Diabetic Ketoacidosis

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Diabetic Ketoacidosis

• Gary David Goulin, MD

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Goals Objectives

• Understand the action of insulin on the
  metabolism of carbohydrates, protein, and fat
• Understand the pathophysiology of IDDM and DKA
• Understand the management approach to the patient
  with DKA
• Appreciate the complications that can occur
  during treatment of DKA

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Introduction

• 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

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Introduction

• 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

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Introduction

• 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

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Classification

• 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

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Classification

• 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
• As the prevalence of childhood obesity increases,
  more adolescents are presenting with NIDDM
• insulin secretion is generally adequate insulin
  resistance is present
• no associated genetic predisposition

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Classification

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

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Type I Diabetes Mellitus Epidemiology

• 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
  Caucasian-Americans

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Type I Diabetes Mellitus Epidemiology

• 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

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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 Addisons
  disease, Hashimotos thyroiditis, and pernicious
  anemia

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Type I Diabetes Mellitus Etiology and
Pathogenesis

• 80 - 90 of newly diagnosed patients with IDDM
  have anti-islet cell antibodies

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Type I Diabetes Mellitus Pathophysiology
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Type I Diabetes Mellitus Pathophysiology

• 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 decompensation

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Type I Diabetes Mellitus Pathophysiology

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

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Type I Diabetes Mellitus Pathophysiology

• Hyperosmolality as a result of progressive
  hyperglycemia contributes to cerebral obtundation
  in DKA
• Serum osmolality
• Serum Na K x 2 glucose BUN

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Type I Diabetes Mellitus Pathophysiology

• 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

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Type I Diabetes Mellitus Pathophysiology

• With progressive dehydration, acidosis,
  hyperosmolality, and diminished cerebral oxygen
  utilization, consciousness becomes impaired, and
  the patient ultimately becomes comatose

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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

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Type I Diabetes Mellitus Clinical Manifestations

• Keotacidosis is responsible for the initial
  presentation of IDDM in 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

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Type I Diabetes Mellitus Diagnosis

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

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Type I Diabetes Mellitus Diagnosis

• DKA exists when there is hyperglycemia (gt 300
  mg/dL), ketonemia, acidosis, glucosuria, and
  ketonuria

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Type I Diabetes Mellitus Treatment

• Treatment is divided into 3 phases
• treatment of ketoacidosis
• transition period
• continuing phase and guidance

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Type I Diabetes Mellitus Treatment

• 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

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Type I Diabetes Mellitus Treatment

• Intravascular volume expansion
• dehydration is most commonly in the order of 10
• initial hydrating fluid should be isotonic saline
• this alone will often slightly lower the blood
  glucose
• rarely is more than 20 cc/kg fluid required to
  restore hemodynamics
• Treatment of electrolyte abnormalities
• serum K is often elevated, though total body K
  is depleted
• K is started early as resolution of acidosis and
  the administration of insulin will cause a
  decrease in serum K

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Type I Diabetes Mellitus Treatment

• 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 0.016(measured
  glucose - 100)
• If Na does not rise, true hyponatremia may be
  present (possibly increasing cerebral edema risk)
  and should be treated

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Type I Diabetes Mellitus Treatment

• BICARBONATE IS ALMOST NEVER ADMINISTERED
• 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
  depression

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Type I Diabetes Mellitus Treatment

• 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

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Type I Diabetes Mellitus Treatment

• Cerebral edema is the major life-threatening
  complication seen in the treatment of children
  with DKA
• clinically apparent cerebral edema occurs in 1
  of episodes of DKA
• mortality is 40 - 90
• cerebral edema is responsible for 50 - 60 of
  diabetes deaths in children

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Type I Diabetes Mellitus Treatment

• Cerebral edema 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

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Type I Diabetes Mellitus Treatment

• Excessive use of fluids, large doses of insulin,
  and especially the use of bicarbonate have been
  linked to the increased formation of cerebral
  edema
• fluids are generally limited to 3 L/m2/24 hours
• Children who present with elevated BUN, PaCO2 lt
  15 torr, or who demonstrate a lack of an increase
  in serum Na during therapy have an increased
  probability of cerebral edema
• Therapy of cerebral edema may include treatment
  with mannitol, hypertonic saline and
  hyperventilation

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Type I Diabetes Mellitus Treatment

• 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 (lt 100
  mg/dL/hr
• frequent laboratory and blood gas analyses are
  obtained to ensure ongoing resolution of
  metabolic acidosis

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Type I Diabetes Mellitus Treatment

• 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

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Type I Diabetes Mellitus Treatment

• Insulin is used to treat acidosis, not
  hyperglycemia
• insulin should never be stopped if ongoing
  acidosis persists
• When the acidosis is corrected, the continuous
  insulin infusion may be discontinued and
  subcutaneous insulin initiated
• With this regimen, DKA usually is usually fully
  corrected in 36 to 48 hours

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Type I Diabetes Mellitus Treatment

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

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Suggested Reading

• Glaser N, et al. Risk factors for cerebral edema
  in children with diabetic ketoacidosis. NEJM
  3554264-269.
• Menon RK, Sperling MA. Diabetic Ketoacidosis.
  In Fuhrman BP, Zimmerman JJ, ed. Pediatric
  Critical Care. Second Edition. St. Louis
  Mosby-Year Book, Inc., 1998844-52.
• Kohane DS, Tobin JR, Kohane IS. Endocrine,
  Mineral, and Metabolic Disease in Pediatric
  Intensive Care. In Rogers, ed. Textbook of
  Pediatric Intensive Care. Third Edition.
  Baltimore Williams Wilkins, 19961261-72.
• Magee MF, Bhatt BA. Management of Decompensated
  Diabetes Diabetic Ketoacidosis and
  Hyperglycemic Hyperosmolar Syndrome. In Zaloga
  GP, Marik P, ed. Critical Care Clinics
  Endocrine and Metabolic Dysfunction Syndromes in
  the Critically Ill. Volume 171. Philadelphia
  W.B. Saunders Company, 2001 75-106.

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Case Scenario 1

• A 10 y/o male (30 kg) presents to the ED with a
  one-day history of emesis and lethargy.
• Vitals show T 37C, HR 110, RR 25 BP 99/65.
  Patient is lethargic, but oriented x 3. Exam
  reveals the odor of acetone on the breath, dry
  lips, but otherwise unremarkable
• Labs pH 7.05 PaCO2 20, PaO2 100, BE -20, Na
  133, K 5.2, Cl 96 CO2 8. Urine shows 4
  glucose and large ketones

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Case Scenario 1

• How much fluid would you administer as a bolus?
• Would you administer bicarbonate?
• What is the true serum sodium?
• How much insulin would you administer?
• What IVF would you start? At what rate?

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Case Scenario 2

• A 4 y/o female in the PICU is undergoing
  treatment for new onset IDDM and DKA. She is on
  an insulin infusion at 0.1 u/kg/hr, and fluids
  are running at 2400 cc/m2/day.
• Over the last hour, she has been complaining
  about increasing headache. She is now found to
  be unresponsive with bilateral fixed and dilated
  pupils, HR is 50 with BP 150/100.
• What is your next step in management?