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, effective serum osmolality is ≥320 mOsm/kg, arterial pH is ≥7.30, serum bicarbonate is ≥15 mEq/L, and ketones are absent or minimal (≤3.0 mmol/L). 1, 2

Core Metabolic Thresholds

The American Diabetes Association establishes five mandatory criteria that must all be present for HHS diagnosis:

• Blood glucose ≥600 mg/dL - This severe hyperglycemia distinguishes HHS from other hyperglycemic states 1, 2
• Effective serum osmolality ≥320 mOsm/kg H₂O - Calculate using the formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1, 2
• Arterial pH ≥7.30 - This distinguishes HHS from diabetic ketoacidosis (DKA), which has pH <7.30 1, 2
• Serum bicarbonate ≥15 mEq/L - Reflects minimal metabolic acidosis, unlike DKA 1, 2
• Small or absent ketones - Both urine and serum ketones should be minimal (ketonemia ≤3.0 mmol/L), with β-hydroxybutyrate measurement preferred over nitroprusside method 1, 2, 3

Critical Calculation: Corrected Sodium

You must correct serum sodium for hyperglycemia to accurately assess true sodium status, as hyperglycemia causes pseudohyponatremia. Add 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 an initial rise in measured sodium during treatment is expected and normal—it does not indicate a need for hypotonic fluids. 4

Clinical Presentation (Not Mandatory for Diagnosis)

While altered mental status is common in HHS, the absence of mental status changes does not exclude HHS diagnosis when metabolic criteria are met. 1 Key clinical features include:

• Mental status ranges from full alertness to profound lethargy or coma, with altered consciousness more frequent in HHS than DKA 1, 2
• The degree of mental obtundation typically correlates with the severity of hyperosmolarity 1, 2
• Patients meeting metabolic thresholds warrant HHS management regardless of alertness level 1
• In pediatric protocols, HHS requires either altered mental status OR severe dehydration, not necessarily both 1

Essential Initial Laboratory Workup

Upon suspicion of HHS, immediately obtain: 1, 2

• Plasma glucose
• Serum electrolytes with calculated anion gap
• Serum osmolality (calculate effective osmolality)
• Arterial blood gases
• Blood urea nitrogen and creatinine
• Serum ketones (β-hydroxybutyrate preferred)
• Complete blood count with differential
• Urinalysis with urine ketones by dipstick
• Electrocardiogram
• HbA1c (to distinguish acute decompensation from chronic poor control)
• Bacterial cultures (blood, urine, throat) if infection suspected 1, 2
• Chest X-ray if pneumonia suspected 1

Key Distinctions from DKA

HHS differs fundamentally from DKA in several ways: 1, 2, 3

• Timeline: HHS develops over days to weeks, whereas DKA develops over hours to days 1, 3
• Dehydration: Total body water deficit in HHS is approximately 9 liters (100-220 mL/kg), more severe than DKA 1
• Acidosis: HHS has minimal or no acidosis (pH ≥7.30), while DKA has significant acidosis (pH <7.30) 2, 3
• Ketones: HHS has minimal ketones (≤3.0 mmol/L), while DKA has significant ketonemia 3
• Mental status changes: More common in HHS than DKA 2

Common Diagnostic Pitfalls

• Do not wait for altered mental status to diagnose HHS - Patients can be fully alert and still meet diagnostic criteria 1
• Monitor calculated effective osmolality, not just individual components - The osmolality threshold of ≥320 mOsm/kg is what defines HHS 1
• Hypothermia, if present, is a poor prognostic sign despite infection being the most common precipitant 2
• Mixed DKA/HHS can occur - Some patients may have features of both conditions 3
• Abdominal pain may be present - If it does not resolve with treatment, further evaluation is necessary as it may indicate a precipitating cause rather than a consequence 1

Precipitating Factors to Identify

Infection is the most common precipitant, but also consider: 1, 3

• Acute cerebrovascular accident or myocardial infarction
• Medications affecting carbohydrate metabolism (diuretics, corticosteroids, SGLT2 inhibitors, sympathomimetic agents)
• Non-compliance with diabetes therapy or undiagnosed diabetes
• Substance abuse (e.g., cocaine)