The osmolal gap is the difference between measured and calculated osmolality.

There are a number of formulae for calculating osmolality. The one below is the simplest and probably the most widely used. The result can vary considerably for individuals by using different formulae though the normal ranges are similar. Further work is needed to define whether one formula is better at detecting toxic alcohol ingestions.

• Calculated osmolality = 2 x Na⁺ glucose + urea (in mmol/L)

For laboratories that use non SI units:

• Calculated osmolality = 2 x Na⁺ glucose (mg/dl)/18 + urea (mg/dl)/2.8

The measured osmolality should be done by freezing point depression (other methods are too inaccurate).

The normal range for the osmolal gap is -12 to +12. This range is slightly higher (up to 17) in patients with acidosis from other causes.

In toxicology an osmolal gap of greater than 17 is strongly suggestive of poisoning with one of the following:

• ethanol
• methanol *
• isopropyl alcohol
• ethylene glycol and glycol ethers *

*also associated with a high anion gap acidosis

However an elevated osmolar gap should be correlated with other clinical findings because it is a relatively nonspecific finding that is also commonly seen in alcoholic and diabetic ketoacidosis, lactic acidosis and in chronic renal failure. Elevation in the osmolar gap in these disease states is thought to be due in part to elevations of endogenous glycerol, acetone, acetone metabolites, and in the case of renal failure, retention of unidentified small solutes.

Administration of IV mannitol, sorbitol, ethanol or glycerol causes an osmolal gap. An osmolal gap of less than zero makes significant poisoning with these agents unlikely. Osmolal gaps of 0-17 are not helpful as an aid to diagnosis.

Osmolar Gap = Ethanol (mg/dL)/3.7 or, in SI units: 1.25 (Ethanol [mmol/L]) (Purssell 2001)

See also Calculation of osmolar gap for various alcohols at Medicine Central

See the following for lethal concentrations of alcohols and their corresponding osmolal gaps:

Substance: Ethanol
Molecular Weight: 46
Lethal Concentration (mg/dL): 350
Corresponding Osmolal Gap (mosm/kg H2O): 75

Substance: Methanol
Molecular Weight: 32
Lethal Concentration (mg/dL): 80
Corresponding Osmolal Gap (mosm/kg H2O): 25

Substance: Ethylene glycol
Molecular Weight: 62
Lethal Concentration (mg/dL): 200
Corresponding Osmolal Gap (mosm/kg H2O): 35

Substance: Isopropanol
Molecular Weight: 60
Lethal Concentration (mg/dL): 350
Corresponding Osmolal Gap (mosm/kg H2O): 60

The osmolal gap is easily calculated and an increased gap may be seen with ethylene glycol, ethanol , and methanol poisonings.

Buckley NA, Whyte IM, Dawson AH. Utility of the osmolal gap. J Toxicol Clin Toxicol 1994; 32(1):93-95

Hoffman RS et al. Osmol gaps revisited: Normal Values and Limitations. Clin Toxicol 1993; 31: 81-93PMID8433417

Link to measurement and calculation issues