Serum Osmolality & Osmolar Gap

Methodology

Calculated osmolality

2 × Na (mmol/L) + glucose/18 + BUN/2.8 (+ ethanol/3.7), glucose, BUN and ethanol in mg/dL; urea in mmol/L is converted to BUN first

A raised osmolar gap suggests unmeasured osmoles such as toxic alcohols, mannitol or ketones. The ethanol term uses Purssell's 2001 divisor of 3.7; the traditional divisor of 4.6 gives different gaps, and studies disagree on which is better (Lynd 2008; 2025 volunteer study).

Who it is for

Adults.

Version

1.0.2

How this calculator works

Where the formula comes from

• A raised serum osmolal gap, with or without high anion gap acidosis, is a clue to toxic alcohol exposure (methanol, ethylene glycol, diethylene glycol, propylene glycol or isopropanol).^[1]

The inputs

• Purssell and colleagues (2001) calculated osmolality as 2 × sodium + urea nitrogen (BUN)/2.8 + glucose/18, with BUN and glucose in mg/dL, and derived ethanol (mg/dL)/3.7 as ethanol's contribution (98 observations, validated in 128 patients).^[2]

Versions and alternatives

• With the traditional ethanol divisor of 4.6 the osmol gap was −2 ± 6 mOsm; different equations gave gaps from −5 to +15.^[3]

Where accuracy falls (published evidence)

• The gap and the acidosis may not occur together, depending on the baseline gap, the alcohol's molecular weight and its stage of metabolism; ketoacidosis, kidney injury, CKD and lactic acidosis can also raise the gap.^[1]
• Because the normal range is wide, a small gap should not be used to rule out toxic alcohol ingestion.^[3]
• In one hospital series, a gap threshold of 10 had sensitivity 0.85–0.9 but specificity 0.22–0.5 for toxic alcohol levels needing antidote.^[4]
• In 22 healthy volunteers, 18% had a gap above 10 before any alcohol; after ethanol, the 4.6 divisor gave fewer falsely raised gaps than 3.7 (21% vs 47%).^[5]

Sources

1. 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;58(3):480–484. doi:10.1053/j.ajkd.2011.05.018
2. Purssell RA, Pudek M, Brubacher J, Abu-Laban RB. Derivation and validation of a formula to calculate the contribution of ethanol to the osmolal gap. Ann Emerg Med. 2001;38(6):653–659. doi:10.1067/mem.2001.119455
3. Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR. Osmol gaps revisited: normal values and limitations. J Toxicol Clin Toxicol. 1993;31(1):81–93. doi:10.3109/15563659309000375
4. Lynd LD, Richardson KJ, Purssell RA, et al. An evaluation of the osmole gap as a screening test for toxic alcohol poisoning. BMC Emerg Med. 2008;8:5. doi:10.1186/1471-227X-8-5
5. Ethanol and the limitations of the osmol gap. Ann Emerg Med. 2025;86(3):257–261. doi:10.1016/j.annemergmed.2024.12.022

Compiled from the published sources above. Every statement was agreed independently by three AI research tools (Claude, ChatGPT, DeepSeek) and its source verified in PubMed or Crossref by the Hakeemly editorial team. Not reviewed by a doctor unless stated. Agreed on 2026-10-12

Worked example: how to calculate osmolality / osmolar gap

Calculation:

280 + 5 + 5 = 290

An illustration with sample values, worked out with the same method the tool above uses.

Limitations

• Many formulas exist; the normal gap range is wide (Hoffman 1993: mean −2, SD 6 mOsm, so roughly −14 to +10, not a universal reference interval).
• A normal gap does not exclude toxic alcohol ingestion late in its course.

References

1. 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;58(3):480–484. doi:10.1053/j.ajkd.2011.05.018
2. Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR. Osmol gaps revisited: normal values and limitations. J Toxicol Clin Toxicol. 1993;31(1):81–93. doi:10.3109/15563659309000375
3. Purssell RA, Pudek M, Brubacher J, Abu-Laban RB. Derivation and validation of a formula to calculate the contribution of ethanol to the osmolal gap. Ann Emerg Med. 2001;38(6):653–659. doi:10.1067/mem.2001.119455