Hyperosmolar Hyperglycemic Nonketotic Syndrome

What Is Hyperosmolar Hyperglycemic Nonketotic Syndrome?

Hyperosmolar hyperglycemic nonketotic syndrome (HHNS) is a condition mostly seen in patients with Type 1 or Type 2 diabetes, when it is not properly controlled. HHNS usually affects older people, but it can affect diabetes patients at any age.

Hyperosmolar Hyperglycemic Nonketotic Syndrome is characterized by hyperglycemia, hyperosmolarity and dehydration without signs of ketoacidosis. It is mostly seen in type 2 diabetes patients with a concomitant disease [1]. Diabetes is often present in Prader-Willi syndrome.


Hyperosmolar Hyperglycemic Nonketotic Syndrome is a complication of diabetes. This condition has a high rate of mortality- reaching up to 40%. HHNS is usually present after a period of symptomatic hyperglycemia. When hyperglycemia occurs, it causes osmotic diuresis, in which the fluid intake is usually inadequate to prevent dehydration.

For this reason, any condition that causes dehydration might trigger HHNS. In this syndrome ketones are not present, because the produced insulin is enough to prevent ketogenesis. Diabetic ketoacidosis is more commonly seen complication of diabetes.

It is generally characterized by fatigue, nausea, vomiting, rapid weight loss, altered consciousness and rapid breathing. In Hyperosmolar Hyperglycemic Nonketotic Syndrome these symptoms are not present, most patients endure longer periods of dehydration before presenting with symptoms [2,3].

Hyperosmolar Hyperglycemic Nonketotic Syndrome


HHNS is mostly seen in patients with type 2 diabetes. HHNS is a complication of diabetes, which can be caused by other conditions which lead to reduced hydration, like infection. There are also conditions that trigger a stress response- release of cortisol, glucagon and catecholamines which have a counter action of insulin. These conditions include:

  • Stroke
  • Intracranial hemorrhage
  • Myocardial infarction
  • Pulmonary embolism

Risk factors

  • Congestive heart failure
  • Use of alcohol and cocaine. Also read about fetal alcohol syndrome.
  • Drugs that can raise serum levels of glucose and inhibit function of insulin, like:
    • Antypsichotics
    • Antiepileptics
    • Calcium channel blockers
    • Beta blockers
    • Corticosteroids
    • Diuretics
    • Parenteral nutrition
    • Immunosuppressive therapy (used for treatment of Hemolytic-uremic syndrome)

Hyperosmolar Hyperglycemic Nonketotic Syndrome

Other conditions

  • Acromegaly
  • Burns
  • Cushing syndrome
  • Hypothermia
  • Intestinal obstruction
  • Neuroleptic malignant syndrome
  • Rhabdomyolysis, often seen in compartment syndrome.
  • Trauma
  • Elderly abuse, see Battered woman syndrome [4]


The main symptom of Hyperosmolar Hyperglycemic Nonketotic Syndrome is decreased consciousness. The patient might seem confused and disoriented, but in severe cases the patient might be in a coma. In some cases, focal or generalized seizures might occur, as well as transient hemiplegia- read more about Lennox Gastaut syndrome.

The main signs of Hyperosmolar Hyperglycemic Nonketotic Syndrome, described by the American Diabetes Association are:

  • Blood sugar levels over 600mg/dl
  • Dry mouth
  • Extreme thirst
  • Warm skin
  • No sweatting
  • High fever
  • Altered consciousness
  • Vision loss
  • Hallucinations [1,5]


Blood analyses

Blood analyzes are very important in diagnosing HHNS. Usually hemoglobin and hematocrit levels are increased due to volume loss. Leukocytosis is almost always seen with values higher then 20,00/ µL. which is caused by stress, dehydration and concomitant disease.

Serum glucose levels can be firstly measured with the portable glucometer, but later they need to be measured from vein. The levels often exceed 600 mg/dL, and can even reach concentrations greater than 1000 mg/dL. Higher levels of glucose suggest worse prognosis. Usually hemoglobin A levels are also measured. Hemoglobin A is an important indicator of how well the diabetes is controlled. BUN and creatine levels are usually obtained.

By definition, osmolality greater than 320 mOsm/kg means it is HHNS. Normal serum osmolality ranges from 280 to 290 mOsm/kg. Blood gases and pH level should be measured. In Hyperosmolar Hyperglycemic Nonketotic Syndrome serum pH is usually greater than 7.3.

Before osmotic diuresis occurs, the high levels of glucose in the body cause fluid to move from intracellular to extracellular space. This causes dilution of the blood and relative decrease in electrolyte levels- hyponatremia and hypochloremia.

In patients with renal insufficiency this might not occur. In HHNS mild ketosis might occur, but it usually can be treated with rehydration. If HHNS is also combined with diabetic ketoacidosis, correction can be difficult.

An important sign in HHNS is rise in enzyme levels. Due to dehydration, there is increase in albumin, amylase, calcium, bilirubin, creatine kinase and lactate dehydrogenase. Creatine kinase is a very important marker that should be constantly monitored. Increased CK levels are a sign of myocardial infarction, which can cause HHNS and also be a complication of it.

Other tests

Hyperosmolar Hyperglycemic Nonketotic Syndrome diagnosis is mostly based on blood analyzes and clinical presentation. Other tests are used to find the possible cause. Tests that should be performed include:

  • Blood cultures- to diagnose bacteremia. Also see staphylococcal scalded skin syndrome.
  • Chest X-ray- very important in patients with leukocytosis
  • CT- scanning the brain and performing CT angiography can diagnose stroke, myocardial infarction or possible brain hemorrhage
  • MRI scanning- valuable diagnostic method for brain examination.


Intravenous fluids

Before administering intravenous fluids, the hydration status should be determined. If the patient is in cardiogenic shock, they should be closely monitored and fluids have to be administered with caution. Patients who are in a hypovolemic shock should receive 0,9% NaCl fluid 1l per hour. For patients with mild hypotension hydration therapy depends on the serum natrium levels:

  • With normal and high Na- administer 0.45% NaCl fluid with 14ml/kg/h.
  • With low serum Na- 0.9% NaCl fluid 4-14 ml/kg/h.

When serum glucose levels are at 250 mg/dl, fluids have to be switched to 5% dextrose with 0.45% NaCl plus adequate dosage of insulin.


Intravenously insulin is usually given in bolus with 0.15U/kg, and then switched to an infusion of 0.1 U/kg/h.

Subcutaneous or intramuscular insulin should be given 0.4 U/kg. The effect of insulin therapy has to be closely monitored, and if necessary, increased.


Usually patients with Hyperosmolar Hyperglycemic Nonketotic Syndrome have increased levels of potassium. Usually insulin and fluid therapy reduces potassium levels, since it moves back in cells from the blood. For this reason, extra potassium should be administered to prevent hypokalemia [6].


Although it occurs rare, one of the most dangerous complications of HHNS is cerebral edema. cerebral edema is usually due to rapid fluid intake and use of hypotonic fluids. Still, these procedures are necessary to treat HHNS. More commonly death occurs due to undertreatment rather than overtreatment. See Exploding head syndrome.

Treatment with insulin and crystalloid solutions can cause significant edema. Patients with existing cardiovascular disease can develop heart failure, pulmonary edema and pulmonary hypertension.

Other possible complications are mesenteric artery occlusion. Myocardial infarction and disseminated intravascular coagulopathy [7].

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  1. General information: http://www.diabetes.org/living-with-diabetes/complications/hyperosmolar-hyperglycemic.html?referrer=https://www.google.de/
  2. Diabetic ketoacidosis symptoms: http://emedicine.medscape.com/article/118361-overview
  3. Pathogenesis: http://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/nonketotic-hyperosmolar-syndrome-nkhs
  4. Causes: http://emedicine.medscape.com/article/1914705-overview#a3
  5. Symptoms: https://medlineplus.gov/ency/article/000304.htm
  6. Therapy: http://spectrum.diabetesjournals.org/content/15/1/28
  7. Complications: http://www.aafp.org/afp/1999/1001/p1468.html

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