Diabetic ketoacidosis

Diabetes mellitus (DM) is a common, chronic, metabolic syndromecharacterized by hyperglycemia as a cardinal biochemical feature. Themajor forms of diabetes are classified according to those caused byß-cell damage (type 1DM, or T1DM) and those that are a consequence of insulin resistance occurring at the level of skeletal muscle, liver, and adipose tissue, with various degree of β-cell impairment (type 2 DM, or T2DM). T1DM isthe most common endocrine-metabolic disorder of childhood andadolescence, with important consequences for physical and emotional development. Individuals with T1DM confront serious lifestylealterations that include an absolute daily requirement for exogenousinsulin, the need to monitor their own glucose level, and the need to payattention to dietary intake. The acute clinical manifestations are due tohypoinsulinemic hyperglycemic ketoacidosis. Autoimmune mechanisms are factors in the genesis of T1DM.

Diabetic Ketoacidosis DKA is the end result of the metabolic abnormalities resulting from a severe deficiency of insulin or insulin effectiveness. The latter occurs during stress as counter-regulatory hormones block insulin action. DKA occurs in 20-40% of children with new-onset diabetes and in children with known diabetes who omit insulin doses or who do not successfully manage an intercurrent illness. DKA may be arbitrarily classified as mild, moderate, or severe (Table 1), and the range of symptoms depends on the depth of ketoacidosis. There is a large amount of ketonuria, an increased ion gap, a decreased serum bicarbonate (or total CO2) and pH,

Table (1): Classification Of Diabetic Ketoacidosis

pathophysiology  DKA is the end result of metabolic abnormalities resulting from a severe deficiency of insulin→3 physiologic processes: 1. increased glucose production coupled with decreased glucose utilization raises serum glucose→increased serum osmolality →hypertonic dehydration. 2. increased release of free fatty acids from peripheral fat stores supplies substrate for hepatic ketoacid production→ accumulation of large amounts of ketoacids→ ketonuria, increase ion gap, decrease serum bicarbonate,and decrease PH. 3. Metabolic acidosis→ cellular losses of potassium, phosphorus and sodium.

Clinical features Insidious increased thirst (ie, polydipsia) and urination (ie, polyuria) are the most common early symptoms of diabetic ketoacidosis (DKA). Malaise, generalized weakness, and fatigability also can present as symptoms of DKA. Nausea and vomiting usually occur and may be associated with diffuse abdominal pain, decreased appetite, and anorexia. A history of rapid weight loss is a symptom in patients who are newly diagnosed with type 1 diabetes.

Patients may present with a history of failure to comply with insulin therapy or missed insulin injections due to vomiting or psychological reasons. Decreased perspiration is another possible symptom of DKA. Altered consciousness in the form of mild disorientation or confusion can occur. Although frank coma is uncommon, it may occur when the condition is neglected or if dehydration or acidosis is severe. Among the symptoms of DKA associated with possible intercurrent infection are fever, dysuria, coughing, malaise, chills, chest pain, shortness of breath, and arthralgia.

Physical Examination General signs of diabetic ketoacidosis (DKA) may include the followin:   ٭Ill appearance ٭Dry skin ٭Labored respiration ٭Dry mucous membranes ٭Decreased skin turgor ٭Decreased reflexes ٭Characteristic acetone (ketotic) breath odor

٭ Effects on vital signs that are related to DKA may include the following: Tachycardia Hypotension Tachypnea Hypothermia Fever, if infection is present ٭Specific signs of DKA may include the following: Confusion Coma Abdominal tenderness The physical examination should also include detection of the signs of possible intercurrent illnesses such as urinary tract infection, pneumonia, and perinephric abscess. Search for signs of infection is mandatory in all cases.

Laboratory Finding   Diabetic ketoacidosis is typically characterized by hyperglycemia over 300 mg/dL, a bicarbonate level less than 15 mEq/L, and a pH less than 7.30, with ketonemia and ketonuria. Laboratory studies for diabetic ketoacidosis (DKA) should be scheduled as follows: Blood tests for glucose every 1-2 h until patient is stable, then every 6 h. Serum electrolyte determinations every 1-2 h until patient is stable, then every 4-6 h.

Initial blood urea nitrogen (BUN). Initial arterial blood gas (ABG) measurements, followed with bicarbonate as necessary. Repeat laboratory tests are critical, including potassium, glucose,electrolytes, and, if necessary, phosphorus.

Serum Glucose Study The blood glucose level for patients with DKA usually exceeds 250 mg/dL. The clinician can perform a fingerstick glucose test while waiting for the serum chemistry panel. Urine Dipstick Testing For patients with DKA, the urine dipstick test is highly positive for glucose and ketones.

Arterial Blood Gases In patients with DKA, arterial blood gases (ABGs) frequently show typical manifestations of metabolic acidosis, low bicarbonate, and low pH (< 7.2). Serum Electrolyte Panel Serum potassium levels initially are high or within the reference range in patients with DKA. This is due to the extracellular shift of potassium in exchange of hydrogen, which is accumulated in acidosis, in spite of severely depleted total body potassium. This needs to be checked frequently, as values drop very rapidly with treatment.

An ECG may beused to assess the cardiac effects of extremes in potassium levels. The serum sodium level usually is low in affected patients. The osmotic effect of hyperglycemia moves extravascular water to the intravascular space. For each 100 mg/dL of glucose over 100 mg/dL, theserum sodium level is lowered by approximately 1.6 mEq/L. When glucose levels fall, the serum sodium level rises by a corresponding amount. Additionally, serum chloride levels and phosphorus levels always are lowin these patients.

Bicarbonate Use bicarbonate levels in conjunction with the anion gap to assess the degree of acidosis that is present. Anion Gap In patients with diabetic ketoacidosis, the anion gap is elevated ([Na + K] - [Cl + HCO3] >13 mEq/L). CBC Count Even in the absence of infection, the CBC count shows an increased white blood cell (WBC) count in patients with diabetic ketoacidosis. High WBC counts (>15 X 109/L) or marked left shift may suggest underlying infection.

Renal Function Studies BUN frequently is increased in patients with diabetic ketoacidosis. Osmolarity Plasma osmolarity usually is increased (>290 mosm/L) in patients with diabetic ketoacidosis. Patients with diabetic ketoacidosis who are in a coma typically have osmolalities greater than 330 mosm/kg.. Cultures Urine and blood culture findings help to identify any possible infecting organisms in patients with diabetic ketoacidosis.  

Chest Radiography Chest radiography should be used to rule out pulmonary infection such as pneumonia.   MRI An MRI is helpful in detecting early cerebral edema; it should be ordered only if altered consciousness is present. CT Scanning The threshold should be low for obtaining a head CT scan in children with diabetic ketoacidosis who have altered mental status, as this may be caused by cerebral edema.

Treatment Treatment should aim to restore fluid volume and electrolyte balance and reverse the metabolic derangement over a 24 to 48 hour period by the judicious use of insulin, glucose and IV fluid therapy. Reliable intravenous access is a must and for critically ill patients, central venous line, arterial line and foly urine catheter may be necessary. DKA treatment protocols consist of 3 sequential overlapping phases: rehydration ,insulin therapy , and glucose delivery via IV route.

A bolus of 0.9% saline or lactated ringer solution (10 to 20 ml/kg over onehour) will stabilize circulation while the intravenous insulin infusion at a rate of 0.1U/kg/hr is being prepared. Repair of hyperglycemia occurs well before correction of acidosis. Therefore, insulin is still needed to control fatty acid release after normal glucose level are reached. To continue the insulin infusion without causing hypoglycemia, glucose should be added when the serum glucose has decreased to about 250mg/dl .

potassium should be added as soon as it has been established that the patient has urine output , even if K is on the high side of normal , to anticipate the massive intracellular shift as insulin reverse the catabolic state. Because the patient will receive an excess of chloride ,which may aggravate acidosis , it is prudent to use potassium phosphate rather than potassium chloride as a potassium source

Diabetic Ketoacidosis (DKA) Treatment Protocol:

Complications 1. Cerebral edema   1. Cerebral edema *Cerebral edema occurs in 0.7-1% of children with diabetic ketoacidosis * Causes are multifactorial but may include too-rapid infusion of fluids and electrolytes, overhydration, and overly aggressive correction of acidosis or hyperglycemia. * Treatment includes intubation, hyperventilation, and mannitol 0.25-1 g/kg intravenously.

2. Hypoglycemia * Causes include increased sensitivity to exogenous insulin and insufficient serum glucose for insulin to metabolize. * Treatment includes adding 5-10% dextrose to intravenous fluids when serum glucose level is 250-300 mg/Dl. 3. Hypokalemia * Serum potassium begins to reflect actual total body potassium depletion as volume depletion and acidosis resolve. * Add potassium to intravenous fluids when urine output is present and results ofserum potassium level are available. 4. Cardiac dysrhythmia 5. Pulmonary edema

Morbidity and mortality Diabetic ketoacidosis is the most common cause of diabetes-related death in childhood. Without insulin therapy, the mortality rate is 100%, but current mortality rates are around. Treatment for diabetic ketoacidosis may cause life-threatening, predictable, and avoidable acute complications such as hypokalemia, hypoglycemia, hyponatremia, and fluid overload. Other complications, such as cerebral edema, are not as predictable but are very important. Indeed,Cerebral edema complicating DKA remains the major cause of morbidity and mortality in children and adolescents with T1DM. However, its etiology remains unknown.

Prognosis The overall mortality rate for DKA is 2% or less. The presence of deep coma at the time of diagnosis, hypothermia, and oliguria are signs of poor prognosis. The prognosis of properly treated patients with diabetic ketoacidosis is excellent, especially in younger patients if intercurrent infections are absent. The worst prognosis usually is observed in older patients with severe intercurrent illnesses (eg, myocardial infarction, sepsis, or pneumonia), especially when these patients are treated outside an intensive care unit.

When DKA is treated properly, it rarely produces residual effects. 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%. In the last 20 years, mortality rates from DKA have markedly decreased, from 7.96% to 0.67%.  

Prevention Diabetic ketoacidosis in a patient in whom diabetes is newly diagnosed can be prevented only if the general public and primary care physicians know the symptoms and if physicians are alert, particularly with regard to young children, to the possibility of diabetic ketoacidosis developing. A urine test for glycosuria is easy to perform. Adequate education and support for patients with established diabetes (and for their families) should prevent diabetic ketoacidosis. Identificationof children at risk for such behaviors and intervention with social and psychological support may alleviate these prpblems.

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