The American Diabetes Association has issued a new consensus statement addressing the diagnosis, treatment, and prevention of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults with diabetes.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. Mortality in DKA patients is less than 5% in experienced treatment centers, whereas HHS mortality remains high, at about 11%. The annual incidence rate for DKA ranges from 4.6 to 8 episodes per 1,000 patients with diabetes, with an estimated hospital cost exceeding $1 billion a year, Dr. Abbas E. Kitabchi and his associates said (Diabetes Care 2006;29:2739–48).

Although most patients with DKA have autoimmune type 1 diabetes, patients with type 2 diabetes are also at risk during acute stress, such as that caused by trauma, surgery, or infection. Moreover, during the past decade, an increasing number of DKA cases without precipitating causes have been reported in individuals with type 2 diabetes, particularly those from minority groups.

Inadequate or inappropriate insulin therapy and infection are the two most common precipitating factors in the development of both DKA and HHS. Although HHS typically evolves over several days to weeks, the evolution of DKA in type 1 or type 2 diabetes tends to be much shorter. The classic picture of DKA includes a history of polyuria, polydipsia, weight loss, vomiting, abdominal pain, dehydration, weakness, mental status change, and coma. In HHS, the most common clinical presentation is altered sensorium, with signs of dehydration.

Initial laboratory evaluations of patients with suspected DKA or HHS should include the determination of plasma glucose; blood urea nitrogen; creatinine; serum ketones; electrolytes (with calculated anion gap); osmolality; urinalysis and urine ketones by dipstick; initial arterial blood gases; and complete blood count with differential. If clinically indicated, an electrocardiogram; chest x-ray; and urine, sputum, or blood cultures should also be obtained, said Dr. Kitabchi, chief of the division of endocrinology, diabetes, and metabolism at the University of Tennessee, Memphis, and associates.

Patients with low-normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require very careful cardiac monitoring and more vigorous potassium replacement, because treatment lowers potassium further and can provoke cardiac dysrhythmia, they said.

Successful treatment of DKA and HHS requires the correction of dehydration, hyperglycemia, and electrolyte imbalances, as well as the identification of comorbid precipitating events and—above all—frequent patient monitoring. Protocols for the management of both DKA and HHS are included in the document, which is available free online (http://care.diabetesjournals.org

Initial fluid therapy is directed toward expansion of the intravascular and extravascular volume and restoration of renal perfusion. Successful progress with fluid replacement is judged by hemodynamic monitoring (improvement in blood pressure), measurement of fluid input and output, laboratory values, and clinical examination. Adequate rehydration with subsequent correction of the hyperosmolar state has been shown to result in a more robust response to low-dose insulin therapy.

Unless the episode of DKA is uncomplicated and mild or moderate, regular insulin by continuous intravenous infusion is the treatment of choice. However, recent data suggest that the use of subcutaneous rapid-acting insulin analogs in the management of patients with uncomplicated DKA could allow for treatment in general wards or emergency departments, thus avoiding admission to the intensive care unit. Direct measurement of β-hydroxybutyrate (β—OHB) in the blood is the preferred method for monitoring DKA, and has become more convenient with the recent development of bedside meters capable of measuring β—OHB in whole blood, they noted.

Criteria for resolution of DKA include glucose less than 200 mg/dL, serum bicarbonate greater than or equal to 18 mEq/L, and venous pH greater than 7.3. When a patient is able to eat, a multiple-dose schedule involving a combination of basal and premeal bolus insulins should be initiated as needed to control plasma glucose. To prevent hypokalemia, potassium replacement is started after serum levels drop to less than 5.3 mEq/L, assuming the presence of adequate urine output at 50 mL/hour.

The use of bicarbonate in DKA remains controversial. At a pH greater than 7.0, the administration of insulin blocks lipolysis and resolves ketoacidosis without any added bicarbonate. However, limited data do support the use of bicarbonate—along with potassium supplementation—in patients with pH values lower than 7.0, and particularly in those with levels lower than 6.9, for whom the risk for severe acidosis is elevated.

Routine use of phosphate is not indicated in the treatment of DKA or HHS; data suggest it provides no clinical benefit. However, careful phosphate replacement may be indicated in some patients with cardiac dysfunction, anemia, or respiratory depression in order to minimize the risks associated with hypophosphatemia.

Studies cited in the guideline were supported by grants from the U.S. Public Health Service, National Institutes of Health, Novo-Nordisk Inc., Eli Lilly & Co., American Diabetes Association, and Abe Goodman Fund.

Guidelines Target Hyperglycemic Crises in Adults Diabetics