Diabetic Ketoacidosis

Recognition of diabetic ketoacidosis
The main pathophysiologic features of DKA that require urgent intervention include hyperglycemia, an anion-gap acidosis and dehydration, and possibly hyperosmolar symptoms.

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 > 15) 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 do not contribute to the acidosis itself unless dehydration leads to poor peripheral perfusion. 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 resuscitation
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).

Fluid management
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 with mild symptoms and early presentation can be assumed to have a 5% fluid loss (50 mL/kg), but with delayed presentation may have 10% loss (100 mL/kg). Organ dysfunction can be associated with 15% loss or more. Infants may have 10% loss with few symptoms.

Initiate fluid therapy with balanced electrolyte solution (e.g. Normosol, Plasmalyte, Ringer's). Use of 0.9% saline alone will 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). Oral fluids may be initiated when nausea or vomiting improve, and will help with rehydration.

Electrolyte replacement
Hypokalemia and hypophosphatemia can develop due to previous urinary losses compounded by intracellular shifts during pH correction. Add potassium phosphate to the replacement solution (15 to 30 mM/L ) once urine output is ample and the serum K+ is < 6.0. Additional electrolyte replacement can be supplied as a piggyback infusion for refractory hypokalemia or hypophosphatemia (.3 to .5 mMol/kg). Use potassium phosphate when both are low, potassium acetate when potassium is low, and sodium phosphate when phosphate is low.

Insulin therapy and glucose replacement
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 if there will be a delay in obtaining an infusion. This is 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 half of the iv fluids when glucose level drops under 300 mg/dL, and to all iv fluids when glucose is under 200 mg.dl. Insulin is continued until the ketoacidosis is resolved, as evidenced by an anion gap of 10 or less or two consecutive values of 11-12. If glucose levels drop despite 5% glucose in IV fluids, provide food if nausea is not present  As a last resort, reduce the insulin to 0.05 u/hr until acidosis resolves, but this may increase the time to resolution. 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.

The patient's regularly scheduled long-acting subcutaneous insulin can be started, even if acidosis has not fully resolved. Once acidosis has resolved, reduce the infusion to 0.05 u/kg/hr until the next scheduled dose of long-acting insuling, then discontinue the continuous insulin 1-2 hours later. 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 starting dose of intermediate acting insulin (e.g. NPH) would be 0.5 u/kg every 12 hours, and long-acting insulin would be 1 u/kg/day. A sliding scale for meals can be started once once the patient is eating adequately.

Laboratory monitoring
All therapeutic plans in pediatric 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.
 
 

Extracorporeal Life Support

Extracorporeal Life Support (ECLS) denotes a family of therapies for advanced organ failure that includes extracorporeal membrane oxygenation (ECMO) and related support therapies. The ECLS program at LSUHSC covers all extracorporeal therapies provided in the ICU, including:

• ECMO (extracorporeal membrane oxygenation)
• CRRT (continuous renal replacement therapies)
• TPE (therapeutic plasma exchange)
• Liver support for acute hepatic failure

Extracorporeal Membrane Oxygenation (ECMO)

The ECLS Program at LSU Health Shreveport has been providing ECMO since 1993, first in adults and subsequently in children and neonates, and is internationally recognized. The ECMO team now consists of five ECMO physicians, two perfusionists, and a bedside team of nurses and respiratory therapists. The team has been involved in researching new support modalities, such as intravascular oxygenation and pumpless arteriovenous CO2 removal at both the pre-clinical and clinical stages for over 20 years.

LSU Health Shreveport is recognized as a Center of Excellence by the Extracorporeal Life Support Organization (ELSO), a unique international organization devoted to the application and advancement of prolonged bedside extracorporeal techniques worldwide. This association keeps UH at the forefront of this complex technology.

REFERRING PATIENTS FOR ECMO

Deciding when to transfer a patient for ECMO is often a very difficult one. This decision can be facilitated by early consultation with an ECMO team physician, thereby allowing both teams to cooperatively decide when to transport a patient. However, when a patient is at high risk for failing maximal therapy the referring physician should decide to transfer before the patient is too unstable for safe transport. For this reason, it may be safer to transfer earlier in the course of illness rather than waiting and missing the transport window.

The referring physician should begin to consider the need for ECMO when a patient has received appropriate medical management and continues to have a Pa02 of 50-70 mm Hg when the PIP is >24 cmH20 and the FI02 is over 70% for conventional ventilation, and in neonates after 6 hours of high frequency ventilation without improvement in oxygenation. After consultation with an ECMO physician the time of transfer can be determined through a team approach taking into account such items as transport time, type of transport needed, and availability of ECMO beds. Below are referral guidelines. As these are only guidelines, we prefer to be contacted to discuss any potential transfer.