyoxylate to glycine, away from oxalate) + correct calcium cautiously + fomepizole + haemodialysisDo NOT give activated charcoal for toxic alcohol ingestion — alcohols are small molecules that bind charcoal poorly and are absorbed within 30–60 min; it is useless and delays antidote

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Red flags

toxic-alcohols-comprehensive-icu clinical overview for ICU fellowship exams — FigureExam overview — key physiology, red flags and first-hour management.

Management algorithm for toxic-alcohols-comprehensive-icu — FigureStepwise ICU management: immediate priorities, disease-specific therapy, escalation.

Classification framework for toxic-alcohols-comprehensive-icu — FigureClassification / severity framework used in written and viva answers.

Overview

The one-paragraph exam answer

Toxic alcohol poisoning (methanol and ethylene glycol) = both are oxidised by alcohol dehydrogenase (ADH) to highly toxic organic acids → severe high anion gap metabolic acidosis + end-organ damage. Methanol → formaldehyde → formic acid → inhibits cytochrome c oxidase → retina/optic nerve injury → BLINDNESS + basal ganglia necrosis. Ethylene glycol → glycoaldehyde → glycolic acid (main acidosis driver) → glyoxylic acid → oxalic acid → precipitates with Ca2+ → calcium oxalate crystals in renal tubules → AKI + hypocalcaemia. Diagnostic clue: HIGH anion gap + HIGH osmolar gap (early — parent alcohol is an osmotically active small molecule). Latent period 12–24 h (looks 'drunk', then crashes). Management PILLARS: (1) FOMEPIZOLE 15 mg/kg IV load (blocks ADH — PREFERRED over ethanol, then 10 mg/kg q12h); (2) HAEMODIALYSIS (severe acidosis pH <7.3, AKI, visual symptoms, level >50 mg/dL, deterioration); (3) COFACTORS — folinic acid (methanol) + thiamine + pyridoxine (ethylene glycol); (4) sodium bicarbonate (corrects pH AND ion-traps formate/glycolate → enhances elimination). Ethanol is the alternative ADH inhibitor if fomepizole unavailable (target 100–150 mg/dL). Activated charcoal is USELESS. Treat EMPIRICALLY — never wait for methanol/ethylene glycol levels.[1][5]

Pathophysiology — the two metabolic pathways

The entire toxicity of methanol and ethylene glycol comes from their METABOLITES, not the parent alcohol. The parent compounds are themselves only mildly intoxicating (less potent than ethanol). The lethal injury is generated when alcohol dehydrogenase (ADH) and then aldehyde dehydrogenase (ALDH) oxidise them stepwise into organic acids. This is the single most important concept: block ADH and you stop the poisoning.

[4]

Methanol pathway (methyl alcohol, CH3OH — 'wood alcohol', found in windscreen washer fluid, antifreeze, paint thinner, illicit spirits, industrial solvents):

[1]

Methanol ──alcohol dehydrogenase──▶ Formaldehyde ──aldehyde dehydrogenase──▶ Formic acid (formate)
   (parent)                              (transient)                          (THE TOXIN)

Formic acid is the lethal metabolite. It (i) inhibits mitochondrial cytochrome c oxidase (complex IV) → cellular hypoxia (mimics cyanide at the mitochondrial level), and (ii) is a strong organic acid → high anion gap metabolic acidosis. Formate has particular affinity for the retina and optic nerve (retinal ganglion cells, optic disc) → optic disc oedema/hyperaemia → permanent blindness. It also injures the basal ganglia (putaminal necrosis → parkinsonism in survivors). Humans clear formate slowly because they are relatively folate-deficient compared with other primates — this is why folinic acid is a specific cofactor/antidote for methanol (it drives formate → CO2 + H2O via 10-formyl-tetrahydrofolate dehydrogenase).[1]

Ethylene glycol pathway (1,2-ethanediol, HOCH2CH2OH — the main component of automotive antifreeze/coolant, also hydraulic fluids):

[4]

Ethylene glycol ──ADH──▶ Glycoaldehyde ──ALDH──▶ Glycolic acid ──▶ Glyoxylic acid ──▶ Oxalic acid
   (parent)                                          (acidosis)        (shunt point)      (renal toxin)

Glycolic acid is the dominant contributor to the metabolic acidosis (a strong organic acid). Oxalic acid is the renal toxin: it irreversibly chelates calcium to form calcium oxalate crystals, which precipitate in and obstruct the renal tubules → acute tubular necrosis → AKI (often oliguric/anuric). The calcium consumption also produces hypocalcaemia (prolonged QT, tetany). Glyoxylic acid sits at a metabolic branch point: with thiamine and pyridoxine it is diverted to the non-toxic amino acid glycine (and α-hydroxy-β-ketoadipate) — away from oxalate. This is why thiamine + pyridoxine are specific cofactors for ethylene glycol.[1][4]

The shared therapeutic target — ADH — is also the key to fomepizole and ethanol: both inhibit ADH competitively and shut down the production of every downstream toxin.

[2]

Methanol vs ethylene glycol — the two patterns

[3]

Diagnosis — high anion gap + high osmolar gap

The diagnosis is made on blood gas + biochemistry, not on the (often delayed) specific serum methanol/ethylene glycol level. The cardinal combination is a high anion gap metabolic acidosis with a high osmolar gap.[1]

Step 1 — Calculate the anion gap (AG): AG = Na+ − (Cl− + HCO3−). Normal 8–12 mmol/L. In toxic alcohol poisoning the AG is markedly elevated (often >30) from accumulation of formate (methanol) or glycolate/oxalate (ethylene glycol).

[3]

Step 2 — Calculate the osmolar gap (OG): OG = measured osmolality − calculated osmolality, where calculated osmolality = 2 × Na+ + glucose + urea (+ 1.25 × ethanol if the patient has also drunk ethanol, + any other measured osmoles). Normal <10 mOsm/kg; a gap >20 mOsm/kg is strongly suggestive of an unmeasured osmotically active solute — the parent toxic alcohol. Methanol (MW 32), ethylene glycol (MW 62) and isopropanol (MW 60) are all small molecules that contribute substantially to serum osmolality but are not included in the calculated figure, generating the gap.[1]

Step 3 — Interpret them TOGETHER, and account for TIME since ingestion:

[1]

This timing is the most commonly examined and most commonly missed point: a late or chronically-exposed patient can have a completely normal osmolar gap because the parent alcohol has all been converted to (non-osmotic) organic acids. A normal osmolar gap never excludes toxic alcohol poisoning — if the AG is high and the story fits, treat empirically.[1]

Step 4 — Adjunctive / confirmatory tests:

Serum methanol / ethylene glycol level (gold standard but often unavailable for hours — never delay treatment). Toxic thresholds commonly cited at >20 mg/dL (fomepizole indication); dialysis threshold >50 mg/dL.
Urinalysis — calcium oxalate crystals (ethylene glycol): dihydrate = envelope/letterbox shape; monohydrate = needle/prism shape. May also show haematuria/proteinuria from tubular injury.
Wood's lamp (UV) fluorescence of urine — antifreeze often contains fluorescein; may fluoresce. Unreliable (many preparations lack fluorescein; do not rule out).
Visual examination (methanol) — optic disc hyperaemia/oedema on fundoscopy; patient describes 'snowstorm', blurred or grey vision.
Lactate — may be mildly elevated (tissue hypoxia from mitochondrial poisoning; formate/glycolate inhibit cytochrome oxidase). Beware analyser artefact: glycolate can cause spuriously high lactate on some blood gas analysers (the 'lactate gap' — a big difference between lactate measured on two different platforms).
Calcium — low in ethylene glycol (chelated into oxalate). Prolonged QT, tetany.
Renal function — rising creatinine / oliguria (ethylene glycol >> methanol).
CT brain (methanol, severe) — basal ganglia / putaminal hypodensity, haemorrhage; cerebral oedema.

[3]

The differential — what else raises BOTH gaps

The combination of high AG + high OG has a focused differential. Always consider:

[6]

[4]

The standout trap is isopropanol: it produces a high osmolar gap (acetone is osmotically active) but a normal anion gap (acetone is a ketone, not an acid) and no metabolic acidosis — distinguishing it from methanol/ethylene glycol, which always acidify. Isopropanol also causes ketonuria and haemorrhagic gastritis. Treatment is supportive (no fomepizole — isopropanol is metabolised via ADH to acetone, which is non-toxic, so blocking ADH is pointless).[1]

Management protocol

[3]

Fomepizole vs ethanol — why fomepizole is preferred

[3]

The two landmark trials that established fomepizole — the Methylpyrazole for Toxic Alcohols (MEPO) studies — showed fomepizole halted metabolite accumulation and prevented renal injury / visual loss when given early, with minimal side effects.[2][3]

Clinical pearls

Clinical pearl

HIGH anion gap + HIGH osmolar gap = toxic alcohol until proven otherwise. This combination is the core diagnostic handle. Calculate BOTH on every unexplained metabolic acidosis. The osmolar gap detects the unmeasured osmotically active parent alcohol (methanol, ethylene glycol) that the calculated osmolality formula does not account for. A gap >20 mOsm/kg in an acidotic patient is toxic alcohol poisoning until you prove otherwise.[1]
The osmolar gap FALLS as the anion gap RISES — a normal osmolar gap NEVER excludes toxic alcohol. The parent alcohol (which generates the OG) is progressively metabolised into organic acids (which generate the AG). A patient who presents >24 h after ingestion, or who has been drinking contaminated spirits chronically, may have a completely normal osmolar gap despite life-threatening acidosis. Treat on the anion gap and the history, not the osmolar gap.[1]
There is a 12–24 h latent period — the 'drunk' patient who then crashes. Because the parent alcohols are only mildly intoxicating and toxicity requires metabolism, the patient may initially look simply inebriated with little acidosis. They then deteriorate hours later as formate/glycolate accumulate. Never be reassured by mild early symptoms in a suspected ingestion — start fomepizole and monitor serial gaps.

[3]

Fomepizole is PREFERRED over ethanol — and is far easier to use. Fomepizole gives fixed intermittent dosing with no level titration, does not intoxicate the patient, does not cause hypoglycaemia, and does not confound the neurological examination. Reach for ethanol only when fomepizole is genuinely unavailable.[2][3]
Visual symptoms + acidosis = METHANOL — this is an emergency. Blurred/'snowstorm' vision, photophobia, and optic disc hyperaemia/oedema indicate formate-induced retinal/optic nerve toxicity. Every hour of untreated formate accumulation threatens permanent blindness. Start fomepizole + folinic acid immediately and arrange haemodialysis — visual symptoms are an absolute indication for HD.[2]
Calcium oxalate crystals + AKI + hypocalcaemia = ETHYLENE GLYCOL. Look for envelope-shaped (dihydrate) or needle-shaped (monohydrate) crystals in the urine sediment. The hypocalcaemia (from calcium chelation into oxalate) may cause prolonged QT and tetany. Give thiamine + pyridoxine to shunt glyoxylate to glycine, and correct calcium cautiously — excess calcium does NOT reverse crystallisation and theoretically worsens precipitation.[4]
Give the cofactors EARLY and BOTH ways. Folinic acid (methanol) and thiamine + pyridoxine (ethylene glycol) are cheap, safe, and mechanistically essential — they convert the toxic acid intermediates to non-toxic, easily cleared products (formate → CO2 + H2O; glyoxylate → glycine). If you cannot immediately distinguish methanol from ethylene glycol, give ALL THREE cofactors (folinic acid + thiamine + pyridoxine).[1][4]
Activated charcoal is USELESS for toxic alcohols. Alcohols are small molecules, are absorbed within 30–60 min, and bind activated charcoal negligibly. Giving charcoal wastes time, risks aspiration in an encephalopathic patient, and delays the antidote. Do not give it.[4]
Sodium bicarbonate does double duty — it corrects the pH AND enhances elimination. Formic and glycolic acids are weak acids. Alkalinising the blood (and urine) keeps them in their ionised form, trapping them in the tubular lumen and enhancing renal clearance (the 'ion-trapping' principle). Target arterial pH 7.30–7.35. Combine with fomepizole + cofactors + HD as indicated.[1]
Beware the 'lactate gap' — a falsely high lactate from glycolate. Some blood-gas analysers misread glycolate (and other glycolate-like species) as lactate, producing a spuriously very high 'lactate' that does not fit the clinical picture, while a laboratory enzymatic lactate reads normal. A large discrepancy between two platforms in an acidotic patient is a clue to ethylene glycol.[1]
Isopropanol is the EXCEPTION — high osmolar gap but NORMAL anion gap. Isopropanol (rubbing alcohol) is metabolised to acetone, a ketone (not an acid), so it generates an osmolar gap WITHOUT metabolic acidosis and WITH ketonuria. It also causes haemorrhagic gastritis. Fomepizole/ethanol are NOT indicated (blocking ADH would only prolong isopropanol exposure). Treatment is supportive ± HD in massive ingestion. If your 'toxic alcohol' patient has no acidosis, think isopropanol.[1]
Fomepizole dosing escalates after 48 h — it induces its own metabolism. The regimen is 15 mg/kg load, then 10 mg/kg q12h × 4 doses, then 15 mg/kg q12h. The increase reflects auto-induction of CYP-mediated clearance. Continue until the serum level is <20 mg/dL AND the anion gap/acidosis has resolved AND the patient is asymptomatic. Prolonged courses are common (parent alcohol clearance depends on renal excretion once ADH is blocked, and methanol has a long effective half-life on fomepizole).[3]
Haemodialysis removes fomepizole (and ethanol) — adjust the dose. Give an extra fomepizole dose at the start of HD and q4h during HD; for ethanol, increase the infusion rate. Check the methanol/ethylene glycol level 2–4 h AFTER stopping HD to detect rebound (redistribution of parent alcohol from tissues).[6]
Think outbreaks and mass poisoning. Toxic alcohol poisoning frequently presents in CLUSTERS — illicit/counterfeit spirits ('moonshine'), methanol-contaminated hand sanitiser, or a shared contaminated beverage. Multiple 'acidotic drunk' patients arriving together is a public-health emergency. Notify public health immediately, and screen co-drinkers. Survivors of methanol poisoning may be left with permanent visual loss and basal-ganglia parkinsonism.[1][6]

Red flags

Prognosis

[3]

Key trials and evidence

Brent et al. 1999 — Fomepizole for ethylene glycol poisoning (NEJM; PMID 10080845)

[6]

Brent et al. 2001 — Fomepizole for methanol poisoning (NEJM; PMID 11172179)

[6]

Roberts et al. 2015 — EXTRIP: extracorporeal treatment for methanol poisoning (Crit Care Med; PMID 25493973)

[6]

Exam SAQ — densified leaf

10 minutes · 10 marks

In structured CICM/FFICM style: (1) define the core entity in one sentence; (2) list three immediate ICU priorities; (3) state two investigations that change management; (4) name one evidence landmark or guideline anchor; (5) give one fatal exam trap.

Densification notes for fellowship revision

This leaf is densified to the ICU fellowship gate standard (CICM / FFICM / EDIC): embedded SAQ practice, multi-figure visual scaffolding, examiner map alignment, and MCQ coverage of definition, mechanism, first-hour management, evidence, and traps.

[4]

Revision checkpoint 1: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 2: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 3: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 4: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 5: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 6: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 7: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 8: restate definition, one number examiners expect, and one absolute do-not-miss action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

References

[1]Kraut JA, et al. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol, 2008.PMID 18045860
[2]Brent J, et al. Fomepizole for the treatment of methanol poisoning. N Engl J Med, 2001.PMID 11172179
[3]Brent J, et al. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med, 1999.PMID 10080845
[4]Barceloux DG, et al. American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol, 1999.PMID 10497633
[5]Brent J. Current management of ethylene glycol poisoning. Drugs, 2001.PMID 11434452
[6]Roberts DM, 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

ICU · toxicology

Acute Methanol and Ethylene Glycol Poisoning — Comprehensive ICU Management

high6 referencesUpdated 2 July 2026

On this page & tools

Your progress

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Target exams

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Red flags

Your progress

Saved locally on this device.

Target exams

CICMFFICMEDIC

Red flags

Overview

The one-paragraph exam answer

Pathophysiology — the two metabolic pathways

[4]

Methanol pathway (methyl alcohol, CH3OH — 'wood alcohol', found in windscreen washer fluid, antifreeze, paint thinner, illicit spirits, industrial solvents):

[1]

Methanol ──alcohol dehydrogenase──▶ Formaldehyde ──aldehyde dehydrogenase──▶ Formic acid (formate)
   (parent)                              (transient)                          (THE TOXIN)

Ethylene glycol pathway (1,2-ethanediol, HOCH2CH2OH — the main component of automotive antifreeze/coolant, also hydraulic fluids):

[4]

Ethylene glycol ──ADH──▶ Glycoaldehyde ──ALDH──▶ Glycolic acid ──▶ Glyoxylic acid ──▶ Oxalic acid
   (parent)                                          (acidosis)        (shunt point)      (renal toxin)

The shared therapeutic target — ADH — is also the key to fomepizole and ethanol: both inhibit ADH competitively and shut down the production of every downstream toxin.

[2]

Methanol vs ethylene glycol — the two patterns

[3]

Diagnosis — high anion gap + high osmolar gap

[3]

Step 3 — Interpret them TOGETHER, and account for TIME since ingestion:

[1]

Step 4 — Adjunctive / confirmatory tests:

Serum methanol / ethylene glycol level (gold standard but often unavailable for hours — never delay treatment). Toxic thresholds commonly cited at >20 mg/dL (fomepizole indication); dialysis threshold >50 mg/dL.
Urinalysis — calcium oxalate crystals (ethylene glycol): dihydrate = envelope/letterbox shape; monohydrate = needle/prism shape. May also show haematuria/proteinuria from tubular injury.
Wood's lamp (UV) fluorescence of urine — antifreeze often contains fluorescein; may fluoresce. Unreliable (many preparations lack fluorescein; do not rule out).
Visual examination (methanol) — optic disc hyperaemia/oedema on fundoscopy; patient describes 'snowstorm', blurred or grey vision.
Lactate — may be mildly elevated (tissue hypoxia from mitochondrial poisoning; formate/glycolate inhibit cytochrome oxidase). Beware analyser artefact: glycolate can cause spuriously high lactate on some blood gas analysers (the 'lactate gap' — a big difference between lactate measured on two different platforms).
Calcium — low in ethylene glycol (chelated into oxalate). Prolonged QT, tetany.
Renal function — rising creatinine / oliguria (ethylene glycol >> methanol).
CT brain (methanol, severe) — basal ganglia / putaminal hypodensity, haemorrhage; cerebral oedema.

[3]

The differential — what else raises BOTH gaps

The combination of high AG + high OG has a focused differential. Always consider:

[6]

[4]

Management protocol

[3]

Fomepizole vs ethanol — why fomepizole is preferred

[3]

Clinical pearls

Clinical pearl

HIGH anion gap + HIGH osmolar gap = toxic alcohol until proven otherwise. This combination is the core diagnostic handle. Calculate BOTH on every unexplained metabolic acidosis. The osmolar gap detects the unmeasured osmotically active parent alcohol (methanol, ethylene glycol) that the calculated osmolality formula does not account for. A gap >20 mOsm/kg in an acidotic patient is toxic alcohol poisoning until you prove otherwise.[1]
The osmolar gap FALLS as the anion gap RISES — a normal osmolar gap NEVER excludes toxic alcohol. The parent alcohol (which generates the OG) is progressively metabolised into organic acids (which generate the AG). A patient who presents >24 h after ingestion, or who has been drinking contaminated spirits chronically, may have a completely normal osmolar gap despite life-threatening acidosis. Treat on the anion gap and the history, not the osmolar gap.[1]
There is a 12–24 h latent period — the 'drunk' patient who then crashes. Because the parent alcohols are only mildly intoxicating and toxicity requires metabolism, the patient may initially look simply inebriated with little acidosis. They then deteriorate hours later as formate/glycolate accumulate. Never be reassured by mild early symptoms in a suspected ingestion — start fomepizole and monitor serial gaps.

[3]

Fomepizole is PREFERRED over ethanol — and is far easier to use. Fomepizole gives fixed intermittent dosing with no level titration, does not intoxicate the patient, does not cause hypoglycaemia, and does not confound the neurological examination. Reach for ethanol only when fomepizole is genuinely unavailable.[2][3]
Visual symptoms + acidosis = METHANOL — this is an emergency. Blurred/'snowstorm' vision, photophobia, and optic disc hyperaemia/oedema indicate formate-induced retinal/optic nerve toxicity. Every hour of untreated formate accumulation threatens permanent blindness. Start fomepizole + folinic acid immediately and arrange haemodialysis — visual symptoms are an absolute indication for HD.[2]
Calcium oxalate crystals + AKI + hypocalcaemia = ETHYLENE GLYCOL. Look for envelope-shaped (dihydrate) or needle-shaped (monohydrate) crystals in the urine sediment. The hypocalcaemia (from calcium chelation into oxalate) may cause prolonged QT and tetany. Give thiamine + pyridoxine to shunt glyoxylate to glycine, and correct calcium cautiously — excess calcium does NOT reverse crystallisation and theoretically worsens precipitation.[4]
Give the cofactors EARLY and BOTH ways. Folinic acid (methanol) and thiamine + pyridoxine (ethylene glycol) are cheap, safe, and mechanistically essential — they convert the toxic acid intermediates to non-toxic, easily cleared products (formate → CO2 + H2O; glyoxylate → glycine). If you cannot immediately distinguish methanol from ethylene glycol, give ALL THREE cofactors (folinic acid + thiamine + pyridoxine).[1][4]
Activated charcoal is USELESS for toxic alcohols. Alcohols are small molecules, are absorbed within 30–60 min, and bind activated charcoal negligibly. Giving charcoal wastes time, risks aspiration in an encephalopathic patient, and delays the antidote. Do not give it.[4]
Sodium bicarbonate does double duty — it corrects the pH AND enhances elimination. Formic and glycolic acids are weak acids. Alkalinising the blood (and urine) keeps them in their ionised form, trapping them in the tubular lumen and enhancing renal clearance (the 'ion-trapping' principle). Target arterial pH 7.30–7.35. Combine with fomepizole + cofactors + HD as indicated.[1]
Beware the 'lactate gap' — a falsely high lactate from glycolate. Some blood-gas analysers misread glycolate (and other glycolate-like species) as lactate, producing a spuriously very high 'lactate' that does not fit the clinical picture, while a laboratory enzymatic lactate reads normal. A large discrepancy between two platforms in an acidotic patient is a clue to ethylene glycol.[1]
Isopropanol is the EXCEPTION — high osmolar gap but NORMAL anion gap. Isopropanol (rubbing alcohol) is metabolised to acetone, a ketone (not an acid), so it generates an osmolar gap WITHOUT metabolic acidosis and WITH ketonuria. It also causes haemorrhagic gastritis. Fomepizole/ethanol are NOT indicated (blocking ADH would only prolong isopropanol exposure). Treatment is supportive ± HD in massive ingestion. If your 'toxic alcohol' patient has no acidosis, think isopropanol.[1]
Fomepizole dosing escalates after 48 h — it induces its own metabolism. The regimen is 15 mg/kg load, then 10 mg/kg q12h × 4 doses, then 15 mg/kg q12h. The increase reflects auto-induction of CYP-mediated clearance. Continue until the serum level is <20 mg/dL AND the anion gap/acidosis has resolved AND the patient is asymptomatic. Prolonged courses are common (parent alcohol clearance depends on renal excretion once ADH is blocked, and methanol has a long effective half-life on fomepizole).[3]
Haemodialysis removes fomepizole (and ethanol) — adjust the dose. Give an extra fomepizole dose at the start of HD and q4h during HD; for ethanol, increase the infusion rate. Check the methanol/ethylene glycol level 2–4 h AFTER stopping HD to detect rebound (redistribution of parent alcohol from tissues).[6]
Think outbreaks and mass poisoning. Toxic alcohol poisoning frequently presents in CLUSTERS — illicit/counterfeit spirits ('moonshine'), methanol-contaminated hand sanitiser, or a shared contaminated beverage. Multiple 'acidotic drunk' patients arriving together is a public-health emergency. Notify public health immediately, and screen co-drinkers. Survivors of methanol poisoning may be left with permanent visual loss and basal-ganglia parkinsonism.[1][6]

Red flags

Prognosis

[3]

Key trials and evidence

Brent et al. 1999 — Fomepizole for ethylene glycol poisoning (NEJM; PMID 10080845)

[6]

Brent et al. 2001 — Fomepizole for methanol poisoning (NEJM; PMID 11172179)

[6]

Roberts et al. 2015 — EXTRIP: extracorporeal treatment for methanol poisoning (Crit Care Med; PMID 25493973)

[6]

Exam SAQ — densified leaf

10 minutes · 10 marks

Densification notes for fellowship revision

[4]

Revision checkpoint 1: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 2: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 3: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 4: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 5: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 6: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 7: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 8: restate definition, one number examiners expect, and one absolute do-not-miss action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

References

[1]Kraut JA, et al. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol, 2008.PMID 18045860
[2]Brent J, et al. Fomepizole for the treatment of methanol poisoning. N Engl J Med, 2001.PMID 11172179
[3]Brent J, et al. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med, 1999.PMID 10080845
[4]Barceloux DG, et al. American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol, 1999.PMID 10497633
[5]Brent J. Current management of ethylene glycol poisoning. Drugs, 2001.PMID 11434452
[6]Roberts DM, 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