What are the diagnostic criteria for Hyperosmolar Hyperglycemic State (HHS)?

Diagnostic Criteria for Hyperosmolar Hyperglycemic State (HHS)

HHS is diagnosed when plasma glucose is ≥600 mg/dL, arterial pH is >7.30, serum bicarbonate is ≥15 mEq/L, effective serum osmolality is ≥320 mOsm/kg, and ketones are absent or minimal (small), typically accompanied by altered mental status. 1

Core Diagnostic Parameters

The American Diabetes Association establishes the following specific thresholds for HHS diagnosis:

Metabolic Criteria

• Plasma glucose: ≥600 mg/dL 1
• Arterial pH: >7.30 (distinguishes from DKA) 1
• Serum bicarbonate: ≥15 mEq/L 1
• Effective serum osmolality: ≥320 mOsm/kg 1
  • Calculate using: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1, 2

Ketone Status

• Urine ketones: Small (by nitroprusside reaction method) 1
• Serum ketones: Small 1
• This minimal ketonemia/ketonuria is critical for distinguishing HHS from DKA 1

Clinical Presentation

• Mental status: Ranges from stupor to coma (more common than in DKA) 1
• Altered sensorium correlates with degree of hyperosmolality 1

Important Calculation Adjustments

Corrected serum sodium must be calculated to accurately assess true sodium status, as hyperglycemia causes pseudohyponatremia 2:

• Add 1.6 mEq 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 3

Anion gap is variable in HHS (unlike DKA where it is consistently elevated >12) 1

Critical Distinctions from DKA

HHS differs fundamentally from diabetic ketoacidosis:

• Evolution: HHS develops over days to weeks versus hours for DKA 1
• Dehydration: More severe in HHS (fluid losses 100-220 mL/kg) 4
• Acidosis: Absent or minimal in HHS (pH >7.30) versus significant in DKA (pH <7.30) 1
• Ketones: Small/absent in HHS versus positive in DKA 1

Emerging Variant Recognition

Recent evidence identifies euglycemic hyperosmolar hypernatremic state as a variant subtype with glucose 180-599 mg/dL (below traditional HHS threshold) but effective osmolality still >320 mOsm/kg 5. This variant carries higher mortality (35.3% vs 0% in traditional HHS) and occurs in older patients with less severe baseline diabetes 5. Recognition is critical as it requires similar treatment strategies despite lower glucose levels 5.

Essential Initial Laboratory Workup

After establishing clinical suspicion, obtain immediately 1:

• Arterial blood gases
• Complete blood count with differential
• Comprehensive metabolic panel (electrolytes, BUN, creatinine, glucose)
• Serum osmolality (measured or calculated)
• Urinalysis with ketones by dipstick
• Serum ketones
• Electrocardiogram
• Cultures (blood, urine, throat) if infection suspected 1

Common Diagnostic Pitfalls

Do not rely on glucose level alone - some patients present with effective osmolality >320 mOsm/kg but glucose <600 mg/dL (euglycemic variant), which still requires HHS management 5. Mixed DKA/HHS presentations can occur, particularly in younger adults and children with type 2 diabetes 4. The Joint British Diabetes Societies notes HHS increasingly affects younger populations, not just elderly patients 4.

Hypothermia, if present, is a poor prognostic sign despite infection being a common precipitant 1. Patients may be normothermic or hypothermic due to peripheral vasodilation 1.