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

Diagnosis of Hyperosmolar Hyperglycemic State (HHS)

HHS is diagnosed when blood glucose is ≥600 mg/dL, effective serum osmolality is ≥320 mOsm/kg H₂O, arterial pH is ≥7.30, serum bicarbonate is ≥15 mEq/L, and ketones are minimal or absent in urine and serum. 1, 2

Diagnostic Criteria

The American Diabetes Association establishes five metabolic thresholds that must be met:

• Blood glucose ≥600 mg/dL (significantly higher than DKA's >250 mg/dL threshold) 1, 2
• Effective serum osmolality ≥320 mOsm/kg H₂O, calculated as: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 3, 1
• Arterial pH ≥7.30 (distinguishing it from DKA where pH <7.3) 1, 2
• Serum bicarbonate ≥15 mEq/L (versus <15 mEq/L in DKA) 1, 2
• Minimal or absent ketones in urine and serum (small ketonuria/ketonemia acceptable, but not moderate-to-large) 1, 2

Initial Laboratory Evaluation

Obtain the following tests immediately upon suspicion of HHS:

• Plasma glucose, serum electrolytes with calculated anion gap, and serum osmolality 3
• Blood urea nitrogen, creatinine (to assess renal function and prerenal azotemia) 3
• Serum ketones (to differentiate from DKA or mixed presentations) 3
• Arterial blood gases (to confirm pH ≥7.30) 3
• Complete blood count with differential 3
• Urinalysis with urine ketones by dipstick 3
• Electrocardiogram 3
• HbA1c (helps determine if this represents poorly controlled diabetes versus acute decompensation) 3
• Bacterial cultures (blood, urine, throat) if infection suspected, as infection is the most common precipitating factor 3
• Chest X-ray if clinically indicated 3

Clinical Presentation Features

Mental status changes are common but NOT mandatory for diagnosis. 1 This is a critical distinction:

• Mental status can range from full alertness to profound lethargy or coma 1
• Altered consciousness is more frequent in HHS than DKA, and the degree of mental obtundation typically correlates with hyperosmolarity severity 1
• Patients meeting metabolic thresholds warrant HHS management regardless of alertness level 1
• The absence of altered mental status does not exclude HHS diagnosis when other criteria are met 1

Physical examination findings include:

• Profound dehydration (estimated fluid deficit approximately 9 liters in adults, versus 6 liters in DKA) 2, 4
• Signs of volume depletion: hypotension, tachycardia, poor skin turgor, dry mucous membranes 5
• Neurologic abnormalities when present: lethargy, confusion, focal deficits, or coma 5, 4
• Patients may be normothermic or hypothermic despite infection (hypothermia is a poor prognostic sign) 3

Differential Diagnosis Considerations

Distinguish HHS from other hyperglycemic emergencies:

• DKA: Lower glucose threshold (>250 mg/dL), pH <7.3, bicarbonate <15 mEq/L, moderate-to-large ketones 2
• Mixed DKA/HHS: Increasingly recognized, particularly in younger adults and children with type 2 diabetes 6
• Starvation ketosis: Mildly elevated glucose (rarely >250 mg/dL), bicarbonate usually not <18 mEq/L 3
• Alcoholic ketoacidosis: Variable glucose (can be hypoglycemic to mildly elevated), profound acidosis possible 3

Rule out other causes of altered mental status and high anion gap acidosis:

• Lactic acidosis, salicylate ingestion, methanol/ethylene glycol poisoning, chronic renal failure 3

Common Precipitating Factors to Identify

The most common precipitant is infection (pneumonia, urinary tract infection, sepsis). 3 Other triggers include:

• Acute cerebrovascular accident, myocardial infarction 3
• Medications affecting carbohydrate metabolism: corticosteroids, thiazides, sympathomimetic agents (dobutamine, terbutaline) 3
• Newly diagnosed diabetes (particularly elderly patients in chronic care facilities) 3
• Inadequate fluid intake in patients unable to recognize or respond to thirst 3
• Pancreatitis, trauma, alcohol abuse 3
• Nonadherence to diabetes therapy 4

Critical Diagnostic Pitfalls to Avoid

• Do not rely solely on mental status changes for diagnosis—metabolic criteria are definitive 1
• Correct serum sodium for hyperglycemia before interpreting results: add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation 3
• Monitor calculated effective osmolality, not just individual components 3, 1
• Abdominal pain may be a result OR cause of the hyperglycemic crisis—further evaluation is necessary if pain does not resolve with treatment 3
• HHS develops over days (unlike DKA which develops over hours), so dehydration and metabolic disturbances are more extreme 7