What are the management recommendations for Hyperosmolar Hyperglycemic Nonketotic (HHNK) syndrome?

Management of Hyperosmolar Hyperglycemic Nonketotic (HHNK) Syndrome

The management of HHNK syndrome requires aggressive fluid resuscitation with isotonic saline initially, followed by insulin therapy and electrolyte replacement, with careful monitoring to prevent complications. 1

Diagnostic Criteria

• HHNK is characterized by blood glucose >600 mg/dl, arterial pH >7.3, bicarbonate >15 mEq/l, mild ketonuria or ketonemia, and effective serum osmolality >320 mOsm/kg H₂O 2, 1
• Initial laboratory evaluation should include arterial blood gases, complete blood count with differential, urinalysis, plasma glucose, blood urea nitrogen, electrolytes, chemistry profile, creatinine levels, and an electrocardiogram 2, 1
• Serum sodium should be corrected for hyperglycemia (for each 100 mg/dl glucose >100 mg/dl, add 1.6 mEq to sodium value for corrected serum value) 2, 1

Fluid Therapy

• Begin with isotonic saline (0.9% NaCl) at 15-20 ml/kg/h during the first hour to restore circulatory volume and tissue perfusion 2, 1
• Total body water deficit in HHNK is typically 100-200 ml/kg (approximately 9 liters) 1
• After hemodynamic stabilization, switch to 0.45% NaCl if corrected serum sodium is normal or elevated 3
• Fluid replacement should correct estimated deficits within the first 24 hours, with the induced change in serum osmolality not exceeding 3 mOsm/kg/h 2
• Monitor fluid input/output, hemodynamic parameters (blood pressure improvement), and clinical examination to assess progress with fluid replacement 2, 1

Insulin Therapy

• Once hypokalemia (K+ <3.3 mEq/l) is excluded, administer an intravenous bolus of regular insulin at 0.15 units/kg body weight, followed by a 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 the initial value in the first hour, check hydration status; if acceptable, double the insulin infusion every hour until a steady glucose decline between 50-75 mg/h is achieved 2, 1
• When plasma glucose reaches 300 mg/dl in HHNK, add 5-10% dextrose to intravenous fluids and reduce insulin infusion to 0.05-0.1 U/kg/h (3-6 U/h) 2, 1
• Continue insulin infusion until mental status improves and hyperosmolarity resolves 1

Electrolyte Management

• Total body deficits in HHNK typically include sodium (5-15 mEq/kg), potassium (4-6 mEq/kg), chloride (5-13 mEq/kg), and phosphate (3-7 mmol/kg) 1
• Once renal function is assured and serum potassium is known, add 20-40 mEq/l potassium (2/3 KCl or potassium-acetate and 1/3 KPO₄) to the infusion 2, 1
• Phosphate replacement may be considered in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 1

Monitoring and Complications

• During therapy, blood should be drawn every 2-4 hours for determination of serum electrolytes, glucose, blood urea nitrogen, creatinine, and osmolality 2, 1
• Monitor for signs of cerebral edema (lethargy, behavioral changes, seizures, incontinence, pupillary changes, bradycardia, respiratory arrest) 1
• Potential complications include hypoglycemia (from overzealous insulin treatment), hypokalemia (from insulin administration and fluid shifts), and hyperchloremic metabolic acidosis (from excessive saline administration) 1, 4
• Bicarbonate administration is not recommended as it does not improve outcomes 1

Transition of Care and Follow-up

• For successful transition from intravenous to subcutaneous insulin, administer basal insulin 2-4 hours before stopping the intravenous insulin to prevent rebound hyperglycemia 2, 1
• After recovery, many patients may not require long-term insulin therapy and can be managed with diet or oral agents 3
• A structured discharge plan should be tailored to the individual patient to reduce length of hospital stay and readmission rates 2, 1

Special Considerations

• Elderly patients are particularly susceptible to HHNK due to reduced glomerular filtration rate, elevated renal threshold for glucose, and diminished thirst response 5
• Identify and treat precipitating causes such as infection, myocardial infarction, stroke, medications (diuretics, corticosteroids, beta-blockers), or discontinuation of diabetes medications 1, 5
• Patients on maintenance hemodialysis with HHNK require special attention to fluid management as they may not experience dehydration via the renal route 6

Pediatric Considerations

• Initial fluid therapy in pediatric patients (<20 years) should be isotonic saline (0.9% NaCl) at 10-20 ml/kg/h, not exceeding 50 ml/kg over the first 4 hours 2
• An initial insulin bolus is not recommended in pediatric patients; start with a continuous insulin infusion at 0.1 unit/kg/h 2
• Obese adolescents with type 2 diabetes are at increased risk for HHNK and may present with severe dehydration and depressed mental status 4