Diabetic Ketoacidosis - Diabetic Ketoacidosis (DKA)

Diabetic Ketoacidosis

Diabetic Ketoacidosis
February 12, 2008
Donald W Rucker, MD, MBA, MS
eMedicine

Background

Diabetic ketoacidosis (DKA) is a state of absolute or relative insulin deficiency aggravated by ensuing hyperglycemia, dehydration, and acidosis-producing derangements in intermediary metabolism. The most common causes are underlying infection, disruption of insulin treatment, and new onset of diabetes. DKA is typically characterized by hyperglycemia over 300 mg/dL, low bicarbonate level (<15 mEq/L), and acidosis (pH <7.30) with ketonemia and ketonuria.

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Pathophysiology

Many of the underlying pathophysiologic disturbances in DKA are directly measurable by the clinician and need to be monitored throughout the course of treatment. Close attention to clinical laboratory data allows for tracking of the underlying acidosis and hyperglycemia as well as prevention of common potentially lethal complications such as hypoglycemia, hyponatremia, and hypokalemia.

The absence of insulin, the primary anabolic hormone, means that tissues such as muscle, fat, and liver do not take up glucose. Counterregulatory hormones, such as glucagon, growth hormone, and catecholamines, enhance triglyceride breakdown into free fatty acids and gluconeogenesis, which is the main cause for the elevation in serum glucose level in DKA. Beta-oxidation of these free fatty acids leads to increased formation of ketone bodies. Overall, metabolism in DKA shifts from the normal fed state characterized by carbohydrate metabolism to a fasting state characterized by fat metabolism.

Secondary consequences of the primary metabolic derangements in DKA include an ensuing metabolic acidosis as the ketone bodies produced by beta-oxidation of free fatty acids deplete extracellular and cellular acid buffers. The hyperglycemia-induced osmotic diuresis depletes sodium, potassium, phosphates, and water as well as ketones and glucose. Patients are often profoundly dehydrated and have a significantly depleted potassium level (as high as 5 mEq per kg of body weight). A normal or even elevated serum potassium concentration may be seen due to the extracellular shift of potassium in acidotic conditions, and this very poorly reflects the patient's total potassium stores. The serum potassium concentration can drop precipitously once insulin treatment is started, so great care must be taken to repeatedly monitor serum levels. Urinary loss of ketoanions with brisk diuresis and intact renal function may also lead to a component of hyperchloremic metabolic acidosis.
Frequency
United States

DKA occurs primarily in patients with type 1 diabetes. The incidence is roughly 2 episodes per 100 patient years of diabetes, with about 3% of patients with type 1 diabetes initially presenting with DKA. It can occur in patients with type 2 diabetes as well; however, this is less common.
Mortality/Morbidity

With modern fluid management, the mortality rate of DKA is about 2% per episode. Before the discovery of insulin in 1922, the mortality rate was 100%.
Sex

No predilection exists.
Age

DKA tends to occur in individuals younger than 19 years, but it may occur in patients with diabetes at any age.

CLINICAL
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* Authors and Editors
* Introduction
* Clinical
* Differentials
* Workup
* Treatment
* Medication
* Follow-up
* Miscellaneous
* References


History

* Classic symptoms of hyperglycemia
*
o Thirst
o Polyuria, polydipsia
o Nocturia
* Other symptoms
*
o Generalized weakness
o Malaise/lethargy
o Nausea/vomiting
o Decreased perspiration
o Fatigue
o Anorexia or increased appetite
o Confusion
* Symptoms of associated infections and conditions
*
o Fever
o Dysuria
o Chills
o Chest pain
o Abdominal pain
o Shortness of breath

Physical

* General signs
*
o Ill appearance
o Dry skin
o Labored respirations
o Dry mucous membranes
o Decreased skin turgor
o Decreased reflexes
* Vital signs
*
o Tachycardia
o Hypotension
o Tachypnea
o Hypothermia
o Fever, if infection
* Specific signs
*
o Ketotic breath (fruity, with acetone smell)
o Confusion
o Coma
o Abdominal tenderness

Causes

* The most common scenarios are underlying or concomitant infection (40%), missed insulin treatments (25%), and newly diagnosed, previously unknown diabetes (15%). Other associated causes make up roughly 20% in the various series.
* Urinary tract infections (UTIs) are the single most common infection associated with DKA, but many other associated illnesses need to be considered as well.
* Myocardial infarction
* Cerebrovascular accident
* Complicated pregnancy
* Trauma
* Stress
* Cocaine
* Surgery
* Heavy use of concentrated carbohydrate beverages such as sodas and sports drinks
* Acromegaly
* Idiopathic (20-30%)


DIFFERENTIALS
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* Authors and Editors
* Introduction
* Clinical
* Differentials
* Workup
* Treatment
* Medication
* Follow-up
* Miscellaneous
* References


Alcoholic Ketoacidosis
Appendicitis, Acute
Hyperosmolar Hyperglycemic Nonketotic Coma
Hypokalemia
Hyponatremia
Lactic Acidosis
Metabolic Acidosis
Myocardial Infarction
Pneumonia, Immunocompromised
Shock, Septic
Toxicity, Salicylate
Urinary Tract Infection, Female
Urinary Tract Infection, Male

Other Problems to be Considered

Uremia
Acute hypoglycemia coma
Catheter-related venous thrombosis, especially with femoral central venous catheters in children

WORKUP
Section 5 of 10 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

* Authors and Editors
* Introduction
* Clinical
* Differentials
* Workup
* Treatment
* Medication
* Follow-up
* Miscellaneous
* References


Lab Studies

* Glucose: Levels may be as low as 250 mg/dL. The clinician can do a fingerstick glucose test while waiting for the serum chemistry panel.
* Sodium: The osmotic effect of hyperglycemia moves extravascular water to the intravascular space. For each 100 mg/dL of glucose over 100 mg/dL, the serum sodium level is lowered by approximately 1.6 mEq/L. When glucose levels fall, the serum sodium level rises by a corresponding amount.
* Potassium: This needs to be checked frequently, as values drop very rapidly with treatment. An ECG may be used to assess the cardiac effects of extremes in potassium levels.
* Bicarbonate: Use these levels in conjunction with the anion gap to assess degree of acidosis.
* Complete blood cell (CBC) count: High white blood cell (WBC) counts (>15 X 109/L) or marked left shift may suggest underlying infection.
* Arterial blood gas (ABG) levels: pH is often <7.3. Venous pH may be used for repeat pH measurements.1 Brandenburg and Dire found that pH on a venous blood gas level in patients with DKA was 0.03 lower than pH on an ABG.2 Because this difference is relatively reliable and not of clinical significance, there is almost no reason to perform the more painful ABG. End tidal CO2 has been reported as a way to assess acidosis as well.
* Ketones: The Acetest and Ketostix products measure blood and urine acetone and acetoacetic acid. They do not measure the more common ketone body, beta-hydroxybutyrate, so the patient may have paradoxical worsening as the latter is converted into the former during treatment. Specific testing for beta-hydroxybutyrate can be performed by many laboratories.
* Urinalysis (UA): Look for glycosuria and urine ketosis. Use this to detect underlying urinary infection.
* Osmolality: Measured as 2(Na+) (mEq/L) + glucose (mg/dL)/18 + BUN(mg/dL)/2.8. Patients with DKA who are in a coma typically have osmolalities >330 mOsm/kg H2O. If the osmolality is less than this in a patient who is comatose, search for another cause of obtundation.
* Phosphorous: If the patient is at risk for hypophosphatemia (eg, poor nutritional status, chronic alcoholism), then the serum phosphorous level should be determined.
* Hyperamylasemia may be seen, even in the absence of pancreatitis.
* BUN level is increased.
* Anion gap is higher than normal.
* Repeat laboratory tests are critical. Potassium level needs to be checked every 1-2 hours during initial treatment. Glucose and other electrolyte levels should be checked every 2 hours or so during initial aggressive volume, glucose, and electrolyte management. If the initial phosphorous level was low, it should be monitored every 4 hours during therapy.
* Be aware that high serum glucose levels may lead to dilutional hyponatremia; high triglyceride levels may lead to factitious low glucose level; and high levels of ketone bodies may lead to factitious elevation of creatinine level.

Imaging Studies

* Chest radiography: Use this to rule out pulmonary infection.
* CT scanning: The threshold should be low for obtaining a head CT scan in children with DKA who have altered mental status, as this may be caused by cerebral edema. Many of the changes may be seen late on head imaging and should not delay administration of hypertonic saline or mannitol in those pediatric cases where cerebral edema is suspected.

Other Tests

* Electrocardiography (ECG): DKA may be precipitated by a cardiac event, and the physiological disturbances of DKA may cause cardiac complications. An ECG is also a rapid way to assess significant hypokalemia or hyperkalemia.
* Telemetry: Consider telemetry in those with comorbidities (especially cardiac), known significant electrolyte abnormalities, severe dehydration, or profound acidosis.

Procedures

* Airway management and potential intubation should be a primary concern in any patient with a significantly depressed mental status or with respiratory distress.


TREATMENT
Section 6 of 10 Click here to go to the previous section in this topic Click here to go to the top of this page Click here to go to the next section in this topic

* Authors and Editors
* Introduction
* Clinical
* Differentials
* Workup
* Treatment
* Medication
* Follow-up
* Miscellaneous
* References


Prehospital Care

Infusion of an isotonic saline solution should be initiated early, especially in the presence of hypotension, tachycardia, or other overt signs of volume depletion.
Emergency Department Care

Maintain extreme vigilance for any concomitant process such as infection, cerebrovascular accident (CVA), MI, sepsis, or deep venous thrombosis (DVT).

* Fluid resuscitation is a critical part of treating diabetic ketoacidosis (DKA). Intravenous solutions replace extravascular and intravascular fluids and electrolyte losses. They also dilute both the glucose level and the levels of circulating counterregulatory hormones. Insulin is needed to help switch from a catabolic state to an anabolic state, with uptake of glucose in tissues and the reduction of gluconeogenesis as well as free fatty acid and ketone production.
*
o Administer high volumes of isotonic saline (1-3 L) in the first hour. Further isotonic saline should be administered at a rate appropriate to maintain adequate blood pressure and pulse, urinary output, and mental status. If a patient is severely dehydrated and significant fluid resuscitation is needed, switching to a balanced electrolyte solution (such as Normosol-R, in which some of the chloride in isotonic saline is replaced with acetate) may help to avoid the development of a hyperchloremic acidosis.
o After initial stabilization with isotonic saline, switch to half-normal saline at 200-1000 mL/h (half-normal saline matches losses due to osmotic diuresis).
o Insulin should be started about an hour after intravenous fluid replacement is started to allow for checking potassium levels and because insulin may be more dangerous and less effective before some fluid replacement has been obtained. Although the incidence of life-threatening hypokalemia due to aggressive insulin administration is very low, there is little to no advantage in starting insulin prior to rehydration and evaluation of serum potassium levels.
o Pediatric protocols to minimize the risk of cerebral edema by reducing the rate of fluid repletion vary. Initial fluid repletion in pediatric patients should be 10-20 mL/kg over the first 1-2 hours with a maximum of 50 mL/kg over the first 4 hours. Although classically thought to result in cerebral edema, rapid administration of intravenous fluids itself is not likely the cause of the edema. It is therefore important to not be overly cautious with fluid administration, because rehydration remains as vital in children as in adults.
* Potassium replacement
*
o Potassium replacement should be started with initial fluid replacement if potassium levels are normal or low.
o Add 20-40 mEq/L of KCl to each liter of fluid once K+ is under 5.5 mEq/L.
o Potassium can be given as follows: two thirds as KCl, one third as KPO4.
* Bicarbonate typically is not replaced since acidosis will improve with the above treatments alone. Administration of bicarbonate has been correlated with cerebral edema in children.
* Phosphate and magnesium replacements are not typically needed, since levels correct when patient resumes eating.
* Use data flow sheets to monitor timing of laboratory tests and therapy.

Consultations

Consultation with an intensivist may be required for admission to an intensive care unit and assistance with care of patients who are critically ill. An endocrinologist may also be consulted to assist with management after the patient has been adequately stabilized.