(See also Diabetes Mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more and Complications of Diabetes Mellitus Complications of Diabetes Mellitus In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more .)
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.
The fluid deficit can exceed 10 L and acute circulatory collapse is a common cause of death. Widespread thrombosis is a frequent finding on autopsy and in some cases bleeding may occur as a consequence of disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more . Other complications include aspiration pneumonia Aspiration Pneumonitis and Pneumonia Aspiration pneumonitis and pneumonia are caused by inhaling toxic and/or irritant substances, most commonly large volumes of upper airway secretions or gastric contents, into the lungs. Chemical... read more , acute renal failure Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more , and acute respiratory distress syndrome Acute Hypoxemic Respiratory Failure (AHRF, ARDS) Acute hypoxemic respiratory failure is defined as severe hypoxemia (PaO2 (See also Overview of Mechanical Ventilation.) Airspace filling in acute hypoxemic respiratory failure (AHRF) may result... read more .
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 consists of IV saline, correction of hypokalemia, and IV insulin (1, 2 Treatment references Hyperosmolar hyperglycemic state is a metabolic complication of diabetes mellitus characterized by severe hyperglycemia, extreme dehydration, hyperosmolar plasma, and altered consciousness.... read more ).
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
1. Kitabchi AE, Umpierrez GE, Miles JM, et al: Hyperglycemic crises in adult patients with diabetes. Diabetes Care 32: 1335–1343, 2009.
2. French EK, Donihi AC, Korytkowski MT: Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ 365:l1114, 2019. doi: 10.1136/bmj.l1114
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 |
---|---|
insulin |
Afrezza, Exubera |
urea |
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 |
dextrose |
Advocate Glucose SOS, BD Glucose, Dex4 Glucose, Glutol , Glutose 15 , Glutose 45 , Glutose 5 |