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

Treatment of Hyperosmolar Hyperglycemic State (HHS)

Begin immediate fluid resuscitation with 0.9% sodium chloride at 15-20 mL/kg/hour for the first hour, and delay insulin administration until fluid replacement alone stops lowering blood glucose, unless significant ketonemia is present. 1, 2, 3

Initial Assessment and Monitoring

Diagnostic Criteria

• Blood glucose ≥600 mg/dL 4
• Serum osmolality ≥320 mOsm/kg (calculated as: [2×Na+] + glucose + urea) 3
• Venous pH >7.3 and bicarbonate ≥15 mEq/L (minimal or no acidosis) 4, 3
• Ketones ≤3.0 mmol/L (minimal ketonemia) 3
• Altered mental status or severe dehydration 4, 1

Laboratory Monitoring Schedule

• Draw blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 4, 1
• Monitor blood glucose at least every 2-4 hours 1
• Measure or calculate serum osmolality regularly to track treatment response 2, 3

Phase 1: Fluid Resuscitation (First Priority)

Initial Fluid Management (0-60 minutes)

• Administer 0.9% sodium chloride at 15-20 mL/kg/hour during the first hour to restore circulating volume and tissue perfusion 1, 3
• Total fluid deficit typically averages 9 liters in adults (100-220 mL/kg) 1, 5, 3
• Continue fluid replacement to correct estimated deficits within 24 hours 1

Critical Monitoring Parameter

• Aim to reduce osmolality by 3-8 mOsm/kg/hour to prevent cerebral edema and central pontine myelinolysis 1, 2, 3
• An initial rise in sodium level is expected and normal—this is NOT an indication to switch to hypotonic fluids 2

Common Pitfall to Avoid

Fluid replacement alone will cause blood glucose to fall initially 2, 3. Do not start insulin prematurely, as early insulin use (before adequate fluid resuscitation) may be detrimental 2.

Phase 2: Insulin Therapy (Delayed Start)

When to Initiate Insulin

• Withhold insulin until blood glucose stops falling with IV fluids alone, unless significant ketonemia is present 2, 3
• If ketonemia is present (>3.0 mmol/L), start insulin simultaneously with fluid resuscitation 3

Insulin Dosing Protocol

• Administer IV bolus of regular insulin at 0.1-0.15 units/kg body weight 1, 5
• Follow with continuous infusion at 0.1 units/kg/hour 4, 1, 5
• Target blood glucose of 10-15 mmol/L (180-270 mg/dL) in the first 24 hours 3

Glucose Management During Insulin Therapy

• When blood glucose reaches 250-300 mg/dL, add 5% or 10% dextrose to IV fluids 1, 3
• Continue insulin infusion at reduced rate while adding dextrose to prevent hypoglycemia 1, 3

Phase 3: Electrolyte Management

Potassium Replacement

• Monitor potassium levels every 2-4 hours, as insulin therapy drives potassium intracellularly and can cause life-threatening hypokalemia 1
• Begin potassium replacement when serum levels fall below 5.5 mEq/L, assuming adequate urine output (≥0.5 mL/kg/hour) 1, 3
• Do NOT start insulin if potassium is <3.3 mEq/L—correct hypokalemia first 4

Sodium Monitoring

• Expect initial rise in measured sodium as hyperglycemia corrects 2
• Calculate corrected sodium: add 1.6 mEq/L for every 100 mg/dL glucose above normal 4

Phase 4: Identifying and Treating Precipitating Causes

Most Common Precipitants

• Infection is the most common precipitating factor 1, 5
• Other causes include myocardial infarction, stroke, medications (diuretics, corticosteroids, beta-blockers), and non-adherence to diabetes therapy 6, 5

Concurrent Management

• Identify and treat any correctable underlying cause simultaneously with metabolic correction 1, 5
• Obtain chest X-ray, cultures, electrocardiogram, and urinalysis as clinically indicated 4

Resolution Criteria and Transition

HHS Resolution Defined As:

• Osmolality <300 mOsm/kg 3
• Hypovolaemia corrected (urine output ≥0.5 mL/kg/hour) 3
• Cognitive status returned to baseline 3
• Blood glucose <15 mmol/L (270 mg/dL) 3

Transition to Subcutaneous Insulin

• Administer basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 1
• Many patients with HHS will not require long-term insulin and can be managed with diet or oral agents after recovery 6

Special Considerations

Pediatric Patients

• Correct dehydration at a rate not exceeding 3 mOsm/hour to avoid cerebral edema 5
• Do not give initial insulin bolus in children—start continuous infusion only 4

High-Risk Complications

• Cerebral edema (rare but potentially fatal, especially in children and young adults) 1
• Central pontine myelinolysis (associated with rapid osmolality changes) 2
• Thromboembolism—consider VTE prophylaxis 3

Level of Care

• Patients require intensive care unit admission with experienced nursing staff 2, 7
• Involve diabetes specialist team as soon as possible 2, 3