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For further information, see CMDT Part 27-04: Hyperglycemic Hyperosmolar State

Key Features

Essentials of Diagnosis

  • Hyperglycemia, serum glucose > 600 mg/dL (33.3 mmol/L)

  • Serum osmolality > 310 mOsm/kg

  • No acidosis; blood pH > 7.3

  • Serum bicarbonate > 15 mEq/L

  • Normal anion gap (< 14 mEq/L)

General Considerations

  • Frequently occurs with mild or occult diabetes mellitus

  • Infection, myocardial infarction, stroke, or recent operation is often a precipitating event

  • Drugs (phenytoin, diazoxide, corticosteroids, and diuretics) or procedures associated with glucose loading such as peritoneal dialysis can also precipitate the syndrome

  • Acute kidney dysfunction develops from hypovolemia, leading to increasingly higher blood glucose concentrations

  • Underlying chronic kidney disease or heart failure is common, and the presence of either worsens the prognosis


  • Rarer than diabetic ketoacidosis even in older age groups

  • Affects middle-aged to elderly

Clinical Findings

Symptoms and Signs

  • Onset may be insidious over days or weeks, with weakness, polyuria, and polydipsia

  • The lack of features of diabetic ketoacidosis (eg, vomiting, rapid deep breathing, acetone odor) may retard recognition until dehydration becomes more profound than in ketoacidosis

  • Fluid intake is usually reduced from inappropriate lack of thirst, nausea, or inaccessibility of fluids to bedridden patients

  • Lethargy and confusion develop as serum osmolality exceeds 310 mOsm/kg

  • Convulsions and coma can occur if osmolality exceeds 320–330 mOsm/kg

  • Physical examination shows profound dehydration, lethargy, or coma without Kussmaul respirations

Differential Diagnosis

  • Diabetic ketoacidosis

  • Cerebrovascular accident or head trauma

  • Hypoglycemia

  • Sepsis

  • Diabetes insipidus


Laboratory Tests

  • Severe hyperglycemia (serum glucose 800–2400 mg/dL [44.4 to 133.2 mmol/L])

  • When dehydration is less severe, dilutional hyponatremia as well as urinary sodium losses may reduce serum sodium to 120–125 mEq/L

  • As dehydration progresses, serum sodium can exceed 140 mEq/L, producing serum osmolality readings of 330–440 mOsm/kg

  • Ketosis and acidosis are usually absent or mild

  • Prerenal azotemia with blood urea nitrogen elevations > 100 mg/dL (35.7 mmol/L) typical



Fluid Replacement

  • Fluid deficit may be as much as 6–10 L

  • In hypovolemic oliguric hypotension, initiate fluid resuscitation with isotonic 0.9% saline

  • Otherwise, hypotonic (0.45%) saline preferred because of hyperosmolality

  • As much as 4–6 L of fluid may be required in first 8–10 h

  • Once blood glucose reaches 250 mg/dL (13.9 mmol/L), add 5% dextrose to either water, 0.45% saline solution, or 0.9% saline solution at a rate to maintain serum glucose levels of 250–300 mg/dL (13.9 to 16.7 mmol/L) to reduce risk of cerebral edema

  • Goal of fluid therapy is to restore urinary output to ≥ 50 mL/h


  • Less insulin is required ...

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