Diabetic emergencies: Ketoacidosis
Diabetic ketoacidosis (DKA) results from severe insulin deficiency and leads to the disordered metabolism of proteins, carbohydrates, and fats
Our flight crew was dispatched to a small local hospital for a 58 year old male with an altered level of consciousness and elevated blood sugar.
His son had found him unresponsive on the couch and called EMS for help.
While en route to the local hospital a bedside glucose was checked reporting “high.” His respiratory rate was 36 and his heart rate was in the 150s. He was slow to respond, but woke to verbal commands and was orientated to person only.
At the hospital, another bedside glucose returned “high” and he received 10 units of insulin IV. A foley catheter was inserted draining 1400 ml of urine immediately.
The flight crew arrived to find our patient’s LOC without change. Pupils were equal at 3 mm, and sluggish in response to light. Mucous membranes were dry. He had a respiratory rate of 36 breaths per minute and shallow. His lung sounds were clear and equal bilateral. An incision at his right shoulder from a surgery one week ago appeared well healed with no redness or signs of infection.
Lab results available at the time of transport were limited to:
Glucose — 799 mg/dl
CO2 — 3.1 mEq/L
ph — 6.77 (venous)
Fluid intake — 800 ml 0.9% sodium chloride
Urine output — 1400 ml
The only medication given so far was regular insulin 10 units IV.
Definition: Diabetes mellitus is a chronic disease comprised of a group of hyperglycemic disorders, characterized by high serum glucose, and disturbances of carbohydrate and lipid metabolism.
The patient is usually less than 40 years old at the time of onset. Peak age of onset is 10 to 14 years old. They are typically lean and ketosis prone. Plasma insulin levels are low to absent.
This patient is usually 45 to 65 years old at the time of onset. These patients are typically overweight, with normal to high insulin levels. However insulin levels are less than would be predicted for glucose levels. Type 2 patients demonstrate impaired insulin function.
Diabetic Emergencies — Ketoacidosis
Maintenance of normal serum glucose requires precise matching of glucose production, use, and regulation via hormonal secretion. The primarily regulatory glucose lowering hormone is insulin. The glucose raising hormone is glucagon.
Diabetic ketoacidosis (DKA) results from severe insulin deficiency and leads to the disordered metabolism of proteins, carbohydrates, and fats.
When an insulin imbalance occurs, serum glucose becomes elevated. As this progresses and glucose is not transported to the cells, the body perceives a fasting state. In this fasting state, protein and (incomplete) fat metabolism ensue. This leads to ketosis and, as the body attempts to compensate, ketoacidosis. The process continues and glucagon is released as a result of cellular need for glucose, causing gluconeogenesis from stored sources in the liver and muscles and serum glucose levels continue to become elevated.
Ketoacidosis patients present with elevated serum glucose (>300 mg/dL), ketones in the serum and urine, serum pH < 7.3, bicarb levels < 15 mEq/L, polyuria, polydipsia, lethargy, and a rapid respiratory rate (Kussmaul respirations) with “fruity odor”.
The first sequela of DKA is hyperosmolality due to hyperglycemia. The result is volume depletion, leading to lethargy and coma.
When blood sugar exceeds the normal serum threshold, glucose escapes into the urine and is removed from the body. This glucose rich filtrate also carries with it sodium and potassium along with other electrolytes and byproducts. The overall water loss of a 70kg adult can be 5 to 7 liters. In the body free glucose is mostly limited to extracellular water. This results in an osmotic pressure gradient across the cell membrane. Thus water shifts from the intracellular to the extracellular and intravascular space, and is removed from the body. If, during the treatment phase, serum glucose is lowered too rapidly a large fluid shift will result. This will be from the intravascular to the intracellular space causing vascular collapse, cerebral edema and death.
The second sequela brings uncontrolled ketogenesis. This results in an acidotic state, aggravated by the volume depletion. The body attempts to compensate for the acidotic state by breaking down the ketoacids with a bicarbonate ion buffer forming carbonic acid. Carbonic acid is then broken down into water and CO2 gas. When ketoacid anions accumulate and bicarbonate continues to be utilized, the serum bicarbonate level falls as the body attempts to maintain a normal pH. As the bicarbonate continues to be utilized, the extra CO2 is driven off at the lung with hyperventilation. This is referred to as Kussmaul’s respiration and is a sign that serum pH is approximately 7.2 or less. If the patient requires intubation at this point a great deal of caution should be used during ventilation. After the airway is secured the minute ventilation should be high enough to mimic that of the pre-intubation state. Acidosis will worsen if this is not accomplished.
The third sequela of DKA is volume depletion. As the body rids itself of glucose via the kidneys, the glucose-rich filtrate takes with it sodium and potassium. This osmotic diuresis continues throughout the course of the illness. The result can be extensive total body depletion of fluid volume and electrolytes. Serum levels of potassium may initially show a false normal due to the acidotic state that causes potassium to shift into the extracellular space. As volume replacement is started, levels can rapidly fall due to dilution and a slow correction of the acidotic state. The serum potassium levels will also be reduced by insulin therapy, which causes a potassium shift to the intracellular space. Since the total body stores of potassium can be markedly depleted, a profound serum hypokalemia may become evident.
General management dictates starting with the ABCs, securing the airway if indicated and matching preintubation minute ventilation as able. This continues to offload CO2.
Aggressive management of the volume deficit with 0.9% normal saline should be started next. General guidelines are rapid volume replacement until vital signs improve, then continue at 250 ml/hour. This can be coupled with a second IV line of 0.9% saline until volume replacement is accomplished. Then, if glucose remains above 250 mg/dL, change the fluid to 0.45% saline. Or, if < 250 mg/dL, change to D5 0.45% saline.
It is important to know the serum potassium before starting insulin therapy. Life threatening hypokalemia can rapidly develop once insulin is given. If potassium levels are < 3.3 mEq/L insulin should be withheld until replacement therapy can be given. Generally, hold insulin for at least 30 minutes, initiate a second IV of 0.45% saline with 60 mEq KCl added per liter at 250 ml/hour, and infuse until serum potassium levels are > 3.3.
Once a normal range is reached, add 20 to 40 mEq KCl to each liter of fluid. Generally 100 to 200 mEq KCl will be required during the first 24 hours of treatment.
Insulin therapy can safely be started now. In the adult patient an IV bolus dose is optional at 0.1 unit/kg of regular insulin, but continuous infusion therapy at 0.1 unit/kg/hour of regular insulin is preferred. This allows for a gradual correction of abnormal serum glucose, electrolytes and ketosis, and also allows a safe, steady fluid volume redistribution.
Acidosis is being treated by volume replacement as it improves cellular perfusion and insulin therapy slows then halts ketosis. Sodium bicarb is generally not recommended unless a severe acidosis (pH < 7.0) is not resolving despite aggressive DKA therapy.
Osmotic diuresis may cause magnesium depletion. This can lead to cardiac arrhythmias, hypocalcemia and hyperphosphatemia. If the serum magnesium level is less than 2.0 mg/dL, oral magnesium oxide may be given if tolerated, or IV magnesium sulfate 2 grams over 1 hour.
Mortality from DKA is low. More often it is related to the precipitating event such as infection or myocardial infarction. Cerebral edema is a major non-metabolic complication. The etiology of cerebral edema is not well established but the mortality rate is 90%. It is more common in children than adults. It generally occurs after 6 to 10 hours of therapy, has been associated with low partial pressure of arterial carbon dioxide, elevated BUN, and bicarbonate use. Clinical signs do not usually occur unless the blood sugar is less than 250 mg/dL and insulin is being used. Any change in neurologic function during treatment is an indication for IV mannitol 1 to 2 grams/kg. Because giving mannitol early can prevent serious morbidity and mortality therapy should be started early, before respiratory failure ensues or obtaining CT scans for confirmation.
Our patient was treated with insulin prematurely. It is paramount to know the serum potassium level prior to initiating treatment. An insulin bolus had been given before the flight crew arrived, and now a drip was being started at 0.1 unit/kg/hour. He was also being given sodium bicarbonate 50 mEq IVP by the ER staff due to his ph of 6.77. A second IV was established with 0.9% saline run wide open due to the heart rate of 152 and systolic blood pressures in the 70 to 80’s.
During the flight back, his bedside glucose result was 514 and the insulin infusion rate was reduced to half the original rate. His blood pressure improved to mid-100s, systolic with a heart rate of 108. IV fluids were slowed to 125 ml/hour per site. At hand-off to the ICU staff his level of consciousness had improved to person and place, but he remained fatigued and slow to respond.
It is important to identify the precipitating event for DKA. Post operative infection was suspected for our patient, but had yet to be confirmed. Some important causes are infection, myocardial infarction, medications and pulmonary embolism.
This is an abbreviated compilation of treatments for DKA. It is intended as a guideline to review the main points of therapies, not an all-encompassing article. As always, consult local protocols for your treatment guidelines.
Take home points:
- Start aggressive volume replacement immediately
- Know the serum potassium before starting insulin
- Reduce blood glucose slowly
- Recheck serum glucose and potassium frequently
1. Marx J.A., Hockberger R.S., Walls R.M., et al; Rosen’s Emergency Medicine: seventh edition. Philadelphia, Lippincott Williams & Wilkins, 2010. pp 1633-1644.
2. Tintinalli J.E., Kelen G.D., et al; Emergency Medicine, A Comprehensive Guide: seventh edition. New York, McGraw-Hill, 2010. pp 1432-1438.
3. Fauci A.S., Kasper D.L., et al; Harrison’s Principals of Internal Medicine: seventeenth edition. New York, McGraw-Hill, 2008. pp 2283-2285.