Necrotizing Enterocolitis

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Necrotizing Enterocolitis
Priscilla Joe, MD Childrens Hospital and
Research Center Oakland
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Incidence

• Most common GI emergency in premies
• 2-10 of VLBW infants lt 1500 grams
• Inverse relationship with gestational age
• Males and females equally effected
• Mean age _at_ diagnosis 20 days (premies) vs. 7 days
  (term)
• Jejunum, ileum, and colon most commonly affected
• 10 term infants (usually in those with
  pre-existing illness)

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Clinical Findings

• Abdominal distension (70-98)
• Increased gastric residuals ( gt70)
• Emesis (gt70)
• Gross blood per rectum (25-63)
• Occult GI bleeding (22-59)
• Diarrhea (4-26)
• Lethargy, temperature instability,
  apnea/bradycardia, hypotension

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Physical Findings

• Absent bowel sounds
• Abdominal tenderness
• Abdominal wall erythema
• Fixed abdominal mass (RLQ)

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Pathophysiology

• Bacterial proliferation
• Ischemic mucosal damage
• Transmural necrosis allowing bacterial
  translocation, increasing risk for perforation
• Endotoxin activation of inflammatory cascade

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Risk Factors

• Prematurity
• Feeding
• Circulatory Instability
• Medications (vasoactive agents, indocin)
• Bacterial Overgrowth/Infection

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Prematurity

• Deficient mucosal barrier (suppressed GI hormones
  and mucosal enzymes)
• Dysfunctional intestinal host defense system
• Decreased motility
• Dysregulation of intestinal microcirculation
  (increased bacterial overgrowth)

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Feeding and NEC

• 90 of babies receive enteral feedings
• Disrupts mucosal integrity
• Reduces gut motility
• Alters GI blood flow
• Abnormal bacterial colonization
• -Formula Enterobacter
• -Breastmilk Enterobacter and Bifidobacterium
• Rate of feeding advancement
• Hyperosmolar feeding

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Intestinal Ischemia

• Term infants (polycythemia, asphyxia, exchange
  transfusion, congenital heart disease, IUGR)
• PDA
• Indocin
• Cocaine exposure in utero
• UAC lines?
• Gastroschisis

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Bacterial Colonization

• High risk infants susceptible to bacterial
  overgrowth
• Breast milk (lactobacilli and facultative
  anaerobes)
• Formula fed (potentially pathogenic gram-negative
  bacteria)

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Work Up
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Radiographic Findings

• Intestinal ileus
• Dilated and thickened bowel loops, air-fluid
  levels
• Intramural gas (pneumatosis intestinalis) cystic
  and/or linear patterns, terminal ileum and
  proximal colon
• Free air (football sign)
• Portal venous gas
• Fixed or persistent dilated loop of bowel
  (sentinel loop)
• Gasless abdomen with ascites

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Laboratory Findings

• CBC
• Elevated or decreased WBCs
• Thrombocytopenia
• Low ANC poor prognosis
• Elevated CRP
• Cultures (blood, /- stool, /- CSF)
• Usually reveals enteric flora
• Stool Analysis - heme , check for C. diff toxin

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Laboratory Findings

• Coagulopathy
• Prolonged PT/PTT
• Low fibrinogen
• Elevated D-dimers
• Electrolytes
• Hypo- or hyperglycemia
• Hyponatremia
• Low bicarb
• ABG/VBG
• Metabolic acidosis

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Differential Diagnosis

• Sepsis with ileus
• Bacterial enterocolitis C. diff, other gram
  negatives
• Mechanical bowel obstruction
• Hirschsprung
• Ileal atresia
• Volvulus
• Meconium ileus
• Intussusception
• Isolated gastric perforation (indocin, steroids)

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Mean Age at Presentation

• Gestational age (weeks)
• lt 30
• 31-33
• 34
• Full term

• Age at onset (days)
• 20
• 14
• 5
• 2

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Clinical Management

• Medical Vs. Surgical

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Medical Management

• Successfully treats ½ to 2/3 of patients
• Consult surgery from the start
• Bowel rest - NPO, gastric decompression, TPN
• Broad spectrum antibiotics for 7-14 days
• Cardiopulmonary support
• Correction of metabolic acidosis and electrolyte
  abnormalities
• Treatment of coagulopathy and/or
  thrombocytopenia
• Serial exams, labs, and x-rays

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Signs Of Ongoing Necrosis

• Increasing distension
• Persistent
• Metabolic acidosis
• Thrombocytopenia
• Hypotension from third spacing

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Indications for Surgical Intervention

• Severe peritonitis
• Pneumoperitoneum
• Intra-abdominal abscess
• Positive paracentesis findings (bile stool)
• Portal venous gas seen on X-ray

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Surgical Management

• 34-50 of patients
• Laparotomy with resection, formation of
  enterostomy and mucous fistula
• Patch, drain, and wait
• Primary peritoneal drainage
• Eventual reanastomosis

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Potential Complications

• Short bowel syndrome
• TPN-associated cholestasis with liver cirrhosis
  and liver failure
• Catheter related sepsis
• Intestinal strictures and partial small bowel
  obstruction
• Enterocolic fistulas
• Developmental and growth delay (50)

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Long-term Outcome Whats Important?

• Length of residual bowel
• Ileum vs. jejunum (better adaptation)
• Presence of ileocecal valve
• Presence of intact colon
• Maturity of infant and general condition

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Survival Without Transplantation

• Patients with gt 25cm of normal bowel who have an
  intact ileocecal valve
• Normal bowel length
• Term infants 200-300 cm
• Preterm infants 100-200 cm

• Patients with gt40cm of normal bowel who have no
  ileocecal valve

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Short Bowel Syndrome

• Fluid electrolyte losses
• Bile acid and Vit B12 malabsorption
• Gastric acid hypersecretion inactivates
  pancreatic enzymes and causes fat malabsorption
• Secretory diarrhea
• Bacterial overgrowth
• - Increases malabsorption, lactic acidosis,
  colitis, Vit B12 deficiency

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Malabsorption

• Fat Bacterial deconjugation of bile salts and
  acids
• Protein and carbohydrates enzyme and transport
  deficiencies
• Vit B12 bacterial uptake

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Sites of Nutrient Absorption

• Duodenum iron
• Jejunum Carbohydrates, proteins, fats and
  vitamins, copper
• Ileum Bile acids, Vit B12

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Short Gut Symptoms

• Distension
• Diarrhea
• Cramping
• Weight loss
• Anemia (occult blood loss, Vit B12 deficiency)

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Treatment of Short Gut Syndrome

• Promotion of villous hyperplasia
• Drip feedings using elemental formulas
• Long-chain fats stimulate intestinal adaptation
• MCT diet bypasses need for bile acids
• Hydrolyzed proteins absorbed rapidly
• Cholestyramine (bile acid binder)
• Trimethoprim-sulfa, metronidazole treats
  bacterial overgrowth
• Proton pump inhibitors or H2 blockers

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Formulas

• Elemental
• Require minimal digestive function and cause less
  pancreatic secretion
• Individual amino acids or short peptides
• Glucose polymers
• Low fat (long chain triglycerides)
• MCT absorbed in absence of lipase or bile salts

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Monitoring

• Stool output for fluid losses
• Carbohydrate malabsorption (low stool pH or stool
  reducing substances)
• Anticipate slow gut adaptation over years
• Weight gain and growth

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Lengthening Procedures
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Prevention of NEC

• Prenatal steroids
• Correction of hypovolemia and hyperviscosity
• Slow, gradual advancement of feeds
• Breastfeeding
• Probiotics - Oral immunoglobulins and
• bifidobacterium?
• Oral antibiotics?
• Acidification of feedings (avoidance of PPIs and
  H2 blockers)?
• Glutamine or arginine supplemenation?

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Trophic Feedings

• No increased risk of NEC
• Increases gut motility
• Reduces cholestasis
• Improves tolerance of subsequent feedings
• May prevent gut atrophy, inflammation, and
  bacterial translocation