Dott. M. M. Ciammaichella
Dirigente Medico
SC Medicina Interna I° per l'Urgenza
(Direttore: Dott. G. Cerqua)
A.C.O. S. Giovanni – Addolorata, Roma, Italia

KEY-WORDS: Diabetic ketoacidosis

INTRODUCTION
CLINICAL
WORKUP
TREATMENT
MEDICATION
FOLLOW-UP
MISCELLANEOUS
BIBLIOGRAPHY

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INTRODUCTION

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 associated causes are underlying infection, disruption of insulin treatment and new onset of diabetes. DKA typically consists of hyperglycemia over 300 mg/dl, low bicarbonate (< 15 mEq/L) and acidosis (ph < 7.30) with ketonemia and ketonuria.

Pathophysiology: DKA is an illness where much of the underlying pathophysiologic disturbances are directly measurable by the clinician and need to be followed throughout the course of treatment. Close attention to clinical lab data allows the emergency physician to not only track the underlying acidosis and hyperglycemia but also prevent common potentially lethal complications such as hypoglycemia, hyponatremia and hypokalemia.

The absence of insulin, which is the primary anabolic hormone, means that tissues such as muscle, fat and liver do not take up glucose. Counter-regulatory 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 in DKA. Beta oxidation of these free fatty acids leads to increased ketone body formation. Overall, metabolism in DKA shifts from the normal fed state with carbohydrate metabolism to a fasting state with fat metabolism.

Secondary consequences of the primary metabolic derangements include an ensuing metabolic acidosis as the ketone bodies from beta oxidation of free fatty acid production deplete extracellular and cellular acid buffers. The hyperglycemic induced osmotic diuresis depletes sodium, potassium, phosphates and water, as well as ketones and glucose. Commonly, a 10% total body water deficit exists as well as potassium deficits of 5 mEq per kg of body weight. The total body potassium deficit may be masked by the acidosis, which sustains an increased serum potassium level. This can precipitously drop once rehydration and insulin treatment start. Urinary loss of ketoanions with brisk diuresis and intact renal function may also lead to a component of hyperchloremic metabolic acidosis.

Frequency:

Mortality/Morbidity: The mortality rate of DKA with modern fluid management is about 2% per episode. Before the discovery of insulin in 1922, mortality was 100%.

Sex: There is no sex predilection.

• Classic Symptoms of Hyperglycemia:

• Thirst

• Polyuria, polydipsia

• Nocturia

• Other Symptoms:

• Generalized weakness

• Malaise/lethargy

• Nausea/vomiting

• Decreased perspiration

• Fatigue

• Anorexia or increased appetite

• Confusion

• Symptoms of Associated Infections and Conditions:

• Fever

• Dysuria

• Chills

• Chest pain

• Abdominal pain

• Shortness of breath

• General Signs:

• Ill appearance

• Dry skin

• Labored respirations

• Dry mucous membranes

• Decreased skin turgor

• Decreased reflexes

• Vital Signs:

• Tachycardia

• Hypotension

• Tachypnea

• Hypothermia

• Fever, if infection

• Specific Signs:

• Ketotic breath (fruity, with acetone smell)

• Confusion

• Coma

• Abdominal tenderness

• 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, but many other associated illnesses such as an acute MI or a complicated pregnancy need to be considered as well.

• Myocardial infarction

• Cerebrovascular accident (CVA)

• Trauma

• Stress

• Surgery
  
  
• Idiopathic (20-30%)

• Glucose:
  
  Levels may be as low as 250 mg/dL. The clinician can do a finger stick glucose while waiting for the SMA7.

• 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 is lowered by approximately 1.6 mEq/L. When glucose levels fall, the serum sodium will rise by a corresponding amount.

• Potassium:
  
  Needs to be checked frequently, as values will drop very rapidly with treatment. An ECG may be used to assess extremes in potassium levels.

• Bicarbonate:
  
  Use in conjunction with the anion gap to assess degree of acidosis.

• Complete Blood Count (CBC):
  
  High white counts (over 15,000) or marked left shift suggest underlying bacterial infection.

• Arterial Blood Gas (ABG):
  
  pH is often under 7.3. Can use venous pH for repeat pH measurements.

• Ketones:
  
  Acetest and Ketostix 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.

• Electrocardiogram (ECG):
  
  DKA may be precipitated by a cardiac event, and the physiological disturbances of DKA may cause cardiac complications.

• Urinalysis (UA):
  
  Glycosuria
  Urine ketosis
  Use to detect underlying urinary tract infection (UTI).

• Osmolality:
  
  Measured as 2(Na+) (mEq/L) + glucose(mg/dL)/18 + BUN(mg/dL)/2.8
  DKA patients in coma have osmolality greater than 330 mOsm/kg H20. If less than this and comatose, search for other cause of obtundation.

• Phosphorous:
  
  If the patient is at risk for hypophosphatemia (poor nutritional status, chronic alcoholism, etc.) then serum phosphorous should be determined.

• Hyperamylasemia (may be seen in the absence of pancreatitis)

• Increased Blood Urea Nitrogen (BUN)

• Increased Anion Gap

• Repeat labs are critical. Potassium needs to be checked every 1-2 hours during initial treatment. Glucose and other electrolytes should be checked every two hours or so during initial aggressive volume, glucose and electrolyte management. If the initial phosphorous was low, it should be monitored every four hours during therapy.

• Be aware that high glucose may lead to dilutional low sodium; high triglycerides may lead to factitious low glucose; and high ketone bodies may lead to factitious elevation of creatinine.

• Chest X-Ray (CXR):
  
  To rule out pulmonary infection

• CT Scan:
  
  There should be a low threshold for obtaining a head CT to assess altered mental status in pediatric DKA patients, as this may be caused by cerebral edema.

• Telemetry:
  
  Consider telemetry to monitor for ischemia and hypokalemia.
  

• Intubation and airway management should be considered for coma (especially if the patient is hypoventilating or unable to protect the airway), or for cerebral edema.
  
  
• NG tube should be considered if the patient is comatose, for aspiration prevention.

• Normal saline solution should be given as a bolus up to 1L, depending on the patient's vital signs and other indicators of hypovolemia.

• Fluid resuscitation is a critical part of treating the state of diabetic ketoacidosis. IV solutions replace extravascular and intravascular fluid 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 to an anabolic state, with uptake of glucose in tissues and the reduction of gluconeogenesis as well as free fatty acid and ketone production.

• Finish 1 L of normal saline (or more if needed for significant hypovolemia) in the first hour. Further normal saline titrated to maintain adequate blood pressure and pulse, urinary output and mental status. If severe dehydration is present and significant fluid resuscitation is needed, switching to a balanced electrolyte solution (such as Normosol-R which replaces some of the "Cl-" in normal saline with acetate) may help to avoid the development of a hyperchloremic acidosis.

• After initial stabilization with normal saline, switch to half-normal saline at 200-1000 cc/hr (half-normal saline matches losses due to osmotic diuresis).

• Potassium Replacement:

• Add 20-40 mEq/L of KCl to each liter once K+ is under 5.5 mEq/L.

• Can give potassium 2/3 as KCl, 1/3 as KPO4.

• Bicarbonate replacement is typically not given, although some do so when pH < 7.0.

• Phosphate and magnesium replacement are typically not needed and will correct when patient resumes eating.

• Use data flow sheets to monitor timing of labs and therapy.

• Intensivist

• Admit to ICU or floors depending on clinical status. Patients undergoing continuous insulin require frequent monitoring which is best done in the ICU.

• Occasionally, there may be patients with mild acidosis and fluid/electrolyte deficits who can be adequately stabilized in the ED if very close follow-up can be arranged.

• Typically, patients with DKA are admitted.

• Complications of associated illnesses, including sepsis and diffuse ischemic processes are possible.

• The leading cause for pediatric DKA mortality is cerebral edema, which occurs 4-12 hours into treatment.

• Cerebral edema begins with mental status changes and is felt to be partially due to "idiogenic osmoles," which have stabilized brain cells from shrinking while the DKA was developing, but then lead to cerebral edema with fluid resuscitation that is either too aggressive or too hypotonic. The laboratory hallmark is ongoing low serum sodium.

• Cerebral edema is largely a pediatric complication.

• Hypokalemia is a complication from failing to rapidly address total body potassium deficit brought out by rehydration and insulin treatment, which reduce acidosis as well as directly facilitating potassium reentry into the cell.

• Hypoglycemia may occur from inadequate monitoring of glucose levels during insulin therapy.

• Acute pulmonary edema is potentially related to aggressive or excessive fluid therapy.

• Other Complications:
  
  Venous thrombosis
  Myocardial infarction
  Acute gastric dilatation
  Late hypoglycemia
  Erosive gastritis
  Infection
  Respiratory distress
  Hypophosphatemia
  Mucormycosis

• DKA accounts for 14% of all hospital admissions for diabetes and 16% of all diabetic related fatalities.

• The overall mortality is 2% or less currently.

• In children less than 10 years of age, DKA causes 70% of diabetes related fatalities.

• Careful control of blood glucose
  
  
• Monitor glucose particularly closely during periods of stress, infection, trauma, etc.

• Failure to consider other coexisting illnesses, such as pelvic or rectal abscess, pneumonia and silent MI

• Failure to evaluate for other causes of coma if osmolality is relatively normal

• Pregnant Patients:

• There is up to a 30% fetal mortality with DKA with acidosis. This is increased to 60% with DKA and coma.

• This is typically seen in women with overt diabetes but it may occur with gestational diabetes.

• Pediatric Patients:
  
  Be alert to headache and decreased mental status since these are signs of impending cerebral edema

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