Serum Osmolality Values in Normal, DKA, and HHS
Normal serum osmolality ranges from 275-295 mOsm/kg, while HHS is defined by effective serum osmolality ≥320 mOsm/kg H₂O, and DKA typically presents with variable osmolality (<320 mOsm/kg) that is lower than HHS. 1
Normal Serum Osmolality
- Normal range: 275-295 mOsm/kg 2
- Sodium, chloride, bicarbonate, and potassium are the primary electrolytes contributing to serum osmolality 2
- Hyperosmolality is defined as >300 mOsm/kg, which indicates low-intake dehydration and is associated with increased mortality risk 2
Calculation of Effective Serum Osmolality
- Formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1
- Alternative comprehensive formula: Osmolarity = 1.86 × (Na⁺ + K⁺) + 1.15 × glucose + urea + 14 (all in mmol/L) 2
- Serum sodium must be corrected for hyperglycemia: for each 100 mg/dL glucose above 100 mg/dL, add 1.6 mEq to the sodium value 1
Hyperosmolar Hyperglycemic State (HHS)
Diagnostic Criteria
- Effective serum osmolality ≥320 mOsm/kg H₂O 1
- Blood glucose ≥600 mg/dL 1
- Arterial pH ≥7.3 1
- Bicarbonate ≥15 mEq/L 1
- Mild ketonuria or ketonemia only 1
Clinical Significance
- HHS presents with significantly higher osmolality than DKA, which is the key distinguishing feature 3, 4
- The hyperosmolar state is associated with altered mental status and severe dehydration 1, 4
- Mortality rates range from 10-20%, with higher osmolarity adversely affecting survival 5
Diabetic Ketoacidosis (DKA)
Diagnostic Criteria
- Serum osmolality is typically <320 mOsm/kg (variable, but lower than HHS threshold) 6
- Blood glucose ≥250 mg/dL 1
- Arterial pH <7.3 1
- Bicarbonate <15 mEq/L 1
- Moderate to severe ketonuria or ketonemia 1
Clinical Significance
- DKA is more common in younger patients with type 1 diabetes, while HHS occurs predominantly in type 2 diabetes 3
- Osmolality in DKA is elevated but does not reach the ≥320 mOsm/kg threshold that defines HHS 6
Overlap Syndrome: Hyperosmolar DKA (H-DKA)
- A distinct clinical entity exists where both conditions overlap, defined by: glucose >600 mg/dL, pH <7.3, bicarbonate <15 mEq/L, AND serum osmolality >320 mOsm/kg 6
- Average serum osmolality in H-DKA cases: 394.8 ± 55 mOsm/kg, indicating severe hyperosmolality with concurrent ketoacidosis 6
- This overlap presentation carries high risk for multi-organ complications including acute kidney injury, rhabdomyolysis, and cardiac arrhythmias 6
Critical Management Considerations
Rate of Osmolality Correction
- The induced change in serum osmolality should not exceed 3 mOsm/kg/h during treatment 1
- This applies to both adult and pediatric patients to prevent cerebral edema 1
- Monitoring serum osmolality every 2-4 hours during active treatment is essential 1
Common Pitfall
- Do not rely on clinical signs alone (skin turgor, mouth dryness, urine color) to assess hydration status, especially in older adults, as these are unreliable 2
- Direct measurement of serum osmolality is the gold standard, with calculated osmolarity as a second-line option when direct measurement is unavailable 2