What is the immediate treatment for a patient with Hyperosmolar Hyperglycemic State (HHS) due to diabetes?

Immediate Treatment of Hyperosmolar Hyperglycemic State (HHS)

Begin aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 ml/kg/h immediately, and delay insulin therapy until blood glucose stops falling with fluids alone unless significant ketonemia is present. 1, 2, 3

Initial Assessment and Monitoring (0-60 minutes)

Confirm the diagnosis by checking for:

• Blood glucose ≥600 mg/dl 4
• Effective serum osmolality ≥320 mOsm/kg (calculated as: 2[measured Na] + glucose/18) 4
• Arterial pH >7.3 and bicarbonate ≥15 mEq/l (minimal acidosis) 4
• Ketones ≤3.0 mmol/L (absent or mild ketonemia) 2

Obtain immediate laboratory studies: arterial blood gases, complete blood count with differential, urinalysis, glucose, BUN, creatinine, electrolytes, and electrocardiogram 4, 1

Calculate corrected serum sodium by adding 1.6 mEq for each 100 mg/dl glucose above 100 mg/dl to assess true sodium status 4, 1

Fluid Resuscitation Strategy

First Hour

• Start with 0.9% NaCl at 15-20 ml/kg/h to restore intravascular volume and renal perfusion 1, 2
• This aggressive initial resuscitation is critical even in patients with cardiac or renal compromise, though these patients require more intensive monitoring 4, 1
• Typical total fluid deficits in HHS are 100-220 ml/kg (average 9 liters) 1, 2, 5

After First Hour (1-6 hours)

Switch fluids based on corrected serum sodium: 4, 1

• If corrected sodium is normal or elevated: change 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

An initial rise in measured sodium is expected and normal as glucose falls with fluid therapy alone—this does not indicate need for hypotonic fluids 3

Critical Monitoring Parameters

• Monitor serum osmolality every 2-4 hours 1, 2
• Target osmolality reduction of 3-8 mOsm/kg/h to minimize risk of osmotic demyelination syndrome 1, 2, 3
• Assess hemodynamic status through blood pressure, urine output (target ≥0.5 ml/kg/h), and clinical examination 4, 1, 2
• Correct estimated fluid deficits within 24-48 hours 4, 1

Insulin Therapy: The Critical Timing Difference

This is where HHS differs fundamentally from DKA: 2, 3

When to START Insulin

• Withhold insulin initially until blood glucose stops falling with IV fluids alone 2, 3
• Fluid replacement alone will cause significant glucose decline in HHS 3
• Exception: Start insulin immediately if significant ketonemia is present (>3.0 mmol/L) 2, 3
• Early insulin use before adequate fluid resuscitation may be detrimental 3

Insulin Dosing Protocol

Once glucose plateaus with fluids or if ketonemia present: 4

• Exclude hypokalemia first (K+ must be >3.3 mEq/l before starting insulin) 4
• Give IV bolus of regular insulin 0.15 units/kg 4
• Follow with continuous infusion at 0.1 units/kg/h (typically 5-7 units/h in adults) 4
• Target glucose decline of 50-75 mg/dl/h 4

Glucose Management During Treatment

• When glucose reaches 300 mg/dl in HHS, add 5-10% dextrose to IV fluids 4, 1
• Reduce insulin infusion to 0.05-0.1 units/kg/h 4
• Target glucose 10-15 mmol/L (180-270 mg/dl) in first 24 hours, not normoglycemia 1, 2

Potassium Replacement

Critical timing considerations: 4, 1

• Do not give potassium if K+ <3.3 mEq/l—correct this first before insulin
• Once renal function confirmed and K+ known, add 20-30 mEq/l potassium to IV fluids
• Use 2/3 KCl and 1/3 KPO4 4, 1
• Continue until patient stable and tolerating oral intake

Special Considerations for Renal or Cardiac Compromise

Patients with renal or cardiac disease require heightened vigilance: 4, 1

• Monitor serum osmolality more frequently (every 2 hours initially) 4, 1
• Perform frequent cardiac, renal, and mental status assessments 4, 1
• Consider central venous pressure monitoring or other hemodynamic assessment 1
• Watch for fluid overload signs: pulmonary edema, worsening oxygenation, elevated jugular venous pressure 1

Common Pitfalls to Avoid

Osmolality correction too rapid: The most dangerous complication is osmotic demyelination syndrome from dropping osmolality >8 mOsm/kg/h 1, 2, 3

Starting insulin too early: Unlike DKA, premature insulin in HHS before adequate fluid resuscitation may worsen outcomes 2, 3

Using hypotonic fluids too early: An initial rise in measured sodium is expected and appropriate—do not switch to hypotonic fluids based on rising sodium alone 3

Inadequate potassium monitoring: Insulin drives potassium intracellularly, risking life-threatening hypokalemia if not monitored and replaced 4

Resolution Criteria

HHS is resolved when: 2

• Osmolality <300 mOsm/kg
• Hypovolaemia corrected (urine output ≥0.5 ml/kg/h)
• Mental status returned to baseline
• Blood glucose <15 mmol/L (270 mg/dl)

Transition from IV to Subcutaneous Insulin

When transitioning off IV insulin: 4

• Administer basal insulin 2-4 hours before stopping IV insulin infusion 4
• This prevents rebound hyperglycemia and recurrence of metabolic decompensation 4
• Recent evidence supports adding low-dose basal insulin analog during IV insulin infusion to prevent rebound 4

Underlying Precipitants

Identify and treat simultaneously: 4, 2, 5

• Infections are the most common precipitant 5
• Other causes: myocardial infarction, stroke, medications (diuretics, corticosteroids), non-compliance 4, 5, 6
• Failure to treat underlying causes contributes to the high mortality of HHS 5, 6