The osmolar gap is determined by subtracting the calculated osmolality from the measured osmolality. While there are many formulae for the calculated osmolality, the most commonly used is:
Calculated osmolality = 2 x serum sodium + serum glucose + serum urea (all in mmol/L).
The normal osmolar gap is up to 10 mmol/L and values in excess of this usually indicate the presence of an exogenous agent. The most common by far is ethanol, but methanol, ethylene glycol, acetone and isopropyl alcohol can occasionally be present in sufficient quantities to produce an increased osmolar gap. The equation to calculate the osmolar gap when ethanol has been measured, as a sceren for the presence of other substances, is as follows:
Calculated osmolality = 2 x serum sodium + serum glucose + serum urea - 270 x ethanol
(all in mmol/L except ethanol in mg/dL or % ).
Calculated serum osmolality = 2 x sodium + glucose + urea - 1.25 x ethanol
(all in mmol/L including ethanol ).
Clinically significant toxicities, particularly from ethylene glycol, can occur with a normal osmolar gap as the toxic concentrations are quite low. With the passing of time from ingestion of alcohol, methanol or ethylene glycol the osmolar gap falls and the anion gap rises due to conversion to negatively charged substances. In diabetic ketoacidosis an increased osmolar gap may be due to acetone accumulation. * the factor of 1.25, which is included in the factor of 270 in the preceeding equation, is due to ethanol contributing more to the osmolar gap than would be expected from its molecular weight of 46 (Pursell RA et al Ann Emerg Med 2001;38:653-659).