Osmolar Gap

Calculates the osmolar gap as the difference between measured and calculated serum osmolality. An elevated osmolar gap may suggest toxic alcohol ingestion (methanol, ethylene glycol) or other osmotically active substances.

Internal Medicine Internal MedicineEvidence-BasedUpdated 2026-08-06

Clinical decision-support tool for qualified healthcare professionals. Results are not a diagnosis and should not replace professional clinical judgment.

Clinical Notes

The osmolar gap is the difference between measured serum osmolality and the osmolality calculated from sodium, glucose, and BUN: measured − (2 × Na + glucose/18 + BUN/2.8). When the measured value exceeds the calculated estimate, osmotically active substances that are not accounted for by sodium, glucose, or BUN are present in the blood. In the emergency setting, an elevated osmolar gap can indicate ingestion of osmotically active small molecules such as methanol, ethylene glycol, isopropanol, or propylene glycol. Because the toxic alcohols are metabolized to their acid products, the osmolar gap may normalize as the parent alcohol is cleared while the anion gap acidosis develops; a normal gap therefore does not exclude toxic alcohol exposure in delayed presentations. The calculation assumes sodium in mmol/L and glucose and BUN in mg/dL, with osmolality reported in mOsm/kg; unit mismatches produce a misleading gap. The result is a supportive rather than diagnostic finding and must be weighed together with the timing of any potential exposure, the anion gap, the acid-base status, and the full clinical picture, including direct measurement of suspected alcohols when exposure is a concern.

Calculator Information

Specialty

Internal Medicine

📋 Reference Ranges

Normal Range

-10 to +10 mOsm/kg

Reference ranges for this calculator
Classification	Range
Negatively elevated gap (lab error or dilutional)	<-9.9
Normal osmolar gap	-10–10
Elevated osmolar gap	≥11
Markedly elevated osmolar gap — toxic ingestion likely	≥50

What This Calculator Measures

Calculates the difference between measured and calculated serum osmolality to detect the presence of unmeasured osmoles, which may indicate toxic alcohol ingestion.

How to Use

Enter the measured serum osmolality (mOsm/kg) from the laboratory.
Enter serum sodium (mmol/L), glucose (mg/dL), and BUN (mg/dL).
Review the osmolar gap and its interpretation.

How the Calculation Works

The osmolar gap is measured osmolality minus calculated osmolality, where calculated = 2 x sodium + glucose / 18 + BUN / 2.8. A positive gap suggests unmeasured osmotically active substances.

Variables Explained

Measured Osmolality

Laboratory-measured serum osmolality in mOsm/kg, the minuend.

Sodium

Serum sodium in mmol/L, multiplied by 2 in the calculated osmolality.

Glucose

Serum glucose in mg/dL, divided by 18 in the calculated osmolality.

BUN

Blood urea nitrogen in mg/dL, divided by 2.8 in the calculated osmolality.

Interpretation Guide

An osmolar gap >10 mOsm/kg may indicate the presence of unmeasured osmoles such as toxic alcohols (methanol, ethylene glycol), ethanol, or other ingestions. A normal osmolar gap does not completely exclude toxic ingestion in delayed presentations.

Clinical Significance

An elevated osmolar gap in the appropriate clinical setting suggests the presence of an unmeasured osmole, which may be a toxic alcohol. Early identification is critical because specific antidotes (fomepizole, ethanol) and dialysis can be life-saving.

When It Is Useful

Suspected toxic alcohol ingestion (methanol, ethylene glycol, isopropanol)
Emergency department evaluation of unknown ingestion
Altered mental status with metabolic acidosis
Evaluation of elevated anion gap with suspected ingestion

When It Is Not Useful

When measured osmolality is not available
As a standalone diagnostic test for toxic ingestion
When the clinical picture clearly points to a non-toxicological cause

Common Mistakes

Computing the gap without a laboratory-measured osmolality, since the calculation needs the measured value as its starting point.
Concluding that a normal gap excludes toxic alcohol, when metabolism during a delayed presentation can normalize it before the patient arrives.
Blaming a toxic alcohol for an elevated gap when uremia or ketoacidosis may be the actual source of the unmeasured osmoles.

Limitations

A normal osmolar gap does not exclude toxic ingestion, particularly in delayed presentations where metabolism has occurred.
Requires a measured serum osmolality from the laboratory.
Ethanol ingestion elevates the osmolar gap but is not necessarily toxic.
Uremia, ketoacidosis, and alcohol can also elevate the osmolar gap.

Worked Example

A 30-year-old man presents with altered mental status and metabolic acidosis. Measured serum osmolality is 330 mOsm/kg, sodium is 140 mmol/L, glucose is 100 mg/dL, and BUN is 15 mg/dL.

Inputs:

measured: 330

sodium: 140

glucose: 100

bun: 15

Expected Result: Calculated osmolality ≈ 2 × 140 + 100/18 + 15/2.8 = 280 + 5.6 + 5.4 = 291 mOsm/kg. Osmolar gap ≈ 330 − 291 = 39 mOsm/kg. This elevated osmolar gap, in the context of metabolic acidosis, raises concern for unmeasured osmoles such as toxic alcohol ingestion.

Evidence & References

Source:: Emergency Medicine / Toxicology
Content updated:: 2026-08

Brent J, et al. N Engl J Med. 2001;344:424-429.

References

Brent J, et al. Fomepizole for the treatment of methanol poisoning. N Engl J Med. 2001;344:424-429. (Level I)

Frequently Asked Questions

What does an elevated osmolar gap mean?

An elevated osmolar gap (> 10 mOsm/kg) indicates the presence of unmeasured osmotically active substances. In the emergency setting, this may suggest toxic alcohol ingestion (methanol, ethylene glycol), ethanol, or propylene glycol. Other causes include DKA, uremia, and alcohol intoxication.

Can the osmolar gap be normal in toxic ingestion?

Yes. In delayed presentations of toxic alcohol ingestion, the parent alcohol may have been metabolized to its toxic metabolites, normalizing the osmolar gap while toxicity persists. The anion gap may be elevated in these cases.

What is the normal osmolar gap?

A normal osmolar gap is generally considered to be between -10 and +10 mOsm/kg. Values above this range are considered elevated.

Disclaimer: This calculator is intended for educational and clinical decision support purposes only. An elevated osmolar gap requires urgent clinical evaluation. Do not delay treatment while awaiting laboratory confirmation.