NECROTIZING ENTEROCOLITIS

Dr Afnan Shamraiz

Necrotizing Enterocolitis: an acquired neonatal acute intestinal necrosis of unknown etiology .

NEC is the most common life-threatening emergency of the gastrointestinal tract in the newborn.

Various degrees of mucosal or transmural necrosis of the intestine occurs.

The incidence of NEC is 1–5% of infants in NICU. Although rare, the disease does occur in term infants (10%)

Birth weight

incidence,fatality

Gestational age

Introduction:

Epidemiology

Incidence: 0.3-2.4 / 1000 live births2-5 % of all NICU admissions5-10 % of VLBW infants Over 90 % of cases occur in preterm babiesAbout 10 % occur in term newborns: essentially limited to those that have some underlying illness or condition requiring NICU admission Sex, race, geography, climate has no role in

determining the incidence of NEC

Intestinal ischemia (injury)

Enteral nutrition Pathogenic organisms

NEC

Risk Factors for NEC - Triad

Risk factors influencing NEC prediposition.

Enteral feeding: Aggressive advancement of feeding. Non human milk feeding

Abnormal bacterial colonization Prolonged emperical antibiotic therapy Decreased commensal flora Increased pathogenic bacteria

Maternal cocaine abuse – 2.5 times increases risk

Prematurity is the single greatest risk factor

6

Prematurity

Deficient mucosal barrier (suppressed GI hormones and mucosal enzymes)

Dysfunctional intestinal host defense system

Decreased motility Dysregulation of intestinal microcirculation

(increased bacterial overgrowth)

7

Intestinal Ischemia

Term infants (polycythemia, asphyxia, exchange transfusion, congenital heart disease, IUGR)

PDA Indocin Cocaine exposure in utero Gastroschisis

Risk Factors: in Term Babies

Limited to those that have some underlying illness or condition requiring NICU admission.

Congenital Heart Disease Intrauterine growth restriction Polycythemia Hypoxic-ischemic events

The mean gestational age of infants with NEC is 30 to 32 weeks,

PATHOLOGY AND PATHOGENESIS:

Distal part of the ileum

Involved most frequently

Proximal segment of colon

In fatal cases, gangrene may extend from the stomach to the rectum.

NEC probably results from an interaction between loss of mucosal integrity due to factors like ischemia, infection, inflammation,

and the host's response to that injury like circulatory, immunologic, inflammatory responses resulting in necrosis of the affected area.

PATHOLOGY AND PATHOGENESIS: contd..

Various bacterial and viral agents, including Escherichia coli, Klebsiella, Clostridium

perfringens, Staphylococcus epidermidis, and rotavirus, have been recovered from cultures.

However, in most situations, no pathogen is identified.

NEC rarely occurs before the initiation of enteral feeding and is much less common in infants fed human milk.

Coagulation necrosis is the characteristic histologic finding of intestinal specimens.

PRIMARY INFECTIOUS AGENTS

Bacteria, Bacterial toxin, Virus, Fungus

CIRCULATORY INSTABILITY

Hypoxic-ischemic event Polycythemia

MUCOSAL INJURY

ENTERAL FEEDINGS

Malabsorption, gaseous distention H2 gas production, Endotoxin production

INFLAMMATORY MEDIATORS

Inflammatory cells (macrophage) Platelet activating factor (PAF) Tumor necrosis factor (TNF) Leukotriene C4, Interleukin 1; 6

Ischemic or toxic mucosal damage

Loss of mucosal integrity

Intramural gas

TransmuralnecrosisI

Perforation

Peritonitis

nvasion of mucosa and submucosa

Enteral feeding

Bacterial proliferation

Microbiologic Flora and Infection

Several organisms have been accused, but non has been proven to be causative:EnterobacteriaceaeEnterobactersakazakiiCoagulase-negative staphylococci: SIPClosrtidium perfringensCandida species: SIPCytomegalovirusTorovirusHIVMucormycosis

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Mean Age at PresentationGestational age (weeks)

< 30

31-33

34

Full term

Age at onset (days)

20

14

5

2

Clinical Presentation

Course of the diseaseFulminant presentationSlow, paroxysmal presentation

The onset of NEC usually occurs in the 1st 2 weeks of life (with a mean age at onset of 12 days) but can be as late as 3 months of age in VLBW infants

Clinical Presentation Abdominal

(enteric) signs: Distension Tenderness Gastric aspirate,

vomiting Ileus Abdominal wall

erythema, induration Ascites Abdominal mass Bloody stool

Systemic signs: Respiratory

distress, apnea, bradycardia

Lethargy, irritability

Temp. instability Poor feeding Hypotension Acidosis Oligurea Bleeding

diathesis

Stage I (suspected disease):

mild systemic signs

(apnoea, bradycardia, temperature instability),

mild GIT signs (abdominal distension, large gastric aspirates, bloody stools),

non-specific or normal radiological

signs)

Stage II (definite disease):

mild systemic signs with additional GI signs (absent bowel

sounds, abdominal tenderness), specific radiological signs (dilated loops

of intestines, pneumatosis intestinalis or portal venous air),

abnormal laboratory investigations (e.g. metabolic acidosis, thrombocytopenia)

Stage III (advanced disease):

severe systemic illness (with haemodynamic instability), .

additional GI signs (gross abdominal distension, peritonitis),

severe radiological signs (pneumoperitoneum),

additional laboratory findings (e.g. metabolic and respiratory acidosis, disseminated intravascular coagulopathy

Staging NEC – Bell’s Classification

Stage Clinical findings Radiographic findings

I: Suspected NEC

Ia Temp instability, apnea, lethargy, increased residuals, abd distention.

Normal or mild ileus.

Ib See above. + grossly bloody stool.

II: Proven NEC

IIa See above. + absent bowel sounds. +abd tenderness. Appear mildly ill.

Intestinal dilation, ileus, ascites, pneumatosis intestinalis.IIb See above. Appear moderately ill.

+metabolic acidosis. +thrombocytopenia.

III: Advanced NEC

IIIa See II. Bowel intact. Hypotension, bradycardia, apnea. +peritoneal signs. DIC, neutropenia.

Portal venous gas.Pneumoperitoneum (football sign) – specific for stage IIIb. IIIb See III. + Bowel perforation.

MODIFIED BELL’S STAGING OF NEC: Based on:

1. Systemic Signs

2. Intestinal Signs

3. Radiological Signs

Classified into:

I. Suspected:

II. Definite :

A (Mildly ill) ,

B (Moderately ill)

III. Advanced:

A (Severely ill,bowel intact),

B (Severely ill,bowel perforated)

SIR

Initial work up: what to look forNo lab test is specific for NEC

CBC ↑WBC, ↓WBC, ↓PMN

Thrombocytopenia Neutropenia (<1500/microL) –poor

prognosis DIC panel (PT/INR, PTT, Fibrinogen,

D-dimer) Elevated PT/INR, PTT, D-dimer Decreased Fibrinogen

METABOLIC (may have values similar to those found in sepsis) Hyponatremia (<130) Hyperglycemia Hyperkalemia

Blood gas Metabolic acidosis

Blood culture Fecal occult blood test

Serial measurements of CRP – diagnostic and prognostic

Blood studies:

Thrombocytopenia

COMMON TRIAD

OF SIGNS

Persistent Severe Refractory

Hyponatremia Metabolic Acidosis

HAT

Radiology studies

Abdominal X-ray:○ Abnormal gas pattern, ileus○ Bowel wall edema○ Pneumatosis intestinalis○ Fixed position loop○ Intra hepatic-portal venous gas ( in the

absence of UVC)○ Pneumoperitonium - left lateral decubitus or

cross-table lateral views

RADIOLOGICAL FINDINGS Pneumatosis Intestinalis

hydrogen gas within the bowel wall○ product of bacterial metabolism

a. linear streaking pattern○ more diagnostic

b. bubbly pattern○ appears like retained meconium ○ less specific

Pneumatosis Intestinalis

Supine AXR, The bowel is mildly dilated with gas, mainly on the left side. The bubbly pattern of gas seen mainly in the right lower quadrant represents intramural gas.

Fixed Loop SignThe finding of a single

loop or several loops of dilated(enlarged) small intestine that remain unchanged in position for 24 to 36 hours is referred to as the persistent “rigid” loop sign and suggests lack of movement of the intestine due to death of a segment of intestine

RADIOLOGICAL FINDINGS

Portal Venous Gasextension of pneumatosis intestinalis into the

portal venous circulation○ linear branching lucencies overlying the liver and

extending to the periphery○ associated with severe disease and high

mortality

Dilated stomach & loops of bowel

Portal Air

Hepatic portal venous gas

Pneumatosis

intestinalis

RADIOLOGICAL FINDINGS

Pneumoperitoneumfree air in the peritoneal cavity secondary to

perforation○ falciform ligament may be outlined

“football” sign

surgical emergency

Example of football sign:

Intestinal perforation. Abdominal Xray in NEC demonstrates marked distention and massive

pneumoperitoneum

Free air below the anterior abdominal wall.

Example of cross-table lateral x-ray with free air

NEC with perforation

Rigler signRigler's sign, also known as the double wall sign, is seen on an x-ray of the abdomen when air is present on both sides of the intestine, i.e. when there is air on both the luminal and peritoneal side of the bowel wall.

Abdominal ultrasound:Thick-walled loops of bowel with hypomotility.Intraperitoneal fluid is often present.Intramural gas can be identified in early-stage NEC In the presence of pneumatosis intestinalis, gas is

identified in the portal venous circulation within the liver.

Color Doppler US is more accurate than abdominal radiography in depicting bowel necrosis in NEC.

Gas bubbles in hepatic parenchymaPseudo-kidney sign- central echogenic focus and

hypoechoic rim

Sonogram of a bowel loop shows differentiation of inter luminal gas from intramural gas. The intraluminal gas (L) is surrounded by a thickened bowel wall. Within the bowel wall are multiple hyperechoicfoci (arrows), which represent intramural gas

Sonogram shows a bowel loop with a large amount of intramural gas (arrows) in the more dependent and vertically oriented parts of the loop. This gives the bowel wall a typical granular appearance and causes a posterior artifact.

Pneumatosis

Necrosis

Histopathology

Normal small bowel

NEC:Hemorrhagic necrosis beginning at the mucosa and working its way down into the wall

http://library.med.utah.edu/WebPath/PEDHTML/PED045.html

Histopathology

Pneumatosis in the submucosa of the small bowel

http://library.med.utah.edu/WebPath/PEDHTML/PED049.html

Differential diagnosis of NEC : Specific infections (systemic or intestinal)- Pneumonia,

Sepsis.

Gastrointestinal obstruction, volvulus, malrotation,

Isolated intestinal perforation.

Severe Inherited Metabolic disorders. (e.g., galactosemia with Escherichia coli sepsis)

Feeding intolerance

Idiopathic focal intestinal perforation can occur spontaneously or after the early use of postnatal steroids and indomethacin.

TREATMENT: Rapid initiation of therapy is required for suspected as well

as proven NEC cases.

There is no definitive treatment for established NEC and, therapy is directed at supportive care and preventing further injury with

-Cessation of feeding,

-Nasogastric decompression, and

-Administration of intravenous fluids.

Once blood has been drawn for culture, systemic antibiotics (with broad coverage for gram-positive, gram-negative, and anaerobic organisms) should be started immediately.

Algorithm for the treatment of necrotizing enterocolitis

TREATMENT: Contd.. Umbilical catheters if present should be removed.

Ventilation should be assisted as required.

Intravascular volume replacement with crystalloid or blood products.

Cardiovascular support with volume and/or inotropes.

Correction of hematologic, metabolic, and electrolyte abnormalities.

Careful attention to respiratory status, coagulation profile, and acid-base and electrolyte balance are important.

MONITORING:

Sequential abdominal grith measuremet

Sequential anteroposterior and cross-table lateral or lateral decubitus abdominal x-rays to detect intestinal perforation;

Serial determination of hematologic status,

Serial determination of electrolyte status, and

Serial determination of acid-base status.

Indications for surgery : Absolute indications: Evidence of perforation on abdominal roentgenograms

(pneumoperitoneum) or Positive abdominal paracentesis (stool or organism on

Gram stain from peritoneal fluid).

Relative indications: Failure of medical management, Single fixed bowel loop on roentgenograms, Abdominal wall erythema, or A palpable mass.

Ideally, surgery should be performed after intestinal necrosis develops, but before perforation and peritonitis occurs.

Peritoneal drainage may be helpful for patients with peritonitis who are too unstable to undergo surgery. Peritoneal drainage is more successful in patients with isolated intestinal perforation.

Initial signs of possible NEC (bell’s stage I )

•NPO•GI decompression- low constant sucton, replace output with electrolytes•CBC with differentials, blood culture, CRP, S.Electrolytes•Abdominal radiograph•Begin antibiotics

Mild to Moderate (Bell’s stage II)•Serial abdominal radiographs•Broad spectrum antibiotics for 7- 10 days•NPO for 5-10 days, parentaral nutrition•Monitor electrolytes•Serial CBCs every 12h to 24h for 2-3 days

Advanced (Bell’s Stage III)•Serial abdominal radiographs•Broad spectrum antibiotics for 7- 10 days•NPO for 10-14 days, parentaral nutrition•Monitor electrolytes•Serial CBCs every 12h to 24h for 2-3 days•Co-mangement with paediatric surgeon•Hemodynamic support•Monitor coagulation abnormalities and correct Indications for surgery

•Intestinal perforation•Fixed adynamic loop – necrotic gut•Signs suggestive of necrotic gut –persistent severe thrombocytopenia, severe metabolic acidosis

PROGNOSIS.:

Medical management fails in about 20–40% of patients with pneumatosis intestinalis at diagnosis; of these, 10–30% die.

Early postoperative complications : Wound infection, dehiscence, and stomal problems (prolapse, necrosis).

Later complications : Intestinal strictures develop at the site of the necrotizing lesion in about 10% of surgically or medically managed patients.

complications….

After massive intestinal resection,

-Complications from postoperative NEC include short-bowel syndrome (malabsorption, growth failure, malnutrition),

Premature infants with NEC who require surgical

intervention or who have concomitant bacteremia are at increased risk for adverse growth and neurodevelopmental outcome.

The overall mortality is 9% to 28% regardless of surgical or medical intervention.

PREVENTION: Always better than cure! Newborns exclusively breast-fed have a reduced risk of NEC.

Early initiation of aggressive feeding may increase the risk of NEC in VLBW infants.

Gut stimulation protocol of minimal enteral feeds followed by judicious volume advancement may decrease the risk.

Probiotic preparations have also decreased the incidence of NEC. . Induction of GI maturation.

Incidence of NEC is significantly reduced after prenatal steroid therapy.

Alteration of the immunologic status of the intestine using immunoglobulin A (IgA) and immunoglobulin G (IgG) supplementation.

Thank You