Plasma Osmolality Formula
The standard formula for calculating plasma osmolality is: 2 × Na (mEq/L) + glucose (mg/dL)/18 + BUN (mg/dL)/2.8, which is recommended by the American Diabetes Association and American Academy of Pediatrics for routine clinical use. 1, 2
Standard Clinical Formula
The most widely accepted and guideline-endorsed formula is:
Calculated Osmolality = 2 × [Na] + (Glucose/18) + (BUN/2.8)
Where:
- Sodium (Na) is measured in mEq/L 1, 2
- Glucose is measured in mg/dL and divided by 18 to convert to mOsm/L 1, 2
- Blood Urea Nitrogen (BUN) is measured in mg/dL and divided by 2.8 to convert to mOsm/L 1, 2
This formula provides acceptable accuracy for clinical screening and is endorsed by major medical societies including the American Diabetes Association and American Academy of Pediatrics. 1, 2
Alternative Formula for Enhanced Accuracy
For situations requiring greater precision, particularly when computer-linked equipment is available, an alternative formula incorporating potassium can be used:
Osmolality = 1.86 × (Na + K) + 1.15 × (Glucose/18) + (Urea/2.8) + 14
This formula has been validated in research studies to provide superior accuracy compared to the standard formula, though it is more complex for manual calculations. 2, 3, 4
Normal Values and Clinical Thresholds
- Normal plasma osmolality range: 275-295 mOsm/kg 1, 2, 5
- Hyperosmolality threshold: >300 mOsm/kg indicates dehydration requiring intervention 2, 5
- Hyperosmolar Hyperglycemic State (HHS): ≥320 mOsm/kg 1, 5
Effective Osmolality (Tonicity)
When assessing tonicity rather than total osmolality, BUN should be excluded because urea freely crosses cell membranes and does not affect cellular water shifts:
Effective Osmolality = 2 × [Na] + (Glucose/18)
This formula is specifically recommended by the American Diabetes Association for evaluating tonicity in hyperglycemic crises. 1, 5
Important Clinical Caveats
Direct measurement is the gold standard: Calculated osmolality is acceptable for screening but may miss unmeasured osmoles such as alcohols, mannitol, or other exogenous substances. 2, 5
Osmolal gap: The difference between measured and calculated osmolality should be 0 ± 2 mOsm/L; an elevated gap (>10 mOsm/L) suggests the presence of unmeasured osmoles. 2, 6
Hyperglycemia correction: When interpreting sodium in hyperglycemic states, add 1.6 mEq/L to the measured sodium for every 100 mg/dL of glucose above 100 mg/dL to obtain the corrected sodium value. 1, 5
Rate of change monitoring: During treatment of hyperosmolar states, the decrease in osmolality should not exceed 3 mOsm/kg/h to prevent cerebral edema. 1, 5