Nonketotic hyperosmolar syndrome (NKHS) is a metabolic complication of diabetes mellitus (DM) characterized by hyperglycemia, extreme dehydration, hyperosmolar plasma,

and altered consciousness. It most often occurs in type 2 DM, often in the setting of physiologic stress. NKHS is diagnosed by severe hyperglycemia and serum hyperosmolarity and absence of significant ketosis. Treatment is IV saline solution and insulin. Complications include coma, seizures, and death.

NKHS is a complication of type 2 DM and has a mortality rate of up to 40%. It usually develops after a period of symptomatic hyperglycemia in which fluid intake is inadequate to prevent extreme dehydration from the hyperglycemia-induced osmotic diuresis. The precipitating factor may be a coexisting acute infection, drugs that impair glucose tolerance (glucocorticoids) or increase fluid loss (diuretics), medical nonadherence, or other medical conditions. Serum ketones are not present because the amounts of insulin present in most patients with type 2 DM are adequate to suppress ketogenesis. Because symptoms of acidosis are not present, most patients endure a significantly longer period of osmotic dehydration before presentation, and thus plasma glucose and osmolarity are typically much higher than in diabetic ketoacidosis (DKA): > 600 mg/dL (> 33 mmol/L) and > 320 mOsm/L, respectively.

Symptoms and Signs

The primary symptom of NKHS is altered consciousness varying from confusion or disorientation to coma, usually as a result of extreme dehydration with or without prerenal azotemia, hyperglycemia, and hyperosmolarity. In contrast to DKA, focal or generalized seizures and transient hemiplegia may occur.

Diagnosis
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Blood glucose level Serum osmolarity

Generally, NKHS 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, measurement of serum electrolytes, BUN and creatinine, glucose, ketones, and osmolarity should be done. Urine should be tested for ketones. Serum K levels are usually normal, but Na 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 due to lactate accumulation.

The average fluid deficit is 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. Other complications include aspiration pneumonia, acute renal failure, and acute respiratory distress syndrome.

Treatment
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IV 0.9% saline Correction of any hypokalemia

IV insulin (as long as serum K is 3.3 mEq/L)

Treatment is 0.9% saline solution 1 L IV over 30 min, then at 1 L/h to raise BP and improve circulation and urine output. It can be replaced by 0.45% saline when BP becomes normal and plasma glucose reaches 300 mg/dL. The rate of infusion of IV fluids should be adjusted depending on BP, cardiac status, and the balance between fluid input and output. Insulin SOME TRADE NAMES

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is given at 0.15 unit/kg IV bolus followed by a 0.1 unit/kg/h infusion after the first liter of saline has been infused. Hydration alone can sometimes precipitously decrease plasma glucose, so insulin SOME TRADE

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dose may need to be reduced. A too-quick reduction in osmolality can lead to cerebral edema. Occasional patients with insulin-resistant type 2 DM with NKHS require larger insulin SOME TRADE NAMES

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doses. Once plasma glucose reaches 200 to 250 mg/dL, insulin SOME TRADE NAMES

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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 adjusted doses of sc insulin SOME

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. Most patients can resume using oral antihyperglycemic drugs once their condition is stable.

K replacement is similar to DKA: 40 mEq/h for serum K < 3.3 mEq/L; 20 to 30 mEq/h for serum K between 3.3 and 4.9 mEq/L; and none for serum K 5 mEq/L.