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

Treatment of Hyperosmolar Hyperglycemic State (HHS)

The treatment of Hyperosmolar Hyperglycemic State requires aggressive fluid resuscitation as the primary intervention, followed by insulin therapy, electrolyte management, and identification and treatment of underlying causes. 1

Initial Assessment and Diagnosis

• HHS is characterized by severe hyperglycemia (typically ≥30 mmol/L or ≥540 mg/dL), hyperosmolality (≥320 mOsm/kg), profound dehydration, and minimal or absent ketosis (≤3.0 mmol/L) without significant acidosis (pH >7.3, bicarbonate ≥15 mmol/L) 2
• Clinical presentation ranges from mild hyperglycemia to severe hyperglycemia with dehydration, altered mental status, and coma 1
• Initial 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 3

Treatment Algorithm

1. Fluid Resuscitation (Primary Intervention)

• Begin with 0.9% sodium chloride solution at 15-20 mL/kg/hour during the first hour to restore circulatory volume and tissue perfusion 3, 2
• Fluid losses in HHS are extensive (100-220 mL/kg) and require aggressive replacement 2
• Continue fluid replacement to correct estimated deficits within the first 24 hours 3
• Monitor the rate of osmolality decline, aiming for 3-8 mOsm/kg/hour to minimize the risk of cerebral edema and other neurological complications 2, 4
• Fluid replacement alone will initially cause a fall in blood glucose levels 4

2. Insulin Therapy

• Important: Withhold insulin until fluid resuscitation has been initiated and blood glucose is no longer falling with IV fluids alone (unless ketonaemia is present) 4
• When insulin is required, administer an intravenous bolus of regular insulin at 0.1 units/kg body weight, followed by a continuous infusion at 0.1 units/kg/hour 3, 1
• If plasma glucose does not fall by 50 mg/dL from the initial value in the first hour, double the insulin infusion rate until a steady glucose decline is achieved 3
• Target blood glucose levels of 10-15 mmol/L (180-270 mg/dL) in the first 24 hours 2
• Once blood glucose falls below 14 mmol/L (250 mg/dL), start glucose infusion (5% or 10%) while continuing insulin to prevent hypoglycemia 2

3. Electrolyte Management

• Monitor potassium levels closely as total body potassium deficits are common despite potentially normal or elevated initial serum levels due to dehydration 3
• Begin potassium replacement after serum levels fall below 5.5 mEq/L, assuming adequate urine output 3
• Add 20-30 mEq potassium in each liter of infusion fluid to maintain serum potassium concentration within 4-5 mEq/L 3
• If significant hypokalemia is present initially, delay insulin treatment until potassium concentration is restored to >3.3 mEq/L to avoid arrhythmias, cardiac arrest, and respiratory muscle weakness 3

4. Transition from IV to Subcutaneous Insulin

• 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
• When HHS is resolved and the patient can eat, transition to a multiple-dose regimen using a combination of short/rapid-acting and intermediate/long-acting insulin 3

Monitoring During Treatment

• Monitor blood glucose at least every 2-4 hours 1
• Regularly measure or calculate serum osmolality to monitor response to treatment 4
• Monitor fluid input/output, hemodynamic parameters, and clinical examination to assess progress with fluid replacement 3
• Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 3
• Continuous cardiac monitoring is crucial in severe cases to detect arrhythmias early 5, 3

Identifying and Treating Precipitating Causes

• Identify and treat any correctable underlying cause such as sepsis, myocardial infarction, or stroke 1
• Obtain bacterial cultures of urine, blood, and other sites as needed and administer appropriate antibiotics if infection is suspected 3
• Infection is the most common precipitating factor in the development of HHS 6, 7

Resolution Criteria

• HHS resolution criteria are: 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

Common Pitfalls and Caveats

• Too rapid correction of osmolality (>8 mOsm/kg/hour) may lead to cerebral edema and central pontine myelinolysis 2, 4
• Early use of insulin before adequate fluid resuscitation may be detrimental 4
• An initial rise in sodium level is expected and is not itself an indication for hypotonic fluids 4
• HHS patients may be normothermic or even hypothermic despite having infection, primarily due to peripheral vasodilation 6
• Abdominal pain in HHS patients may be either a result of the metabolic derangement or a sign of intra-abdominal infection requiring further evaluation 6
• HHS has a higher mortality rate than DKA and may be complicated by myocardial infarction, stroke, seizures, and cerebral edema 4

Discharge Planning

• A structured discharge plan tailored to the individual patient should be developed to reduce length of hospital stay and readmission rates 1
• Include education on the recognition, prevention, and management of HHS 3
• Schedule an outpatient follow-up visit with the primary care provider, endocrinologist, or diabetes educator within 1 month of discharge 1