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Hyperosmolar Hyperglycemic State (HHS)


Erika F. Brutsaert

, MD, New York Medical College

Reviewed/Revised Sep 2022
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Hyperosmolar hyperglycemic state is a metabolic complication of diabetes mellitus characterized by severe hyperglycemia, extreme dehydration, hyperosmolar plasma, and altered consciousness. It most often occurs in type 2 diabetes, often in the setting of physiologic stress. Hyperosmolar hyperglycemic state is diagnosed by severe hyperglycemia and plasma hyperosmolality and absence of significant ketosis. Treatment is IV saline solution and insulin. Complications include coma, seizures, and death.

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 Diabetic Ketoacidosis (DKA) Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with... read more (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

  • Acute infections and other medical conditions

  • Drugs that impair glucose tolerance (glucocorticoids) or increase fluid loss (diuretics)

  • Nonadherence to diabetes treatment

Serum ketones are not present because the amount of insulin present in most patients with type 2 diabetes is adequate to suppress ketogenesis. Because symptoms of acidosis are not present, most patients endure a significantly longer period of osmotic diuresis (high solute concentrations from glucose in the renal tubules, leading to excess water loss). This causes more severe 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.

Symptoms and Signs of HHS

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.

Diagnosis of HHS

  • Blood glucose level

  • Serum osmolarity

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, urine should be tested for ketones and the following should be measured in a blood sample:

  • Serum electrolytes

  • Blood urea nitrogen (BUN)

  • Creatinine

  • Glucose

  • Ketones

  • Plasma osmolality

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 Metabolic Acidosis Metabolic acidosis is primary reduction in bicarbonate (HCO3), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly... read more develops due to lactate accumulation.

Treatment of HHS

  • IV 0.9% saline

  • Correction of any hypokalemia

  • IV insulin (as long as serum potassium is 3.3 mEq/L [ 3.3 mmol/L])

Treatment is 0.9% (isotonic) saline solution; 1000 mL is given in the first hour. Smaller boluses (500 mL) can be given if there is risk for exacerbation of heart failure or volume overload. Additional boluses may be needed for hypotensive patients. After the first hour, intravenous fluids should be adjusted based on hemodynamic and electrolyte status but should generally be continued at a rate of 250 to 500 mL/hour. A corrected sodium should be calculated. If the corrected sodium is < 135 mEq/L (< 135 mmol/L), then isotonic saline can be continued. 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 Insulin General treatment of diabetes mellitus for all patients involves lifestyle changes, including diet and exercise. Appropriate monitoring of blood glucose levels is essential to prevent complications... read more 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 and hypokalemia has been corrected. 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).

Treatment references

Key Points

  • Hyperosmolar hyperglycemic state (HHS) is a metabolic complication of diabetes mellitus characterized by severe hyperglycemia, extreme dehydration, hyperosmolar plasma, and altered consciousness.

  • HHS can occur if infections, nonadherence, and certain drugs 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.

Drugs Mentioned In This Article

Drug Name Select Trade
Afrezza, Exubera
Aluvea , BP-50% Urea , BP-K50, Carmol, CEM-Urea, Cerovel, DermacinRx Urea, Epimide-50, Gord Urea, Gordons Urea, Hydro 35 , Hydro 40, Kerafoam, Kerafoam 42, Keralac, Keralac Nailstik, Keratol, Keratol Plus, Kerol, Kerol AD, Kerol ZX, Latrix, Mectalyte, Nutraplus, RE Urea 40, RE Urea 50 , Rea Lo, Remeven, RE-U40, RYNODERM , U40, U-Kera, Ultra Mide 25, Ultralytic-2, Umecta, Umecta Nail Film, URALISS, Uramaxin , Uramaxin GT, Urea, Ureacin-10, Ureacin-20, Urealac , Ureaphil, Uredeb, URE-K , Uremez-40, Ure-Na, Uresol, Utopic, Vanamide, Xurea, X-VIATE
Advocate Glucose SOS, BD Glucose, Dex4 Glucose, Glutol , Glutose 15 , Glutose 45 , Glutose 5
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