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

Diagnostic Criteria and Treatment for Hyperosmolar Hyperglycemic State (HHS)

The diagnosis of HHS requires blood glucose ≥600 mg/dL, effective serum osmolality ≥320 mOsm/kg H₂O, arterial pH >7.3, serum bicarbonate >15 mEq/L, and minimal or absent ketones, typically with altered mental status ranging from confusion to coma. 1

Diagnostic Criteria

HHS is characterized by the following laboratory findings:

• Plasma glucose >600 mg/dL
• Arterial pH >7.30
• Serum bicarbonate >15 mEq/L
• Effective serum osmolality >320 mOsm/kg
• Small or absent urine and serum ketones
• Altered mental status (ranging from drowsiness to coma)
• Variable anion gap 2, 1

The effective serum osmolality can be calculated using the formula: 2[measured Na⁺ (mEq/L)] + glucose (mg/dL)/18 2

Clinical Presentation

HHS typically develops more gradually than DKA, evolving over days to weeks, with:

• Polyuria, polydipsia, polyphagia
• Weight loss
• Dehydration signs (poor skin turgor, dry mucous membranes)
• Progressive alteration in mental status
• Absence of Kussmaul respirations (unlike DKA)
• Potential hypothermia (a poor prognostic sign) 2, 1

Laboratory Evaluation

When HHS is suspected, immediate laboratory tests should include:

• Arterial blood gases
• Complete blood count with differential
• Urinalysis
• Plasma glucose
• Blood urea nitrogen/creatinine
• Electrolytes (with calculated anion gap)
• Serum osmolality
• Serum ketones
• Electrocardiogram 1

Treatment Protocol

1. Fluid Therapy (Priority)

• Initial phase (0-60 min): Isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour (1-1.5 L in average adult) 2, 1
• Hours 1-6: Continue fluid replacement based on hemodynamic status and corrected serum sodium
• Goal: Correct estimated fluid deficit (100-220 mL/kg) within 24 hours 1, 3
• Caution: Avoid exceeding osmolality change of 3-8 mOsm/kg/hour to prevent neurological complications 1

2. Insulin Therapy

• Start only after initial fluid resuscitation has begun and hypokalemia has been excluded 1
• Initial dosing: IV bolus of regular insulin at 0.15 U/kg body weight, followed by continuous infusion at 0.1 U/kg/hour (5-7 U/hour in adults) 1
• Adjustment: Titrate to achieve glucose decrease of 50-75 mg/dL/hour
• Transition: When glucose reaches 300 mg/dL, reduce insulin to 0.05-0.1 U/kg/hour and add dextrose (5-10%) to IV fluids 1, 3

3. Electrolyte Management

• Potassium: Add 20-30 mEq/L to IV fluids once renal function is assured and serum potassium is known (typically 2/3 KCl and 1/3 KPO₄) 1
• Monitor: Sodium, potassium, phosphate, magnesium, and calcium levels regularly
• Caution: An initial rise in sodium level is expected and is not itself an indication for hypotonic fluids 4

4. Monitoring

• Vital signs, hemodynamic status, mental status every 1-2 hours
• Fluid input/output hourly
• Serum electrolytes, glucose, BUN, creatinine, and osmolality every 2-4 hours
• Calculate effective osmolality regularly to monitor treatment response 1

Resolution Criteria

HHS is considered resolved when:

• Blood glucose <300 mg/dL
• Serum osmolality <315 mOsm/kg
• Patient is alert and can ingest liquids 1, 3

Complications and Pitfalls

Common Complications

• Cerebral edema (especially with rapid osmolality correction)
• Central pontine myelinolysis
• Thromboembolism (high risk)
• Myocardial infarction
• Stroke
• Rhabdomyolysis 1

Treatment Pitfalls to Avoid

1. Early insulin use before adequate fluid resuscitation - may worsen dehydration and precipitate shock 4
2. Too rapid correction of osmolality - aim for 3-8 mOsm/kg/hour to prevent neurological complications 1
3. Failure to identify and treat precipitating factors - infections are most common, but also consider medications, stroke, MI, etc. 2, 1
4. Inadequate monitoring - HHS has 10-20% mortality rate requiring close observation 1
5. Overlooking mixed DKA/HHS - can occur and requires modified management 3

Special Considerations

• Elderly patients: Require more cautious fluid management
• Cardiac/renal disease: Increased risk of fluid overload, requiring closer monitoring
• Pregnancy: Rare but carries high fetal and maternal risk 1

HHS management requires intensive monitoring and careful correction of multiple metabolic derangements. The high mortality rate (10-20%) emphasizes the importance of early diagnosis, aggressive treatment, and prevention of complications.