Osmolality revisited--deriving and validating the best formula for calculated osmolality

Clin Biochem. 2005 Jun;38(6):514-9. doi: 10.1016/j.clinbiochem.2005.03.001.


Objective: To derive a formula that can be used (i) to calculate osmolality in normal patients as well as those that are hyperglycemic and intoxicated, and (ii) to predict the presence of unexplained compounds with the osmol gap calculation in the presence and absence of ethanol. DESIGN AND EXPERIMENTS: We performed in vitro experiments to determine the relationship of serum osmolality with sodium, potassium, urea, glucose, ethanol, methanol, and ethylene glycol. Several formulas were then tested for their validity in predicting osmolality in normal individuals. Finally, we assessed whether these formulas would allow us to calculate the osmolality gap (OG) that may be indicative of the presence of other osmotically active compounds. The OG calculation was done both in the presence and absence of ethanol. In this way, the OG should be able to detect compounds like methanol and ethylene glycol even in the presence of ethanol which is easily measured and is very often present in the above-named poisonings.

Results: Experimental results show that glucose, ethanol, methanol, and ethylene glycol need factors of 1.15, 1.20, 1.07, and 1.00, respectively, to accurately predict osmolality. The factors for glucose and ethanol were then validated in normal subjects as well as in a large patient database. The formulas below predicted osmolality very well in patients whether ethanol was present or not. All concentrations are expressed in mmol/L. The mean osmol gap for healthy subjects without ethanol present was 0.77 +/- 3.80 mosM/kg with the reference interval being -6.68 to 8.23 mosM/kg for formula 1 and -8.04 to 6.50 mosM/kg for formula 2. The mean osmol gap (OG) in patients who had ethanol present was 1.22 +/- 5.32 for formula 1 and -0.2 +/- 5.0 for formula 2.

Conclusions: This study shows that factors of 1.20 and 1.15 have to be applied to ethanol and glucose to allow for accurate calculation of osmolality and osmolality gap. There were insufficient patient data to verify the factors for methanol and ethylene glycol.

MeSH terms

  • Alcoholic Intoxication / blood
  • Alcoholic Intoxication / diagnosis
  • Blood Glucose
  • Ethanol / blood*
  • Ethylene Glycol / blood
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / diagnosis
  • In Vitro Techniques
  • Mathematics
  • Methanol / blood
  • Osmolar Concentration*
  • Potassium / blood*
  • Reproducibility of Results
  • Sodium / blood*
  • Urea / blood*


  • Blood Glucose
  • Ethanol
  • Urea
  • Sodium
  • Ethylene Glycol
  • Potassium
  • Methanol