What is the treatment for Hyperosmolar Hyperglycemic State (HHS)?

Treatment of Hyperosmolar Hyperglycemic State (HHS)

The treatment of Hyperosmolar Hyperglycemic State (HHS) requires aggressive fluid resuscitation as the primary initial intervention, followed by insulin therapy and electrolyte management, with careful monitoring to prevent complications. 1

Clinical Presentation and Diagnosis

HHS is characterized by:

• Severe hyperglycemia (typically ≥30 mmol/L or >600 mg/dL) 2
• Hyperosmolality (≥320 mOsm/kg) 2
• Profound dehydration without significant ketosis (ketones ≤3.0 mmol/L) 2
• Minimal or no acidosis (pH >7.3, bicarbonate ≥15 mmol/L) 2
• Change in cognitive state (ranging from lethargy to coma) 1
• Develops over days to a week (slower onset than DKA) 1

Management Algorithm

Phase 1: Initial Assessment and Stabilization (0-60 minutes)

1. Fluid Resuscitation

   • Begin with 0.9% sodium chloride (normal saline) to restore circulatory volume and tissue perfusion 1
   • Initial fluid losses in HHS are estimated at 100-220 mL/kg (average 9L in adults) 3, 2
   • Use caution in elderly patients and those with cardiac or renal disease 2

2. Laboratory Assessment

   • Monitor blood glucose, electrolytes (especially potassium), renal function, osmolality, and acid-base status 1
   • Calculate serum osmolality: 2 × Na⁺ + glucose + urea (mOsm/kg) 2

3. Identify and Treat Underlying Causes

   • Infection is the most common precipitant 4
   • Other causes: medications (glucocorticoids, diuretics), nonadherence to therapy, undiagnosed diabetes, substance abuse 3

Phase 2: Ongoing Management (1-24 hours)

1. Fluid Management

   • Continue aggressive fluid replacement with 0.9% sodium chloride until hemodynamically stable 1, 5
   • Once stabilized, consider switching to 0.45% sodium chloride (hypotonic saline) 6
   • Aim to reduce osmolality by 3-8 mOsm/kg/hour to prevent neurological complications 5, 2

2. Insulin Therapy

   • Important: Withhold insulin until blood glucose stops falling with IV fluids alone, unless ketonaemia is present 5
   • When started, administer IV insulin as:
     • Initial bolus of 0.1 units/kg followed by continuous infusion at 0.1 units/kg/hour, OR
     • Continuous infusion at 0.14 units/kg/hour without bolus 3
   • Reduce insulin rate once blood glucose falls below 300 mg/dL (16.7 mmol/L) 1, 3

3. Glucose Management

   • Add 5% or 10% dextrose to IV fluids when blood glucose falls below 250-300 mg/dL (14-16.7 mmol/L) 1, 2
   • Target blood glucose: 10-15 mmol/L (180-270 mg/dL) in first 24 hours 2

4. Electrolyte Replacement

   • Begin potassium replacement once urine output is established and serum potassium falls below 5.5 mEq/L 7
   • Monitor potassium levels every 2-4 hours during initial treatment 7

Phase 3: Monitoring and Preventing Complications

1. Regular Monitoring

   • Measure or calculate serum osmolality regularly to monitor treatment response 5
   • Monitor vital signs, mental status, fluid balance, and electrolytes 1
   • Cardiac monitoring is recommended in severe cases 7

2. Prevention of Complications

   • Avoid rapid changes in osmolality to prevent cerebral edema and central pontine myelinolysis 5
   • Implement venous thromboembolism prophylaxis 2
   • Prevent pressure ulcers and foot complications 2
   • Monitor for fluid overload, especially in elderly patients 2

Resolution Criteria

HHS is considered resolved when:

• Serum osmolality <300 mOsm/kg 2
• Hypovolemia corrected (urine output ≥0.5 mL/kg/hour) 2
• Cognitive status returns to pre-morbid state 2
• Blood glucose <15 mmol/L (270 mg/dL) 2

Special Considerations

• Elderly patients: Use caution with fluid administration due to risk of fluid overload 2
• Mixed DKA/HHS: About one-third of hyperglycemic emergencies present with features of both conditions, requiring treatment for both 1
• Transition to subcutaneous insulin: For patients requiring ongoing insulin therapy, start basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 1

Common Pitfalls to Avoid

• Initiating insulin before adequate fluid resuscitation, which may worsen dehydration 5
• Correcting sodium and osmolality too rapidly, which can lead to neurological complications 5, 2
• Failing to identify and treat the underlying precipitating cause 1, 4
• Inadequate monitoring of electrolytes, particularly potassium 7
• Neglecting to arrange appropriate follow-up after discharge 1