Necrotizing Enterocolitis

Introduction

• NEC is the most common newborn surgical emergency.¹
• NEC is commonly a disease of the premature neonate, affecting 5-12% of those born at very-low birth weight.² The incidence and severity of disease are inversely proportional to gestational age and birth weight.
• The incidence of NEC ranges from 0.7 to 1.1 cases per 1,000 live births. NEC is most common in premature neonates, with only 7-13% of cases occurring in patients born at full-term.¹

Risk Factors^1,2

• Low gestational age
• Low birth weight
  • Incidence may be up to 10% in extremely low and very low birth weight neonates
  • Small for gestational age patients are not at increased risk
• Prenatal events
  • Absent or reversed end-diastolic umbilical artery blood flow
  • Maternal eclampsia
  • Maternal drug abuse
  • Placental abruption
  • Fetal distress
  • Premature rupture of membranes
  • Chorioamnionitis
  • Immature intestinal development.
• Postnatal risk factors
  • Asphyxia
  • Respiratory distress syndrome
  • Need for respiratory support
  • Congenital heart disease
  • Persistent fetal circulation
  • Patent ductus arteriosus
  • Sepsis
  • Gastroparesis
  • Hirschsprung Disease
• Abnormal gut microbiota colonization
• Familial predisposition

Pathophysiology and Prevention

• NEC occurs secondary to mucosal compromise following enteral feeding, thereby allowing pathogenic bacteria to enter the gastrointestinal tract.¹
• NEC is multifactorial, with much of its etiology not yet understood. NEC is a result of damaged intestinal epithelium with multiple factors: (Figure 1)
  • Microcirculatory changes and abnormal inflammatory response
  • Intestinal epithelial breakdown with introduction of enteric bacteria to the lymphatic and portal venous systems, with subsequent pneumatosis and portal venous gas
  • Decreased motility and intestinal absorption in premature infants, secondary to insufficient time for maturation in utero
  • Immature tight junctions and goblet cells in premature neonatal epithelium
  • Decreased epidermal growth factor (EGF) and heparin-binding EGF-like growth factor
  • Increased levels of interleukin-2 and platelet-activating factor

• Prevention strategies include early introduction of human breast milk, with fortifiers added as needed; minimization of unnecessary antibiotics or antacids; and appropriate transfusion goals.

Presentation and Management

• The presentation of NEC varies among patients, with a range of nonspecific clinical findings. Early presentation can present with various hemodynamic changes, respiratory failure, hypoglycemia, poor feeding, and lethargy.
• As NEC progresses, exam findings include absent bowel sounds, abdominal tenderness, or abdominal discoloration.
• Laboratory findings may include thrombocytopenia, leukocytosis, neutropenia, metabolic acidosis, and disseminated intravascular coagulation. Thrombocytopenia may occur in up to 90% of patients, and more severe thrombocytopenia is associated with a worse prognosis.¹
• NEC is a disease of the small bowel, with clinical findings that vary with the degree of intestinal necrosis. The diagnosis of NEC is made by clinical findings and radiographic assessment.
• Pneumatosis intestinalis on abdominal radiograph is a common finding. Fixed bowel dilation is a common, albeit nonspecific finding. Portal venous gas and pneumoperitoneum are radiographic findings consistent with more severe disease1.

Modified Bell’s Staging

• Staging criteria developed by Bell et al. (1978) and further modified by Kliegman and Walsh (1986) are often used to stage patients and guide treatment, given variable presentation and severity.^4,5

• Medical management, with bowel rest and antibiotics, is the initial treatment in patients with Stage I or Stage II disease. Additional management includes gastric decompression, intravenous fluid resuscitation, total parenteral nutrition, and serial abdominal radiographs. Patients may require invasive ventilation and vasopressor support in the setting of respiratory failure and hemodynamic compromise. Antibiotic coverage should be broad-spectrum, including anaerobic coverage. Even with successful medical management, patients remain at risk of developing intestinal strictures and should be followed closely.
• Bowel perforation is an absolute indication for surgery. In the setting of bowel perforation, pneumoperitoneum is not always present on radiograph, so paracentesis demonstrating bile, stool, or a positive Gram stain is also an absolute indication for surgical intervention. However, patients with full-thickness bowel necrosis do not always demonstrate pneumoperitoneum or have a positive paracentesis. Therefore, the decision to proceed with surgery in the absence of pneumoperitoneum or a positive paracentesis should be based on the clinical presentation and progression.
• Initial surgical intervention often consists of primary peritoneal drainage, particularly in premature neonates weighing less than 1500 gm without signs of intestinal perforation.¹ However, most patients will still require exploratory laparotomy despite undergoing peritoneal drainage (Figure 3).

Anesthetic Considerations

Preoperative Evaluation

• Patients may already be intubated in the NICU. Blood products (including red blood cells, fresh-frozen plasma, and platelets) should be made available prior to the start of the surgical procedure.

Intraoperative Considerations

• General endotracheal anesthesia is required.
• If not already intubated, consider rapid-sequence induction with standard full-stomach precautions.
• Standard American Society of Anesthesiologists monitors should be used. Additional invasive monitors, such as an arterial line, may be considered in the setting of hemodynamic instability.
• High doses of a short-acting opioid (e.g., fentanyl) and a muscle relaxant are commonly used for the induction and maintenance of general anesthesia.⁶
• Volatile anesthetics, although not contraindicated, may not be tolerated due to hemodynamic instability.⁶
• Nitrous oxide is contraindicated as it worsens bowel distension.
• Assessing intravascular volume status and blood loss can be challenging.
• Aggressive fluid resuscitation with isotonic crystalloids (often requiring up to 100mL/kg) and boluses of 5% albumin is often necessary.⁷
• Hemodynamic support with vasopressors and/or inotropes is commonly used.
• Blood loss should be replaced with packed red blood cells, fresh-frozen plasma, and platelet transfusions.

Postoperative Care

• Postoperative ventilation is often required, and patients may return to the operating room for repeat surgical intervention. May consider regional techniques such as a caudal block or truncal blocks for postoperative pain management in addition to multimodal analgesia.³
• Pain management in the neonate is difficult, as both inadequate analgesia and heavy opioid use can lead to adverse neonatal outcomes, emphasizing the importance of multimodal analgesia.
  • Inadequate analgesia may lead to unfavorable physiologic responses (tachycardia, hypoxia), delayed wound healing, and increased morbidity and mortality.⁹
  • Long term effects of inadequate neonatal analgesia may lead to developmental delay, decreased emotional bonding, and inappropriate response to pain/stress.⁹
  • In addition to common side effects (hypoventilation, hemodynamic instability, tolerance, etc.), excess opioid administration may lead to poor neurodevelopmental outcomes, including behavioral, cognitive, and motor delays.⁹ Preterm infants are more susceptible to adverse effects and have been shown to have increased risk of cognitive and motor delays and decreased cerebellar volume.⁹
  • The use of intravenous acetaminophen in the postoperative setting may decrease opioid requirements as compared to continuous opioid infusion.¹⁰