Printed on 3/17/2026
For informational purposes only. This is not medical advice.
Calculated serum osmolality estimates the total concentration of dissolved particles in the blood using three commonly measured values: sodium, glucose, and BUN. The formula is 2×Na + Glucose/18 + BUN/2.8. Normal serum osmolality is 275–295 mOsm/kg. An osmolal gap (measured − calculated > 10 mOsm/kg) suggests the presence of unmeasured osmoles such as methanol, ethylene glycol, ethanol, isopropyl alcohol, or mannitol. This calculation is essential in toxicology workups and hyponatremia evaluation. Use alongside [Anion Gap Calculator](/tools/anion-gap) in toxicology workup (toxic alcohols cause both osmolal gap AND elevated anion gap). For hyponatremia evaluation, also use [Sodium Correction Calculator](/tools/sodium-correction) and [Free Water Deficit Calculator](/tools/free-water-deficit). Monitor kidney function with [BUN/Creatinine Ratio](/tools/bun-creatinine-ratio) and [eGFR Calculator](/tools/egfr-calculator).
Formula: Osmolality = 2×Na + Glucose/18 + BUN/2.8
Serum osmolality represents the total concentration of dissolved particles (solutes) per kilogram of water. The three major contributors to osmolality are sodium (and its accompanying anions), glucose, and urea (measured as BUN). Formula: Osmolality = 2 × Na + Glucose/18 + BUN/2.8. The factor of 2 for sodium accounts for sodium plus its accompanying anions (mainly chloride and bicarbonate). Glucose/18 and BUN/2.8 convert mg/dL to mOsm/kg. Together these account for ~95% of normal serum osmolality (275-295 mOsm/kg).
The laboratory can directly measure serum osmolality using an osmometer (typically by freezing point depression). The difference between measured osmolality and calculated osmolality is the osmolal gap. Osmolal gap = Measured osmolality − Calculated osmolality. A normal osmolal gap is −10 to +10 mOsm/kg (most labs use <10 as normal). An elevated gap (>10 mOsm/kg) indicates the presence of unmeasured osmotically active substances not accounted for in the calculation.
If the osmolal gap is elevated (>10 mOsm/kg), suspect the presence of unmeasured osmoles. In emergency/toxicology contexts, this most importantly includes toxic alcohols: methanol, ethylene glycol, isopropyl alcohol. Other causes include ethanol (most common non-toxic cause), mannitol or hypertonic saline therapy, IV contrast dye, propylene glycol (found in IV lorazepam, diazepam), severe ketoacidosis (acetone), and severe lactic acidosis. The combination of an elevated osmolal gap PLUS an elevated anion gap strongly suggests toxic alcohol ingestion (methanol or ethylene glycol), which is a medical emergency requiring immediate treatment.
Emergency physicians, medical toxicologists
A patient with altered mental status, visual complaints, and metabolic acidosis has labs: Na 140, glucose 100, BUN 15, anion gap 28. Calculated osmolality = 2×140 + 100/18 + 15/2.8 = 280 + 5.6 + 5.4 = 291 mOsm/kg. Measured osmolality is 335 mOsm/kg. Osmolal gap = 335 − 291 = 44 mOsm/kg (markedly elevated). Combined with high anion gap acidosis, this is methanol or ethylene glycol ingestion until proven otherwise. Immediate treatment: fomepizole (blocks alcohol dehydrogenase), sodium bicarbonate for acidosis, consider hemodialysis. Check serum methanol/ethylene glycol levels, but don't wait for results to start treatment — delay increases mortality and permanent disability (blindness from methanol, renal failure from ethylene glycol).
Emergency physicians, hospitalists
A patient found unconscious has Na 138, glucose 90, BUN 12. Calculated osmolality = 287 mOsm/kg. Measured osmolality = 325 mOsm/kg. Osmolal gap = 38 mOsm/kg. The patient has no anion gap elevation (AG = 12). This pattern suggests ethanol intoxication. Each 100 mg/dL of ethanol raises osmolality by ~22 mOsm/kg, so an osmolal gap of 38 suggests ethanol level ~170 mg/dL (17 times the legal limit). Confirm with serum ethanol level. Because there's no anion gap elevation, toxic alcohols are less likely (though co-ingestion is possible). Management: supportive care, thiamine, monitor for withdrawal.
Nephrologists, endocrinologists, hospitalists
A patient with Na 118 mEq/L needs hyponatremia workup. Calculate osmolality: 2×118 + 100/18 + 15/2.8 = 247 mOsm/kg (low). Measured osmolality is 245 mOsm/kg (osmolal gap near zero). This confirms true hypotonic hyponatremia — the patient has excess water relative to solute. Next steps: assess volume status (hypovolemic vs euvolemic vs hypervolemic), check urine sodium and osmolality, consider SIADH, adrenal insufficiency, hypothyroidism, diuretics. Contrast this with pseudohyponatremia (normal measured osmolality despite low sodium) or hypertonic hyponatremia (high measured osmolality from glucose or mannitol), where the approach is completely different.
Emergency physicians, endocrinologists, intensivists
A patient with HHS has glucose 1100 mg/dL, Na 148 mEq/L, BUN 45 mg/dL. Calculated osmolality = 2×148 + 1100/18 + 45/2.8 = 296 + 61 + 16 = 373 mOsm/kg (severely elevated). This profound hyperosmolality (>350 mOsm/kg) drives neurological symptoms (altered mental status, seizures, coma) and predicts higher mortality. The osmolality guides treatment intensity and monitoring. Target: reduce osmolality gradually (no more than 3-8 mOsm/kg/hr) to prevent cerebral edema. Serial osmolality calculations track treatment response as glucose falls and sodium normalizes. HHS osmolality >340 mOsm/kg has ~15% mortality.
Intensivists, neurosurgeons
A TBI patient receiving mannitol for cerebral edema has Na 152, glucose 140, BUN 30. Calculated osmolality = 2×152 + 140/18 + 30/2.8 = 315 mOsm/kg. Measured osmolality is 345 mOsm/kg. Osmolal gap = 30 mOsm/kg (elevated from mannitol). This is expected and therapeutic — mannitol creates an osmotic gradient that draws fluid from brain tissue, reducing ICP. However, serum osmolality should not exceed 320-330 mOsm/kg to avoid acute kidney injury. In this patient, measured osmolality (345) exceeds target — hold mannitol dose and recheck in 2 hours. If osmolality continues rising, switch to hypertonic saline (3% NaCl), which raises osmolality but without the renal toxicity risk.
Emergency physicians, toxicologists
A patient drank rubbing alcohol (70% isopropyl alcohol) 4 hours ago. Labs show elevated osmolal gap (50 mOsm/kg) but normal anion gap (12 mEq/L). This pattern is characteristic of isopropyl alcohol, which metabolizes to acetone (not an acid), so it produces osmolal gap without anion gap elevation. The patient appears intoxicated with fruity breath odor (acetone). Treatment is supportive — isopropyl alcohol rarely causes severe toxicity. Do NOT give fomepizole (not indicated for isopropyl alcohol). Hemodialysis is rarely needed unless level >400 mg/dL with refractory hypotension. Key: distinguish from methanol/ethylene glycol (which cause anion gap acidosis and require urgent fomepizole).
The combination of elevated osmolal gap (>10) and elevated anion gap (>12) is methanol or ethylene glycol ingestion until proven otherwise. This is a medical emergency. Start fomepizole immediately (within 1 hour) — waiting for confirmatory levels delays life-saving treatment. Mortality increases with delayed treatment. Remember: 'Osmolal gap opens first (parent alcohol present), anion gap opens later (toxic metabolites accumulate).'
In late presentations (>12-24 hours post-ingestion), the parent alcohol may be fully metabolized. Methanol becomes formic acid, ethylene glycol becomes glycolic and oxalic acid. These acid metabolites cause anion gap elevation but don't contribute to osmolal gap. You'll see high anion gap acidosis with normal osmolal gap. Check both osmolal gap AND anion gap. If anion gap is severely elevated (>25) with unexplained acidosis, consider late toxic alcohol even if osmolal gap is normal.
You can estimate blood ethanol level from the osmolal gap: Ethanol (mg/dL) ≈ Osmolal gap × 4.6. Example: osmolal gap of 30 suggests ethanol level ~138 mg/dL. This is useful when ethanol level is pending or unavailable. If a patient has elevated osmolal gap but normal anion gap, check ethanol level first (most common cause) before worrying about toxic alcohols.
The osmolal gap only exists if you have BOTH calculated and measured osmolality. Always order measured serum osmolality from the lab when you suspect toxic alcohol, severe ketoacidosis, or unexplained altered mental status. Some EDs include it reflexively in toxic ingestion panels. Without measured osmolality, you only have half the equation.
Propylene glycol is a solvent in IV lorazepam, diazepam, phenobarbital, esmolol, nitroglycerin, and pentobarbital. High-dose infusions (especially lorazepam >1 mg/kg/hr for >48 hours) can cause propylene glycol toxicity: elevated osmolal gap, lactic acidosis, acute kidney injury, hypotension. Suspect this in ICU patients on prolonged high-dose sedation with unexplained metabolic acidosis and osmolal gap. Treatment: stop the infusion, switch to alternative sedation (propofol, fentanyl).
Severe DKA or alcoholic ketoacidosis can produce an osmolal gap of 10-20 mOsm/kg from acetone (which is osmotically active but not captured in the calculation). This is usually mild. If osmolal gap is >25 in DKA, suspect co-ingestion of ethanol or toxic alcohol, especially in alcoholic ketoacidosis patients.
Urea (BUN) is osmotically active but freely crosses cell membranes, so it doesn't cause water shifts or symptoms. Effective (or 'tonicity') osmolality excludes BUN: Effective osmolality = 2 × Na + Glucose/18. Normal is 285-295 mOsm/kg. This better predicts neurological symptoms (cerebral edema in hypo-osmolality, altered mental status in hyperosmolality). For toxicology, use total osmolality (including BUN) to calculate osmolal gap.
If calculated osmolality significantly exceeds measured osmolality (negative gap < −10), suspect: (1) laboratory error (recheck sample), (2) severe hyperlipidemia or hyperproteinemia causing pseudohyponatremia (measured sodium falsely low on some older analyzers, though this is rare with modern direct ion-selective electrode methods), or (3) mathematical error in your calculation. True negative gaps are uncommon.
Mannitol raises osmolality and creates an osmolal gap (mannitol is not in the formula). Hypertonic saline (3% NaCl) raises osmolality by increasing sodium, which IS in the formula, so no osmolal gap is created. Both are used for cerebral edema, but mannitol can cause acute kidney injury if serum osmolality >320-330 mOsm/kg. Monitor total osmolality when using either therapy.
Don't rely on osmolal gap alone. Integrate with history (what did the patient drink? antifreeze = ethylene glycol, windshield fluid = methanol, rubbing alcohol = isopropyl), exam findings (visual changes in methanol, oxalate crystals in urine for ethylene glycol), and other labs (anion gap, lactate, ketones). The osmolal gap is a clue, not a diagnosis.
Your calculated serum osmolality reflects the estimated total concentration of dissolved particles in the blood based on sodium, glucose, and BUN — the three major osmotically active solutes. A normal calculated osmolality is 275–295 mOsm/kg. Values below 275 suggest hypo-osmolality, which is most commonly associated with hyponatremia and can cause cerebral edema and neurological symptoms. Values above 295 suggest hyperosmolality, seen in dehydration, diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), and toxic ingestions.
The calculated osmolality becomes especially powerful when compared to the measured osmolality from the laboratory. The difference between measured and calculated osmolality is called the osmolal gap. A gap greater than 10 mOsm/kg suggests the presence of unmeasured osmotically active substances — most importantly toxic alcohols (methanol, ethylene glycol, isopropyl alcohol) but also ethanol, mannitol, or contrast dye. This makes the osmolal gap a critical tool in the emergency toxicology workup.
Use the calculated serum osmolality whenever you need to assess a patient's overall osmolar status or when you suspect the presence of unmeasured osmoles. The most important clinical applications include the workup of suspected toxic alcohol ingestion (methanol, ethylene glycol, isopropyl alcohol), evaluation of hyponatremia (to distinguish true hypotonic hyponatremia from pseudohyponatremia and hypertonic hyponatremia), and assessment of hyperosmolar states such as DKA and HHS.
In the emergency department, calculating the osmolal gap is a standard step when a patient presents with altered mental status, unexplained metabolic acidosis with an elevated anion gap, or a history concerning for toxic ingestion. It is also used in the ICU for monitoring patients receiving mannitol or hypertonic saline therapy.
The calculated osmolality is an estimate that accounts only for sodium, glucose, and BUN. It does not capture the contribution of other osmotically active substances that may be present in the blood, which is precisely why the osmolal gap exists as a diagnostic tool. However, the accuracy of the osmolal gap depends on the precision of both the measured and calculated values, and small errors in either can produce misleading results.
Different formulas for calculating osmolality exist, and they can yield slightly different results. This tool uses the most commonly cited formula (2×Na + Glucose/18 + BUN/2.8), but some institutions use variations that include ethanol as a fourth term. Additionally, a normal osmolal gap does not completely rule out toxic alcohol ingestion — in late presentations, the parent alcohol may have been metabolized to its acid metabolites (e.g., formic acid from methanol), which do not contribute to the osmolal gap but do raise the anion gap. The osmolal gap and anion gap should be interpreted together in suspected poisoning cases.
Disclaimer: This tool is for educational and informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider with questions about your health.
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