Toxic Alcohols: Methanol & Ethylene Glycol Poisoning

Meet the patient

A 38-year-old labourer is brought to ED at dawn, "drunk" but with a serum ethanol level of zero. He says the ceiling lights have become a "snowstorm", his vision is closing in, and he vomits. His pH is 7.05, anion gap is 28, osmolal gap is over 30 mOsm/kg. Overnight he shared a bottle of country liquor with friends — two of whom are already blind.[1][2]

Across the resus bay, a 26-year-old drank antifreeze "for a bet". She is oliguric, her calcium is low, her QT is long, and her fresh urine shows envelope-shaped calcium oxalate crystals. Two patients, one mechanism, and one demand on you: block alcohol dehydrogenase before the parent alcohol becomes the poison.[2]

Overview & Definition

The whole disease sits downstream of a single enzyme — so the whole disease is preventable. Methanol (CH3OH, wood alcohol) and ethylene glycol (antifreeze) intoxicate but rarely kill on their own; the killers are their metabolites, forged by hepatic alcohol dehydrogenase (ADH) — the same enzyme that clears your gin. Block that enzyme with fomepizole (or ethanol) and no end-organ damage ever forms. Few poisons hand you so clean a target.[1]

The picture moves, and that movement is the trap. Early, the patient carries only an osmolal gap — the unmetabolised parent is osmotically active — and looks merely drunk. Hours later ADH has converted that parent into organic acids, the anion gap climbs, and the osmolal gap falls; measure the gaps at one time point, especially late, and you will be badly misled.[2]

Two traps recur in every exam. First, co-ingested ethanol delays symptoms — it wins the competition for ADH, so the chronic alcoholic presents late, "better than they should be", then collapses when the ethanol wears off. Second, a "normal" osmolal gap late does NOT exclude the diagnosis — the toxicity has simply moved from the osmolal gap into the anion gap. The clinching clues stay organ-specific: visual disturbance in methanol, renal failure with calcium oxalate crystals in ethylene glycol.[2]

This page covers the duo — methanol and ethylene glycol — which share the ADH mechanism and the dual-gap signature. The wider family (isopropanol: ketosis without a high anion gap; propylene glycol: an iatrogenic ICU cause of both gaps; diethylene glycol: the recurring contaminated-medicine disaster) is kept for Differential Diagnosis and Specific Subtypes, because every examiner will probe the distinction.[2]

Classification

Classify on two axes: which parent alcohol (sets the metabolite and the dying organ), and which laboratory stage (sets which gap dominates). The first axis answers what will die — retina and basal ganglia for methanol, kidney for ethylene glycol; the second answers what the blood will show, and when.[1]

[5] [7] [15] [16] [18]

[1]

The second axis is the clock — and the clock is why toxic-alcohol poisoning is a moving target. As ADH works through the night, the osmolal gap empties into the anion gap; the picture you see depends entirely on when in the cascade the blood was drawn.[1]

Epidemiology & Risk Factors

Toxic alcohols kill where regulation is weak. Rare in markets that control alcohol and antifreeze, they are a leading cause of preventable poisoning death wherever illicit alcohol circulates. Methanol mass outbreaks — tainted moonshine, country liquor, denatured alcohol, even methanol-adulterated hand sanitiser during the COVID-19 pandemic — sweep through whole communities at once, with untreated case-fatality of 10-40% and many survivors left permanently blind.[2]

[5] [8] [9] [10]

The sources worth memorising — each points to a risk group and a way in:[1]

• Methanol — illicit spirits ('moonshine', country liquor/toddy, tainted arrack), windscreen washer fluid, antifreeze, paint thinner and remover, varnish/shellac, photocopying fluid, camp-stove (canned heat) fuel, denatured alcohol, and methanol-contaminated hand sanitiser. Risk groups: alcoholics (substituting cheap denatured alcohol), people in poverty, suicide attempts, painters/printers/mechanics (occupational), and whole communities in mass outbreaks (illicit-alcohol contamination after tax changes, prohibition, or hand-sanitiser ingestion).
• Ethylene glycol — antifreeze/coolant (the classic source, with a sweet taste that attracts children and is used in suicide attempts), brake and hydraulic fluid, and industrial dehydrating agents. Many jurisdictions now mandate a bittering agent (denatonium benzoate) and fluorescein dye to deter and diagnose ingestion. Risk groups: children (accidental, sweet), suicidal adults, and industrial/occupational exposure.
• Diethylene glycol (DEG) — a recurring drug-safety disaster: contamination of pharmaceutical glycerin used in paediatric syrups and toothpaste has caused repeated mass poisonings with renal failure (India 1998, Panama 2006, the Gambia/Nigeria 2022). DEG is partly metabolised by ADH; management is largely supportive + dialysis.[2]

Pathophysiology

One enzyme, two cascades, two dying organs — learn the cascade and the therapy writes itself. Both toxic alcohols are oxidised first by cytosolic, NAD+-dependent alcohol dehydrogenase (ADH), then by aldehyde dehydrogenase (ALDH); ADH is the rate-limiting, targetable step, which is why fomepizole exists.[1]

Etymology for viva gold: methanol is literally "wood alcohol", first distilled from wood; glycol comes from Greek glykys, "sweet" — the sweetness that lures children and the suicidal to drink the antifreeze that kills them.[1]

[1]

The methanol cascade

Formate is the methanol toxin, and it kills by suffocating mitochondria. ADH oxidises methanol to formaldehyde, then formaldehyde dehydrogenase oxidises that to formic acid (formate) — the toxin. Formate inhibits cytochrome oxidase and is the prime cause of ocular toxicity; the acidosis itself increases toxicity further by enabling greater diffusion of formic acid into cells. There is a direct correlation between the formic acid concentration and increased morbidity and mortality.[5]

Formate clearance is folate-dependent. Formic acid is converted by 10-formyl tetrahydrofolate synthetase to carbon dioxide and water, and intravenous folinic acid enhances formate metabolism — which is why folinic acid sits in every methanol protocol.[5]

The ethylene glycol cascade

Oxalate is the ethylene glycol toxin, and it kills the kidney by crystallising inside the tubule. Ethylene glycol is metabolised by ADH into glycolate and oxalate; these toxic metabolites cause metabolic acidosis, renal failure, hypocalcaemia and aciduria, and calcium oxalate contributes to acute tubular necrosis. Urinary calcium oxalate crystals are the bedside signature of the renal injury.[7][15]

Antidotal blockade and extracorporeal removal are the interventions with the strongest evidence in ethylene glycol poisoning. Fomepizole (or ethanol) prevents conversion of the parent alcohol to its toxic metabolites; intermittent haemodialysis removes ethylene glycol and glycolate in severe poisoning, and antidote dosing must be adjusted during extracorporeal treatment. Adjunctive B-vitamin cofactor regimens vary between guidelines — follow local toxicology advice.[6][7]

The dual laboratory signature — and why it moves

The two gaps are the same poison, photographed at two different clocks. The parent alcohol is small and uncharged, so it raises measured osmolality without touching the anion gap — the osmolal gap. As ADH converts it into dissociating organic acids, those anions eat bicarbonate and raise the anion gap while the osmotically active parent is spent. They move in opposite directions — osmolal gap high and falling, anion gap low and rising — so a single snapshot misleads, especially late, when the osmolal gap has normalised just as the patient turns toxic.[2]

[9]

The kinetic basis of therapy

Ethanol was the original antidote; fomepizole does the same job more cleanly. Ethanol is the traditional antidote for ethylene glycol poisoning but has never been studied prospectively and is not FDA-approved for this indication. Fomepizole (4-methylpyrazole) is a potent ADH inhibitor with validated efficacy, predictable pharmacokinetics, ease of administration and lack of adverse effects; its disadvantage is acquisition cost.[3][6]

The presentation is a latent period, then evolving organ failure — and the tempo is the discriminator examiners test. Methanol declares itself through the eye, ethylene glycol through the kidney; both hide behind a "drunk" façade until the acidosis unmasks them.[1]

Shared early features (both toxic alcohols)

After the latent period — approximately 12-24 h for methanol, depending in part on the dose ingested — both toxic alcohols paint the same early picture:[5]

• CNS depression disproportionate to a low or absent serum ethanol — ataxia, slurred speech, confusion, drowsiness, progressing to obtundation and coma. (A drunk-looking patient with a near-zero ethanol level is a toxic-alcohol clue.)
• Headache, nausea, vomiting, abdominal and back pain.
• Kussmaul (deep, sighing) breathing — the respiratory compensation for severe metabolic acidosis.
• Tachycardia, hypotension, and hyperventilation. [1]

Methanol-specific features

[5]

The eye is the signature organ of methanol — and "snowstorm" vision is the phrase that earns the mark. After the latent period, visual function becomes impaired, ranging from blurred vision and altered visual fields to complete blindness; nausea, vomiting, abdominal pain and mild CNS depression precede the visual loss. Administered early, fomepizole prevents methanol-related visual and neurological injuries — the reason not to wait for concentrations.[3][5]

Ethylene-glycol-specific features

[15]

The kidney is the signature organ of ethylene glycol — and calcium oxalate crystals are the finding that earns the mark. The toxic metabolites cause metabolic acidosis, renal failure, hypocalcaemia and aciduria, and calcium oxalate contributes to acute tubular necrosis. Urinary calcium oxalate crystals on microscopy are the diagnostic signature, and because antifreeze carries a fluorescein dye, the urine may fluoresce under Wood's lamp — a supportive bedside clue while the serum level is pending.[15][18]

Atypical and special-context presentations

• The chronic alcoholic who "looks better than they should" — ethanol is itself the traditional ADH-blocking antidote, so co-ingestion alters the time-course of toxicity; the patient may present late with established injury. Still start antidotal blockade and continue until the parent-alcohol concentration is below the treatment threshold.[3][5]
• Children — a mouthful of sweet antifreeze or methanol product is lethal by weight; early drowsiness, hypocalcaemic seizures, and crystalluria.
• The late presentation — deep coma, shock, refractory metabolic acidosis, seizures, respiratory failure, established renal failure or established blindness; high mortality, permanent sequelae in survivors.
• The mass-outbreak presentation — clusters from a single illicit-alcohol source presenting over hours to days with visual symptoms and severe acidosis; a public-health emergency.[8]

Differential Diagnosis

The frame that unlocks everything is the high anion-gap metabolic acidosis — and toxic alcohols sit first among its causes. Memorise the differential once, as a single word, and toxic alcohols take their seat inside it:[1]

Within that list, toxic alcohols are the only members that widen BOTH gaps. A high anion gap plus an elevated osmolal gap, with an organ-specific clue bolted on, is the dual-gap signature — everything else widens only the anion gap. The discriminating features:[1]

Two distinctions decide the bedside. Methanol versus ethylene glycol: visual symptoms, optic disc change, and basal ganglia signs point to methanol; AKI with calcium oxalate crystals, hypocalcaemia, and Wood's-lamp-positive urine point to ethylene glycol — both share the dual-gap signature. The classic trap: isopropanol is excluded from the duo for one reason. It makes ketosis (acetone) without a high anion-gap acidosis, so the dual-gap signature is absent; the serum acetone is high, the acidosis is not, and ADH blockade with fomepizole or ethanol does nothing.[2]

Clinical & Bedside Assessment

The assessment has two jobs: confirm the metabolic picture, and catch the one organ-specific clue that names the alcohol. History and examination do the second; the gas machine and the gaps do the first.[1]

History — name the substance, the timing, the quantity, and the co-ingestants. Ethanol is the co-ingestant that matters: it delays onset and confuses the clock. Probe occupation and intent (painter, printer, mechanic; illicit alcohol; suicide; accidental child; hand sanitiser), then ask pointedly about visual symptoms (methanol) and urine output or flank pain (ethylene glycol), and about comorbidity — alcoholism, renal disease.[1]

Examination — let the breath and the eyes do the talking. Look for Kussmaul breathing (the acidotic compensation), tachycardia, hypotension, and a GCS depressed out of proportion to the ethanol level. In suspected methanol, examine the eyes properly: visual acuity, colour vision, fields, pupils, and fundoscopy (optic disc hyperaemia/oedema, retinal oedema). Add abdominal exam (pain, pancreatitis), a basal-ganglia neurological check (bradykinesia, rigidity), and skin (needle tracks, solvent smell).[1]

Bedside tests — four moves that buy the diagnosis in minutes:[1]

• Fresh urine microscopy — hunt for calcium oxalate crystals (envelope/prism and needle forms, birefringent); strongly supportive of ethylene glycol, though a negative slide does not exclude it.
• Wood's lamp on the urine — many antifreezes carry fluorescein, so the urine glows; a clue, not a verdict.
• ECG — QT prolongation in ethylene glycol (hypocalcaemia); watch for Torsades.
• Bedside glucose — exclude hypoglycaemia and separate the picture from DKA.
• IV access and monitoring — continuous ECG, pulse oximetry, ABCDE.[1]

[1]

Investigations

Investigations do three jobs: confirm the acidosis and the dual gap, exclude the mimics, and quantify the parent-alcohol level to time the therapy. Do all three in parallel — never let a slow level delay the antidote.[1]

The first-line panel — sent as a single draw the moment you suspect a toxic alcohol:[1]

• Venous/arterial blood gas — low pH, low bicarbonate, high base deficit with respiratory compensation (low pCO2); confirms the metabolic acidosis.
• Serum electrolytes + calculated anion gap.
• Serum osmolality (measured) plus calculated osmolality and the osmolal gap — the reference value lacks consensus, so interpret alongside the clinical picture.
• Serum ethanol level — a high level delays toxicity and is itself a clue; you need it to interpret the osmolal gap and to titrate ethanol if you use it.
• Serum methanol and ethylene glycol levels — confirm and guide duration, but turnaround is often slow, so treat empirically.
• Serum lactate — to exclude lactic acidosis as the primary cause. The classic trap: ethylene glycol metabolites (glycolate and glyoxylic acid) cross-react in several lactate assays, producing falsely elevated lactate results with most blood-gas and many chemistry methods.[12]
• Urea, creatinine, eGFR (renal involvement), glucose (DKA), calcium (low in ethylene glycol), magnesium, CK, lipase (methanol pancreatitis), LFTs, FBC, troponin.
• Urinalysis + microscopy — calcium oxalate crystals, haematuria, proteinuria.
• Pregnancy test in women of childbearing age.
• ECG — QT prolongation, arrhythmias.
• Paracetamol and salicylate levels in any intentional overdose.[3][9]

The anion gap — reproduced verbatim

[9] [10]

The timing caveat — the single most-tested fact

The classic trap: a normal osmolal gap does NOT exclude the diagnosis. The osmolal gap is a screening tool whose reference value lacks consensus; when no alcohol concentration is available it "may be informative" in methanol poisoning, but it is adjunctive — the decision to block ADH rests on the history and the anion-gap metabolic acidosis, never on a single gap value.[8][9]

[9] [10]

Empiric treatment thresholds (do not wait for levels)

[3] [5]

Levels confirm and guide duration; they never decide whether to treat. Start fomepizole on the history and the anion-gap acidosis while awaiting concentrations, and continue until the alcohol concentration is under 30 mg/dL. Severe methanol poisoning brings visual and neurological injury — one more reason not to wait.[3]

Management — Resuscitation

[3] [7] [8]

Resuscitate and block ADH at the same moment — they are not sequential. The airway and the antidote are the two things that must happen in the first minutes; everything else is refinement.[1]

1. ABCDE. Secure the airway (intubate if GCS under 8 or the airway is unprotected); give high-flow oxygen only if hypoxic; IV access; continuous ECG and pulse oximetry; isotonic crystalloid to correct hypovolaemia and wash out metabolites.
2. Block alcohol dehydrogenase IMMEDIATELY — fomepizole (preferred) or ethanol, on suspicion, do not wait for levels. This one act prevents all downstream toxicity; definitive doses below.
3. Sodium bicarbonate for significant acidosis — in methanol poisoning presenting with ophthalmologic abnormalities or significant acidosis, the acidosis should be corrected with intravenous sodium bicarbonate.[5]
4. Give the methanol cofactor at once — intravenous folinic acid (leucovorin) to enhance formate metabolism; folic acid is the alternative named in the guidelines.[5][8]
5. Correct hypoglycaemia (IV dextrose); give thiamine to alcoholics to prevent Wernicke; control seizures with benzodiazepines.
6. Hypocalcaemia (ethylene glycol) — monitor calcium; replace cautiously, because the metabolic picture includes hypocalcaemia from calcium oxalate deposition.[15]
7. Definitive removal — haemodialysis removes the parent compound and its toxic metabolites, reduces the duration of antidotal treatment and shortens the observation period in severe poisoning.[4]

Management — Definitive & Stepwise

The definitive ladder braids five strands: resuscitation, ADH blockade, acidosis correction, cofactors, and extracorporeal removal. The antidote and dialysis run in parallel, and the antidote must continue through and after dialysis — tissue stores rebound.[1]

Step 1 — Block alcohol dehydrogenase

[3] [5] [6] [8]

Consultant confession: in a centre without fomepizole, do not abandon the blockade — ethanol works, it just demands more of everyone. The fomepizole-versus-ethanol choice is an access decision, not a mechanistic one; both block ADH, but ethanol brings complex dosing, difficulty maintaining therapeutic concentrations, the need for more comprehensive clinical and laboratory monitoring, and more adverse effects, while fomepizole is easier and safer but costlier.[5][6]

Step 2 — Correct the acidosis

Sodium bicarbonate corrects the acidosis — and in methanol it is part of the formal recommendation. For the patient presenting with ophthalmologic abnormalities or significant acidosis, correct the acidosis with intravenous sodium bicarbonate. Watch sodium, potassium and volume as with any alkalinising regimen.[5]

Step 3 — Cofactor therapy

[5] [7] [8]

Step 4 — Haemodialysis (indications)

[7] [8]

Indications for extracorporeal treatment (EXTRIP) — methanol:[8]

1. Severe methanol poisoning attributed to it: coma, seizures, new vision deficits, or impaired kidney function.
2. Metabolic acidosis — blood pH under 7.15, or persistent acidosis despite adequate supportive measures and antidotes.
3. Anion gap over 24 mmol/L.
4. Serum methanol concentration over 700 mg/L on fomepizole, over 600 mg/L on ethanol, or over 500 mg/L with no ADH blocker; if no level is available, the osmolal gap may be informative.
5. Ethylene glycol (EXTRIP): ECTR recommended for severe clinical features (coma, seizures, AKI), glycolate over 12 mmol/L or anion gap over 27 mmol/L (suggested at 23-27); recommended where ethanol is the antidote and the EG concentration or osmolal gap exceeds thresholds.[7]
6. Modality and cessation: intermittent haemodialysis is the modality of choice; stop when methanol is under 200 mg/L with clinical improvement, or in EG when the anion gap is under 18 mmol/L; avoid systemic anticoagulation in methanol (intracerebral haemorrhage risk).[7][8]

In the fomepizole era the dialysis threshold is debated, not abandoned. EXTRIP states the indications for extracorporeal treatment in ethylene glycol poisoning are debated precisely because fomepizole is now widely available; fomepizole given before significant acidosis or organ injury may obviate the need for haemodialysis, and cohorts managed with fomepizole but without haemodialysis have been reported. In methanol poisoning without severe features, extracorporeal treatment is not immediately required if the concentration is elevated and alcohol dehydrogenase blockade is adequate — severity, not the number, carries the decision.[3][7][8][17]

Step 5 — Endpoints and continuation

Continue the antidote during extracorporeal treatment — and let biomarkers call the stop. Antidotes and folic/folinic acid should be continued during extracorporeal treatment, and the duration of therapy is guided by careful monitoring of biomarkers of exposure and toxicity. The endpoints of therapy:[8]

• Alcohol concentration under 30 mg/dL (the fomepizole continuation threshold).
• Metabolic acidosis resolved.
• For extracorporeal treatment in methanol: concentration under 200 mg/L with observed clinical improvement; in ethylene glycol, anion gap under 18 mmol/L.[3][7][8]

[5] [6] [7] [8]

Specific Subtypes & Scenarios

[3] [5] [7] [8] [13] [14] [15]

Complications & Pitfalls

The disease breaks the eye and brain in methanol, the kidney and heart in ethylene glycol:[1]

• Methanol — visual impairment progressing to complete blindness; neurological injury; coma and death. There is a direct correlation between the formic acid concentration and morbidity and mortality.[5]
• Ethylene glycol — acute kidney injury (calcium oxalate contributes to acute tubular necrosis); hypocalcaemia; central nervous and cardiovascular dysfunction; death. [15]

The treatment carries its own harm list — and over-replacement of calcium is the sneaky one:[1]

• Ethanol infusion — more adverse effects than fomepizole, difficulty maintaining therapeutic concentrations, and a need for more comprehensive clinical and laboratory monitoring.[5]
• Fomepizole — side-effects are rarely serious and occur less often than with ethanol.[3]
• Haemodialysis — vascular-access complications, hypotension, disequilibrium, heparin-related bleeding, line infection.
• Sodium bicarbonate — hypernatraemia, hypokalaemia, volume overload, alkalosis.
• Calcium over-replacement (ethylene glycol) — can worsen crystal deposition. [1]

Two timing pitfalls repeat in every exam. First, the osmolal gap is a screening tool with a reference value that lacks consensus — interpret it with the clinical picture, never alone. Second, continuation: antidotes and folic/folinic acid are continued during extracorporeal treatment, with duration guided by monitoring biomarkers of exposure and toxicity.[8][9]

Prognosis & Disposition

Mortality is set by the clock — and by the outbreak. In the Haiti diethylene glycol epidemic, 98% of the 87 local-treatment patients with follow-up died; in EXTRIP's ethylene glycol review, overall mortality across 446 analysed patients was 18.7%, falling to 3.6% in the subgroup with glycolate at or under 12 mmol/L (or anion gap at or under 28 mmol/L). Early ADH blockade — fomepizole given before significant acidosis or organ injury — may obviate haemodialysis altogether and prevents methanol-related visual and neurological injuries.[3][7][14]

The predictors of a bad outcome are proxies for severity and late presentation. In methanol, formate concentration correlates directly with morbidity and mortality; EXTRIP grades its extracorporeal indications on risk factors for poor outcomes — coma, seizures, new vision deficits, pH under 7.15, persistent acidosis, anion gap over 24 mmol/L, impaired kidney function.[5][8]

Disposition — where the patient goes:[1]

• Suspected or confirmed toxic alcohol poisoning — Emergency Department with ICU input.
• Any patient receiving fomepizole/ethanol or dialysis — ICU.
• Asymptomatic patient with documented small ingestion and observation — observed with serial anion/osmolal gaps and levels for at least 6-12 h; discharge only if levels undetectable, gaps normal, and no symptoms.
• After recovery — screen for suicidality and alcohol use disorder; psychiatric and addiction referral as appropriate. [1]

Long-term sequelae track the organ that died. Methanol leaves permanent blindness, optic atrophy, parkinsonism, and neuropsychiatric impairment; ethylene glycol leaves CKD when the AKI was severe; both carry a recurrence risk from alcoholism or repeated self-harm.[1]

Prevention is regulation, not willpower. Fomepizole on every hospital formulary; bittering agents and fluorescein dye mandated in antifreeze; control of illicit alcohol; drug-safety policing of pharmaceutical glycerin against DEG contamination; and methanol surveillance of hand sanitisers.[1]

Special Populations

[1]

Evidence, Guidelines & Regional Differences

The evidence base is small but decisive. The Methylpyrazole for Toxic Alcohols (MEP) programme — a prospective, multicentre, open-label trial of fomepizole in ethylene glycol poisoning, a multicentre study in methanol poisoning, and a toxicokinetic analysis of ethylene glycol during fomepizole therapy — established the antidote, and Brent's 2009 NEJM review consolidated its use.[1][11][19] The Kraut and Mullins 2018 NEJM review ('Toxic Alcohols') is the contemporary narrative reference.[2] The Megarbane and Rietjens groups frame the practical fomepizole-versus-ethanol decision, and EXTRIP grades the extracorporeal indications.[3][4][7][8]

The guidelines agree on the spine. AACT concludes fomepizole is the preferred antidote for methanol poisoning; fomepizole is recommended first-line and continued until alcohol concentrations are under 30 mg/dL; sodium bicarbonate corrects significant acidosis; intravenous folinic acid enhances formate metabolism; and antidotes with folic/folinic acid continue during extracorporeal treatment.[3][5][8]

Regional deltas — the antidote actually in the cupboard decides the rest:[1]

• US (AACT) — fomepizole standard; ethanol second-line.
• UK (NPIS/TOXBASE) — fomepizole now standard, though ethanol dominated historically on cost and availability.
• India / South-Asia — methanol mass outbreaks (illicit alcohol; hand-sanitiser ingestion in COVID-19); ethanol infusion is often the practical antidote on fomepizole cost and availability; DEG contamination of paediatric syrups is a recurring drug-safety disaster; folate and B-vitamins are cheap, effective, and under-used.[1]

Two controversies to name calmly. First, whether dialysis is needed in every patient with a high level is unsettled — EXTRIP explicitly notes the ethylene glycol ECTR indications are debated in the fomepizole era, and in methanol poisoning without severe features ECTR is not immediately required when ADH blockade is adequate; severity, not the number, carries the decision.[7][8] Second, the osmolal-gap reference value lacks consensus — at most 5 mOsm/kg has been proposed for healthy subjects, while 20 mOsm/kg or more remains the practical suspicion threshold — so correlate clinically and never trust a single value.[9]

Exam Pearls

[1] [5] [9] [10] [12] [13] [15] [16] [3] [5] [8] [9]

Ward-round test — three stems, thirty seconds each

Stem 1 — the country-liquor drinker who is going blind (answer)

A 40-year-old arrives 18 hours after a session of illicit country liquor, complaining that his vision has become a "snowstorm". His pH is 7.02, anion gap is 30, osmolal gap is over 25 mOsm/kg, and his serum ethanol is zero. What is the diagnosis, and what do you do in the next 15 minutes? Model: This is methanol poisoning — formic acid toxicity, signalled by the visual symptoms beside a high-anion-gap acidosis plus an elevated osmolal gap. Give fomepizole 15 mg/kg load, start intravenous folinic acid, begin sodium bicarbonate for the significant acidosis, and call for haemodialysis — new vision deficits and pH under 7.15 are EXTRIP extracorporeal indications. Do not wait for the methanol level; the visual signs and the gaps are enough to treat.[3][5][8]

Stem 2 — the antifreeze bet that closes the kidneys (answer)

A 26-year-old drank antifreeze on a bet. She is oliguric, her calcium is low, her QT is prolonged, and fresh urine shows envelope-shaped calcium oxalate crystals beside a high-anion-gap acidosis and a raised osmolal gap. What is the diagnosis, and what do you do? Model: This is ethylene glycol poisoning — oxalate injuring the tubules, signalled by AKI, hypocalcaemia, and calcium oxalate crystalluria beside the dual gap. Give fomepizole 15 mg/kg load, start sodium bicarbonate for the acidosis, monitor and replace calcium cautiously, and arrange haemodialysis — AKI is one of EXTRIP's severe clinical features prompting extracorporeal treatment.[3][7][15]

Stem 3 — the alcoholic who looks better for a day, then collapses (answer)

A chronic alcoholic ingested methanol 30 hours ago but seemed well overnight because he had also drunk ethanol. Now, as the ethanol clears, he turns acidaemic and confused with a rising anion gap. What happened, and why does the timing matter? Model: Co-ingested ethanol — itself the traditional ADH-blocking antidote — altered the time-course, so he "looked better than he should" for a day; as the ethanol cleared, ADH turned on the methanol and the formate surged. This is the classic late-presentation trap. Start fomepizole now — do not be reassured by the delayed onset — give folinic acid, correct the acidosis with bicarbonate, dialyse for severe features, and continue antidote and folic/folinic acid through extracorporeal treatment with duration guided by biomarkers.[3][5][8]

The mantra: block alcohol dehydrogenase before the parent becomes the poison — fomepizole early, dialysis for the formed acid.[1]

References

1. [1]Brent J. Fomepizole for ethylene glycol and methanol poisoning N Engl J Med, 2009.PMID 19458366
2. [2]Kraut JA, Mullins ME Toxic Alcohols N Engl J Med, 2018.PMID 29342392
3. [3]Mégarbane B Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole Open Access Emerg Med, 2010.PMID 27147840
4. [4]Rietjens SJ, de Lange DW, Meulenbelt J Ethylene glycol or methanol intoxication: which antidote should be used, fomepizole or ethanol? Neth J Med, 2014.PMID 24659589
5. [5]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
6. [6]Barceloux DG, Krenzelok EP, Olson K, Watson W American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning J Toxicol Clin Toxicol, 1999.PMID 10497633
7. [7]Ghannoum M, Yamamura M, Degeeter M, et al Extracorporeal treatment for ethylene glycol poisoning: systematic review and recommendations from the EXTRIP workgroup Crit Care, 2023.PMID 36765419
8. [8]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 Crit Care Med, 2015.PMID 25493973
9. [9]Skaaland H, Aabakken L, Stiksrud B, et al Reference values for osmolal gap in healthy subjects and in medical inpatients Scand J Clin Lab Invest, 2020.PMID 31809199
10. [10]Seifter JL Anion-gap metabolic acidemia: case-based analyses Eur J Clin Nutr, 2020.PMID 32873962
11. [11]Brent J, McMartin K, Phillips S, et al Fomepizole for the treatment of methanol poisoning N Engl J Med, 2001.PMID 11172179
12. [12]Tintu A, Vanholder R, Biesen WV Interference of ethylene glycol with (L)-lactate measurement is assay-dependent Ann Clin Biochem, 2013.PMID 23129723
13. [13]Pillai U, Kuzniar T Severe propylene glycol toxicity secondary to use of anti-epileptics Am J Ther, 2014.PMID 22926232
14. [14]O'Brien KL, Selanikio JD, Hecdivert C, et al Epidemic of pediatric deaths from acute renal failure caused by diethylene glycol poisoning JAMA, 1998.PMID 9555756
15. [15]Taira S, Aoki Y, Sakai K, et al Clinical manifestations and renal pathology of ethylene glycol CEN Case Rep, 2025.PMID 39134788
16. [16]Slaughter RJ, Mason RW, Beasley DM, et al Isopropanol poisoning Clin Toxicol (Phila), 2014.PMID 24815348
17. [17]Levine M, Curry SC, Ruha AM, et al Ethylene glycol elimination kinetics and outcomes in patients managed without hemodialysis Ann Emerg Med, 2012.PMID 22226175
18. [18]Varshavsky T, Lieberman A, Raita Y, et al Antifreeze ingestion and urine fluorescence J Educ Teach Emerg Med, 2020.PMID 37465606
19. [19]Brent J, McMartin K, Phillips S, Burkhart K, Watson W Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management J Toxicol Clin Toxicol, 2000.PMID 10918102