Approach to Increased Osmolar Gap

Background and Calculations

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

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

Caution

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.

References

• 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]