What is Hyperosmolar Hyperglycemic State (HHS)?

Hyperosmolar Hyperglycemic State (HHS)

Hyperosmolar Hyperglycemic State (HHS) is a serious acute metabolic complication of diabetes characterized by severe hyperglycemia (blood glucose ≥600 mg/dl), hyperosmolality (≥320 mOsm/kg H₂O), minimal ketosis, and altered mental status, with significant dehydration but without significant acidosis.

Diagnostic Criteria

HHS is defined by the American Diabetes Association by the following criteria 1, 2:

• Blood glucose ≥600 mg/dl
• Effective serum osmolality ≥320 mOsm/kg H₂O (calculated as 2[measured Na (mEq/l)] + glucose (mg/dl)/18)
• Arterial pH >7.3
• Serum bicarbonate >15 mEq/l
• Mild or absent ketonuria/ketonemia
• Altered mental status ranging from confusion to coma

Pathophysiology

The underlying mechanism of HHS involves 1:

• Reduction in effective circulating insulin
• Elevation of counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone)
• Increased hepatic and renal glucose production
• Impaired peripheral glucose utilization
• Unlike DKA, insulin levels in HHS may be sufficient to prevent significant lipolysis and ketogenesis but inadequate for glucose utilization

Clinical Presentation

HHS typically develops more gradually than DKA, evolving over days to weeks rather than hours 1. Key clinical features include:

• Neurological symptoms: Altered mental status (ranging from confusion to coma) is more common in HHS than in DKA
• Dehydration signs: Poor skin turgor, tachycardia, hypotension
• Classic symptoms: Polyuria, polydipsia, polyphagia, weight loss
• Absence of Kussmaul respirations (unlike in DKA)

Precipitating Factors

Common precipitants include 1, 2:

• Infections (most common)
• Cerebrovascular accidents
• Myocardial infarction
• Medications (glucocorticoids, thiazide diuretics, atypical antipsychotics)
• Nonadherence to diabetes treatment
• New-onset diabetes (especially in elderly)
• Substance abuse
• Pancreatitis

Management

1. Fluid Replacement

• Initial fluid therapy: Isotonic saline (0.9% NaCl) at 15-20 ml/kg/hour during the first hour 1, 2
• Subsequent fluid therapy: Based on corrected serum sodium and hemodynamic status
  • If sodium is normal or elevated: Switch to 0.45% saline
  • If sodium is low: Continue 0.9% saline
• Goal: Correct estimated fluid deficit within 24 hours
• Caution: Do not exceed a change in serum osmolality of 3 mOsm/kg/hour to prevent neurological complications 2

2. Insulin Therapy

• Begin insulin only after:
  • Initial fluid resuscitation has started
  • Hypokalemia (K <3.3 mEq/l) has been excluded
• 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, 2
• Adjustment: If glucose does not fall by 50 mg/dl in the first hour, double the insulin infusion rate hourly until achieving a steady decline 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 5-10% dextrose to IV fluids 1

3. Electrolyte Management

• Potassium: Add 20-30 mEq/l potassium (2/3 KCl and 1/3 KPO₄) to IV fluids once renal function is assured and serum potassium is known 1, 2
• Monitoring: Check electrolytes every 2-4 hours initially

4. Monitoring

• Frequent assessment of:
  • Vital signs and hemodynamic status
  • Mental status
  • Fluid input/output
  • Serum electrolytes, glucose, BUN, creatinine, osmolality every 2-4 hours 1

Complications and Prognosis

• Mortality: HHS has a higher mortality rate (15%) compared to DKA (5%) 1
• Complications:
  • Cerebral edema
  • Central pontine myelinolysis (from rapid changes in osmolality)
  • Thromboembolism
  • Myocardial infarction
  • Stroke
  • Rhabdomyolysis

Special Considerations

• Elderly patients: Require more cautious fluid management and closer monitoring 2
• Cardiac or renal disease: May necessitate central venous pressure monitoring and more careful fluid replacement 2
• Pregnancy: HHS is rare in pregnancy but carries high fetal and maternal risk 1
• Mixed HHS-DKA: About 30% of patients may present with features of both conditions 3

Prevention

• Education about:
  • Sick day management
  • Never discontinuing insulin during illness
  • Early recognition of symptoms
  • When to seek medical attention
• Regular monitoring of glucose levels, especially during illness or stress

HHS requires prompt recognition and aggressive management in an intensive care setting to reduce the high associated mortality and morbidity.