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 primary 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 the 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 thresholds, defining HHS as osmolality ≥320 mOsm/kg using [(2×Na+) + glucose + urea], hyperglycemia ≥30 mmol/L (≥540 mg/dL), 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:
- Altered mental status ranges from stupor to coma and correlates with the degree of hyperosmolality 1, 4
- Mental obtundation is more frequent in HHS than DKA, but patients meeting metabolic thresholds warrant HHS management regardless of alertness 2
- In pediatric protocols, HHS requires either "altered mental status OR severe dehydration," indicating mental status change alone is not mandatory if severe dehydration is present 2
- Suspect HHS based on metabolic criteria even if mental status is preserved 2
Essential Laboratory Workup
Immediately obtain the following tests upon clinical suspicion 1, 2:
- Arterial blood gases
- Complete blood count with differential
- Comprehensive metabolic panel (including serum electrolytes with calculated anion gap)
- Blood urea nitrogen and creatinine
- Serum ketones and urinalysis with urine ketones by dipstick
- Serum osmolality (measured or calculated)
- Electrocardiogram
- HbA1c
- Bacterial cultures (blood, urine, throat) if infection suspected 1, 2
- Chest X-ray if clinically indicated 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 elevation above 100 mg/dL 1, 2
- An initial rise in sodium level during treatment is expected and is not itself an indication for hypotonic fluids 5
- Monitor calculated effective osmolality, not just individual components, to ensure accurate diagnosis 2
Key Distinctions from DKA
HHS differs fundamentally from DKA in several ways 1:
- Temporal evolution: HHS develops over days to weeks versus DKA developing over hours 1, 2
- Dehydration severity: Total body water deficit in HHS is approximately 9 liters (100-220 mL/kg) versus less severe in DKA 2
- Acidosis: Absent or minimal in HHS (pH >7.30) versus significant in DKA (pH <7.30) 1
- Ketone status: Minimal or absent in HHS versus prominent in DKA 1
Common Diagnostic Pitfalls
- Hypothermia or normothermia may be present despite infection being a common precipitant, and hypothermia is a poor prognostic sign 1
- Patients may be normothermic or hypothermic due to peripheral vasodilation, so absence of fever does not exclude infection 1
- Abdominal pain may be a result or cause of the hyperglycemic crisis; further evaluation is necessary if pain does not resolve with treatment 2
- Starvation ketosis can mimic HHS but has mildly elevated glucose (rarely >250 mg/dL) and bicarbonate usually not <18 mEq/L 2
- Alcoholic ketoacidosis presents with variable glucose (can be hypoglycemic to mildly elevated) and profound acidosis 2
Variant Presentation: Euglycemic Hyperosmolar Hypernatremic State
A recently recognized variant subtype presents with glucose ≥180 mg/dL but <600 mg/dL, hypernatremia, and effective osmolality >320 mOsm/kg 6: