Hyperglycemic Hyperosmolar State

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

Demographics

• Rarer than diabetic ketoacidosis even in older age groups

• Affects middle-aged to elderly

Symptoms and Signs

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

• The lack of features of diabetic ketoacidosis may delay 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

Medications

Fluid Replacement

• Fluid replacement paramount to correct fluid deficits of 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

Insulin

• Less insulin is required than in diabetic ketoacidotic coma

• Fluid replacement alone can reduce hyperglycemia by increasing glomerular filtration and renal excretion of glucose

• Insulin treatment should therefore be delayed unless the patient has significant ketonemia (β-hydroxybutyrate > 1 mmol/L)

• Start the insulin infusion rate at 0.05 units/kg/h (bolus is not needed) and titrate to lower blood glucose levels by 50–70 mg/dL per hour (2.8–3.9 mmol/L/h)

• Once patient has stabilized and the blood glucose falls to around 250 mg/dL (13.9 mmol/L), insulin can be given subcutaneously

Potassium

• Add potassium chloride (10 mEq/L) to initial fluids if serum potassium is not elevated. Adjust subsequent potassium replacement based on serum potassium level

Phosphate

• If severe hypophosphatemia (serum phosphate < 1 mg/dL [0.32 mmol/L]) develops during therapy, phosphate replacement can be given as its potassium salt

  • To minimize the risk of tetany from an overload of phosphate replacement, an average deficit of 40–50 mmol phosphate should be replaced by intravenous infusion at a rate not to exceed 3–4 mmol/h in a 60- to 70-kg person

  • A stock solution (Abbott Laboratories) provides a mixture of 1.12 g KH₂PO₄ and 1.18 g KH₂PO₄ in a 5-mL single-dose vial representing 22 mmol potassium and 15 mmol phosphate; 5 mL of this stock solution in 2 L of 0.45% saline or 5% dextrose in water, infused at 400 mL/h, will replace the phosphate at the optimal rate of 3 mmol/h and provide 4.4 mEq potassium per hour

  • If serum phosphate remains < 2.5 mg/dL, a repeat 5-h infusion can be given

Therapeutic Procedures

• Using a flow sheet, document vital signs, time sequence of laboratory values (arterial pH, plasma glucose, acetone, bicarbonate, blood urea nitrogen, electrolytes, serum osmolality) in relation to therapy

Complications

• Myocardial infarction, stroke, pulmonary embolism, mesenteric vein thrombosis, and disseminated intravascular coagulation

  • May result from severe dehydration and low output state

  • Fluid replacement remains the primary approach to preventing these complications

• Rhabdomyolysis should be looked for and treated

Prognosis

• The overall mortality rate is > 10 times that of diabetic ketoacidosis because of its higher incidence in older patients and greater dehydration

• When prompt therapy is instituted, the mortality rate can be reduced from nearly 50% to that related to the severity of coexistent disorders

When to Admit

• Altered mental status

• Severe volume depletion