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Necrotizing enterocolitis (NEC) continues to be associated with extreme prematurity, resulting in increased morbidity and mortality. Various studies have reported an incidence of NEC of 14% in infants with a birth weight of 501–750 g and an odds ratio for death of 14 for nonsurgical NEC and 25 for surgical NEC. There remains some controversy regarding the diagnosis of perforated NEC vs spontaneous intestinal perforation, and an ongoing multicenter, randomized, controlled trial is attempting to better define the 2 conditions. Regardless of the etiology, severe inflammation and subsequent necrosis, ischemia, perforation, and peritonitis may result in not only death but also severe neurodevelopmental impairment and intestinal failure (IF).
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The 2 common surgical interventions for intestinal perforation are exploratory laparotomy and peritoneal drainage. Several case series and observational studies examined the utility and outcome of both operations. To date, only 2 randomized studies compared the 2 operations, with conflicting results concerning mortality. There is a paucity of data regarding the long-term outcomes of either operation.
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This chapter focuses on the dilemma of surgical intervention for intestinal perforation/NEC. This discussion includes preoperative, operative, and postoperative management. In addition, the chapter reviews novel therapies designed to prevent the complications associated with surgical NEC.
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PREOPERATIVE MANAGEMENT
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It is essential first to determine if a patient actually has perforated NEC. Whenever possible, it is strongly recommended to obtain a pediatric surgical consultation when concerned about perforation. Several clinical scenarios of perforation can present to the caregivers. The first is the presence of free abdominal gas within the peritoneal cavity. A patient may demonstrate a large pneumoperitoneum that is easily appreciated on supine abdominal imaging. Radiographic findings include a large gas bubble or gas surrounding the liver, as well as the so-called football sign by which free abdominal gas highlights the falciform ligament. It can be more difficult to detect when there is less free abdominal gas. In these cases, it is imperative to obtain both supine and left lateral decubitus radiographs. The left lateral decubitus image is preferred to a “cross-table” supine study as the former allows free abdominal gas to migrate between the body wall and the liver and not be confused with a gas-filled loop of intestine. In the absence of free abdominal gas, the determination of intestinal perforation is more challenging.
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To date, there are no studies designed to confirm perforation by either radiographic or biomarker methods. There are case reports of clinicians utilizing abdominal paracentesis to detect perforation. This technique is associated with significant complications and should be reserved for patients who require therapeutic paracentesis for severe abdominal distension that is having an impact on ventilation. Often, patients with a “gasless” abdomen or with presumed NEC totalis (extensive NEC involving the entire intestinal tract) may require surgical intervention even with no clinical evidence of perforation.
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Once the diagnosis of proven or presumed intestinal perforation is made, the patient needs to be quickly moved to a center where pediatric surgical evaluation can be obtained. Regardless of the location, the ABCs of resuscitation need to be applied. Most patients require tracheal intubation and mechanical ventilation. Establishing arterial catheter monitoring of both ventilation and hemodynamics is desirable. The clinician needs to correct any acid-base imbalance and maintain normal age-appropriate arterial blood pressure. Commonly, there is marked fluid loss into the peritoneal spaces, and patients with NEC and sepsis may become markedly edematous. Resuscitation with large amounts of volume may be necessary to support blood pressure and perfusion of the bowel and kidneys. Maintaining adequate urine output has been associated with improved outcome. It is important to remember that patients with perforated NEC will often deteriorate after their operation, so establishing secure vascular access before the surgery will avoid the potential need for subsequent surgically obtained venous catheters.
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Although only 25% of patients with NEC have culture-proven bacteremia, broad-spectrum antibiotics need to be administered. Common initial choices are vancomycin, gram-negative coverage such as an aminoglycoside or piperacillin/tazobactam, and metronidazole as an aerobic bacterial antibiotic. As mentioned, many of these patients have extensive abdominal distention, so placing a large-diameter sump-type orogastric tube with adequate continuous suction will assist in decompression and improve mesenteric perfusion and diaphragmatic excursion.
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By developing a long-standing and collegial relationship with pediatric surgeons, the preoperative period can be streamlined. Two major impediments to timely surgical intervention are the availability of an operating room/team and blood products for operation. Many institutions have developed protocols permitting both peritoneal drainage and exploratory laparotomy at the bedside in the neonatal intensive care unit (NICU), thus eliminating the need for an operating room and the time and risk involved in moving the patient. It is important for the nonsurgical clinician to remember that performing a laparotomy requires an entire surgical team and often a pediatric anesthesiologist. Thus, consulting a surgeon early will avoid delays. Last, regardless of surgical procedure choice, cross-matched blood products need to be available prior to any operation.
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Once the decision has been to proceed with surgical intervention, the next step is to determine what type of operation would result in the best outcome. The debate over the preferred operation has a long history and even now is a subject of ongoing clinical research. Prior to 1978, the standard surgical approach for premature infants with perforated NEC was an exploratory laparotomy with resection of diseased intestine. That year, Ein et al reported their experience with a novel surgical intervention in which 5 premature infants underwent peritoneal drainage as a temporizing therapy. The decision to delay laparotomy and default to peritoneal drainage was based on the surgeons’ assessment that the patients were too medically unstable to tolerate a definitive operation. In this case series, 3 patients survived and did not require a subsequent laparotomy. The other 2 infants died but were found to have intact intestines at autopsy.
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Over the next 20 years, myriad case studies were published comparing primary peritoneal drainage (PPD) to standard laparotomy. Moss et al published a meta-analysis of these studies in 2001. The results of that study demonstrated marked bias in operation choice based on patient birth weight and gestational age, thus making it impossible to determine the best surgical approach. This study was the basis of the first multicenter, randomized, controlled trial comparing patient survival between PPD and laparotomy. The mortality rate in both groups was approximately 35%; thus, the conclusion of the trial was neither operation was superior to the other. A similar study by Rees et al in Europe published in 2008 had similar results, although the authors suggested laparotomy might result in better survival.
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At the time of writing, a third multicenter trial funded by the National Institutes of Health was under way, comparing PPD to laparotomy with regard to not only survival but also long-term complications (ie, neurodevelopment and the development of IF).
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If the decision is PPD, this operation is usually not performed in the operating room. After adequate sedation, the surgeon surgically places a Penrose drain in the right lower abdominal quadrant through a small incision and secures the drain with a suture. The advantage of PPD is that it avoids a long operation and patient transport. The disadvantages are that the abdomen is not visualized and diseased tissue not resected.
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When undergoing laparotomy, the patient receives general anesthesia in the operating room. Once the abdominal cavity is exposed, the surgeon inspects the intestine to determine the site or sites of perforation as well as the extent of necrotic intestine. In some cases, the surgeon is able to resect the affected intestine and perform a primary anastomosis. More often, an enterostomy is created using the proximal portion of the intestine. In some cases, the distal portion of the intestine is used to create a mucous fistula. The fistula promotes drainage and decompression of the distal intestinal tract and can be used for “refeeding” (see postoperative management). If a mucous fistula is not established, the distal intestine is surgically sutured to create a blind pouch. The advantages of a laparotomy are that the surgeon sees the extent of NEC and perforation and any ischemic bowel is removed.
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The disadvantages include not only the inherent stress from a large operation but also the quandary about how much intestine to remove. Some patients have obvious demarcation between healthy and diseased intestine, but in others, the line between dead and inflamed/ischemic intestine is unclear. The surgeon can also be presented with a situation where there the entire intestinal tract is necrotic. Historically, in this case no resection is attempted and the patient’s abdomen is closed with the anticipation that the infant will receive comfort care and expire. With the advent of novel interventions that are mentioned further in the chapter, some surgeons will resect extensive amounts of intestine in the hope that intestinal rehabilitation or multivisceral transplantation may be possible.
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POSTOPERATIVE MANAGEMENT
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The postoperative management, both short term and long term, is unique for both surgical approaches. That stated, all patients receive a long course of broad-spectrum antimicrobial therapy. As in the preoperative period, the patients may require escalated ventilator assistance, correction of acidosis (both metabolic and respiratory), multiple transfusions of various blood products, pressor support to maintain adequate hemodynamics, and pain control.
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Patients undergoing PPD are closely monitored for worsening clinical parameters. As mentioned, PPD was initially designed as a temporizing operation that evolved into definitive surgical management. Some surgeons will perform a so-called salvage laparotomy soon after PPD if they feel the patient’s clinical presentation warrants. More often, the infant is managed with only medical intervention. Most surgeons will wait at least 6 weeks after PPD to assess intestinal integrity. If the patient’s abdominal examination normalizes and defecation has resumed, a trial of trophic feedings may be initiated without further intestinal imaging. If, however, there are concerns for an intestinal stricture or other post-NEC complications, contrast imaging is required. The standard decision is to have the patient undergo a contrast enema first as most NEC-associated strictures occur in the distal bowel. Following passage of the contrast material, the proximal bowel is studied using fluoroscopy to investigate the stomach and duodenum, followed by serial supine radiographs to detect normal passage of contrast material. If there is concern for post-NEC complications, the patient is taken to the operating room for an exploratory laparotomy.
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Patients undergoing initial laparotomy have a different postoperative course. The enterostomy is kept moist and observed for signs of necrosis. Once there is passage of intestinal content, an ostomy bag is placed. The nature and volume of ostomy output need to be closely monitored. The mucous fistula, if present, is maintained in a similar manner. Once intestinal function has returned, enteral feedings can be resumed. The location of the enterostomy will dictate enteral feedings based on the volume of output. The surgical teaching for normal output is less than 50 mL/kg/d or 2 mL/kg/h. If there is a proximal enterostomy, there may be a large amount of ostomy output when feedings are resumed. It may be necessary to utilize continuous gavage feedings to prevent “dumping.” Human breast milk is the preferred feeding substrate, but patients with a proximal enterostomy or extensive short-bowel may need an elemental formula to allow adequate absorption.
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As mentioned, some patients may have a mucous fistula. The fistula can be used to allow enteral feeding advancement. In this technique, the distal intestine is examined using either antegrade or retrograde contrast imaging. If no strictures are present, the contents from the proximal ostomy can be collected into a syringe and infused using a catheter into the distal mucous fistula. This practice has several advantages. By refeeding, the clinician essentially provides a conduit that approximates bowel integrity. Thus, feeding advancement is not limited by the volume of proximal ostomy output but rather by rectal stooling pattern. If the mucous fistula includes a portion of small intestine, it also provides additional absorption of enteral nutrition. In addition, refeeding the distal small intestine promotes the normal enterohepatic circulation and thus prevents cholestasis. Refeeding promotes small intestinal adaptation, which is essential when large amounts of intestine were resected. Last, this technique “primes” the colon for eventual surgical anastomosis by establishing water absorption and a more normal microbiome.
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Once the patient is clinically stable and enteral feedings are tolerated, the next decision is when to the patient should undergo intestinal anastomosis. As with PPD, a 6-week waiting period is commonly used before any subsequent operation is performed. Following an anastomosis and return of bowel function, enteral feedings can be resumed.
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INTESTINAL REHABILITATION AND INTESTINAL FAILURE-ASSOCIATED LIVER DISEASE
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Often, infants who require surgical intervention for perforated NEC develop IF. The current definition of IF is the inability to establish enteral nutrition adequate for reasonable growth without the need for at least some parenteral nutrition. IF is associated with intestinal motility dysfunction, small-bowel bacterial overgrowth, and intestinal failure-associated liver disease (IFALD). Patients with IF may require medications that alter motility, not only to promote normal peristalsis but also to prevent extensive defecation. Some patients with proven or presumed small intestinal bacterial overgrowth respond to a short course of enteral antibiotics followed by a similar course of probiotic therapy.
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The etiology of IFALD is likely multifactorial. Ongoing intestinal inflammation and bacterial translocation, lack of enteral feeding with associated cholestasis, and parenteral nutrition have all been thought to contribute to ongoing liver disease. Recently, the amount and composition of the lipid component of parenteral nutrition has been shown to be a major cause of IFALD. One technique to avoid IFALD is lipid restriction. Restricting to 1 g/kg/d or less of a standard omega-6 lipid emulsion has been associated with resolution of IFALD. Even more recently, several centers have reported using a similar dose of reduced omega-3 lipids with even better results. To date, no randomized, controlled trial has compared the 2 lipid preparations for efficacy and safety.
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As mentioned, there is often concern regarding the ethical nature of extensive intestinal resection. Although the patient may survive in the short term, the long-term course of patients with short bowel can be difficult. It is important that the clinician understand this when counseling parents about therapeutic options. There are, however, novel therapies that may provide some promise with regard to patients with ultrashort bowel. Many centers have established dedicated multidisciplinary intestinal rehabilitation teams that have been shown to have better outcomes than more traditional caregivers. Bowel-lengthening operations are becoming less complicated and have better results. One such operation is the serial transverse enteroplasty (STEP). This is a simpler operation and can double the length of dilated intestine. Last, the outcomes of multivisceral transplantation have improved over since the mid-2000s, with some centers reporting a 5-year survival of 70%. All of these modalities may provide a degree of hope for parents and caregivers in the face of perforated NEC and extensive necrosis.
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