Document Sample
					    Diabetic Ketoacidosis


• Diabetes mellitus is a syndrome of
  disturbed energy homeostasis caused by a
  deficiency of insulin or of its action
  resulting in abnormal metabolism of
  carbohydrate, protein, and fat
• Diabetes mellitus is the most common
  endocrine-metabolic disorder of childhood
  and adolescence

• Individuals affected by insulin-dependent
  diabetes confront serious burdens that
  include an absolute daily requirement for
  exogenous insulin, the need to monitor their
  own metabolic control, and the need to pay
  constant attention to dietary intake

• Morbidity and mortality stem from
  metabolic derangements and from long-
  term complications that affect small and
  large vessels and result in retinopathy,
  nephropathy, neuropathy, ischemic heart
  disease, and arterial obstruction with
  gangrene of the extremities

• Type I Diabetes (insulin-dependent diabetes
  mellitus, IDDM)
  – characterized by severe insulinopenia and
    dependence on exogenous insulin to prevent
    ketosis and to preserve life
  – onset occurs predominantly in childhood
  – probably has some genetic predisposition and is
    likely autoimmune-mediated

• Type II Diabetes (non-insulin-dependent
  diabetes mellitus, NIDDM)
  – patients are not insulin dependent and rarely
    develop ketosis
  – generally occurs after age 40, and there is a
    high incidence of associated obesity
  – insulin secretion generally adequate; insulin
    resistance is present
  – no associated genetic predisposition

• Secondary Diabetes
  – occurs in response to other disease processes:
     • exocrine pancreatic disease (cystic fibrosis)
     • Cushing syndrome
     • poison ingestion (rodenticides)
           Type I Diabetes Mellitus:

• Prevalence of IDDM among school-age
  children in the US is 1.9 per 1000
• The annual incidence in the US is about 12 -
  15 new cases per 100,000
• Male to female ratio is equal
• Among African-Americans, the occurrence
  of IDDM is about 20 - 30% of that seen in
           Type I Diabetes Mellitus:

• Peaks of presentation occur at 5 - 7 years of
  age and at adolescence
• Newly recognized cases appear with greater
  frequency in the autumn and winter
• Definite increased incidence of IDDM in
  children with congenital rubella syndrome
          Type I Diabetes Mellitus:
         Etiology and Pathogenesis

• Basic cause of clinical findings is sharply
  diminished secretion of insulin
• The mechanisms that lead to failure of
  pancreatic -cell function are likely
  autoimmune destruction of pancreatic islets
• IDDM is more prevalent in persons with
  Addison’s disease, Hashimoto’s thyroiditis,
  and pernicious anemia
          Type I Diabetes Mellitus:
         Etiology and Pathogenesis

• 80 - 90% of newly diagnosed patients with
  IDDM have anti-islet cell antibodies
Type I Diabetes Mellitus:
            Type I Diabetes Mellitus:

• Progressive destruction of -cells leads to a
  progressive deficiency of insulin
• As IDDM evolves, it becomes a permanent
  low-insulin catabolic state which feeding
  does not reverse
• Secondary changes involving stress
  hormones accelerate the metabolic
           Type I Diabetes Mellitus:

• With progressive insulin deficiency,
  excessive glucose production and
  impairment of its utilization result in
  hyperglycemia with glucosuria when the
  renal threshold of ~ 180 mg/dL is exceeded
• The resultant osmotic diuresis produces
  polyuria, urinary losses of electrolytes,
  dehydration, and compensatory polydipsia
           Type I Diabetes Mellitus:

• Hyperosmolality as a result of progressive
  hyperglycemia contributes to cerebral
  obtundation in DKA
• Serum osmolality:
  – {Serum Na+ + K+} x 2 + glucose + BUN
                              18      3
            Type I Diabetes Mellitus:

• DKA results in altered lipid metabolism
  – increased concentrations of total lipids,
    cholesterol, triglycerides, and free fatty acids
  – free fatty acids are shunted into ketone body
    formation due to lack of insulin; the rate of
    formation exceeds the capacity for their
    peripheral utilization and renal excretion
    leading to accumulation of ketoacids, and
    therefore metabolic acidosis
           Type I Diabetes Mellitus:

• With progressive dehydration, acidosis,
  hyperosmolality, and diminished cerebral
  oxygen utilization, consciousness becomes
  impaired, and the patient ultimately
  becomes comatose
           Type I Diabetes Mellitus:
            Clinical Manifestations

• Classic presentation of diabetes in children
  is a history of polyuria, polydipsia,
  polyphagia, and weight loss, usually for up
  to one month
• Laboratory findings include glucosuria,
  ketonuria, hyperglycemia, ketonemia, and
  metabolic acidosis. Serum amylase may be
  elevated. Leukocytosis is common
            Type I Diabetes Mellitus:
             Clinical Manifestations

• Keotacidosis is responsible for the initial
  presentation of up to 25% of children
  – early manifestations are mild and include
    vomiting, polyuria, and dehydration
  – More severe cases include Kussmaul
    respirations, odor of acetone on the breath
  – abdominal pain or rigidity may be present and
    mimic acute appendicitis or pancreatitis
  – cerebral obtundation and coma ultimately ensue
            Type I Diabetes Mellitus:

• Diagnosis of IDDM is dependent on the
  demonstration of hyperglycemia in
  association with glucosuria with or without
• DKA must be differentiated from acidosis
  and coma due to other causes:
  – hypoglycemia, uremia, gastroenteritis with
    metabolic acidosis, lactic acidosis, salicylate
    intoxication, encephalitis
          Type I Diabetes Mellitus:

• DKA exists when there is hyperglycemia (>
  300 mg/dL), ketonemia, acidosis,
  glucosuria, and ketonuria
           Type I Diabetes Mellitus:

• Treatment is divided into 3 phases
  – treatment of ketoacidosis
  – transition period
  – continuing phase and guidance
            Type I Diabetes Mellitus:

• Goals of treatment of DKA
  – intravascular volume expansion
  – correction of deficits in fluids, electrolytes, and
    acid-base status
  – initiation of insulin therapy to correct
    catabolism, acidosis
             Type I Diabetes Mellitus:

• Intravascular volume expansion
  – dehydration is most commonly in the order of
  – initial hydrating fluid should be isotonic saline
     • this alone will often slightly lower the blood glucose
• Treatment of electrolyte abnormalities
  – serum K+ is often elevated, though total body
    K+ is depleted
                 Type I Diabetes Mellitus:
   – K+ is started early as resolution of acidosis and the administration
     of insulin will cause a decrease in serum K +
• Phosphate is depleted as well. Phosphate may be added as
  KPO4 especially if serum chloride becomes elevated
• “Pseudohyponatremia” is often present
   – Expect that the Na level will rise during treatment
   – Corrected Na = Measured Na + {(glucose - 100) x
   – If Na does not rise, true hyponatremia may be present
     (possibly increasing cerebral edema risk) and should be
            Type I Diabetes Mellitus:

 – bicarbonate administration leads to increased
   cerebral acidosis
    • HCO3- combines with H+ and dissociated to CO2
      and H2O. Whereas bicarbonate passes the blood-
      brain barrier slowly, CO2 diffuses freely, thereby
      exacerbating cerebral acidosis and cerebral
            Type I Diabetes Mellitus:

• Indications for bicarbonate administration
  include severe acidosis leading to
  cardiorespiratory compromise
• Increasing evidence suggests that
  subclinical cerebral edema occurs in the
  majority of patients treated with fluids and
  insulin for DKA
            Type I Diabetes Mellitus:

• Cerebral edema is the major life-threatening
  complication seen in the treatment of
  children with DKA
  – usually develops several hours after the
    institution of therapy
  – manifestations include headache, alteration in
    level of consciousness, bradycardia, emesis,
    diminished responsiveness to painful stimuli,
    and unequal or fixed, dilated pupils
            Type I Diabetes Mellitus:

• Therapy of cerebral edema includes
  treatment with mannitol and
• Excessive use of fluids, use of bicarbonate,
  and large doses of insulin have been linked
  to the increased formation of cerebral
  – fluids are limited to ~ 3 L/m2/24 hours
            Type I Diabetes Mellitus:

• Insulin Therapy
  – continuous infusion of low-dose insulin IV (~
    0.1 U/kg/hr) is effective, simple, and
    physiologically sound
  – goal is to slowly decrease serum glucose (< 100
  – frequent laboratory and blood gas analyses are
    obtained to ensure ongoing resolution of
    metabolic acidosis
           Type I Diabetes Mellitus:

• “Maintenance” IV fluid at a rate of 2000 -
  2400 cc/m2/day consists of 2/3 NS (0.66%)
  or NS
  – 5% Dextrose is added to IVF when blood
    glucose is ~ 300 mg/dL
  – 10% Dextrose is added when blood glucose is ~
    200 mg/dL
               Type I Diabetes Mellitus:
• Insulin is used to treat acidosis, not hyperglycemia
   – insulin should never be stopped if ongoing acidosis
• When the acidosis is corrected, the continuous insulin
  infusion may be discontinued and subcutaneous insulin
• With the regimen, DKA usually is usually fully corrected
  in 36 to 48 hours
           Type I Diabetes Mellitus:

• Hypoglycemic Reactions (Insulin Shock)
  – symptoms and signs include pallor, sweating,
    apprehension, trembling, tachycardia, hunger,
    drowsiness, mental confusion, seizures and
  – management includes administration (if
    conscious) of carbohydrate-containing snack or
  – glucagon 0.5 mg is administered to an
    unconscious or vomiting child