Nonketotic Hyperosmolar Syndrome

Nonketotic hyperosmolar syndrome is a metabolic complication of type 2 diabetes mellitus that is characterized by hyperglycemia, extreme dehydration, hyperosmolar plasma, and altered consciousness. It most often occurs in the setting of physiologic stress. Diagnosis is by history and measurement of plasma glucose, osmolarity, and arterial blood gas sampling. Treatment is IV saline solution and insulin. Complications include coma, seizures, and death.

Geriatric Essentials

• Nonketotic hyperosmolar syndrome (NKHS) is more common among the elderly and is often accompanied or precipitated by acute infection.
• Patients with dementia are at especially high risk because of insensitivity to thirst, leading to dehydration, a risk factor.
• Symptoms, signs, diagnosis, and treatment are otherwise similar to those in younger adults.

Nonketotic hyperosmolar syndrome (NKHS) is a complication of type 2 diabetes mellitus (DM) with a high mortality rate. NKHS usually develops after a period of symptomatic hyperglycemia during which fluid intake is inadequate to prevent extreme dehydration due to the hyperglycemia-induced osmotic diuresis. NKHS is more common among the elderly and is often accompanied or precipitated by acute infection, eg, gram-negative pneumonia or sepsis associated with a UTI. NKHS occurs in some patients with undiagnosed or neglected type 2 DM when they are given drugs that impair glucose tolerance (eg, glucocorticoids) or that increase fluid loss (eg, diuretics). People with severe dementia may be particularly insensitive to thirst, leading to dehydration, which, if uncorrected, increases risk of NKHS.

Symptoms and Signs

Patients with NKHS have CNS dysfunction and symptoms and signs of dehydration. The state of consciousness at presentation varies from confusion and disorientation to coma. Focal or generalized seizures and transient hemiplegia are more common among elderly than among younger patients with NKHS. Serum K levels are usually normal, but Na levels may be low or high depending on volume deficits. BUN and serum creatinine levels are markedly increased. Arterial pH is usually > 7.3, but occasionally mild metabolic acidosis develops because lactate accumulates.

The average fluid deficit is 10 L, and acute circulatory collapse is a common cause of death. In some patients, bleeding results from disseminated intravascular coagulation. Widespread thrombosis is a frequent finding on autopsy. Other complications include aspiration pneumonia, acute renal failure, and acute respiratory distress syndrome.

Diagnosis

Diagnosis is made by history and measurement of plasma glucose and osmolarity, and ABG sampling. These tests show extreme hyperglycemia, hyperosmolarity, mild metabolic acidosis without marked hyperketonemia, and prerenal azotemia (or preexisting chronic renal failure). The plasma glucose level is usually > 500 mg/dL (> 27.8 mmol/L), which is higher than in most cases of diabetic ketoacidosis. The calculated serum osmolality at admission is > 350 mOsm/kg (normal is about 290 mOsm/kg). Initial plasma HCO₃ levels are often mildly depressed, reflecting increased lactate levels due to poor perfusion or associated sepsis. Plasma ketone levels may be low to moderate, reflecting low insulin levels, prolonged fasting, and high glucagon levels.

Treatment

The immediate aim of treatment is to rapidly expand the contracted intravascular volume to stabilize BP and to improve circulation and urine flow.

Treatment is started by infusing 2 to 3 L of 0.9% saline solution over 1 to 2 h. If BP and circulation stabilize and good urine flow is restored, the IV infusion can be changed to 0.45% saline solution to provide additional free water. The infusion rate of the 0.45% saline solution must be adjusted based on frequent assessments of BP, cardiovascular status, and the balance between fluid input and output. Central venous pressure monitoring may be necessary to guide fluid replacement in patients with heart failure or impaired renal function. K replacement is similar to that in diabetic ketoacidosis: 40 mEq/h for serum K < 3.3 mEq/L; 20 to 30 mEq/h for serum K 3.3 to 4.9 mEq/L; and none for serum K >= 5 mEq/L.

Insulin is infused at a rate of 0.1 unit/kg/h after the first liter of saline has been infused. Hydration alone can sometimes precipitously decrease plasma glucose, so the insulin dose may need to be reduced; if osmolality is reduced too quickly, cerebral edema can result. Plasma glucose levels must be monitored every 1 to 2 h until the patient has stabilized. A few patients require larger insulin doses. Once plasma glucose reaches 200 to 250 mg/dL, insulin infusion should be reduced to basal levels (1 to 2 units/h) until rehydration is complete and the patient is able to eat. Addition of 5% dextrose infusion may occasionally be needed to avoid hypoglycemia. After recovery from the acute episode, patients are usually switched to sc insulin. Most patients can convert back to oral antihyperglycemic drugs once their condition is stable; a few patients may not require any antihyperglycemic drugs once the acute episode has resolved.

This topic was last updated February 2006.