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

Diagnostic Criteria and Management of Hyperosmolar Hyperglycemic State (HHS)

The diagnosis of HHS requires blood glucose ≥600 mg/dL, arterial pH >7.3, serum bicarbonate >15 mEq/L, effective serum osmolality ≥320 mOsm/kg H₂O, mild ketonuria or ketonemia, and altered mental status or severe dehydration. 1

Diagnostic Criteria

• Blood glucose ≥600 mg/dL 2, 1
• Arterial pH >7.3 2, 1
• Serum bicarbonate >15 mEq/L 2, 1
• Effective serum osmolality ≥320 mOsm/kg H₂O, calculated as: 2[measured Na⁺ (mEq/L)] + glucose (mg/dL)/18 1
• Mild ketonuria or ketonemia 2, 1
• Altered mental status or severe dehydration 2, 1

Initial Assessment

• Obtain arterial blood gases, complete blood count with differential, urinalysis, plasma glucose, blood urea nitrogen, electrolytes, chemistry profile, and creatinine levels STAT 2, 1
• Perform electrocardiogram 2
• Obtain chest X-ray and cultures as needed to identify potential infectious triggers 1
• Calculate corrected serum sodium: for each 100 mg/dL glucose >100 mg/dL, add 1.6 mEq to sodium value 2

Management Algorithm

1. Fluid Therapy

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/h (approximately 1-1.5 L in first hour for adults) to restore circulatory volume and renal perfusion 1
• After initial resuscitation, adjust fluid rate based on hemodynamic status, electrolytes, and urine output 2
• Total body water deficit in HHS is approximately 100-200 mL/kg (about 9 liters in adults) 1
• Aim to correct estimated fluid deficits within 24 hours 2, 1
• Monitor for fluid overload, especially in elderly patients or those with cardiac or renal disease 3

2. Insulin Therapy

• Important: Unlike DKA, fluid replacement alone will cause a fall in blood glucose in HHS 4
• Consider withholding insulin until blood glucose is no longer falling with IV fluids alone (unless ketonemic) 1, 4
• When insulin is needed, administer IV bolus of regular insulin at 0.15 units/kg body weight, followed by continuous infusion at 0.1 unit/kg/h (5-7 units/h in adults) 2, 1
• If plasma glucose does not fall by 50 mg/dL from initial value in first hour, check hydration status; if acceptable, double insulin infusion hourly until steady glucose decline of 50-75 mg/h is achieved 2
• When plasma glucose reaches 300 mg/dL, decrease insulin infusion to 0.05-0.1 units/kg/h (3-6 units/h) and add 5-10% dextrose to IV fluids 2, 1

3. Electrolyte Management

• Monitor serum potassium closely - total body potassium deficit in HHS is 5-15 mEq/kg 1
• Once renal function is assured and serum potassium is known, add potassium to IV fluids at 20-30 mEq/L (2/3 KCl and 1/3 KPO₄) 2, 1
• Do not administer potassium if serum K⁺ is >5.3 mEq/L 2
• If K⁺ <3.3 mEq/L, hold insulin and give potassium replacement first 2

4. Monitoring During Treatment

• Check blood glucose every 1-2 hours until stable 1
• Monitor serum electrolytes, blood urea nitrogen, creatinine, and calculated osmolality every 2-4 hours 2, 1
• Measure or calculate serum osmolality regularly to monitor response to treatment 4
• Aim to reduce osmolality by 3-8 mOsm/kg/h to avoid neurological complications 1, 3
• An initial rise in sodium level is expected and is not itself an indication for hypotonic fluids 4

5. Transition to Subcutaneous Insulin

• Administer basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 1
• When patient is able to eat, transition to a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 2

6. Resolution Criteria

• Serum osmolality <300 mOsm/kg 3
• Blood glucose <15 mmol/L (270 mg/dL) 3
• Mental status returned to pre-morbid state 3
• Hypovolemia corrected (urine output ≥0.5 mL/kg/h) 3

Common Pitfalls and Caveats

• HHS has a higher mortality rate than DKA and requires careful monitoring 4
• Rapid changes in osmolality during treatment may precipitate cerebral edema or central pontine myelinolysis 4
• Early use of insulin (before adequate fluid resuscitation) may be detrimental 1, 4
• Mixed DKA/HHS can occur and requires careful assessment of ketones and pH 3
• Elderly patients are at higher risk for fluid overload and require more cautious fluid administration 3
• Always identify and treat the underlying precipitant (most commonly infection, but also stroke, myocardial infarction, or medication effects) 1, 5