Diagnostic Criteria for Hyperosmolar Hyperglycemic State (HHS)
HHS is diagnosed when plasma glucose is ≥600 mg/dL, effective serum osmolality is ≥320 mOsm/kg, arterial pH is >7.30, serum bicarbonate is ≥15 mEq/L, and ketones are absent or minimal. 1
Core Metabolic Thresholds
The American Diabetes Association establishes five essential diagnostic parameters that must be met:
- Plasma glucose ≥600 mg/dL is the glycemic threshold for HHS diagnosis 1, 2
- Effective serum osmolality ≥320 mOsm/kg H₂O, calculated using the formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1, 2
- Arterial pH >7.30 distinguishes HHS from diabetic ketoacidosis (DKA) 1, 2
- Serum bicarbonate ≥15 mEq/L confirms absence of significant acidosis 1, 2
- Ketones absent or minimal in both urine (small by nitroprusside reaction) and serum 1, 2
The Joint British Diabetes Societies uses slightly different osmolality calculation [(2×Na+) + glucose + urea] and may accept glucose ≥30 mmol/L (≥540 mg/dL) with osmolality ≥320 mOsm/kg, ketonaemia ≤3.0 mmol/L, pH >7.3, and bicarbonate ≥15 mmol/L 3
Clinical Presentation Considerations
Mental status changes are common but NOT mandatory for diagnosis when metabolic criteria are met 2:
- Altered consciousness ranges from full alertness to stupor or coma, with severity typically correlating with degree of hyperosmolality 1, 2
- Mental status changes occur more frequently in HHS than DKA 2, 4
- Patients meeting metabolic thresholds warrant HHS management regardless of alertness level 2
- In pediatric protocols, altered mental status OR severe dehydration satisfies clinical criteria 2
Critical Calculation Adjustments
Corrected serum sodium must be calculated because hyperglycemia causes pseudohyponatremia 1:
- Add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose above 100 mg/dL 1, 2
- An initial rise in sodium during treatment is expected and does not indicate need for hypotonic fluids 5
- Monitor calculated effective osmolality, not just individual components 2
Key Distinctions from DKA
HHS differs fundamentally from DKA in presentation and evolution 1:
- Time course: HHS develops over days to weeks versus DKA developing over hours 1, 2
- Dehydration: Total body water deficit is approximately 9 liters (100-220 mL/kg) in HHS, more severe than DKA 2
- Acidosis: Absent or minimal in HHS (pH >7.30) versus significant in DKA (pH <7.30) 1
- Ketone status: Small or absent in HHS versus prominent in DKA 1
Essential Initial Laboratory Workup
Obtain immediately upon clinical suspicion 1, 2:
- Arterial blood gases
- Complete blood count with differential
- Comprehensive metabolic panel (including calculated anion gap)
- Serum osmolality and electrolytes
- Blood urea nitrogen and creatinine
- Urinalysis with ketones by dipstick
- Serum ketones
- Electrocardiogram
- HbA1c
- Cultures (blood, urine, throat) if infection suspected 1, 2
- Chest X-ray if clinically indicated 2
Common Diagnostic Pitfalls
Beware of atypical presentations that can mislead diagnosis:
- Hypothermia or normothermia may occur despite infection being the most common precipitant, due to peripheral vasodilation; hypothermia is a poor prognostic sign 1, 2
- Abdominal pain may be result or cause of the crisis; further evaluation needed if pain persists despite treatment 2
- Euglycemic variant exists: Patients with glucose ≥180 mg/dL but <600 mg/dL, hypernatremia, and osmolality >320 mOsm/kg represent a variant subtype with higher mortality (35.3% vs 0% in traditional HHS) 6
- Starvation ketosis can mimic HHS but has glucose rarely >250 mg/dL and bicarbonate usually not <18 mEq/L 2
- Alcoholic ketoacidosis shows variable glucose (can be hypoglycemic to mildly elevated) with profound acidosis 2
Mortality Considerations
HHS carries significant mortality risk that exceeds DKA 7: