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, electrolyte management, and identification and treatment of underlying causes.

Diagnostic Criteria for HHS

• Blood glucose ≥600 mg/dL 1
• Arterial pH >7.3 1
• Serum bicarbonate >15 mEq/L 1
• Effective serum osmolality ≥320 mOsm/kg H₂O 1
• Mild ketonuria or ketonemia 1
• Altered mental status or severe dehydration 1

Initial Assessment and Monitoring

• Obtain arterial blood gases, complete blood count with differential, urinalysis, plasma glucose, blood urea nitrogen, electrolytes, chemistry profile, and creatinine levels immediately 1
• Calculate effective serum osmolality: 2[measured Na⁺ (mEq/L)] + glucose (mg/dL)/18 1
• Obtain chest X-ray and cultures as needed to identify underlying infections 1
• Correct serum sodium for hyperglycemia (for each 100 mg/dL glucose >100 mg/dL, add 1.6 mEq to sodium value) 1

Fluid Therapy (Primary Initial Intervention)

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/h (1-1.5 L in average adult) during the first hour to restore circulatory volume and renal perfusion 1
• Subsequent fluid choice depends on hydration state, serum electrolytes, and urine output 1
• Use 0.45% NaCl at 4-14 mL/kg/h if corrected serum sodium is normal or elevated; continue 0.9% NaCl if corrected sodium is low 1
• Fluid replacement alone will cause a fall in blood glucose level 2
• Total body water deficit in HHS is approximately 9 liters (100-200 mL/kg) 1
• Aim to correct estimated fluid deficits within 24 hours 1
• Monitor rate of change in serum osmolality - should not exceed 3 mOsm/kg/h to prevent neurological complications 2, 3

Insulin Therapy

• Withhold insulin until blood glucose is no longer falling with IV fluids alone, unless the patient has significant ketonemia 2
• Once initiated, administer an 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) 1
• If plasma glucose does not fall by 50 mg/dL in the first hour, check hydration status; if acceptable, double the insulin infusion rate hourly until achieving a steady glucose decline of 50-75 mg/h 1
• When plasma glucose reaches 300 mg/dL, decrease insulin infusion to 0.05-0.1 units/kg/h (3-6 units/h) 1
• Add 5-10% dextrose to IV fluids when blood glucose falls below 300 mg/dL to prevent hypoglycemia 1, 4

Electrolyte Management

• Once renal function is assured, add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to IV fluids 1
• Monitor serum potassium closely as total body potassium deficit in HHS is 5-15 mEq/kg 1
• Replace other electrolytes as needed based on laboratory values 1
• Monitor sodium, correcting for hyperglycemia 1
• An initial rise in sodium level is expected and is not itself an indication for hypotonic fluids 2

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 1
• Assess fluid input/output, vital signs, and mental status frequently 1
• Calculate osmolality regularly to monitor treatment response 2

Transition from IV to Subcutaneous Insulin

• Administer basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 1
• Recent studies show that low-dose basal insulin analog given with IV insulin may prevent rebound hyperglycemia 1

Resolution Criteria for HHS

• Blood glucose <15 mmol/L (270 mg/dL) 3
• Serum osmolality <300 mOsm/kg 3
• Correction of hypovolemia (urine output ≥0.5 mL/kg/h) 3
• Return of cognitive status to pre-morbid state 3

Common Pitfalls and Caveats

• Avoid rapid changes in osmolality during treatment as this may precipitate cerebral edema or central pontine myelinolysis 2
• Early use of insulin before adequate fluid resuscitation may be detrimental 2
• Patients with HHS have more extreme dehydration and metabolic disturbances compared to DKA 2
• HHS has a higher mortality rate than DKA and may be complicated by myocardial infarction, stroke, seizures, and cerebral edema 2
• Bicarbonate administration is generally not recommended 1
• Patients should be managed in areas where staff are experienced in treating HHS, ideally with diabetes specialist team involvement 2

Treatment of Underlying Causes

• Identify and treat precipitating factors, especially infections 1
• Other common precipitants include certain medications, nonadherence to therapy, undiagnosed diabetes, substance abuse, and coexisting diseases 4
• Appropriate management of precipitating illnesses will help reduce the high mortality associated with HHS 5