NEC

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NEC

• Necrotizing Enterocolitis and Spontaneous
  Intestinal Perforation

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Definitions

•   A. Necrotizing enterocolitis (NEC) is an
  acquired neonatal disorder representing an end
  expression of serious intestinal injury after a
  combination of vascular, mucosal, and metabolic
  (and other unidentified) insults to a relatively
  immature gut.
•     B. Spontaneous intestinal perforation is a
  clinical syndrome of undetermined cause
  resembling NEC with less systemic involvement and
  a less severe clinical course. It may represent a
  variant of classic NEC.

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II. Incidence

•     A. NEC is predominantly a disorder of preterm
  infants
• 6-10 in lt1.5 kg.
• 70 to 90 of cases high-risk LBW
• 10-25 in full-term
• NEC 2-5 of (NICU) admissions
•     B. NEC occurs sporadically or in epidemic
  clusters

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III. Pathophysiology.

• Currently, there is no single unifying theory for
  the pathogenesis of NEC that satisfactorily
  explains all of the clinical observations
  associated with this disorder.
• loss of mucosal integrity( ischemic, toxic).
• Then, (with feeding) bacterial proliferation
• followed by invasion of the damaged intestinal
  mucosa by gas-producing (methane and hydrogen)
  organisms that cause intramural bowel gas
  (pneumatosis intestinalis).
• This sequence of events may then progress to
  transmural necrosis or gangrene of the bowel and
  finally to perforation and peritonitis.

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IV. Risk factors

•     A. Prematurity.
•     B. Asphyxia and acute cardiopulmonary disease
  lead to low cardiac output and diminished
  perfusion states, resulting in redistribution of
  cardiac output away from the mesenteric
  circulation and causing episodic intestinal
  ischemia.
•     C. Enteral feedings. NEC is rare in unfed
  infants. About 90-95 of infants with NEC have
  received at least one enteral feeding. The
  explanations for this include the following
•         1. Enteral feeding provides necessary
  substrate for proliferation of enteric pathogens.
•         2. Hyperosmolar formula or medications
  cause altered mucosal permeability and direct
  mucosal damage.
•         3. There is a loss or lack of
  immunoprotective factors in commercially prepared
  formulas and in stored breast milk.
•         4. Breast-feeding significantly lowers
  the risk of NEC.
•   D. Polycythemia and hyperviscosity syndromes.
  
•     E. Exchange transfusions.  

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IV. Risk factors

•   F. Feeding volumes, timing of enteral feeding,
  and rapid advancement in enteral feedings. These
  appear to play a role, but clinical evidence
  remains controversial.
•     G. Enteric pathogenic microorganisms.
  Bacterial and viral pathogens, including
  Escherichia coli, Klebsiella, Enterobacter,
  Pseudomonas, Salmonella, Staphylococcus
  epidermidis, Clostridium sp, coronaviruses,
  rotaviruses, and enteroviruses, have been
  implicated, either directly or indirectly, by
  blood, stool, or peritoneal space cultures.

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V. Clinical presentation.

• The time of NEC onset varies inversely with
  gestational age.
• In the (VLBW) group, onset invariably follows
  initiation of enteral feedings and is usually
  diagnosed between 14 and 20 days of age.
• In full-term infants, age of onset is within the
  first week of life.
• The presentation may vary from abdominal
  distention (the most frequent early sign, noted
  in 70 of cases), ileus, and increased volume of
  gastric aspirate or bilious aspirate (two thirds
  of cases) to frank signs of shock, bloody stools,
  peritonitis, and perforation. NEC may also
  present insidiously with nonspecific signs such
  as labile temperature, apnea, bradycardia, or
  other signs of suspect sepsis.

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Clinical presentation

• The clinical syndrome has been classified into
  stages by Walsh and Kliegman (1986) to include
  systemic, intestinal, and radiographic findings

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A. Stage I suspected NEC

•             1. Systemic signs are nonspecific,
  including apnea, bradycardia, lethargy, and
  temperature instability.
•         2. Intestinal findings include feeding
  intolerance, recurrent gastric residuals, and
  guaiac-positive stools.
•         3. Radiographic findings are normal or
  nonspecific.

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B. Stage IIA mild NEC

•             1. Systemic signs are similar to
  those in stage I.
•         2. Intestinal findings include prominent
  abdominal distention with or without tenderness,
  absent bowel sounds, and gross blood in the
  stools.
•         3. Radiographic findings include ileus,
  with dilated loops with focal areas of
  pneumatosis intestinalis.

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C. Stage IIB moderate NEC

•         1. Systemic signs include stage 1 signs
  plus mild acidosis and thrombocytopenia.
•         2. Intestinal findings include increasing
  distention, abdominal wall edema, and tenderness
  with or without a palpable mass.
•         3. Radiographic findings include
  extensive pneumatosis and early ascites.
  Intrahepatic portal venous gas may be present.

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D. Stage IIIA advanced NEC

•         1. Systemic findings include respiratory
  and metabolic acidosis, assisted ventilation for
  apnea, decreasing blood pressure and urine
  output, neutropenia, and coagulopathy.
•         2. Intestinal findings include spreading
  edema, erythema or discoloration, and induration
  of the abdominal wall.
•         3. Radiographic findings include
  prominent ascites, paucity of bowel gas, and
  possibly a persistent sentinel loop.

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E. Stage IIIB advanced NEC

•         1. Systemic findings reveal generalized
  edema, deteriorating vital signs and laboratory
  indices, refractory hypotension, shock syndrome,
  disseminated intravascular coagulation (DIC), and
  electrolyte imbalance.
•         2. Intestinal findings reveal a tense,
  discolored abdomen and ascites.
•         3. Radiographic findings commonly show
  absent bowel gas and often evidence of
  intraperitoneal free air.

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VI. Diagnosis.

•     A. Clinical diagnosis. NEC is a tentative
  diagnosis in any infant presenting with the triad
  of feeding intolerance, abdominal distention, and
  grossly bloody stools (hematochezia) or acute
  change in stool character. Alternatively, the
  earliest signs may be identical to those of
  neonatal sepsis.

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•     B. Laboratory studies. The following should
  be performed as baseline studies. If there is
  clinical progression of disease or if these
  laboratory tests are abnormal, the tests should
  be repeated every 8-12 h.
•         1. Complete blood cell count (CBC) with
  differential.
•         2. Platelet count. Thrombocytopenia is
  seen. 50v of NEC Pts have PLTlt50,000/uL.
•         3. Blood culture
•         4. Stool screening for occult blood.
•         5. Arterial blood gas measurements.
  Metabolic or combined acidosis or hypoxia may be
  seen.
•         6. Electrolyte panel., particularly hypo-
  or hypernatremia, and hyperkalemia are common.
•         7. Stool cultures for rotaviruses and
  enteroviruses should be obtained if diarrhea is
  an epidemic in the nursery.

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•     C. Radiologic studies
•         1. Flat plate x-ray studies of the
  abdomen
•             a. Supportive for NEC. Look for
  abnormal bowel gas patterns, ileus, a fixed
  sentinel loop of bowel, or areas suspicious for
  pneumatosis intestinalis.
•             b. Confirmatory of NEC. Look for (1)
  intramural bowel gas (pneumatosis intestinalis)
  and (2) intrahepatic portal venous gas (in the
  absence of an umbilical venous catheter).
•         2. Lateral decubitus and cross-table
  lateral studies of the abdomen. These studies are
  more likely to demonstrate a pneumoperitoneum.
•        

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Note

• Perforation commonly occurs within 48-72 h after
  pneumatosis or portal venous gas.
• In the presence of pneumatosis intestinalis or
  portal venous gas, flat plate and left lateral
  decubitus or cross-table lateral x-ray studies of
  the abdomen should be obtained every 6-8 h to
  check for the development of pneumoperitoneum,
  signaling intestinal perforation. Serial x-ray
  studies may be discontinued with clinical
  improvement, usually after 48-72 h.

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VII. Management.

• The main principle of management for confirmed
  NEC is to treat it as an acute abdomen with
  impending or septic peritonitis.
• The goal is to prevent progression of disease,
  intestinal perforation, and shock. If NEC occurs
  in epidemic clusters, cohort isolation has been
  shown to limit transmission. Signs to watch
  closely for include progressive distention and
  discoloration of the abdomen, refractory
  metabolic acidosis, falling platelet counts, and
  shock.
•    .

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• A. Basic NEC protocol. Any infant with suspected
  NEC should be managed according to the following
  protocol
•         1. Nothing by mouth
•         2. Use of a nasogastric tube
•         3. Close monitoring of vital signs and
  abdominal circumference.
•         4. Removal of the umbilical catheter and
  placement of peripheral venous and arterial
  catheters, depending on severity of illness
  (controversial).
•         5. Antibiotics. Start ampicillin and
  gentamicin or cefotaxime intravenously. Add
  anaerobic coverage (clindamycin or metronidazole
  Flagyl) if peritonitis or perforation is
  suspected.
•         6. Monitoring for gastrointestinal
  bleeding.
•         7. Strict monitoring of fluid intake and
  output.
•         8. Removal of potassium from intravenous
  fluids in the presence of hyperkalemia or anuria.
•         9. Laboratory monitoring. Check CBC,
  platelet count, and electrolyte panel every 12-24
  h until stable.
•         10. Septic workup L p ??
•         11. Radiologic studies.

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•     B. Management of stage I.
• Start the basic NEC protocol described in section
  VII,A. If all cultures are negative and the
  infant has improved clinically, antibiotics can
  be stopped after 3 days. The infant may also be
  fed after 3 days if clinically improved.
•     C. Management of stages IIA and B
•         1. Basic NEC protocol, including
  antibiotics for 10 days (see section VII,A,5).
•         2. NPO for 2 weeks. Oral feedings may be
  started 7-10 days after radiographic resolution
  of pneumatosis.
•         3. Continue and advance TPN to achieve a
  caloric intake of ³90-110 cal/ kg/day.
•         4. Respiratory support. Appropriate level
  of ventilatory support to correct hypoxia and
  respiratory and metabolic acidosis and maintain
  acceptable arterial blood gas parameters.
  Progressive abdominal distention causing loss of
  lung volume may increase the need for
  positive-pressure ventilation.
•         5. Fluid and electrolyte management.
  Adjust total fluid intake, making allowance for
  third space losses, transfusion of blood and
  blood products, and prerenal and renal failure.
  Hyperglycemia resulting from glucose intolerance
  frequently complicates fluid and electrolyte
  management of the extremely low birth weight
  (ELBW) infant with NEC.
•         6. Surgical consultation is required.
•         7. Low-dose dopamine infusion. Low-dose
  dopamine infusion (2-4 mg/ kg/min) to improve
  intestinal blood and renal perfusion in low-flow
  states. (This practice varies among
  institutions.)
•     D. Management of stages IIIA and IIIB
•         1. Basic NEC protocol, as described in
  section VII,A.
•         2. Plus stage II management, as described
  in section VII,C.
•         3. Blood pressure support. Refractory
  hypotension is common and multifactorial in
  origin. Treatment includes replacement of ongoing
  fluid losses, volume expansion with colloids (see
  Chapter 46), and vasopressors such as dopamine
  (for dosage, see Chapter 80). The goal is to
  maintain adequate mean blood pressure (see
  Appendix C) and urine output (1-3 mL/kg/h).
•         4. Progressive leukopenia,
  granulocytopenia, and thrombocytopenia usually
  parallel a deteriorating clinical status.
  Granulocyte transfusion and granulocyte
  colony-stimulating factor (G-CSF) are not
  routinely indicated. Blood and platelet
  transfusions are frequently needed.

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•     E. Surgical management
•         1. Exploratory laparotomy is indicated if
  there is evidence of intestinal perforation.
•         2. Peritoneal drainage. In selected cases
  in unstable (or ELBW) infants,
•         3. Deteriorating clinical condition with
  failure to respond to appropriate medical
  management.
•             a. Evidence of a persistent, fixed
  sentinel loop over 24 h,
•             b. Metrizamide,
•         4. Right lower quadrant mass.
•         5. Abdominal wall erythema
•         6. Spontaneous intestinal perforation in
  the VLBW infant.

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VIII. Prevention.

• Breast milk has been shown to decrease the risk
  and incidence of NEC.
• Studies with the use of immunoglobulins and
  prophylactic enteral antibiotics to prevent NEC
  remain largely experimental.

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IX. Prognosis

•     A. NEC with perforation is associated with a
  mortality of 20-40.
•     B. Recurrent NEC is a rare complication.
•     C. Subacute or intermittent symptoms of bowel
  obstruction resulting from stenosis or strictures
  of the colon and, less commonly, of the small
  bowel are seen in 10-20 of cases. A barium
  enema is usually confirmatory.
•     D. Infants undergoing extensive surgical
  resection require long-term parenteral nutrition,
  enterostomy care, and management of short-gut
  syndrome. Chronic electrolyte imbalance and
  failure to thrive are common.
•     E. In the absence of short-gut syndrome,
  growth, nutrition, and gastrointestinal function
  appear to catch up and are normal by the end of
  the first year.