What is the best treatment approach for a patient presenting with hyperosmolar hyperglycemic state (HHS)?

Treatment of Hyperosmolar Hyperglycemic State (HHS)

Aggressive fluid resuscitation with isotonic saline is the cornerstone of HHS management and must be initiated immediately, followed by cautious insulin therapy only after fluid replacement has begun and glucose is no longer falling with fluids alone. 1, 2

Diagnostic Confirmation

Before initiating treatment, confirm HHS with these specific criteria:

• Blood glucose >600 mg/dL 3, 1
• Effective serum osmolality ≥320 mOsm/kg (calculated as: 2[measured Na] + glucose/18) 3, 1
• Arterial pH >7.3 and bicarbonate >15 mEq/L (distinguishes from DKA) 3, 1
• Minimal or absent ketones 1, 2

Obtain immediately: arterial blood gases, complete blood count, urinalysis, electrolytes, BUN, creatinine, and ECG. 3, 1

Phase 1: Initial Fluid Resuscitation (First Hour)

Start with 0.9% normal saline at 15-20 mL/kg/h (approximately 1-1.5 L in average adult) during the first hour. 3, 1 This is non-negotiable regardless of corrected sodium level, as the priority is restoring intravascular volume and tissue perfusion. 3, 2

The 2023 Joint British Diabetes Societies guideline emphasizes that fluid replacement alone will cause blood glucose to fall, and this is the desired initial effect. 2 Do not rush to insulin.

Phase 2: Ongoing Fluid Management (Hours 1-24)

After initial resuscitation, adjust fluid type based on corrected serum sodium (add 1.6 mEq to measured sodium for every 100 mg/dL glucose above normal): 3

• If corrected sodium is normal or elevated: Use 0.45% NaCl at 4-14 mL/kg/h 3
• If corrected sodium is low: Continue 0.9% NaCl at similar rate 3

Critical monitoring target: Reduce osmolality by 3-8 mOsm/kg/h—no faster. 1, 2 Rapid correction risks catastrophic central pontine myelinolysis and cerebral edema. 4, 2 Calculate osmolality every 2-4 hours to ensure you're not exceeding this rate. 1

Total fluid deficit is typically 100-220 mL/kg and should be corrected within 24 hours. 2

Phase 3: Insulin Therapy—Timing Is Everything

The most important pitfall to avoid: Do NOT start insulin until blood glucose stops falling with IV fluids alone, unless significant ketonemia is present. 4, 2 The 2023 JBDS guideline and 2015 British guidance both emphasize that early insulin use before adequate fluid resuscitation may be detrimental. 4, 2

When to start insulin:

• Once glucose plateaus despite ongoing fluid resuscitation 2
• OR if ketones are ≥3.0 mmol/L (indicating mixed DKA/HHS), start immediately 2

Insulin dosing:

• Continuous IV infusion at 0.1 units/kg/h (typically 5-10 units/hour) 1
• When glucose reaches 300 mg/dL, reduce to 0.05-0.1 units/kg/h (3-6 units/hour) 1
• Add 5-10% dextrose to IV fluids when glucose falls below 300 mg/dL 1
• Target glucose 250-300 mg/dL (NOT lower) until osmolality normalizes 1

The 2024 American Diabetes Association guidelines note that adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk. 3

Phase 4: Electrolyte Replacement

Potassium management is critical—most patients are severely depleted despite normal initial levels: 3

• Once renal function confirmed and K+ known, add 20-30 mEq/L to IV fluids (2/3 KCl, 1/3 KPO4) 3, 1
• Monitor potassium every 2-4 hours 1
• Never start insulin if K+ <3.3 mEq/L 3

Do NOT use bicarbonate therapy—multiple studies show no benefit in HHS or DKA and it is not recommended. 3

Phase 5: Monitoring During Treatment

Check hourly: 1

• Vital signs and mental status
• Fluid input/output
• Capillary glucose

Check every 2-4 hours: 1

• Serum electrolytes (Na, K, Cl, HCO3)
• Calculated osmolality
• BUN and creatinine

An initial rise in sodium is expected and normal as glucose falls—this is NOT an indication for hypotonic fluids. 4 Only switch to 0.45% saline based on corrected sodium calculations. 3

Resolution Criteria

HHS is resolved when ALL of the following are met: 2

• Osmolality <300 mOsm/kg
• Patient alert and oriented to baseline
• Adequate urine output (≥0.5 mL/kg/h)
• Blood glucose <15 mmol/L (270 mg/dL)

Transition to Subcutaneous Insulin

Give basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin—failure to overlap is a common cause of rebound hyperglycemia and DKA. 3, 1 Many patients with HHS will not require long-term insulin and can transition to oral agents after recovery. 5

Special Populations and Pitfalls

Elderly patients and those with cardiac/renal disease: Use more conservative fluid rates with closer hemodynamic monitoring to avoid fluid overload. 1, 2 These patients have the highest mortality risk. 4, 6

Identify and treat precipitating causes simultaneously: infection (most common), MI, stroke, medications (diuretics, steroids, SGLT2 inhibitors). 1, 7 Failure to address underlying triggers increases mortality. 5, 8

ICU admission is mandatory for patients with altered mental status or severe dehydration. 3, 6 These are critically ill patients requiring experienced nursing care. 4