NEC

Necrotizing Enterocolitis and Spontaneous Intestinal Perforation

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.

II. Incidence

    A. NEC is predominantly a disorder of preterm infants

6-10% in <1.5 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

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.

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.  

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.

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.

Clinical presentation

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

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.

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.

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.

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.

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.

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.

    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. 50%v of NEC Pts

have PLT<50,000/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.

    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.

       

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.

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.

   .

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.

    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.

    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.

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.

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.