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

Treatment of Hyperosmolar Hyperglycemic State (HHS)

Begin immediate fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/h for the first hour, and critically, withhold insulin until blood glucose stops falling with IV fluids alone unless ketonemia is present. 1, 2

Initial Assessment and Diagnosis

Before initiating treatment, confirm HHS diagnosis with the following criteria 1, 3:

• Blood glucose ≥600 mg/dL
• Effective serum osmolality ≥320 mOsm/kg H₂O (calculated as: 2[measured Na⁺] + glucose/18)
• Arterial pH >7.3
• Serum bicarbonate ≥15 mEq/L
• Minimal or absent ketones

Obtain immediate laboratory studies including arterial blood gases, complete blood count, comprehensive metabolic panel, urinalysis, and calculate corrected sodium (add 1.6 mEq/L for each 100 mg/dL glucose elevation above 100 mg/dL) 1, 3. Identify and treat precipitating causes, particularly infections, with chest X-ray and cultures as indicated 1.

Fluid Resuscitation Strategy

The cornerstone of HHS treatment is aggressive fluid replacement, as patients have profound total body water deficits of approximately 9 liters (100-220 mL/kg). 1, 2

Phase 1: Initial Hour

• Administer 0.9% NaCl at 15-20 mL/kg/h (1-1.5 L in average adult) to restore circulatory volume and renal perfusion 1

Phase 2: Subsequent Fluid Management

After the first hour, adjust fluid choice based on corrected serum sodium 1:

• If corrected sodium is normal or elevated: Switch to 0.45% NaCl at 4-14 mL/kg/h
• If corrected sodium is low: Continue 0.9% NaCl at 4-14 mL/kg/h

Critical safety parameter: Aim for osmolality reduction of 3-8 mOsm/kg/h to minimize risk of central pontine myelinolysis and other neurological complications. 1, 2, 4 The goal is to correct estimated fluid deficits within 24 hours 1.

Special Population Considerations

In elderly patients and those with renal or cardiac compromise, perform frequent cardiac and renal assessments during fluid resuscitation to avoid iatrogenic fluid overload 1. For pediatric patients, limit initial fluid to 10-20 mL/kg/h for the first hour, not exceeding 50 mL/kg over the first 4 hours, then continue at 1.5 times maintenance over 48 hours 1.

Insulin Therapy

A critical distinction from DKA management: Withhold insulin until blood glucose stops falling with IV fluids alone, unless ketonemia is present. 1, 2, 4 This is because fluid replacement alone will cause significant glucose decline, and early insulin use may be detrimental 4.

When to Initiate Insulin

Once glucose stabilizes with fluids or if ketonemia is present 1, 2:

• IV bolus: 0.15 units/kg regular insulin
• Continuous infusion: 0.1 unit/kg/h (5-7 units/h in adults)

For pediatric patients, start continuous infusion at 0.1 unit/kg/h without an initial bolus 1.

Insulin Adjustment Protocol

• Target glucose decline of 50-75 mg/dL/h 1
• If glucose does not fall by 50 mg/dL in the first hour, check hydration status; if acceptable, double insulin infusion hourly until steady decline achieved 1
• When plasma glucose reaches 300 mg/dL: Decrease insulin to 0.05-0.1 units/kg/h (3-6 units/h) 1
• When glucose reaches <14 mmol/L (252 mg/dL): Add 5% or 10% dextrose infusion and maintain glucose 10-15 mmol/L (180-270 mg/dL) in first 24 hours 1, 2

Electrolyte Management

Potassium Replacement

Total body potassium deficit in HHS is 5-15 mEq/kg and requires aggressive replacement. 1

Once renal function is assured and serum potassium is known 1:

• If K+ <3.3 mEq/L: Hold insulin and give potassium replacement until K+ ≥3.3 mEq/L
• If K+ ≥3.3 mEq/L: Add 20-30 mEq/L to IV fluids (2/3 KCl and 1/3 KPO₄)

Monitor serum potassium closely throughout treatment 1.

Sodium Management

An initial rise in sodium level is expected and is not itself an indication for hypotonic fluids 4. Use corrected sodium calculations to guide fluid choice 1, 3.

Bicarbonate

Bicarbonate administration is generally not recommended in HHS 1.

Monitoring During Treatment

Frequent Monitoring Parameters 1

• Blood glucose: Every 1-2 hours until stable
• Serum electrolytes, BUN, creatinine, calculated osmolality: Every 2-4 hours
• Vital signs, fluid input/output, mental status: Continuously

The degree of mental obtundation typically correlates with hyperosmolarity severity and should improve with treatment 3.

Transition to Subcutaneous Insulin

Administer basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia. 1 Recent evidence suggests that low-dose basal insulin analog given concurrently with IV insulin may prevent rebound hyperglycemia 1.

Resolution Criteria

HHS is considered resolved when 2:

• Osmolality <300 mOsm/kg
• Hypovolaemia corrected (urine output ≥0.5 mL/kg/h)
• Cognitive status returned to pre-morbid state
• Blood glucose <15 mmol/L (270 mg/dL)

Critical Pitfalls to Avoid

Do not start insulin before adequate fluid resuscitation unless ketonemia is present - this is the most important distinction from DKA management and early insulin may worsen outcomes 1, 2, 4.

Do not correct osmolality too rapidly - keep reduction to 3-8 mOsm/kg/h to prevent central pontine myelinolysis 1, 2, 4.

Do not overlook potassium replacement - hold insulin if K+ <3.3 mEq/L to prevent life-threatening hypokalemia 1.

Do not use hypotonic fluids initially - begin with isotonic saline regardless of elevated sodium, as corrected sodium guides subsequent fluid choice 1, 4.

Care Setting

Patients with HHS should be managed in an intensive care unit with involvement of the diabetes specialist team as soon as possible, given the higher mortality rate compared to DKA and the complexity of management 2, 4, 5.