Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) is an emergency that the diabetes mellitus (DM) patient may experience. The condition is also commonly referred to as hyperglycemic hyperosmolar nonketotic coma (HHNC). However, recent literature has changed the name and reference from “coma” to “syndrome” since less than 10 percent of the patients truly become comatose.
As the name implies, this condition is associated with an excessively elevated blood glucose level and hyperosmolar extracellular fluid (ECF) without the production and accumulation of a mass amount of ketones in the blood. The primary pathophysiology associated with the condition produces severe dehydration and electrolyte disturbances.
Epidemiology
HHNS is most commonly found in elderly patients in their 70s who have Type II DM; however, it has also been reported in pediatric patients as young as 18 months and in some patients with Type I DM. The incidence is higher than diabetic ketoacidosis (DKA) with 17.5 cases occurring for every 100,000 people. HHNS is slightly more prevalent in females than in males. Elderly residents of nursing homes who have preexisting disease or an acute onset of illness — especially if associated with an infection, poor fluid intake, or an increase in urine output — and who are demented are at the highest risk for experiencing HHNS. The dementia typically causes a poor fluid intake from a lack of recognition of dehydration. Any condition or illness that results in dehydration increases the risk of HHNS in the patient with Type II DM. The mortality has been reported as high as 10 to 20 percent.
Approximately 20 to 33 percent of the patients who suffer an acute onset of HHNS have no previous history of DM. These patients are at the highest risk since they often do not recognize the early warning signs and symptoms of severe dehydration. When assessing a patient with signs and symptoms of dehydration, it is imperative to assess the blood glucose level regardless of a known medical history of DM. You may be the first person to initially diagnose the DM condition in the prehospital setting.
Pathophysiology
HHNS is associated with severe elevations in the blood glucose level, often exceeding 600 mg/dL, from an absolute or relative insulin deficiency or from a decreased response of the tissue to the circulating insulin (insulin resistance). This results in glycogenolysis, gluconeogenesis, and a decreased uptake of glucose by the peripheral tissue. A decline in renal function, which is typically found in the elderly patient or in patients with renal disease, also contributes to a decrease in glucose clearance. Glycogenolysis may have a limited contribution to the hyperglycemic state since many of the patients are debilitated or suffer from an acute illness and have a poor diet as a result, causing the glycogen stores in the liver to deplete over time.
The elevated blood glucose level creates a hyperosmolar extracellular space that begins to pull fluid and dehydrate the intracellular space. Initially, this influx of fluid will maintain the blood pressure and perfusion. Once the blood glucose level exceeds 180 to 250 mg/dL, a significant amount of glucose will spill into the urine. As the osmotic diuresis continues, the intravascular volume is profoundly depleted, which further decreases renal perfusion and the ability of the kidneys to remove glucose from the blood. The average fluid loss is typically 9 to ten liters in a 70 kg patient. A common cause of death is circulatory collapse.
The change in the serum osmotic pressure may cause potassium, sodium, chloride, phosphate, magnesium and bicarbonate to be depleted from the tissues, even though the serum electrolyte levels may appear to be normal or elevated. Sodium, potassium, phosphate and magnesium are typically lost during the osmotic diuresis leading to electrolyte imbalances.
Unlike DKA, the patient with HHNS does not develop ketoacidosis. There are many theories as to why there is a lack of ketogenesis; however, the exact cause is not well understood. It is thought that the continued secretion and availability of small amounts of insulin decreases the mass release of counter-regulatory hormones and reduces the availability of free fatty acids needed to produce ketones. With no ketoacidosis, the patient will not present with Kussmaul’s respirations or a fruity (acetone) odor on the breath.
Pneumonia, chronic renal insufficiency, gastrointestinal bleeding, urinary tract infection, and sepsis are common precipitating factors of HHNS. Factors that stress the body, such as trauma or burns, will trigger a stress-response, releasing a number of hormones (epinephrine, cortisol, and glucagon) that have a tendency to counter the effects of insulin and raise the blood glucose level. Other common underlying causes are:
- Stroke
- Myocardial infarction
- Intracranial hemorrhage
- Cushing’s syndrome
- Poor compliance with oral hypoglycemics or insulin therapy
- Hemorrhage
- Elder abuse or neglect leading to under-hydration
- Renal disease
- Dialysis
- Cushing’s syndrome
- Diuretics
- Beta-blockers
- Histamine 2 (H2) blockers
- Glucocorticoids
- Phenytoin
- Immunosuppressants
Signs and Symptoms
The clinical presentation of HHNS is related to volume depletion and dehydration with a slow onset of signs and symptoms, usually progressing over a few days. In the early phase of HHNS, the signs and symptoms may be vague such as leg cramps, weakness and visual disturbances. As the blood glucose level continues to increase and the patient further dehydrates, the signs and symptoms usually progress in severity to include an alteration in mental status. Other signs and symptoms include:
- Thirst
- Fever (may suggest sepsis or infection as the predisposing factor)
- Polyuria (early)
- Oliguria (often a late sign of a severe dehydrated state)
- Drowsiness, confusion, lethargy, or coma
- Focal seizures that may be continuous (epilepsia partialis continua) or intermittent
- Generalized seizures
- Hemiparesis or sensory deficits
- Tachycardia
- Orthostatic hypotension
- Hypotension (late signs of profound dehydration)
- Poor skin turgor (not a reliable sign in the elderly)
- Dry skin and mucous membranes
- Sunken eyes
- Excessively elevated blood glucose level
Emergency Care
Even though the pathophysiology, signs, and symptoms of HHNS are related to severe dehydration, the condition carries a significant mortality rate. Aggressive assessment and management of the airway, ventilation, oxygenation and circulation may be necessary. Emergency care may include the following:
 Even though the major complication of the disease is severe dehydration, HHNS carries the highest mortality rate of the diabetic emergencies.  |
Establish and maintain a patent airway. If the patient presents with an altered mental status or is comatose, it may be necessary to establish an airway by a manual maneuver. If the patient has a severely altered mental state, a mechanical device including endotracheal intubation may be necessary, due to potential aspiration of secretions.
Establish and maintain adequate ventilation. If the patient’s respiratory rate or tidal volume is inadequate, it is necessary to provide positive pressure ventilation.
Establish and maintain adequate oxygenation. Assess the patient for evidence of hypoxia. Apply a pulse oximeter and determine the SpO2 reading. If either clinical evidence of hypoxia exists or a SpO2 reading of less than 95 percent on room air is present, administer a high concentration of oxygen via a nonrebreather mask. If the patient is exhibiting no signs of hypoxia or the SpO2 reading is greater than 95 percent, supplemental oxygen may be applied via a nasal cannula at two to 4 lpm.
Provide continuous ECG monitoring. Due to the electrolyte imbalance, cardiac dysrhythmias may occur. Also, many of the patients experiencing HHNS have preexisting cardiovascular disease making them prone to cardiac dysrhythmias.
Initiate an intravenous line of normal saline. Patients lose significant amounts of fluid from the osmotic diuresis. Aggressive fluid resuscitation may be necessary in severe cases. Administer a bolus of 500 mL of normal saline in severely dehydrated patients. Lactated Ringer’s may also be used if normal saline is not available. In patients with a history of cardiac disease, congestive heart failure, or renal insufficiency, a 250 mL bolus should be used. Continuously reassess the patient for a response to the fluid administration and for evidence of over-hydration. Continue to administer fluid based on the patient’s hemodynamic status.
Assess the blood glucose level of any patient with preexisting disease who presents with signs and symptoms of dehydration or an altered mental status, especially the elderly, regardless of a positive history of diabetes mellitus. Hyperglycemic hyperosmolar nonketotic syndrome may be the first indication that the patient has diabetes mellitus. Even though the major complication of the disease is severe dehydration, HHNS carries the highest mortality rate of the diabetic emergencies.
References
- Guyton, A.C., and J.E. Hall. Textbook of Medical Physiology. 10th ed. Philadelphia: W.B. Sauders, 2001.
- Marx, J.A., R.S. Hockberger, R.M. Walls. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 5th ed. St. Louis: Mosby, Inc., 2002.
- Sagarin, M. Hyperosmolar Hyperglycemic Nonketotic Coma. http://www.emedicin.com/emerg/topic264.htm. January 13, 2005.
