Hyperosmolar Hyperglycemic State (HHS)
Hyperosmolar hyperglycemic state (previously referred to as hyperglycemic hyperosmolar nonketotic coma [HHNK] and nonketotic hyperosmolar syndrome [NKHS]) is a complication of type 2 diabetes mellitus and has an estimated mortality rate of up to 20%, which is significantly higher than the mortality for diabetic ketoacidosis (currently < 1%). It usually develops after a period of symptomatic hyperglycemia in which fluid intake is inadequate to prevent extreme dehydration due to the hyperglycemia-induced osmotic diuresis.
Precipitating factors include
Serum ketones are not present because the amounts of insulin present in most patients with type 2 diabetes are adequate to suppress ketogenesis. Because symptoms of acidosis are not present, most patients endure a significantly longer period of osmotic dehydration before presentation, and thus plasma glucose (> 600 mg/dL [> 33.3 mmol/L]) and osmolality (> 320 mOsm/L) are typically much higher than in diabetic ketoacidosis.
The primary symptom of hyperosmolar hyperglycemic state is altered consciousness varying from confusion or disorientation to coma, usually as a result of extreme dehydration with or without prerenal azotemia, hyperglycemia, and hyperosmolality. In contrast to diabetic ketoacidosis, focal or generalized seizures and transient hemiplegia may occur.
Generally, hyperosmolar hyperglycemic state is initially suspected when a markedly elevated glucose level is found in a fingerstick specimen obtained in the course of a workup of altered mental status. If measurements have not already been obtained, measurement of serum electrolytes, blood urea nitrogen (BUN) and creatinine, glucose, ketones, and plasma osmolality should be done. Urine should be tested for ketones. Serum potassium levels are usually normal, but sodium may be low or high depending on volume deficits. Hyperglycemia may cause dilutional hyponatremia, so measured serum sodium is corrected by adding 1.6 mEq/L (1.6 mmol/L) for each 100 mg/dL (5.6 mmol/L) elevation of serum glucose over 100 mg/dL (5.6 mmol/L). BUN and serum creatinine levels are markedly increased. Arterial pH is usually > 7.3, but occasionally mild metabolic acidosis develops due to lactate accumulation.
The fluid deficit can exceed 10 L, and acute circulatory collapse is a common cause of death. Widespread thrombosis is a frequent finding on autopsy, and in some cases bleeding may occur as a consequence of disseminated intravascular coagulation. Other complications include aspiration pneumonia, acute renal failure, and acute respiratory distress syndrome.
Treatment consists of IV saline, correction of hypokalemia, and IV insulin (1).
Treatment is 0.9% (isotonic) saline solution at a rate of 15 to 20 mL/kg/hour, for the first few hours. After that, the corrected sodium should be calculated. If the corrected sodium is < 135 mEq/L (< 135 mmol/L), then isotonic saline should be continued at a rate of 250 to 500 mL/hour. If the corrected sodium is normal or elevated, then 0.45% saline (half normal) should be used.
Dextrose should be added once the glucose level reaches 250 to 300 mg/dL (13.9 to 16.7 mmol/L). The rate of infusion of IV fluids should be adjusted depending on blood pressure, cardiac status, and the balance between fluid input and output.
Insulin is given at 0.1 unit/kg IV bolus followed by a 0.1 unit/kg/hour infusion after the first liter of saline has been infused. Hydration alone can sometimes precipitously decrease plasma glucose, so insulin dose may need to be reduced. A too-quick reduction in osmolality can lead to cerebral edema. Occasional patients with insulin-resistant type 2 diabetes with hyperosmolar hyperglycemic state require larger insulin doses. Once plasma glucose reaches 300 mg/dL (16.7 mmol/L), insulin infusion should be reduced to basal levels (1 to 2 units/hour) until rehydration is complete and the patient is able to eat.
Target plasma glucose is between 250 and 300 mg/dL (13.9 to 16.7 mmol/L). After recovery from the acute episode, patients are usually switched to adjusted doses of subcutaneous insulin.
Potassium replacement is similar to that in diabetic ketoacidosis: 40 mEq/hour for serum potassium < 3.3 mEq/L (< 3.3 mmol/L); 20 to 30 mEq/hour for serum potassium between 3.3 and 4.9 mEq/L (3.3 and 4.9 mmol/L); and none for serum potassium ≥ 5 mEq/L (≥ 5 mmol/L).
Infections, nonadherence, and certain drugs can trigger marked glucose elevation, dehydration, and altered consciousness in patients with type 2 diabetes.
Patients have adequate insulin present to prevent ketoacidosis.
The fluid deficit can exceed 10 L; treatment is 0.9% saline solution IV plus insulin infusion.
Target plasma glucose in acute treatment is between 250 and 300 mg/dL (13.9 to 16.7 mmol/L).
Give potassium replacement depending on serum potassium levels.