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, careful insulin management, electrolyte correction, and identification of underlying causes to reduce mortality and prevent complications. 1

Clinical Presentation and Diagnosis

• HHS typically develops over days to a week (unlike DKA which develops over hours to days) and is characterized by severe hyperglycemia, hyperosmolality, and profound dehydration without significant ketosis 1
• Common clinical features include altered mental status, extreme dehydration, and often copresentation with an acute illness 1
• Diagnostic criteria include:
  • Serum osmolality ≥320 mOsm/kg
  • Marked hyperglycemia (typically ≥30 mmol/L or >600 mg/dL)
  • Absence of significant ketosis (≤3.0 mmol/L)
  • Absence of significant acidosis (pH >7.3, bicarbonate ≥15 mmol/L) 2

Treatment Algorithm

1. Fluid Resuscitation (First Priority)

• Begin with intravenous 0.9% sodium chloride solution as the principal fluid to restore circulatory volume 3
• Adults typically require an average of 9L of 0.9% saline over 48 hours 4
• Initial fluid rate: 15-20 mL/kg/hour during the first hour (1-1.5 L in average adult) 1
• After hemodynamic stability is achieved, adjust rate based on hydration status, electrolyte levels, and urine output 1
• Switch to 0.45% saline once hemodynamic stability is achieved and sodium levels are normal or elevated 5
• Fluid replacement alone will cause a fall in blood glucose; monitor closely 3

2. Insulin Therapy

• Important: Withhold insulin until fluid resuscitation is initiated and blood glucose is no longer falling with IV fluids alone, unless ketonemia is present 3
• Once initiated, administer an initial bolus of 0.1 units/kg of intravenous regular insulin, followed by continuous infusion at 0.1 units/kg/hour 4
• Alternatively, start with continuous infusion at 0.14 units/kg/hour without bolus 4
• Reduce insulin infusion rate when blood glucose falls below 300 mg/dL (16.7 mmol/L) 5
• Add 5-10% dextrose to IV fluids when glucose reaches 250-300 mg/dL (13.9-16.7 mmol/L) to prevent hypoglycemia 5

3. Electrolyte Management

• Monitor potassium levels closely and begin replacement once serum levels fall below 5.5 mEq/L and urine output is established 6
• Monitor sodium, phosphate, and magnesium levels and replace as needed 1
• An initial rise in sodium level is expected and is not itself an indication for hypotonic fluids 3

4. Monitoring Response to Treatment

• Calculate serum osmolality regularly to monitor response to treatment 3
• Aim to reduce osmolality by 3-8 mOsm/kg/hour to prevent neurological complications 2
• Monitor vital signs, mental status, fluid input/output, and laboratory values (glucose, electrolytes, osmolality) every 1-2 hours initially 1

5. Identifying and Treating Underlying Causes

• Common precipitating factors include:
  • Infections (most common) 7
  • Medications (glucocorticoids, diuretics, beta-blockers) 5
  • Nonadherence to diabetes therapy 4
  • Undiagnosed diabetes 4
  • Substance abuse 4
  • Acute illness (stroke, myocardial infarction) 1
• Appropriate antibiotics should be initiated if infection is suspected 7

Resolution Criteria

• Osmolality <300 mOsm/kg
• Corrected hypovolemia (urine output ≥0.5 mL/kg/hour)
• Return of cognitive status to pre-morbid state
• Blood glucose <15 mmol/L (270 mg/dL) 2

Potential Complications and Prevention

• HHS has a higher mortality rate than DKA 3
• Complications include myocardial infarction, stroke, seizures, cerebral edema, and central pontine myelinolysis 3
• Rapid changes in osmolality may precipitate central pontine myelinolysis; maintain controlled correction rate 3
• Venous thromboembolism prophylaxis is recommended due to hypercoagulable state 2
• Monitor for fluid overload, especially in elderly patients or those with cardiac/renal disease 2

Transition of Care

• Successful transition from intravenous to subcutaneous insulin requires administration of basal insulin 2-4 hours before the intravenous insulin is stopped to prevent rebound hyperglycemia 1
• Following recovery, many patients presenting with HHS may not require long-term insulin therapy and can be managed with diet or oral agents 5
• A structured discharge plan should be developed, including diabetes education and close follow-up 1