Hyperosmolar Nonketotic Syndrome

Hyperosmolar Nonketotic Syndrome

Hyperosmolar nonketotic syndrome (HNKS) is an acute complication observed most often in type 2 diabetic patients and is characterized by symp- toms and signs due to volume depletion (caused by excessive hyperglycemia and consequent hyperosmolality and osmotic diuresis), with varying degree of clouding of sensorium, ranging from absence of mental impairment (about 10%) to frank coma (about 10%). HNKS is a serious complication, which entails a mortality rate as high as ?40%.

Pneumonia (favored by sensory clouding which facilitates aspiration of oropharyngeal secretions) may develop in HNKS patients, as well as other infections. The dehydration elevates plasma viscosity and may favor throm- bosis. Disseminated intravascular coagulation (DIC) may also occur, with bleeding manifestations.

Laboratory findings include a marked hyperglycemia (usually higher than that occurring in DKA, reaching a level of ?800 mg/dl or 44 mmol/l) which causes increase in serum osmolality (which may be as high as ?350 mosm/l), whereas sodium is normal or slightly changed. Urea nitrogen and creatinine are elevated, together with inorganic acids (phosphates and sulfates) because of prerenal azotemia consequent to volume depletion. In contrast to DKA, in HNKS the metabolic acidosis is absent or mild, and bicarbonates are slightly changed. When present, acidosis is due to retention of inorganic acids (see above), i.e. a small amount of ketone bodies as well as a certain amount of lactate (due to tissue hypoperfusion consequent to volume depletion).

The extreme hyperglycemia with the ensuing hyperosmolality may be favored by the abundant hyperglycemic diuresis in patients who are unable to compensate the large fluid loss with urine by adequate water drinking, as it often occurs in old patients, who have an attenuated sensation of thirst and who often live alone or in nursing homes. However, it should be kept in mind that HNKS may be precipitated by several factors, including infections, cerebrovascular events, hypertonic peritoneal dialysis, parenteral nutrition or administration of the osmotic agent mannitol or diuretics as well as corticoste- roids and phenytoin.

The lack of acidosis in HNKS may be the result of several factors. (1) HNKS develops in type 2 diabetic patients, who possess a varying degree of residual endogenous insulin secretion. Since lipolysis is more sensitive to insulin than the glucose homeostatic mechanisms, it is possible that the residual insulin secretion, while unable to stimulate glucose utilizaton and to repress hepatic glucose production, is able to refrain lipolysis, thus limiting the FFA afflux to liver and therefore the ketogenic process. (2) The endogenously se- creted insulin reaches, through the portal vein, the liver, which is insulinized to a sufficient degree to prevent activation of ketogenesis (i.e. to allow glucose to be utilized in sufficient amount to produce enough malonyl-CoA, which inhibits the ketogenic process at the level of CPT-1. (3) There may be glucagon resistance, which prevents glucagon to exert its ketogenic effects (see under DKA). (4) There may be an enhanced activity of the Cori cycle, with increased afflux of lactate to the liver, where it may be in part metabolized to malonyl- CoA, thus refraining ketogenesis.

HNKS treatment is primarily directed to restore blood volume and correct hyperosmolality. This may require the supply of intravenous fluid in the total amount up to 8–10 liters. Therapy may be started by intravenous infusion of saline at the rate of 1.5 liters/h for the first 2 h, followed by infusion of 0.5 liter/h of half-normal saline (0.45%) adjusted according to the clinical and laboratory response. Insulin should also be given. This may be done according to the small dose regimen described under DKA, although some patients may HNKS treatment is primarily directed to restore blood volume and correct hyperosmolality. This may require the supply of intravenous fluid in the total amount up to 8–10 liters. Therapy may be started by intravenous infusion of saline at the rate of 1.5 liters/h for the first 2 h, followed by infusion of 0.5 liter/h of half-normal saline (0.45%) adjusted according to the clinical and laboratory response. Insulin should also be given. This may be done according to the small dose regimen described under DKA, although some patients may