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

Diagnostic Criteria for Hyperglycemic Hyperosmolar State

The American Diabetes Association establishes that HHS is diagnosed when five metabolic criteria are met: plasma glucose ≥600 mg/dL, arterial pH >7.30, serum bicarbonate ≥15 mEq/L, effective serum osmolality ≥320 mOsm/kg, and ketones absent or minimal (small by nitroprusside reaction). 1, 2

Core Metabolic Thresholds

The diagnosis of HHS requires all of the following laboratory parameters:

• Plasma glucose ≥600 mg/dL - This distinguishes HHS from other hyperglycemic states 1, 2
• Arterial pH >7.30 - This differentiates HHS from diabetic ketoacidosis (DKA), where pH is <7.30 1, 2
• Serum bicarbonate ≥15 mEq/L - Reflects the absence of significant metabolic acidosis 1, 2
• Effective serum osmolality ≥320 mOsm/kg - Calculated using the formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1, 2
• Ketones small or absent - Both urine ketones (by nitroprusside method) and serum ketones should be small, distinguishing HHS from DKA 1, 2

Critical Calculation Adjustments

When evaluating osmolality and sodium status, you must account for the effect of hyperglycemia:

• Calculate corrected serum sodium by adding 1.6 mEq/L to the measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL 1, 2
• This correction is essential because hyperglycemia causes pseudohyponatremia, and failure to correct can lead to inappropriate fluid management 1
• Monitor calculated effective osmolality, not just individual components, to ensure accurate diagnosis and treatment response 2

Clinical Presentation (Not Mandatory for Diagnosis)

While altered mental status is common in HHS, it is not an absolute diagnostic requirement:

• Mental status typically ranges from full alertness to stupor or coma, with altered consciousness being more frequent in HHS than in DKA 2
• The degree of mental obtundation correlates with the severity of hyperosmolarity 2
• Patients meeting metabolic thresholds warrant HHS management regardless of alertness level 2
• In pediatric protocols, HHS requires either "altered mental status or severe dehydration," indicating that mental status change alone is not mandatory if severe dehydration is present 2

Essential Initial Laboratory Workup

Upon clinical suspicion of HHS, immediately obtain:

• Arterial blood gases, complete blood count with differential, comprehensive metabolic panel with calculated anion gap 1, 2
• Urinalysis with ketones by dipstick and serum ketones 1, 2
• Blood urea nitrogen, creatinine, serum osmolality 2
• Electrocardiogram and HbA1c 1, 2
• Cultures (blood, urine, throat) if infection is suspected, and chest X-ray if clinically indicated 1, 2

Key Distinctions from DKA

HHS differs fundamentally from DKA in several ways:

• Time course: HHS develops over days to weeks, whereas DKA develops over hours 1, 2
• Dehydration: Total body water deficit in HHS is approximately 9 liters (100-220 mL/kg), 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 significant ketonemia in DKA 1

Common Diagnostic Pitfalls

• Do not expect fever: Patients may be normothermic or hypothermic due to peripheral vasodilation, even when infection is the precipitant 1
• Hypothermia, if present, is a poor prognostic sign despite infection being a common trigger 1
• An initial rise in sodium level is expected during treatment and is not itself an indication for hypotonic fluids 3
• Abdominal pain may be a result or cause of the hyperglycemic crisis; further evaluation is necessary if pain does not resolve with treatment 2

Differential Considerations

Distinguish HHS from other conditions presenting with hyperglycemia:

• Starvation ketosis: Mildly elevated glucose (rarely >250 mg/dL) and bicarbonate usually not <18 mEq/L 2
• Alcoholic ketoacidosis: Variable glucose (can be hypoglycemic to mildly elevated) with profound acidosis possible 2
• Mixed DKA/HHS: May occur, particularly in younger adults and children with type 2 diabetes 4