eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Hyperosmolar Hyperglycemic State

Author: Paulina B Sergot, MD, Staff Physician, Department of Emergency Medicine, New York University/Bellevue Hospital Center
Coauthor(s): Lewis S Nelson, MD, FACEP, FACMT, FAACT, Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Attending Physician, Department of Emergency Medicine, Bellevue Hospital Center, New York University Medical Center and New York Harbor Healthcare System
Contributor Information and Disclosures

Updated: Jul 22, 2008

Introduction

Background

Hyperosmolar hyperglycemic state (HHS) is one of two serious metabolic derangements that occurs in patients with diabetes mellitus and can be a life-threatening emergency. The condition is characterized by hyperglycemia, hyperosmolarity, and dehydration without significant ketoacidosis. It less common than the other acute complication of diabetes, diabetic ketoacidosis (DKA), and usually presents in older patients with type 2 diabetes mellitus. HHS carries a higher mortality rate than DKA, estimated at approximately 15%.   

Most patients present with severe dehydration and focal or global neurologic deficits. In many cases, the clinical features of HHS and DKA overlap and are observed simultaneously (overlap cases). The diagnostic features of HHS may include the following:

• Plasma glucose level of 600 mg/dL or greater
• Effective serum osmolality of 320 mOsm/kg or greater
• Profound dehydration (8-12 L) with elevated serum urea nitrogen (BUN)-to-creatinine ratio
• Small ketonuria and absent-to-low ketonemia
• Bicarbonate concentration greater than 15 mEq/L
• Some alteration in consciousness

HHS was previously termed hyperosmolar hyperglycemic nonketotic coma (HHNC). However, the terminology was changed because coma is found in fewer than 10% of patients with HHS.

Pathophysiology

Hyperosmolar hyperglycemic state (HHS) most commonly occurs in patients with type 2 diabetes mellitus who have some concomitant illness that leads to a reduced fluid intake. Infection is the most common cause, but many other conditions can cause altered mentation, dehydration, or both. Frequently, the concomitant illness is not identifiable.

In patients with a preexisting lack of or resistance to insulin, a physiologic stress such as an acute illness can cause further net reduction in circulating insulin. The basic underlying mechanism of HHS is a reduction in the effective circulating insulin with a concomitant elevation of counter-regulatory hormones. Decreased renal clearance and decreased peripheral utilization of glucose lead to hyperglycemia. Hyperglycemia and hyperosmolarity result in an osmotic diuresis and an osmotic shift of fluid to the intravascular space, resulting in further intracellular dehydration. This diuresis also leads to loss of electrolytes, such as sodium and potassium.

Unlike patients with DKA, patients with HHS do not develop significant ketoacidosis, but the reason for this is not known. Contributing factors likely include the availability of insulin in amounts sufficient to inhibit ketogenesis but not sufficient to prevent hyperglycemia. Additionally, hyperosmolarity itself may decrease lipolysis, limiting the amount of free fatty acids available for ketogenesis. Also, lower levels of counter-regulatory hormones have been found in patients with HHS compared with those with DKA.

Frequency

United States

The incidence of HHS is less than 1 case per 1000 person-years, making it significantly less common than DKA. As the prevalence of type 2 diabetes mellitus increases, the incidence of HHS will likely increase as well.

Mortality/Morbidity

The mortality rate is high (10-20%). The mortality rate of HHS increases with increasing age and with higher levels of serum osmolality.

Race

African Americans, Hispanics, and Native Americans are disproportionately affected.

Sex

The prevalence is slightly higher in females than in males.

Age

HHS has a mean age of onset early in the seventh decade of life. In contrast, the mean age for DKA is early in the fourth decade of life. Residents of nursing facilities who are elderly and demented are at the highest risk due to a lack of ability to care for themselves, but the syndrome has been reported in patients as young as 18 months. As rates of obesity increase amongst children, the prevalence of type 2 diabetes mellitus is also rising in this age group. Several cases of HHS have been reported in the pediatric population.

Clinical

History

• Most patients with hyperosmolar hyperglycemic state (HHS) have a known history of diabetes, which is usually type 2.
• In 30-40% of cases, HHS is the initial presentation of a patient’s diabetes.
• HHS usually develops over a course of days to weeks unlike DKA.
• Often, a preceding illness results in several days of increasing dehydration.
• Adequate oral hydration may be impaired by concurrent acute illness (eg, vomiting) or chronic comorbidity (eg, dementia, immobility).
• Patients may complain of polydipsia, polyuria, weight loss, weakness. Patients do not typically report abdominal pain, which is often seen in DKA.
• A wide variety of focal and global neurologic changes may be present, including the following:
  • Drowsiness and lethargy
  • Delirium
  • Coma
  • Focal or generalized seizures
  • Visual changes or disturbances
  • Hemiparesis
  • Sensory deficits

Physical

Examine the patient for evidence of HHS and for signs of its possible underlying causes.

• Vital signs
  • Fingerstick glucose should be checked immediately and is usually greater than 600 mg/dL.
  • Tachycardia is an early indicator of dehydration; hypotension is a later sign suggestive of profound dehydration due to volume loss secondary to osmotic diuresis.
  • Orthostatic vital signs are neither sensitive nor specific.
  • Tachypnea may be seen due to respiratory compensation for metabolic acidosis in overlap cases.
• General appearance and hygiene may provide clues to the state of hydration, presence of chronic illness, and reduced level of mentation.
• Perform a thorough skin examination. Skin turgor is another clue to hydration status.
• Examine the head, eyes, ears, nose, and throat (HEENT).
  • Examination may reveal altered hydration status (eg, sunken eyes, dry mouth).
  • Cranial neuropathies, visual field losses, and nystagmus may be appreciated, which are symptoms of HHS. They are usually reversible with therapy.
• Neck examination may reveal enlarged lymph nodes or meningismus. 
• The extremities may give evidence of peripheral volume sequestration or of dehydration.
• Evidence of underlying triggers of HHS on examination:
  • Vital signs
    • Assess core temperature rectally. Abnormally high or low temperatures suggest sepsis as an underlying cause. Hypothermia is a poor prognostic factor.
    • Hypoxemia can be a concurrent problem affecting mentation. 
  • Skin examination
    • Warm, moist skin suggests early sepsis.
    • Cool, dry skin suggests late sepsis.
    • Can reveal sources of infection, such as cellulitis or abscess.
  • HEENT
    • Potential foci of infection may be revealed (eg, middle ear, sinuses, oropharynx).
    • Palpation of the thyroid may reveal evidence of thyrotoxicosis. Thyrotoxicosis needs to be considered in the differential of HHS as it can also cause tachycardia, fever, and dehydration.
  • The pulmonary and cardiac examinations may reveal signs of pneumonia or of cardiac diseases.
  • Check for costovertebral angle tenderness as a sign of pyelonephritis.
  • Look for Kernig and Brudzinski signs, which may suggest meningitis.
  • A careful abdominal examination can help to rule out an intraperitoneal infection.
  • Rectal examination can screen for prostatitis, perirectal abscess, and GI hemorrhage.
  • Pelvic examination is indicated in women with lower abdominal pain or purulent discharge.
  • During neurologic examination, evaluate overall mental status, cranial nerves, strength, sensation, reflexes, cerebellar function, stance, and gait. Focal findings may prompt further studies such as CT scan and/or lumbar puncture (LP).

Causes

• In general, any illness that predisposes to dehydration may lead to HHS. A wide variety of major illnesses may trigger HHS by limiting patient mobility and free access to water.
• A preceding or intercurrent illness is common, but the underlying cause may be difficult to ascertain. Pneumonia and urinary tract infections (UTIs) are the most common underlying causes of HHS.
• Stress response to any acute illness tends to increase hormones that favor elevated glucose levels. Cortisol, catecholamines, glucagon, and many other hormones have effects that tend to counter those of insulin. Examples of such acute conditions are as follows:
  • Stroke
  • Intracranial hemorrhage
  • Silent myocardial infarction
  • Pulmonary embolism
• Patients with underlying renal dysfunction and/or congestive heart failure are at greater risk.
• Drugs that raise serum glucose level, inhibit insulin, or cause dehydration may cause HHS.
  • Diuretics
  • Beta-blockers
  • Histamine 2 (H2) blockers
  • Antipsychotics (clozapine, olanzapine)
  • Alcohol and cocaine
  • Dialysis, total parenteral nutrition, and fluids that contain dextrose
• Elder abuse and neglect also may contribute to underhydration.
• Noncompliance with oral hypoglycemics or insulin therapy can result in HHS.

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