Bedside Snapshot
- Normal / Therapeutic
- Undetectable methanol and ethylene glycol. Osmol gap normally <10 mOsm/kg. No therapeutic range.
- Toxic Thresholds
- Fomepizole: level >20 mg/dL, or start on suspicion
- Methanol dialysis: >50 mg/dL with no ADH blocker (EXTRIP)
- Ethylene glycol dialysis: >10 mmol/L (62 mg/dL) with no ADH blocker (EXTRIP)
- Toxicity Looks Like
- Anion gap acidosis with a raised osmol gap. Methanol: visual blur, “snowfield” vision, coma. Ethylene glycol: AKI, calcium oxalate crystals, low calcium with QT prolongation.
- Antidote / Definitive Care
- Fomepizole IV now; hemodialysis by EXTRIP criteria, not the level alone; IV ethanol if fomepizole is unavailable
- Act Now If
- Suspected ingestion with anion gap acidosis, raised osmol gap, visual symptoms or AKI: give fomepizole, send levels, pH, calcium, call toxicology, arrange dialysis
- Watch Out For
- A normal osmol gap late in the course does not exclude poisoning; the anion gap is then high.
Reference & Critical Ranges
Lab-specific ranges: Reference intervals vary by lab, analyzer and population. Use the range printed on your lab report. The values below are typical.
Reference ranges
| Population | Conventional | SI | Notes |
|---|---|---|---|
| Adult: methanol | Undetectable | Undetectable | Lab cutoff varies; mg/dL ÷ 3.2 = mmol/L |
| Adult: ethylene glycol | Undetectable | Undetectable | mg/dL ÷ 6.2 = mmol/L |
| Adult: osmol gap | <10 mOsm/kg | <10 mmol/kg | Calculated from the formula below |
| Children | Same as adult | Same as adult | Use the adult thresholds; pediatric dosing is in Management Priorities |
Severity & critical values
| Level | Conventional | SI | What it means |
|---|---|---|---|
| Normal | Undetectable | Undetectable | No methanol or ethylene glycol detected |
| Fomepizole threshold | >20 mg/dL | >6.2 mmol/L methanol; >3.2 mmol/L ethylene glycol | Start fomepizole (FDA label trigger; treat on suspicion without waiting) |
| Methanol, no ADH blocker | >50 mg/dL | >15.6 mmol/L | EXTRIP: extracorporeal treatment (ECTR) recommended; the threshold is >70 mg/dL once fomepizole is given |
| Critical | >50 mg/dL methanol or >62 mg/dL ethylene glycol, with no blocker | >15.6 mmol/L or >10 mmol/L | Dialysis is recommended; coma, seizures, new vision loss, pH ≤7.15 or AKI call for ECTR regardless of level (see Management) |
Critical values (typical; lab-specific): Any detectable methanol or ethylene glycol in a symptomatic patient is critical. Fomepizole at >20 mg/dL. With no ADH blocker, methanol >50 mg/dL or ethylene glycol >10 mmol/L (62 mg/dL) indicates extracorporeal treatment.
Conversion: methanol mg/dL ÷ 3.2 = mmol/L; ethylene glycol mg/dL ÷ 6.2 = mmol/L (molecular weights 32 and 62).
Calculated osmolality (mOsm/kg, mg/dL units)
2(Na⁺) + glucose/18 + BUN/2.8 + ethanol/4.6
Osmol gap
Measured osmolality − calculated osmolality; normal under 10 mOsm/kg
Anion gap
Na⁺ − (Cl⁻ + HCO₃⁻); normal is lab-specific, often about 8–12 mmol/L
Approximate toxic alcohol level from osmol gap
Methanol (mg/dL) ≈ osmol gap × 3.2; ethylene glycol (mg/dL) ≈ osmol gap × 6.2
Treat the osmol gap as an estimate only. It falls as the parent alcohol is metabolized, which makes the estimate least reliable late in the course.
Osmolality method: Some vapor-pressure osmometers read low when volatile alcohols are present. Ask the lab which method it runs. Freezing-point depression is the usual reference method.
Causes of Abnormal Results
Methanol and ethylene glycol
| Feature | Methanol | Ethylene Glycol |
|---|---|---|
| Sources & routes of exposure | Windshield washer fluid, solvents, fuel additives, contaminated or counterfeit spirits | Antifreeze, coolants, de-icers |
| Toxic metabolite | Formaldehyde, then formic acid | Glycolic acid, then oxalic acid |
| Organ toxicity | Optic nerve and retina; CNS | Kidneys (calcium oxalate deposition, AKI); CNS |
| Classic findings | Visual blur, “snowfield” vision, coma, seizures | Flank pain, oliguria or AKI, low calcium, coma, seizures |
| Urine crystals | None | Calcium oxalate (envelope or needle-shaped) |
| Wood lamp of urine | Not useful | Unreliable: some antifreeze contains fluorescein; many products do not |
Osmol gap and anion gap over time
| Phase | Osmol gap | Anion gap | Why |
|---|---|---|---|
| Early (parent alcohol present) | Raised | Normal | Unmetabolized parent alcohol adds osmoles |
| Intermediate | Raised | Raised | Parent alcohol and acid metabolites coexist |
| Late (parent metabolized) | Normal or near normal | Raised | Acid metabolites have accumulated |
A normal osmol gap does not rule out toxic alcohol poisoning. Late in the course, the osmol gap can look nearly normal while the anion gap is large. That is the most dangerous phase. Assess both gaps and trend them.
Other causes of a raised osmol gap
- Ethanol: it adds measured osmoles. Take its term out of the formula, or the gap reads falsely high.
- Isopropanol: acetone and ketosis push the osmol gap up, and no anion gap acidosis follows.
- Diethylene glycol: expect an osmol gap, an acid–base disturbance and kidney injury together. Toxicology should direct the care.
- Propylene glycol: found in some IV lorazepam infusions as the diluent. It can push the osmol gap up and bring on a lactic acidosis, but it is far less toxic.
- Alcoholic and other ketoacidosis: the anion gap climbs, and the osmol gap can rise modestly as well.
Risk factors for toxicity
- Intentional or unintentional ingestion: accidental or deliberate, and that includes children who swallow antifreeze or product mixtures.
- Counterfeit or homemade spirits: methanol contamination
- Kidney disease: an eGFR below 45 mL/min/1.73 m² means ethylene glycol poisoning reaches the extracorporeal treatment threshold sooner.
Interpretation & Bedside Approach
Step-by-step approach
- Is it real? Confirm the osmolality method and specimen, and repeat if the result conflicts with the picture.
- How sick is the patient? Check mental status, vision, seizures, urine output and pH.
- Early or late, and what is the trend? Compare the osmol gap and anion gap on serial samples.
- Calculate derived values. Osmol gap (after subtracting ethanol), anion gap and the estimated level.
- Classify with current criteria. Use the EXTRIP thresholds (methanol 2015; ethylene glycol 2023) for dialysis.
- Escalate. Start fomepizole on suspicion, contact toxicology or the poison center, and arrange nephrology for dialysis.
Pattern table
| Pattern | Suggests |
|---|---|
| Raised osmol gap, normal anion gap | Early exposure to methanol, ethylene glycol or another osmotically active alcohol |
| Raised osmol gap, raised anion gap | Intermediate phase: parent alcohol and metabolites both present |
| Normal osmol gap, raised anion gap | Late phase: toxic alcohol already metabolized; also consider lactic acidosis, ketoacidosis, uremia and salicylate |
| Raised anion gap with visual symptoms | Methanol until proven otherwise |
| Low ionized calcium, raised anion gap, urinary crystals | Ethylene glycol |
One value tells you little. The trend tells you more, because the two gaps move in opposite directions over hours.
Management Priorities
Emergency: Suspected methanol or ethylene glycol poisoning
- Start fomepizole now: 15 mg/kg IV over 30 min. Do not wait for levels.
- Correct acidosis and electrolytes: sodium bicarbonate per protocol to a pH target; monitor K⁺ and ionized calcium.
- Adjuncts per toxicology: folinic or folic acid for methanol; thiamine and pyridoxine are sometimes added for ethylene glycol (benefit unproven).
- Arrange dialysis: consult toxicology and nephrology; apply the EXTRIP criteria below and keep antidote dosing running during treatment.
Medications
| Drug | Adult dose | Pediatric dose (max) | Notes |
|---|---|---|---|
| Fomepizole | Load 15 mg/kg IV over 30 min, then 10 mg/kg IV every 12 hr for 4 doses, then 15 mg/kg every 12 hr. Dosing weight per protocol. Every 4 hr during hemodialysis; no fixed max | Same mg/kg as adults; safety not established in children; neonates: toxicologist only | Dilute in at least 100 mL 0.9% NaCl or D5W; infuse over 30 min; never undiluted or IV push. Dialysis: at the start, do not give if less than 6 hr have passed since the last dose, and give the next scheduled dose if more than 6 hr have passed; every 4 hr during dialysis (the label gives end-of-run rules). Most frequent: headache, nausea, dizziness, metallic taste; phlebitis and transient transaminase rise. Continue until level <20 mg/dL or undetectable, asymptomatic, and pH normal. |
| Ethanol IV (fallback if fomepizole unavailable) | Protocol-dependent. Secondary sources give a target of 100–150 mg/dL | Protocol-dependent; hypoglycemia risk in young children | Needs frequent ethanol and glucose levels; causes intoxication; fomepizole is preferred |
| Folinic or folic acid (methanol adjunct) | Protocol-dependent; sources give different regimens, so no dose is listed here | Protocol-dependent | Continue during extracorporeal treatment |
| Sodium bicarbonate | Titrate to pH and protocol; no fixed max | Titrate to pH and protocol | Monitor K⁺ and ionized calcium with infusion |
| Thiamine and pyridoxine (ethylene glycol adjunct) | Not dosed here; benefit unproven, per toxicology | Per toxicology | Adjunct only; never a substitute for fomepizole or dialysis |
Definitive care & disposition
EXTRIP criteria for extracorporeal treatment (ECTR; methanol 2015, ethylene glycol 2023)
| Finding | Methanol | Ethylene glycol |
|---|---|---|
| Clinical features | Coma, seizures, new vision deficit or impaired kidney function: ECTR recommended | Coma, seizures, or AKI (KDIGO stage 2–3): ECTR recommended; eGFR below 45: suggested |
| Acid–base | pH ≤7.15, anion gap >24 mmol/L, or persistent acidosis despite antidote and supportive care | Anion gap >27 mmol/L or glycolate >12 mmol/L: recommended; anion gap 23–27 or glycolate 8–12 mmol/L: suggested |
| Level on fomepizole | Methanol >70 mg/dL | Ethylene glycol >50 mmol/L (310 mg/dL) or osmol gap >50: suggested |
| Level with no ADH blocker | Methanol >50 mg/dL | Ethylene glycol >10 mmol/L (62 mg/dL) or osmol gap >10: recommended |
| Level on ethanol | Methanol >60 mg/dL (18.7 mmol/L): recommended | Ethylene glycol >50 mmol/L (310 mg/dL) or osmol gap >50: recommended; 20–50 mmol/L or osmol gap 20–50: suggested |
| Stop when | Methanol <20 mg/dL with clinical improvement | Anion gap <18 mmol/L (recommended); ethylene glycol <4 mmol/L (suggested) |
ECTR stands for extracorporeal treatment. Intermittent hemodialysis is the first choice, and CRRT is the backup when it is unavailable. Don't let the antidote lapse on the circuit: keep fomepizole or ethanol and folate going. In methanol poisoning, avoid systemic anticoagulation of the circuit where possible, because of the intracranial hemorrhage risk. The fomepizole label says to consider hemodialysis once the measured level reaches 50 mg/dL or more. This page uses the EXTRIP thresholds above instead. The ethylene glycol thresholds with no ADH blocker (>10 mmol/L or osmol gap >10) are in the full 2023 EXTRIP text. The abstract leaves them out.
Disposition: Coma, seizures, airway compromise, acidosis or ECTR? That patient goes to the ICU or step-down care. Call toxicology, nephrology and the poison center (1-800-222-1222) early. Recheck the anion gap and the toxic alcohol level after every dialysis run.
Doses are typical references. Follow local protocols, medical direction and institutional policy.
Field & Transport Considerations
Point-of-care testing
Methanol, ethylene glycol and osmolality are lab tests. A bedside blood gas or chemistry device still reports pH, bicarbonate and sometimes a calculated anion gap. That can prompt the diagnosis. Your glucometer does not measure toxic alcohols. A normal glucose does not rule out hypoglycemia from ethanol.
Before and during interfacility transport
- Obtain: product name and amount, time of ingestion, dosing weight, latest pH and anion gap, osmol gap, ethanol level, and the time and dose of each fomepizole dose.
- Treat before departure: give the fomepizole loading dose if it has not been given. Note when the next dose is due: every 12 hr, or every 4 hr during dialysis.
- Redirect: anyone who meets EXTRIP criteria needs a center that can start hemodialysis.
- Monitor en route: mental status, seizures, airway, urine output and rhythm. In ethylene glycol poisoning, watch for QT prolongation from low calcium.
EMS scope: Recognize the exposure, protect the airway and treat seizures. Bring the product container along if it is safe to do so. Fomepizole is usually started in the ED, so follow local protocol.
Timing & Kinetics
| Parameter | Value | Clinical implication |
|---|---|---|
| Onset of toxicity | Delayed; metabolite-driven, so symptoms can lag the ingestion | Normal early symptoms do not exclude poisoning; repeat the labs |
| Fomepizole interval | Every 12 hr; every 4 hr during hemodialysis | A missed dose lets metabolism restart |
| Dialysis | Removes parent alcohol and possibly the acid metabolites | Recheck the anion gap and level after each run, because rebound is possible |
| Level turnaround | Lab-dependent; reference labs can take hours to days | Do not wait for the level before fomepizole |
| Stop criteria | Level undetectable or <20 mg/dL, asymptomatic, pH normal | Keep fomepizole running until all three are met |
Special Populations
| Population | What changes | Clinical implication |
|---|---|---|
| Neonates & infants | Fomepizole safety not established; neonatal dosing is toxicologist-directed | Involve toxicology and the poison center early |
| Children & adolescents | Same mg/kg regimen used in published cases; ethanol can cause hypoglycemia in young children | Fomepizole is preferred over ethanol in young children |
| Pregnancy | Limited human data | Do not delay treatment of a life-threatening poisoning; consult toxicology |
| Older adults | Lower kidney reserve; higher risk of AKI | Low threshold to check creatinine and calcium |
| CKD / dialysis | eGFR below 45 lowers the ethylene glycol dialysis threshold (suggested) | Fomepizole interval changes to every 4 hr during dialysis |
| Liver disease | Fomepizole can cause a transient rise in AST and ALT | Monitor; discuss a marked rise with toxicology |
Interfering Factors & Pitfalls
Collection & handling
| Factor | Effect | Why | Avoid / fix |
|---|---|---|---|
| Osmometer type | False − | Vapor-pressure readings can underestimate volatile alcohols | Confirm method; freezing-point preferred |
| Ethanol not in the formula | False + osmol gap | Ethanol adds measured osmoles | Include the ethanol term |
| Late sample | False − osmol gap | Parent alcohol already metabolized | Trend both gaps; do not rule out on one value |
Medications & supplements
| Factor | Effect | Why | Avoid / fix |
|---|---|---|---|
| Propylene glycol (IV lorazepam infusions) | False + osmol gap | Osmotically active diluent | Check infusion history |
| Mannitol | False + osmol gap | Osmotically active | Check timing of any dose before the sample |
Physiologic & assay
| Factor | Effect | Why | Avoid / fix |
|---|---|---|---|
| Ketoacidosis | ↑ anion gap; osmol gap modestly raised | Ketones and their anions | Check ketones and interpret with the clinical picture |
| Wood lamp of urine | False + or False − | Fluorescein in some antifreeze only | Never use it to rule in or rule out ethylene glycol |
Common misinterpretations
- “Isopropanol causes an anion gap.” That is wrong. It raises the osmol gap through acetone, with no anion gap acidosis.
- “A normal osmol gap means no poisoning.” Late presenters can show a normal osmol gap. That is the trap.
- “A negative urine fluorescence rules out ethylene glycol.” It does not.
- “Wait for the level before giving fomepizole.” Treat on suspicion, not on the level.
Ethanol co-ingestion: Ethanol competes for alcohol dehydrogenase. That slows toxic metabolite formation. It buys time. It does not remove the need for fomepizole or dialysis.
Physiology & Test Basics
What it measures
This page covers the serum methanol and ethylene glycol levels and the osmol gap that screens for them. Ethanol and other osmoles live on sibling pages. They are not measured here.
Physiology & regulation
- Alcohol dehydrogenase (ADH) turns methanol into formaldehyde, then formic acid. It turns ethylene glycol into glycolaldehyde, then glycolic acid and oxalic acid.
- Formic acid clears through folate-dependent one-carbon metabolism. That is why folate is used as an adjunct.
- Oxalate binds calcium. The crystals it forms, calcium oxalate, deposit in the kidney.
- Parent alcohols are osmotically active but not acidic. The acid metabolites drive the anion gap acidosis.
- Fomepizole blocks ADH. Ethanol competes for the same enzyme. Both slow metabolite formation.
How it is measured
Serum or plasma goes to the lab. The lab measures methanol and ethylene glycol by its own method, often gas chromatography. Send the ethanol level and serum osmolality with it. Reference labs can take hours to days, so treatment decisions rest on clinical suspicion and the gaps.
Why it matters
A patient can look well early on and still die or go blind from a toxic alcohol. The osmol and anion gaps are your fastest bedside clues. The level confirms the diagnosis and guides dialysis.
Clinical Pearls
The gaps move like a seesaw: One goes down, the other goes up. As the parent alcohol drops, the osmol gap drops and the anion gap rises. A raised anion gap with a normal osmol gap still gets a toxic alcohol screen until another cause is ruled out.
Give fomepizole on suspicion: The label says to start right away on suspicion of ethylene glycol or methanol ingestion. Holding the antidote while you wait for a reference-lab level only delays it.
Visual symptoms are an emergency: Methanol blindness can be permanent. New vision loss means dialysis is indicated under EXTRIP, whatever the level.
Check calcium and the ECG in ethylene glycol poisoning: Oxalate can grab calcium and drag it down with it. Once calcium is low, the QT can stretch out and an arrhythmia can follow. Track calcium and the rhythm closely.
Transport pearl: Put the dosing schedule in the handoff. Miss a fomepizole dose during dialysis and you let metabolism restart. Write the last dose time and the next one on the transfer sheet.
Nursing pearl: Every run needs an anion gap and toxic alcohol recheck. Then watch for a rebound in acidosis or symptoms.
References
- Mylan Institutional. (2021). Fomepizole injection [prescribing information] (revised April 2021). DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=911312e2-3a7c-4c97-88a8-b8d92cd12923
- Roberts, D. M., Yates, C., Megarbane, B., et al. (2015). Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. Critical Care Medicine, 43(2), 461–472. https://doi.org/10.1097/CCM.0000000000000708
- Ghannoum, M., Gosselin, S., Hoffman, R. S., et al. (2023). Extracorporeal treatment for ethylene glycol poisoning: systematic review and recommendations from the EXTRIP workgroup. Critical Care, 27, 56. https://doi.org/10.1186/s13054-022-04227-2
- Kraut, J. A., & Kurtz, I. (2008). Toxic alcohol ingestions: clinical features, diagnosis, and management. Clinical Journal of the American Society of Nephrology, 3(1), 208–225. https://doi.org/10.2215/CJN.03220807
- Brent, J. (2009). Fomepizole for ethylene glycol and methanol poisoning (clinical therapeutics review). New England Journal of Medicine, 360(21), 2216–2223. https://doi.org/10.1056/NEJMct0806112
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- For Educational Purposes Only: This content is intended for educational reference and should not be used for clinical decision-making.
- Not a Substitute for Professional Judgment: Always consult your local protocols, institutional guidelines, and supervising physicians.
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