What are the diagnostic criteria and initial management for Hyperosmolar Hyperglycemic State (HHS)?

Diagnosis and Management of Hyperosmolar Hyperglycemic State (HHS)

Diagnostic Criteria for HHS

HHS is diagnosed when a patient presents with plasma glucose ≥600 mg/dL, effective serum osmolality ≥320 mOsm/kg H₂O, minimal or absent ketones, arterial pH >7.3, serum bicarbonate >15 mEq/L, and altered mental status (typically stupor or coma). 1

The diagnostic criteria that differentiate HHS from other hyperglycemic crises include:

Parameter	HHS Criteria
Plasma glucose	≥600 mg/dL
Arterial pH	>7.3
Serum bicarbonate	>15 mEq/L
Urine ketones	Small/minimal
Serum ketones	Small/minimal
Effective serum osmolality	≥320 mOsm/kg H₂O
Anion gap	Variable
Mental status	Stupor/coma (typically altered)

Key Diagnostic Calculations

• Effective serum osmolality = 2[measured Na⁺ (mEq/L)] + glucose (mg/dL)/18 1
• Anion gap = (Na⁺) - (Cl⁻ + HCO₃⁻) 2

Initial Assessment

When HHS is suspected, the following laboratory tests should be obtained immediately:

• Arterial blood gases
• Complete blood count with differential
• Urinalysis and urine ketones
• Blood glucose
• Blood urea nitrogen (BUN)
• Serum creatinine
• Electrolytes (including calcium and magnesium)
• Serum ketones
• Calculation of effective osmolality 1

Additional evaluations should include:

• Electrocardiogram
• Bacterial cultures (blood, urine, throat) if infection is suspected
• Chest radiograph if indicated 2, 1

Management of HHS

Phase 1: Initial Resuscitation (0-60 minutes)

1. Fluid Replacement:

   • Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour 2, 1
   • Goal: Restore circulating volume and improve renal perfusion

2. Insulin Therapy:

   • Important: Withhold insulin initially unless ketonaemic, as fluid replacement alone will cause blood glucose to fall 1, 3
   • If ketones are present (mixed HHS/DKA), administer 0.15 U/kg IV insulin bolus, followed by continuous infusion at 0.1 U/kg/hour 1

3. Electrolyte Monitoring:

   • Check potassium levels before starting insulin
   • Do not administer insulin if hypokalemia is present until corrected 1

Phase 2: Ongoing Management (1-24 hours)

1. Fluid Management:

   • After initial stabilization, adjust fluid type based on corrected sodium:
     • If normal/elevated corrected sodium: 0.45% NaCl at 4-14 mL/kg/hour
     • If low corrected sodium: continue 0.9% NaCl 1
   • Total fluid deficit in HHS is typically 100-220 mL/kg (much higher than DKA) 4

2. Insulin Administration:

   • Start insulin only after osmolality stops falling with fluid replacement alone (unless ketonaemic) 4
   • Target glucose decrease rate: 50-75 mg/dL/hour 1
   • When glucose reaches <300 mg/dL, add dextrose to IV fluids (5% or 10%) and reduce insulin rate 4, 5

3. Electrolyte Replacement:

   • Add potassium to IV fluids once renal function is confirmed and serum potassium is known
   • Typical dose: 20-30 mEq/L (2/3 KCl and 1/3 KPO₄) 1
   • Monitor and replace magnesium, calcium, and phosphate as needed

4. Osmolality Management:

   • Calculate osmolality regularly to monitor treatment response
   • Critical: Aim to reduce osmolality by 3-8 mOsm/kg/hour to prevent neurological complications 1, 3

5. Treat Precipitating Factors:

   • Administer appropriate antibiotics if infection is suspected
   • Address other common precipitants: cerebrovascular events, myocardial infarction, pancreatitis, medications (corticosteroids, thiazides, sympathomimetics) 2, 1

Resolution Criteria for HHS

HHS is considered resolved when:

• Blood glucose <300 mg/dL
• Serum osmolality <315 mOsm/kg
• Patient is alert and able to ingest liquids 1, 4

Complications and Monitoring

Common Complications to Watch For:

• Cerebral edema
• Osmotic demyelination syndrome (from rapid osmolality correction)
• Thromboembolism
• Hypoglycemia
• Hypokalemia
• Fluid overload (especially in elderly or those with cardiac/renal disease) 1, 4

Monitoring Requirements:

• Hourly vital signs and neurological status
• Fluid input/output
• Electrolytes, glucose, BUN, creatinine every 2-4 hours
• Calculate osmolality regularly
• ECG monitoring if significant electrolyte abnormalities 1

Special Considerations

1. Mixed DKA/HHS presentations are increasingly common and require careful management of both conditions 4

2. Elderly patients require more cautious fluid management due to higher risk of cardiac complications 1, 4

3. HHS has higher mortality than DKA (up to 20%), requiring intensive care management 3

4. Common pitfalls to avoid:

   • Starting insulin before adequate fluid resuscitation
   • Correcting osmolality too rapidly
   • Failing to identify and treat precipitating causes
   • Inadequate monitoring of electrolytes 1

HHS is a medical emergency requiring prompt recognition and careful management, with particular attention to fluid resuscitation, gradual correction of osmolality, and treatment of underlying precipitants.