Diabetic Ketoacidosis (DKA)
Uncontrolled type 1 diabetes mellitus is the most common cause of ketoacidosis. The lack of insulin contributes to this condition not only via decreased glucose uptake but also by promoting lipolysis (triglyceride breakdown) and fatty acid oxidation. It is a state that also includes an increase in counter-regulatory hormones (ie, glucagon, cortisol, growth hormone, epinephrine) which contribute to hyperglycemia by promoting further gluconeogenesis and to ketonemia by promoting acetyl –COA migration into mitochondrion where they can be converted into ketones.
Progressive rise of blood concentration of these acidic organic substances initially leads to a state of ketonemia. Natural body buffers can buffer ketonemia in its early stages. When the accumulated ketones exceed the body's capacity of extracting them, they overflow into urine (ie, ketonuria). If the situation is not treated promptly, more accumulation of organic acids leads to frank clinical metabolic acidosis (ie, ketoacidosis), with a drop in pH and bicarbonate serum levels. Hyperglycemia usually exceeds the renal threshold of glucose absorption and results in significant glycosuria. Consequently, water loss in the urine is increased (polyuria) due to osmotic diuresis induced by glycosuria. This incidence of increased water loss results in severe dehydration, thirst, tissue hypoperfusion, and, possibly, lactic acidosis. In addition, beta hydroxybutyrate induces nausea and vomiting that consequently aggravate fluid loss. Typical free water loss in DKA is approximately 6 liters or nearly 100 mL/kg of body weight.
Hyperglycemia, osmotic diuresis, serum hyperosmolarity, and metabolic acidosis result in severe electrolyte disturbances. The most characteristic disturbance is total body potassium loss. Total body potassium loss is usually present despite normal or high serum potassium levels. Potassium levels may appear to be high due to the transcellular shift of potassium out of cells. This is not due to ketoacidosis directly but rather is due to insulin deficiency and hyperosmolality. A large part of the shifted extracellular potassium is lost in urine because of osmotic diuresis. Also, when ketoacids are excreted, they are usually excreted with Na or K in the urine, leading to further K loss. Vomiting may also contribute to potassium loss in these patients. Patients with initial hypokalemia are considered to have severe and serious total body potassium depletion.
In addition, hyponatremia is usually present, and is usually due to the dilutional effect of hyperosmolality as water is shifted from intracellular to extracellular compartments.
The direct effect of hyperosmolarity is often counteracted by the glucosuria-induced osmotic diuresis. The diuresis results in water loss in excess of sodium and potassium, which will tend to raise the plasma sodium concentration and plasma osmolality unless there is a comparable increase in water intake. As such, hyponatremia is usually mild.
The combined effects of serum hyperosmolarity, dehydration, and acidosis result in increased osmolarity in brain cells that may clinically manifest as an alteration in the level of consciousness.
- 25% of patients present with DKA as first presentation of their diabetes mellitus.
- Usually triggered by illness: UTI, infection, stress (medical or emotional), MI
- May also be due to poor compliance, or missed injections due to vomiting
- Insidious increased thirst (ie, polydipsia) and urination (ie, polyuria) are the most common early symptoms of DKA.
- Nausea and vomiting may occur associated with diffuse abdominal pain
- Lethargy, somnolence, confusion may develop
- Signs of dehydration - Weak and rapid pulse, dry tongue and skin, hypotension, and increased capillary refill time
- Oral odor - Characteristic fruity odor (from acetone, a product of acetoacetate metabolism
- Signs of acidosis - Deep sighing breathing, abdominal tenderness, and disturbance of consciousness
- Body temperature may be within the reference range or low, even in the presence of intercurrent infection.
- Urine dipstick highly positive for glucose, ketones (dipstick detect acetoacetate but not beta-hydroxybutyrate which is the predominant ketone, therefore test not always positive initially for ketones)
- Serum ketones present
- ABG : low bicarbonate, low PCO2, pH < 7.35
- Anion gap > 16
- Serum K normal, high or low.
- Serum Na low phos low.
- Serum phosphate: usually phosphate depleted due to urine losses but are normal or high by labs due to transcellular shift out of cells in the setting of acidosis and insulin deficiency. After treatment with Insulin, phosphate levels usually low
- Serum glucose usually > 300 mg/dl but below 800mg/dl (unlike NKH, where > 1000 mg/dl)
- Leukocytosis, even in the absence of infection
- Bun/Cr high due to prerenal azotemia
The major goals of treatment are 1) rapid fluid volume expansion, 2) correction of hyperglycemia and hyperketonemia, 3) prevention of hypokalemia during treatment, and 4) identification and treatment for any associated bacterial infection
- Fluids: IVF, in adults, rapid infusion of 1L of 0.9% NS (e.g. over 30 min), repeat bolus as necessary to prevent shock. When BP is stable and urine output adequate, can switch to 0.45% NS at a slower rate. This is done to replace the free water loss induced by the osmotic diuresis.
- Insulin infusion: 10-20 unit bolus (0.15 u/kg), then 5-7 units/hr (0.1 unit/kg/hr). This stops the lipolysis and gluconeogenesis and allows for the conversion of ketones to bicarbonate. BS should not be allowed to fall below 250 in the first 4-5 hours of treatment. If does, change rate to 0.03 u/kg/hr. When anion gap normal, initiate SQ insulin, overlap for 1-2hr with insulin infusion. When blood sugar less than 180, can add 5-10% dextrose to IVF.
- Potassium replacement: If initial K >6, then withhold replacement. If K< 4.5, then administer 10-20 meq/hr of K. If initial K < 3, then administer 40 meq/hr.
- Bicarb replacement: If pH < 7.1 and/or cardiac instability present, then give bicarb
- Phosphate replacement: Give K-phos if initial P< 1.0mg/dl. (usually high initially, due to the transcellular shift of phosphate outside the cell in the setting of acidosis and insulin deficiency)