eMedicine Specialties > Pediatrics: Surgery > General Surgery

Necrotizing Enterocolitis: Surgical Perspective

Author: Robert K Minkes, MD, PhD, Staff Pediatric Surgeon, Houston Pediatric Surgeons, Texas Children's Hospital
Coauthor(s): Li Ern Chen, MD, Staff Physician, Department of Surgery, Barnes Jewish Hospital, Washington University School of Medicine; Tapash K Palit, MD, Vascular Surgery Fellow, Department of Surgery, Arizona Heart Institute; Robert S Bloss, MD, Clinical Associate Professor of Surgery and Pediatrics, University of Texas Medical School; Clinical Assistant Professor, Department of Surgery, Baylor College of Medicine; Consulting Staff, Houston Pediatric Surgeons
Contributor Information and Disclosures

Updated: Jan 4, 2008

Introduction

Necrotizing enterocolitis (NEC) is one of the most common reasons for surgical consultation in neonates and is the most common GI emergency in the neonatal population. As advances in neonatal intensive care have progressed over the last 30 years and as premature newborns are surviving long enough for the disease to develop, the incidence of NEC in neonatal intensive care units (NICUs) has increased. NEC remains one of the most challenging diseases confronted by pediatric surgeons and still carries a mortality rate of 30-50% when a perforation occurs. Despite advances in technology and recent clinical trials, NEC likely represents a spectrum of diseases with variable causes and manifestations, and surgical care must therefore be individualized.

NEC typically occurs in the second to third week of life in the infant who is premature and has been formula fed. Although various clinical and radiographic signs and symptoms are used to make the diagnosis, the classic clinical triad consists of abdominal distension, bloody stools, and pneumatosis intestinalis. Occasionally, signs and symptoms include temperature instability, lethargy, or other nonspecific findings of sepsis.

History of the Procedure

Numerous vague reports in 19th-century literature report describe infants who died from peritonitis in the first few weeks of life. The first half of the 20th century brought more reports of peritonitis with ileal perforation due to what was called infectious enteritis. In 1953, Scmid and Quaiser called this condition newborn NEC.¹ The first clear report of NEC did not appear until 1964, when Berdon from the New York Babies Hospital described the clinical and radiographic findings of 21 infants with the disease.²

Problem

NEC is an acute inflammatory disease with a multifactorial and controversial pathogenesis. NEC occurs in newborns and is characterized by variable damage to the intestinal tract ranging from mucosal injury to full-thickness necrosis and perforation.

Frequency

The incidence of NEC is difficult to ascertain. Reports generally indicate an incidence of 1-3 cases per 1000 live births. The incidence among patients in NICU settings is reportedly 2-2.5%. However, this rate widely varies by region, by institutions, and by year within the same institution. Cases tend to cluster, suggesting an environmental component to the pathophysiology.

Nations with a lower rate of premature births than that in the United States generally have a lower rate of NEC as well. For example, a large study of NICUs in Japan identified a 0.3% incidence, which is significantly lower than that in similar patient populations in the United States.³

Etiology

No specific etiology of NEC has been identified; multiple factors are believed to contribute to its development. The principal factors identified are prematurity and enteral feedings.

Prematurity and feeding

NEC is principally a disease of premature infants. Although approximately 5-25% of infants with NEC are born full term, studies have found a markedly decreased risk of NEC with increasing gestational age. This finding suggests that maturation of the GI system plays an important role in the development of NEC.

The premature neonate has numerous physical and immunologic impairments that compromise intestinal integrity. Gastric acid and pepsin production are decreased during the first month of life. Pancreatic exocrine insufficiency is associated with low levels of enterokinase, the enzyme that converts trypsinogen to trypsin, which allows hydrolysis of intestinal toxins. Mucus secretion from immature goblet cells is decreased. Gut motility is impaired, and peristaltic activity is poorly coordinated. Finally, secretory immunoglobulin A (IgA) is deficient in the intestinal tract of premature infants not fed breast milk.

The initiation of early enteral feedings is associated with NEC. Some series have reported decreased rates of NEC when feeding volumes are reduced. In a prospective randomized trial, Book et al found a significant increase in the development of NEC among preterm infants fed a hyperosmolar elemental formula compared with those fed a milk formula.⁴

Infectious organisms

Infectious organisms are thought to play a key role in the development of NEC. Whether bacterial infection has a primary inciting role in NEC or whether an initial intestinal mucosal injury allows secondary bacterial invasion is unclear. Positive blood cultures are found in 30% of patients; the most commonly identified organisms are Escherichia coli and Klebsiella pneumoniae. Proteus mirabilis, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus species, Clostridium perfringens, and Pseudomonas aeruginosa have also been identified.

E coli, Klebsiella species, Enterobacter cloacae, P aeruginosa, Salmonella species, S epidermidis, C perfringens, Clostridium difficile, and Clostridium butyricum commonly grow in stool cultures. Klebsiella species, E coli, S epidermidis, and yeast are most commonly identified on peritoneal cultures. Fungal infection is believed to be an opportunistic infection in the presence of an altered host intestinal defense system.

The observation of an epidemic or cluster of cases in a short period in one nursery after sporadic cases support the key role of infectious organisms in NEC. Nursery personnel are known to experience acute GI illnesses in association with these outbreaks, and the institution of infection control measures has accordingly reduced the rates of NEC.

Medications

The use of numerous medications has been implicated as a risk factor for NEC. Xanthine derivatives, such as theophylline and aminophylline, slow gut motility and produce oxygen free radicals during their metabolism to uric acid. Indomethacin used to treat patent ductus arteriosus may cause splanchnic vasoconstriction leading to impaired intestinal integrity. Vitamin E used to treat retinopathy of prematurity is known to impair leukocyte function and has been associated with NEC.

Experimental studies

In animal models, cytokines, such as platelet-activating factor (PAF), induced intestinal injuries that were grossly and histologically similar to those seen in humans with NEC. In addition, an ischemic-reperfusion model of intestinal injury with reactive vasodilation after an initial ischemic insult was shown to elaborate oxygen free radicals in the intestinal mucosa. These free radicals are extremely toxic to cellular organelles and cell membranes. Pretreatment with free-radical scavengers significantly decreased the intestinal injury.

Pathophysiology

The pathogenesis of NEC most commonly begins with a premature GI tract. An impaired host intestinal defense system and immunologic immaturity combine to allow colonization of the GI tract by the bacterial flora present in the NICU.

Antibiotics frequently administered to treat respiratory distress in the neonate depress the native flora, which provide some protection against pathologic organism overgrowth. Enteral feedings with formula provide a carbohydrate substrate for bacterial proliferation and confer none of the immunoglobulin protection that breast milk provides. Bacteria may violate the intestinal mucosa by migrating through the mucosa or through defects in mucosal continuity. The resulting inflammatory reaction elaborates cytokines and other mediators of cellular injury. This further injures the mucosa and may extend through to the deeper layers of the bowel wall. Progressive intestinal damage may occur as further bacterial invasion through the mucosal injury results in full-thickness necrosis and subsequent perforation.

Presentation

The clinical presentation of NEC includes nonspecific aspects of the history, such as vomiting, diarrhea, feeding intolerance and high gastric residuals following feedings. More specific GI tract symptoms include abdominal distension and frank or occult blood in the stools. With disease progression, abdominal tenderness, abdominal wall edema, erythema, crepitans, or palpable bowel loops indicating a fixed and dilated loop of bowel may develop. Systemic signs, such as apnea, bradycardia, lethargy, labile body temperature, hypoglycemia, and shock, are indicators of physiologic instability.

Indications

The principle indication for operative intervention is perforated or necrotic intestine. Infants with necrotic intestine are identified based on various clinical, laboratory, and radiologic findings. The most compelling predictor of intestinal necrosis indicating a need for operative intervention is pneumoperitoneum.

Other relative indications for operative intervention are erythema in the abdominal wall, gas in the portal vein, and positive paracentesis.

Note that evaluation by a pediatric surgeon early in the course of necrotizing enterocolitis is important to avoid any delay in operative intervention. The most common indication for operative treatment is pneumoperitoneum. Many infants may have isolated perforations or necrotic tissue that wall off the abdominal cavity and do not show free intraperitoneal air. Knowing whether these infants may benefit from early operative intervention is difficult.

Relevant Anatomy

Necrotizing enterocolitis (NEC) most commonly affects the terminal ileum and the proximal ascending colon. However, varying degrees of NEC can affect any segment of the small intestine or colon. The entire bowel may be involved and may be irreversibly damaged.

Contraindications

Contraindications to surgical intervention include patients with stage I or stage II disease, for whom nonoperative medical therapy is the treatment of choice. In addition, surgical intervention should be deferred in patients with more severe disease whose condition responds to initial medical management.

Critically ill newborns with a relative contraindication to formal operative exploration may be treated with the placement of a peritoneal drain. Although this is typically a temporizing measure, these extremely ill infants may recover with drain placement alone and do not require exploratory laparotomy. However, peritoneal drain placement may be the treatment of choice for extremely small (<600 g) premature newborns. Such premature, critically ill infants cannot tolerate formal exploration, and drain placement may be preferred and definitive. Nevertheless, many infants whose condition is too unstable for formal exploration do not survive regardless of intervention.

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