What is the treatment for Hyperglycemic Hyperosmolar Nonketotic Syndrome (HHNS)?

Treatment of Hyperglycemic Hyperosmolar Nonketotic Syndrome (HHNS)

The treatment of Hyperglycemic Hyperosmolar Nonketotic Syndrome (HHNS) requires aggressive fluid replacement as the primary intervention, followed by insulin therapy, electrolyte correction, and identification and treatment of underlying causes.

Initial Assessment and Diagnosis

• HHNS is characterized by severe hyperglycemia (typically ≥600 mg/dl), effective serum osmolality ≥320 mOsm/kg H₂O, arterial pH >7.3, bicarbonate >15 mEq/l, minimal ketonuria/ketonemia, and altered mental status or severe dehydration 1
• Laboratory evaluation should include plasma glucose, blood urea nitrogen, creatinine, serum ketones, electrolytes with calculated anion gap, osmolality, urinalysis, arterial blood gases, complete blood count with differential, and electrocardiogram 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) 1

Fluid Therapy

• Initial fluid therapy should be isotonic saline (0.9% NaCl) at a rate of 15-20 ml/kg/h during the first hour (approximately 1-1.5 liters in the average adult) to restore circulatory volume and tissue perfusion 1
• After hemodynamic stabilization, switch to 0.45% NaCl infused at 4-14 ml/kg/h if the corrected serum sodium is normal or elevated; continue 0.9% NaCl at a similar rate if corrected serum sodium is low 1
• Total body water deficit in HHNS is typically 9 liters (approximately 100-200 ml/kg) 1
• Fluid replacement should correct estimated deficits within the first 24 hours 1
• The induced change in serum osmolality should not exceed 3 mOsm/kg/h to avoid neurological complications 1, 2

Insulin Therapy

• Once hypokalemia (K <3.3 mEq/l) is excluded, administer an intravenous bolus of regular insulin at 0.15 U/kg body weight, followed by a continuous infusion at 0.1 U/kg/h (approximately 5-7 U/h in adults) 1
• If plasma glucose does not fall by 50 mg/dl from the initial value in the first hour, check hydration status; if acceptable, the insulin infusion may be doubled every hour until a steady glucose decline between 50-75 mg/h is achieved 1
• When plasma glucose reaches 300 mg/dl in HHNS, decrease the insulin infusion rate to 0.05-0.1 U/kg/h (3-6 U/h) and add 5-10% dextrose to the intravenous fluids 1, 3
• Continue insulin infusion until mental status improves and hyperosmolarity resolves 1

Electrolyte Management

• 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 1
• Monitor serum electrolytes (sodium, potassium, calcium, magnesium, phosphate) frequently and replace as needed 4
• Total body deficits in HHNS typically include sodium (5-15 mEq/kg), potassium (4-6 mEq/kg), chloride (5-13 mEq/kg), and phosphate (3-7 mmol/kg) 1

Monitoring and Ongoing Management

• During therapy, blood should be drawn every 2-4 hours for determination of serum electrolytes, glucose, blood urea nitrogen, creatinine, and osmolality 1
• Monitor fluid input/output, hemodynamic parameters, and clinical examination to assess progress with fluid replacement 1
• In patients with renal or cardiac compromise, frequent assessment of cardiac, renal, and mental status must be performed during fluid resuscitation to avoid iatrogenic fluid overload 1, 5

Resolution Criteria and Transition of Care

• Resolution criteria for HHNS include: osmolality <300 mOsm/kg, hypovolemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state, and blood glucose <15 mmol/L (270 mg/dL) 2
• Following recovery, many patients presenting with HHNS 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 1

Identification and Treatment of Precipitating Causes

• Identify and treat precipitating causes such as infection, myocardial infarction, stroke, medications (diuretics, corticosteroids, beta-blockers, phenytoin), or other acute illnesses 3, 5
• Obtain bacterial cultures of urine, blood, and other sites as needed and administer appropriate antibiotics if infection is suspected 1

Special Considerations

• In elderly patients, careful monitoring is essential as age is the best known prognostic indicator in HHNS 5
• Avoid rapid changes in osmolality to prevent complications such as cerebral edema and osmotic demyelination 2
• Prevention of HHNS includes ensuring appropriate fluid intake and cautious use of medications that may precipitate hyperglycemia in elderly diabetic patients 5

Common Pitfalls to Avoid

• Premature termination of intravenous insulin therapy before resolution of hyperosmolarity 6
• Insufficient timing or dosing of subcutaneous insulin before discontinuation of intravenous insulin 6
• Failure to identify and treat the underlying precipitating cause 3, 5
• Overly rapid correction of serum osmolality leading to neurological complications 1, 2
• Inadequate monitoring of electrolytes, particularly potassium, leading to dangerous imbalances 4