Approach to Increased Osmolar Gap

Author: Michelle Lin, MD
Updated: 6/1/2012

Approach to Increased Osmolar Gap

Background and Calculations

Serum osmolality: Contributed by ions and low-molecular-weight solutes

Serum osmolality = (2Na) + (BUN/2.8) + (Glucose/18) + (Ethanol/4.6)

Osmolal gap = Calculated osmolality – Measured osmolality

  • Normal OG = -10 to +10 mOsm/kg of H2O

Osmolal gap

  • Most common cause: Ethanol
  • Osmolal gap calculation includes ethanol correction factor (4.6)
  • Osmoloal gap screens for toxic alcohols with decreasing sensitivity:
    • Methanol
    • Ethanol
    • Isopropanol
    • Ethylene glycol
    • Propylene glycol
    • Diethylene glycol
  • A gap ≥ 20 suggests ethanol or toxic alcohol exposure
    • Although case reports of diabetic ketoacidosis causing osmolal gap ≥ 20

Toxic alcohols

  • Parent unmetabolized alcohols --> Contributes to osmolal gap
  • Metabolites of alcohols --> Contributes to toxic effects (except isopropanol)

Causes for High anion gap metabolic acidosis + High osmolal gap

  • Acute kidney injury

  • Intoxication, salicylates

  • Intoxication, toxic alcohol

    • Methanol
    • Ethylene glycol
    • Diethylene glycol
    • Propylene glycol
    • Isopropanol glycol
  • Ketoacidosis, alcoholic or diabetic

  • Lactic acidosis


Toxic alcohols may not cause significant osmolal gap because:

  1. High molecular weight toxic alcohols (eg. propylene glycol, diethylene glycol) do not affect the osmolality as much
  2. Wide range of normal osmolal gap (can be as low as -10)
  3. Only the parent alcohol (not the metabolites) causes osmolal gap

Tip: Consider toxic alcohols for cases of high anion gap metabolic acidosis even with normal osmolal gap.


  • Kraut JA, Xing SX. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis. Am J Kidney Dis. 2011 Sep;58(3):480-4. [PubMed]