Diagnostic Criteria for Hyperosmolar Hyperglycemic State (HHS)
HHS is diagnosed when a patient meets all five metabolic thresholds: blood glucose ≥600 mg/dL, effective serum osmolality ≥320 mOsm/kg H₂O, arterial pH ≥7.30, serum bicarbonate ≥15 mEq/L, and small or absent ketones in urine and serum. 1
Core Metabolic Thresholds
The American Diabetes Association establishes the following mandatory criteria for HHS diagnosis:
- Blood glucose ≥600 mg/dL - This severe hyperglycemia distinguishes HHS from other hyperglycemic states 1
- Effective serum osmolality ≥320 mOsm/kg H₂O - Calculate using the formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 2, 1
- Arterial pH ≥7.30 - This differentiates HHS from diabetic ketoacidosis, which has pH <7.30 1
- Serum bicarbonate ≥15 mEq/L - Reflects minimal metabolic acidosis compared to DKA 1
- Small or absent ketones - Both urine and serum should show minimal ketonuria/ketonemia (≤3.0 mmol/L), distinguishing HHS from ketoacidosis 1
Critical Calculation for Corrected Sodium
Serum sodium must be corrected for hyperglycemia by adding 1.6 mEq/L to the measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL. 1 This correction is essential because the measured sodium will be falsely low due to the osmotic effect of severe hyperglycemia.
Clinical Presentation (Not Required for Diagnosis)
While altered mental status is common in HHS and correlates with the degree of hyperosmolarity, the absence of altered mental status does not exclude HHS diagnosis when metabolic criteria are met. 1 Patients can present anywhere on the spectrum from full alertness to profound coma 1. The key distinction is that mental status changes are part of the typical clinical presentation but are not mandatory diagnostic criteria 1.
Time Course of Development
HHS develops over days to a week, unlike DKA which evolves over hours to days. 1 This prolonged timeline allows for more severe dehydration and metabolic derangements, with total body water deficits approximating 9 liters (100-220 mL/kg). 1
Initial Laboratory Evaluation
Upon suspicion of HHS, immediately obtain:
- Plasma glucose, serum electrolytes with calculated anion gap, and serum osmolality 1
- Blood urea nitrogen, creatinine, serum ketones (preferably β-hydroxybutyrate rather than nitroprusside method) 1
- Arterial blood gases, complete blood count with differential 2
- Urinalysis with urine ketones by dipstick 1
- Electrocardiogram and HbA1c 1
- Bacterial cultures (blood, urine, throat) if infection suspected - Infection is the most common precipitating factor 1
- Chest X-ray if pneumonia suspected 1
Common Pitfalls to Avoid
Do not rely on mental status changes alone to diagnose or exclude HHS. 1 Patients meeting the metabolic thresholds (glucose ≥600 mg/dL, osmolality ≥320 mOsm/kg) warrant HHS management regardless of alertness level. 1
Do not use uncorrected sodium values - Always calculate corrected sodium to avoid misinterpreting the severity of hypernatremia. 1
Do not use the nitroprusside method as the sole indicator of ketone status - This method only measures acetoacetate and acetone, missing β-hydroxybutyrate, the predominant ketoacid. 2 Measurement of β-hydroxybutyrate is preferred. 1
Distinguishing HHS from DKA
The critical differences are:
- HHS: pH ≥7.30, bicarbonate ≥15 mEq/L, minimal ketones, glucose ≥600 mg/dL 1
- DKA: pH <7.30, bicarbonate <15 mEq/L, significant ketones, glucose typically 250-600 mg/dL 1