Hyperosmolar Hyperglycemic State



Paulina B Sergot, MD, Staff Physician, Department of Emergency Medicine, New York University/Bellevue Hospital Center

Nothing to disclose.


Lewis S Nelson, MD, FACEP, FAACT, FACMT, 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

Nothing to disclose.

Specialty Editor(s)

Erik D Schraga, MD, Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Nothing to disclose.

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine

eMedicine Salary Employment

Howard A Bessen, MD, Professor of Medicine, Department of Emergency Medicine, UCLA School of Medicine; Program Director, Harbor-UCLA Medical Center

Nothing to disclose.

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

Nothing to disclose.

Chief Editor

Erik D Schraga, MD, Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Nothing to disclose.


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 differs in the magnitude of dehydration, ketosis, and acidosis. HHS usually presents in older patients with type 2 diabetes mellitus and carries a higher mortality rate than DKA, estimated at approximately 15%.

Most patients present with severe dehydration and focal or global neurologic deficits.[1, 2, 3] In as many as one third of cases, the clinical features of HHS and DKA overlap and are observed simultaneously (overlap cases). Based on the consensus statement published by the American Diabetic Association, diagnostic features of HHS may include the following:[1]

HHS was previously termed hyperosmolar hyperglycemic nonketotic coma (HHNC). However, the terminology was changed because coma is found in fewer than 20% of patients with HHS.[2]


Hyperosmolar hyperglycemic state (HHS) most commonly occurs in patients with type 2 diabetes mellitus who have some concomitant illness that leads to reduced fluid intake. Infection is the most common cause, but many other conditions can cause altered mentation, dehydration, or both. The concomitant illness may not be 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, such as glucagon, catecholamines, cortisol, and growth hormone.[1, 2] 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.[1, 2, 3]

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.[1, 2, 3]



United States

The incidence of hyperosmolar hyperglycemic state (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.[2]


The mortality rate is high (10-20%) and usually due to a comorbid illness The mortality rate of HHS increases with increasing age and with higher levels of serum osmolality.[2, 3]


African Americans, Hispanics, and Native Americans are disproportionately affected due to an increased prevalence of type 2 diabetes mellitus.[2]


The prevalence is slightly higher in females than in males.


Hyperosmolar hyperglycemic state (HHS) has a mean age of onset early in the seventh decade of life. In contrast, the mean age for diabetic ketoacidosis (DKA) is early in the fourth decade of life.[2, 3] Residents of nursing facilities who are elderly and demented are at the highest risk due to a lack of ability to care for themselves.

As rates of obesity increase amongst children, the prevalence of type 2 diabetes mellitus is also rising in this age group and may lead to an increased incidence of HHS in this population.[4, 5] HHS should be considered in children presenting with hyperglycemia and hyperosmolarity without significant ketoacidosis. It is particularly important to distinguish HHS from DKA in children, as they are at higher risk for the development of cerebral edema as a complication of aggressive fluid repletion. The mortality due to HHS in children also appears to be higher as compared to DKA, but there have been too few reported cases to calculate mortality accurately.[4, 5]



Examine the patient for evidence of hyperosmolar hyperglycemic state (HHS), focusing on hydration status, mentation, and signs of possible underlying causes, such as a source of infection.


Laboratory Studies

Imaging Studies


Prehospital Care

Standard care for dehydration and altered mental status is appropriate, including airway management, intravenous access, crystalloid, and any medications routinely given to coma patients.

Emergency Department Care

Diagnosis and management guidelines for hyperglycemic crises are available from the American Diabetes Association.[7]


Medication Summary

Fluids, insulin, and repletion of electrolytes (especially potassium) are the cornerstones of management. Antipyretics, antiemetics, and antibiotics are added, when appropriate, to control fever and vomiting, and treat an underlying infection if suspected.

Class Summary

Although many patients with HHS respond to fluids alone, IV insulin in dosages similar to those used in DKA can facilitate correction of hyperglycemia. Insulin used without concomitant vigorous fluid replacement increases risk of shock.

Insulin (Humulin, Humalog, Novolin)

Clinical Context:  Used to reduce blood glucose levels and decrease ketogenesis. Some authors favor lower bolus and infusion dosages, with rationale that fluids are cornerstone of therapy and that disorder is more one of insulin resistance than of insulin deficiency. Furthermore, lowering serum glucose and serum osmolarity overly rapidly can result in complications.

Class Summary

These agents are used to replenish electrolytes depleted because of the presence of high blood glucose level.

Potassium chloride (Klor-Con, K-Dur, Micro-K)

Clinical Context:  Initial serum potassium in even reference range suggests intracellular potassium depletion. In virtually all cases of HHS, supplemental potassium is necessary, as serum level drops secondary to insulin therapy and correction of metabolic acidosis.

Do not start until initial serum level is ascertained. Administer IV potassium cautiously, with attention to proper dosing and concentration. If patient can tolerate oral medications or has gastric tube in place, KCl can be repleted orally up to 60 mEq per dose, with dosing based upon frequently obtained lab values.

Class Summary

No evidence is found that sodium bicarbonate provides any benefit to patients with HHS. It may be considered if a patient has significant acidosis (pH < 7.0), particularly if inotropic agents are required to maintain blood pressure.

Sodium bicarbonate (NaHCO3)

Clinical Context:  Bicarbonate ion produced on dissociation neutralizes hydrogen ions and raises urinary and blood pH.

Further Inpatient Care

Further Outpatient Care

Inpatient & Outpatient Medications






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