Acidosis. Insulin therapy decreases the production of free fatty acids and protein catabolism and enhances glucose usage in target tissues. These processes correct acidosis. Bicarbonate therapy should be avoided. Potential adverse effects of bicarbonate administration include paradoxical increases in central nervous system (CNS) acidosis caused by increased diffusion of carbon dioxide across the blood-brain barrier, potential tissue hypoxia caused by shifts in the oxyhemoglobin dissociation curve, abrupt osmotic changes, and increased risk of the development of cerebral edema.
As acidosis is corrected, urine ketone concentrations may appear to rise. β-Hydroxybutyrate, which is not detected in urine ketone assays, is converted with treatment to what the assay most detects, acetoacetate. Hence minute-to-minute urine ketone concentrations are not a required index of the adequacy of therapy.
Electrolyte imbalances. Regardless of the serum potassium concentration at presentation, total body potassium depletion is likely. Serum potassium concentrations can decrease rapidly as insulin and then glucose therapy improves acidosis, and potassium is exchanged for intracellular hydrogen ions. When adequate urine output is shown, potassium should be added to the IV fluids. Potassium replacement should be given as 50% potassium chloride and 50% potassium phosphate at a concentration of 20 to 40 mEq/L. This combination provides phosphate for replacement of deficits but avoids excess phosphate administration, which may precipitate hypocalcemia. If the serum potassium level is greater than 6 mEq/L, potassium should not be added to IV fluids until the potassium level decreases.
Monitoring. Initial laboratory measurements should include serum glucose, sodium, potassium, chloride, bicarbonate, BUN, creatinine, calcium, phosphate and magnesium concentrations; arterial or venous pH; and a urinalysis. Serum glucose measurement should be repeated every hour during therapy; electrolyte concentrations should be repeated every 2 to 3 hours. Calcium, phosphate, and magnesium concentrations should be measured every 4 to 6 hours during therapy. Neurologic and mental status should be assessed at frequent intervals. Any complaints of headache or deterioration of mental status should prompt rapid evaluation for possible cerebral edema. Indicative symptoms include a decreased sensorium, sudden severe headache, vomiting, change in vital signs (bradycardia, hypertension, apnea), a dilated pupil, ophthalmoplegia, or seizure.
Clinically apparent cerebral edema occurs in 1% to 5% of cases of DKA. Cerebral edema is the most serious complication of DKA, with a mortality rate of 20% to 80%. The pathogenesis of cerebral edema likely involves osmolar shift resulting in fluid accumulation in the intracellular compartment and cell swelling. Subclinical cerebral edema is common in patients with DKA, but the factors that exacerbate this process leading to symptomatic brain swelling and possible cerebral herniation are not clearly defined. Cerebral edema typically occurs 6 to 12 hours after therapy for DKA is begun, often following a period of apparent clinical improvement. Factors that correlate with increased risk for cerebral edema include higher initial BUN concentration, lower initial Pco2, failure of the serum sodium concentration to increase as glucose concentration decreases during treatment, and treatment with bicarbonate.