Hyperglycemic Hyperosmolar State (HHS)

Hyperosmolar Hyperglycemic State (HHS) is a serious complication of diabetes mellitus, characterized by severe hyperglycemia, hyperosmolality, and dehydration, without significant ketoacidosis.

It is more common in elderly patients with type 2 diabetes and can be triggered by infections, non-compliance with diabetes treatment, or other medical conditions. HHS carries a high risk of morbidity and mortality, with an estimated mortality rate of 10-20%.

Pathophysiology

HHS develops due to a combination of factors:

• Insulin deficiency: Although patients with HHS have some endogenous insulin, it is not sufficient to maintain normal blood glucose levels. The insulin present is usually adequate to suppress lipolysis and prevent significant ketogenesis, distinguishing HHS from diabetic ketoacidosis (DKA).
• Hyperglycemia: Severe hyperglycemia leads to osmotic diuresis, causing profound dehydration and electrolyte disturbances.
• Hyperosmolality: The elevated blood glucose levels increase plasma osmolality, leading to cellular dehydration, particularly affecting the central nervous system and contributing to the altered mental status often seen in HHS.

Epidemiology

• Predominance: HHS primarily occurs in older adults with type 2 diabetes but can also be seen in patients with undiagnosed diabetes or those on medications that impair glucose metabolism (e.g., glucocorticoids, thiazides).
• Precipitating Factors: Infections (e.g., pneumonia, urinary tract infections), non-adherence to diabetes medications, acute illnesses (e.g., stroke, myocardial infarction), and certain medications (e.g., diuretics, antipsychotics) are common triggers.

Clinical Presentation

1. Symptoms:
   • Polydipsia and polyuria: Resulting from hyperglycemia-induced osmotic diuresis.
   • Weakness and fatigue: Due to dehydration and hyperosmolality.
   • Altered mental status: Ranging from lethargy and confusion to coma, depending on the severity of hyperosmolality.
   • Neurological symptoms: Seizures, hemiparesis, or focal neurological deficits may mimic a stroke.
2. Signs:
   • Profound dehydration: Dry mucous membranes, poor skin turgor, hypotension, and tachycardia.
   • Neurological findings: Altered consciousness, focal neurological signs, or seizures.

Diagnostic Criteria

The diagnosis of HHS is based on clinical and laboratory findings:

1. Plasma glucose: >600 mg/dL (33.3 mmol/L).
2. Effective serum osmolality: >320 mOsm/kg (calculated as 2[Na+] + glucose/18).
3. Serum bicarbonate: >18 mEq/L.
4. pH: >7.3 (no significant acidosis).
5. Ketones: Absent or mild ketonemia/ketonuria.

Diagnostic Evaluation

• Laboratory Tests:
  • Serum electrolytes: Check for sodium, potassium, chloride, bicarbonate, and calculate the corrected sodium (corrected sodium = measured sodium + 1.6 × [(glucose – 100)/100]) due to hyperglycemia.
  • Blood urea nitrogen (BUN) and creatinine: Assess renal function and dehydration severity.
  • Serum osmolality: Direct measurement is helpful for confirming hyperosmolality.
  • Serum ketones: To rule out significant ketoacidosis.
  • Arterial blood gases (ABG): To evaluate for acid-base disorders if suspected.
  • Complete blood count (CBC) and blood cultures: Identify infections, a common precipitant.
  • Electrocardiogram (ECG): Assess for arrhythmias, electrolyte imbalances, or myocardial ischemia.
• Imaging: If indicated, perform a chest X-ray or head CT scan for potential infection or neurological causes.

Management

The management of HHS involves aggressive fluid replacement, insulin therapy, and correction of electrolyte imbalances:

1. Fluid Resuscitation:
   • Initial fluid therapy: Start with isotonic saline (0.9% NaCl) at a rate of 15-20 mL/kg/hr (1-1.5 L in the first hour). This addresses hypovolemia and improves tissue perfusion.
   • Ongoing fluid replacement: After initial stabilization, switch to 0.45% NaCl if the serum sodium is normal or elevated, at a rate of 250-500 mL/hr.
   • Total fluid deficit: Usually 8-12 L, with half replaced in the first 12 hours and the rest over the next 12-24 hours.
   • Monitoring: Assess hemodynamic status, urine output, and mental status frequently. Adjust the fluid rate based on these parameters.
2. Insulin Therapy:
   • Initial dose: Administer a continuous infusion of regular insulin at 0.1 units/kg/hr after initial fluid resuscitation.
   • Dose adjustment: If the plasma glucose does not decrease by 50-70 mg/dL in the first hour, the infusion rate can be doubled.
   • Glucose target: Once blood glucose levels reach 250-300 mg/dL, reduce the insulin infusion rate to 0.02-0.05 units/kg/hr and add dextrose to the IV fluids (e.g., D5-0.45% NaCl) to prevent hypoglycemia while continuing to correct hyperosmolality.
3. Electrolyte Management:
   • Potassium: Monitor serum potassium closely, as insulin therapy and rehydration can cause hypokalemia. Replace potassium if serum levels fall below 5.3 mEq/L, typically at a rate of 20-30 mEq/hr.
   • Sodium: Corrected sodium should guide the choice of IV fluids. Avoid overly rapid correction to prevent central pontine myelinolysis.
   • Phosphate: Consider replacement if levels are <1.0 mg/dL, especially in patients with cardiac dysfunction, anemia, or respiratory failure. Administer 20-30 mmol of potassium phosphate over 6 hours.
4. Addressing Precipitating Factors:
   • Infections: Start empiric antibiotic therapy if there is evidence of infection. Adjust based on culture results.
   • Medication review: Identify and discontinue medications that may have contributed to HHS.
   • Chronic disease management: Optimize treatment of co-existing conditions like heart failure, chronic kidney disease, or diabetes.

Complications

1. Cerebral edema: Rare but life-threatening, typically occurring in children and during overly rapid correction of hyperglycemia.
2. Thromboembolism: Due to hyperviscosity from severe dehydration; consider anticoagulation in high-risk patients.
3. Electrolyte disturbances: Hypokalemia, hypernatremia, or hypophosphatemia may develop during treatment.
4. Cardiovascular events: Acute coronary syndrome or arrhythmias may arise from underlying heart disease or electrolyte abnormalities.

Prognosis

• Mortality: Higher in HHS than in DKA, with factors such as older age, presence of comorbidities, and severity of dehydration influencing outcomes.
• Prevention of recurrence: Involves patient education on diabetes management, regular blood glucose monitoring, and addressing potential triggers like infections promptly.