|Louisiana State University
Health Sciences Center
|Critical Care Medicine|
The following guidelines are intended as general guidelines, and may not be appropriate for all patients or in all circumstances.
The main pathophysiologic features of DKA that require urgent intervention include hyperglycemia, an anion-gap acidosis and dehydration.
The glucose level is almost always above 250 mg/dL, and typically 300-500 mg/dL. Higher values (e.g. > 1000 mg/dL) can be associated with a concomitant hyperosmolar syndrome.
The anion-gap acidosis (anion gap > 17) is due primarily to the development of keto-acids resulting from lack of insulin function (insulin deficiency and/or insulin resistance). Use of acidemia (pH) alone for diagnosis may be misleading due to respiratory effects on pH. Moderate ketonemia and ketonuria are also present. Slight elevations in lactate levels may occur due to shifts in the NADH/NAD ratio and lactate/pyruvate ratio, but generally does not contribute to the acidosis itself. The acidosis results in hyperventilation for respiratory compensation (Kussmaul respiration).
Dehydration is also usually a prominent component, unless patients present early and have maintained hydration. Most patients, however, have clinically significant dehydration upon presentation. Dehydration results from an osmotic diuresis as well as diminished oral intake due to gastrointestinal disturbance associated with DKA. Severe dehydration can result in tissue hypoperfusion, with a superimposed Type I lactic acidosis.
CNS symptoms can be present, including alterations in mental status and coma, which are usually due to the hyperosmolar state.
DKA results from a number of causes, including inadequate insulin dosing (family dynamics, denial of disease, adolescent reaction, or depression), inadequate dosing, intercurrent infections, stress, or changes in insulin resistance. It can occur in both type I and type II diabetes. Type I diabetics tend to have a more rapid development of ketoacidosis, and may present with more significant clinical and laboratory abnormalities.
Initial management consists of fluid resuscitation and pharmacologic management with intravenous insulin to reduce glucose and reverse acidosis. Patients presenting with signs of shock (tissue hypoperfusion) and/or hypotension should receive aggressive fluid resuscitation to rapidly restore perfusion. Patients with shock should also undergo an assessment for other contributing etiologies to cardiovascular dysfunction (e.g. acute myocardial ischemia, sepsis). In patients with shock, an electrocardiogram is helpful to exclude myocardial injury or evidence of severe electrolyte abnormalities that may require urgent management (e.g. hyperkalemia with altered cardiac conduction).
Patients with dehydration from DKA have deficits across all fluid compartments: intravascular, interstitial, and intravascular. The general approach is to focus on replacing extracellular losses first, followed by intracellular losses. Weight loss is equal to water loss. If weight loss is not known, an estimate of the degree of dehydration can provide a goal for volume repletion. Most patients can be assumed to have a 10% fluid loss (100 mL/kg). A 5% loss can be assumed for mild symptoms and early presentation, whereas organ dysfunction can be associated with 15% loss or more. Infants may have 15% loss with lesser symptoms.
Initiate fluid therapy with balanced electrolyte solution (e.g. Normosol, Plasmalyte, Ringer's). Use of 0.9% saline alone will typically result in hyperchloremic acidosis, and this can be prevented with solutions that contain more physiologic concentrations of chloride. Additionally, 0.9% saline is slightly hypernatremic and hypertonic, which can worsen intracellular water loss with its administration. .
If hypoperfusion or organ dysfunction is present, initiate resuscitation with 20mL/kg Plasmalyte or Normosol or 5% albumin solution 10 mL/kg boluses, repeated as needed to restore perfusion and urine output, then resume normal deficit replacement (below). Include resuscitation fluids as part of the deficit replacement.
Fluid deficit replacement is given as an additional volume to maintenance fluid rate. In adults, half the deficit can be replaced over the first 8 hours, then the remainder over the next 16 hours. In pediatric patients, slower correction is required to avoid cerebral edema. Correct the deficit over 48 hours, replacing 2/3 of the deficit over the first 24 hours, and the remainder over the second 24 hours. Once the deficit have been replaced, then switch to .45%saline in adults or 1/3 or 1/4 normal saline in pediatrics for continued maintenance (with glucose as needed. see below). Patients are transitioned from intravenous to oral fluids when oral intake is able to provide maintenance support without nausea or vomiting.
Hypokalemia can develop due to previous urinary losses compounded by intracellular shifts during pH correction. Add potassium to the replacement solution (10 to 20 mEq/L) once urine output is ample and the serum K+ is < 6.0. In pediatric patients, the supplementation rate is 0.3 mEq/kg/hr. Potassium phosphate should comprise at least half the potassium supplementation.
Insulin administration stops ketogenesis, reduces proteolysis and lipolysis, and improves glucose uptake by tissues. The initial dose of regular insulin is 0.1 u/kg IV bolus, followed by 0.1 u/kg/hr by continuous IV administration. Follow bedside glucose levels hourly, and add glucose (5%, e.g. D5 Normosol) to fluids when glucose level drops under 300 mg/dL. Insulin is continued until the ketoacidosis is resolved, as evidenced by an anion gap < 10-12. If glucose levels drop despite 5% glucose in IV fluids, provide food if nausea is not present and/or reduce the insulin to 0.05 u/hr until acidosis resolves. Glucose levels should not be allowed drop rapidly (more than 200 mg/dL/hr), as this may increase the risk of CNS complications, and can be managed by addition of glucose to IV fluids.
Patients are transitioned to subcutaneous insulin after acidosis has resolved (anion gap < 10-12). Give the patient's usual morning or afternoon established dose, then discontinue the continuous insulin 1-2 hours later if still being infused. A sliding scale can be used to provide tighter control and allow evaluation for adjustment of the patient's established dose. If this is new onset DKA, then the dose of intermediate acting insulin would be 0.5 u/kg, adjusted as needed. Also give 0.1 u if hyperglycemia (> 200 mg/dL) is present.
Initial laboratory measurements should include a CBC, electrolytes (including magnesium and phosphorous), serum ketones, and urinalysis. If the patient has hypoperfusion or an altered mental status, obtain an arterial blood gas to exclude inadequate respiratory compensation or respiratory acidosis as a contributor. In the absence of shock or CNS findings, ABGs do not provide additional information or result in change in therapy. Other tests to investigate a source of infection should be undertaken if a precipitating event for ketoacidosis is not identified, or if signs of sepsis are present (e.g. chest x-ray, blood cultures, urine culture).
Obtain bedside glucose levels every hour until the anion gap has normalized and while the patient is on continuous insulin. Obtain a renal function profile panel every two hours until the anion gap is normalized.
All therapeutic plans in patients admitted to the PICU should be discussed with the PICU attending.
Consultation with Pediatric Endocrinology should be made before the patient is removed from the insulin infusion to plan transitioning off of iv insulin to a maintenance insulin regimen, and further monitoring and evaluation.