General Observation

Color (e.g., cyanosis and pallor), chest mobility (e.g., bilateral expansion, respiratory pattern, and chest compliance), and palpation (e.g., warmth, pulses, and peripheral perfusion) are often difficult to assess because of the patient’s position and draping on the operating room (OR) bed. The use of specific monitors depends on the planned surgical intervention and the underlying disease state.

Circulatory Monitoring

A precordial stethoscope is a simple and effective means to assess the quality of heart sounds, rate, and rhythm, as well as breath sounds. A change in the intensity of heart sounds indicates a decrease in blood pressure and possibly cardiac output. Depending on the surgical procedure and the method of airway management (mask vs. laryngeal mask airway [LMA] vs. endotracheal tube), an esophageal stethoscope is an alternative monitor for noninvasive beat-to-beat cardiovascular monitoring. Although the sensitivity of the stethoscope has been discussed, the simplicity and accuracy of the precordial and esophageal devices to monitor heart tones and breath sounds during surgery involving pediatric patients cannot be denied (Hubmayr, 2004).

The primary role for continuous electrocardiography during anesthesia for the newborn is to detect arrhythmias, especially in the setting of electrolyte disturbance or as evidence of adverse effects of various drugs. Simple monitoring of heart rate is available via the pulse oximeter, now a routine monitor for all patients in the OR.

In most cases, the blood pressure can be accurately monitored with an automated device based on oscillometry (e.g., Dinamap) or ultrasonic flow (e.g., Arteriosonde) if the appropriate-sized cuff is available. Cuff inflation of the automatic devices should cycle no more frequently than every 3 to 4 minutes to avoid ischemia to the arm (Waugh and Johnson, 1984). Systolic blood pressure measurements correlate with the circulating blood volume and therefore are essential to monitor and guide fluid and blood replacement. Another alternative system is a Doppler ultrasonic transducer, which has a characteristic sound that decreases in intensity with a decrease in blood pressure.

An indwelling arterial cannula allows repeated blood sampling for cardiopulmonary and biochemical evaluation. A 22- or 24-gauge cannula can be inserted percutaneously or by cutdown into a variety of sites, including the radial, dorsalis pedis, or posterior tibial arteries. Before the insertion of the catheter, the adequacy of circulation to the hand should be assessed by applying a modified Allen’s test (Brodsky, 1975). The axillary artery is rarely cannulated. In general, the umbilical artery can be cannulated in the first 4 to 7 days of life, but this is usually avoided after the first 2 days of life because of the risks of infection and vascular emboli. The umbilical catheter tip can be placed high (T10 to T12) or low, above the bifurcation of the aorta and below the level of the renal arteries (L4, L5). The placement of the catheter must be confirmed by a radiograph (Fig. 18-8).

FIGURE 18-8 Umbilical artery-vein x-ray image. A, AP view. B, Lateral view. UA and UV catheters have different courses on plain films. The UV catheter goes directly up to the right atrium from the umbilicus, whereas the UA catheter goes down into the external iliac artery and up into the aorta.

The risk for retinopathy of prematurity necessitates meticulous monitoring of oxygen saturation in the neonate, especially the very low–birth-weight (VLBW) infant. Most neonatologists recommend adjusting the inspired oxygen to maintain oxygen saturation between 90% and 95%, depending on the underlying medical status, gestational age, hemoglobin, and postnatal age (i.e., quantity of HgF). Of importance, if blood is shunting right-to-left through a PDA, the oxygen saturation measured in the lower extremities or umbilical artery (postductal site) does not reflect the oxygen saturation in the retinal vessels (preductal site). To enable simultaneous monitoring of both preductal and postductal oxygen saturation, two pulse oximeters are placed—one on the right hand (preductal) and one on a lower extremity (postductal). During right-to-left shunting through the PDA, the preductal oxygen saturation is higher than the postductal value, and the difference depends on the amount of shunting. If blood is shunting right-to-left only via the foramen ovale or other intracardiac sites (e.g., ventriculoseptal defect), the preductal and postductal oxygen saturation are equal (see Chapters 34, and 23, Respiratory Physiology in Infants and Children, Cardiovascular Physiology, and Anesthesia for General Abdominal, Thoracic, Urologic, and Bariatric Surgery).

An arterial cannula must be connected to a pressure transducer and slowly and continuously infused with a small volume of diluted heparin solution (0.1 to 1 units/mL) at the rate of 0.5 to 1 mL/hr. In the extremely low–birth-weight (ELBW) infant, the flush volume should be measured and included in calculating the total daily fluid intake. In addition, extreme caution is critical while flushing an arterial cannula, because retrograde embolization into the cerebral circulation is possible in the small infant, especially with a patent foramen ovale or PDA.

A central venous catheter may be indicated to administer blood, fluid, total parenteral nutrition (TPN) and medications, and to monitor central venous pressure (CVP). Using the Seldinger technique, a catheter can be inserted percutaneously into the subclavian, internal jugular, external jugular, or femoral veins. In emergencies or situations of difficult venous access, the umbilical catheter can be inserted and passed into the right atrium (Fig. 18-8). Its location must be verified by x-ray or by a CVP tracing. Umbilical vein catheters have been associated with portal vein thrombosis. All central venous catheters are associated with significant morbidity, including thrombosis, emboli, and infection. Central venous catheters in the LBW infant have additional risks, from malpositioning and from the disruption of venous flow (ratio of the size of vessel to the size of the catheter is low).

Ventilatory Monitoring

The combination of immature and fragile central nervous and cardiorespiratory systems coupled with unstable chest wall mechanics and variable responses to anesthetic agents are often indications for mechanical ventilatory support both during and after surgery for the newborn. For each patient and for each procedure, the anesthesiologist must evaluate the needs and the requirements for mechanical ventilation. For some infants, the ventilatory status might be so precarious that using a more advanced ventilator from the neonatal intensive care unit intraoperatively might offer additional options for responding to intraoperative events affecting ventilatory status. Of note, if an infant requires a specific mode of ventilatory support, such as high-frequency oscillation, the OR ventilatory strategy should be coordinated with the critical care team.

Manual ventilation has been proposed as a technique to allow the anesthesiologist to continuously sense changes in compliance of the chest and airways. However, Spears and others (1991) noted that manual ventilation can be extremely unreliable for sensing changes in airway compliance. In addition to monitoring heart sounds, the precordial or esophageal stethoscope is a simple system to monitor ventilation and quality of breath sounds. Peak airway and end-expiratory pressures should also be measured. End-tidal carbon dioxide devices (mass spectrometers or infrared analyzers) are now the “standard of care” to continuously monitor the adequacy of respiratory exchange. These devices provide a breath-to-breath level of carbon dioxide tension, and the waveform of this measurement can provide information about rebreathing, ventilator disconnection, suspected air embolism, and hypermetabolic states (see Chapter 10, Equipment).

The pulse oximeter provides a precise, continuous readout of the hemoglobin oxygen saturation. During the first 1 to 2 weeks of life and without transfusion of autologous blood, the oxygen dissociation curve of HgF is shifted to the left of the adult curve so that hemoglobin saturation of 95% to 97% corresponds to an arterial oxygen tension (Pao₂) of 52 to 77 mm Hg, assuming a Pao₂ at 50% hemoglobin saturation (P₅₀) of 19 mm Hg. The hemoglobin saturation should be correlated with an arterial partial pressure of oxygen (Po₂) measurement to ensure valid interpretation of oxygen saturation data in the OR (see Chapter 3, Respiratory Physiology in Infants and Children).

Monitoring of the Neuromuscular Junction

Neuromuscular blockade can be monitored with a battery-operated nerve stimulator. The simple twitch and train-of-four are elicited by stimulating the ulnar nerve at the wrist or the posterior tibial nerve at the ankle. The neonate’s neuromuscular response to nerve stimulation allows the anesthesiologist to titrate further doses of a muscle relaxant and avoid excessive neuromuscular blockade. However, neuromuscular monitoring is technically challenging for VLBW infants because of the small size of their muscles. Accurate data from the transcutaneous devices are often impossible to obtain. Inserting needles into a tiny infant’s extremity should be justified because such trauma may cause bleeding or infection. Furthermore, even with needles in place, obtaining a reliable response using the standard battery-operated devices is unpredictable. Of significance, most of these infants require mechanical ventilation postoperatively, so that documenting full recovery to neuromuscular blockade is often unnecessary immediately after surgery.

Monitoring Urine Output

Devices that collect urine during surgery (specifically, Foley catheters or modifications) are helpful, because in the absence of glycosuria, urine output is a good indicator of hydration, circulating volume, and renal function. The desirable range of urine output in the neonate under anesthesia is 0.5 to 2.0 mL/kg per hour. Note that for a 1-kg infant, 0.5 to 2 mL of urine per hour is difficult to reliably collect in the setting of surgical drapes, lack of direct access to the patient, and easy kinking of drainage tubing secondary to pressure and positioning. Thus, in actual practice, accurately assessing urine output is difficult.

Embryology

Although experimental models have been described, the embryologic etiology of these lesions is not completely understood (Correia-Pinto et al., 2001). Omphalocele has been described as a failure of the cephalic, lateral, and caudal folds to fuse (closure of the exocelomic space) and as abnormal fusion and differentiation of myotomes to form abdominal wall musculature (7 to 12 weeks of gestation). That is, the abdominal cavity is primarily underdeveloped. During weeks 7 to 12 of development, the midgut elongates and herniates into the umbilical cord. By week 12, the abdominal cavity is large enough for the developing gut to exit the cord and reenter the abdomen. Some believe that the simple failure of this return to the abdomen is a developmental arrest that results in an omphalocele and a small abdominal cavity. The abdominal cavity is small only because the gut remains in the umbilical sac.

Gastroschisis is considered to be an earlier embryologic event, resulting from an abnormality of the development of the right omphalomesenteric artery or right umbilical vein, which in turn results in ischemia to the right paraumbilical area. More recently, abdominal wall defects have been ascribed to an abnormal relationship between cell proliferation and planned cell death (apoptosis) at the critical embryonic folding period (Robinson and Abuhamad, 2000). Inadequate mesoderm development may contribute to dysplastic abdominal wall growth. This underdeveloped site is commonly found just to the right of the umbilicus and ruptures with increased pressure of the growing intraabdominal organs. Similar defects in other areas may produce other lesions, such as extrophy of the bladder.

Gastroschisis is usually an isolated lesion, but recent reports raise the possibility of familial occurrence (Yang et al., 1992; Torfs et al., 1994). In utero exposure to acetaminophen, aspirin, and pseudoephedrine has been associated with an increased incidence of gastroschisis (Werler et al., 2002; Baerg et al., 2003). In the case of either an omphalocele or gastroschisis, rotation of the gut is incomplete in utero, resulting in various “malrotation” phenotypes. Intestinal atresias are common, especially in patients with gastroschisis.

Although neither gastroschisis nor omphalocele is considered to be familial, 50% to 75% of infants with an omphalocele have other anomalies, and 20% to 30% have chromosomal abnormalities (Robinson and Abuhamad, 2000; Weber et al., 2002; Mann et al., 2008). Only 15% to 20% of infants with gastroschisis have associated malformations, and only rarely is there a complex pattern of malformation (Stoll et al., 2008). For example, Beckwith-Wiedemann, Rieger’s, and prune belly (Eagle-Barrett) syndromes are associated with omphaloceles, as are trisomies 13, 15, 18, and 21. If the omphalocele contains only bowel and if oligo- or polyhydramnios are present, the likelihood of an associated chromosomal abnormality increases. Others have noted that omphaloceles that contain liver and other viscera are more likely to have cardiac, renal, or limb anomalies, whereas the smaller omphaloceles are more likely to have gastrointestinal or central nervous system malformations (Mann et al., 2008). Syndromes of midline defects often include an omphalocele, and the lesion has been noted in the nonsyndromic multiple congenital anomalies (MCA) complex.

Single-gene mutations have been identified in omphaloceles with multiple anomalies, such as the filamin A, alpha (FLNA) gene in the otopalatodigital syndrome, which is characterized by abnormalities in the axial and appendicular skeleton plus extraskeletal anomalies such as omphalocele (Robertson, 2007). One syndrome, Pentalogy of Cantrell, includes an omphalocele, diaphragmatic hernia, sternal abnormalities, an ectopic and anomalous heart, and gene abnormalities at Xq25 to Xq26.1. Another syndrome (OEIS Complex) involving the lower abdomen includes omphalocele, bladder or cloacal extrophy, imperforate anus, colonic atresia, sacrovertebral anomalies, and meningomyelocele. No environmental or teratogenic associations have been proposed as etiologic causes. Allen et al. (2006) reported an association with assisted reproductive technology. Thus, identifying an abdominal wall defect in utero demands an intense evaluation for associated anomalies, which may be isolated, part of a recognizable malformation syndrome, or chromosomal. In addition, serial ultrasounds should be conducted to evaluate fetal growth and well being, as well as amniotic fluid volume. Of note, after 20 to 32 weeks’ gestation, a higher incidence of fetal demise has been reported. The mode of delivery for infants with abdominal wall defects remains controversial, but recent studies have shown that in gastroschisis and nongiant omphaloceles (i.e., liver extracorporeal), outcome after vaginal delivery is no different than with caesarean section (Henrich et al., 2008). The controversy centers on delivery with gastroschisis because of the unprotected viscera, but no advantages of cesarean section are consistently apparent when survival and incidence of complications are evaluated (Weber et al., 2002).

Preoperative Management

The preoperative management of abdominal wall defects is concerned primarily with fluid resuscitation, minimizing heat loss, treating sepsis, and avoiding direct trauma to the herniated organs. Rather than “rushing” to close the defect, careful assessment of associated defects, establishing smooth cardiorespiratory transition, and ensuring adequate intravascular volume comprise the critical aspects of preoperative management.

Normothermia should be maintained or achieved by preventing heat loss from the exposed viscera. A bowel bag may be used for this purpose (Towne et al., 1980). Emphasis should be placed on covering the lesion with gauze, nonadherent dressing, and a plastic cover rather than moist (saline-soaked) material, as moisture tends to exacerbate heat loss (Mann et al., 2008). It is critical to avoid distorting the sac or twisting at the base. Decompressing the stomach with an orogastric or nasogastric tube minimizes regurgitation, aspiration pneumonia, and further bowel distention. Broad-spectrum antibiotics are started and intravenous fluid therapy (e.g., lactated Ringer’s solution) at as much as 3 to 4 times (150 to 300 mL/kg per day) the usual maintenance rate (80 to 100 mL/kg per day) is infused to provide adequate hydration and to compensate for a combination of peritonitis, edema, ischemia, protein loss, and significant third-space loss. Without such vigorous fluid resuscitation, hypovolemic shock, hemoconcentration, and metabolic acidosis may develop. A urine output of 1 to 2 mL/kg per hour suggests adequate hydration. Because of the large fluid requirements, acid-base status and electrolyte levels should be monitored carefully by serial arterial or venous blood-gas measurements. Rarely, severe metabolic acidosis develops in spite of aggressive fluid delivery (e.g., coexisting sepsis), and sodium bicarbonate (infusion or bolus) or sodium acetate infusion may be required to maintain the pH at greater than 7.20. In general, delivery of crystalloid and colloid provides adequate support.

Intraoperative Management

Surgical management aims to repair the abdominal wall defect and reduce the protruded viscera. If primary closure is not possible, a staged repair is planned, including the use of the silo chimney or the silastic silo prosthesis (Schuster, 1967). The “silo” consists of a silastic or Teflon mesh that is sutured to the fascia of the defect. The synthetic material used to cover the lesion and the specific mechanism for placing the organs into the abdomen (e.g., umbilical tapes or umbilical cord clamps) vary from center to center. After the silo is in place, the extraabdominal organs are gradually returned to the peritoneal cavity over 3 to 10 days (Fig. 18-12). Improved outcome using the delayed-repair approach after the nonoperative placement of a spring-loaded silo has been described by Schlatter et al. (2003). These authors state that this procedure is accomplished in the neonatal intensive care unit (NICU) or delivery room and requires no anesthesia. The prosthesis is then removed, the lesion is reduced under general anesthesia, and eventually the defect is closed. The authors also claim that the time to both first and full feeds was shorter in infants who underwent delayed closure. Similarly, Pastor et al. (2008) performed a prospective multicenter study of infants with gastroschisis. They noted that the routine use of a preformed silo was associated with similar outcomes as primary closure for infants; however, this method has not gained widespread acceptance.

FIGURE 18-12 A silo is used to aid in the reduction of the abdominal contents when the abdominal cavity is too small. Over time, the intestinal contents are gradually reduced back into the abdominal cavity.

Forcing the viscera into an underdeveloped abdominal cavity that cannot accommodate the herniated bowel and tight closure of the defect can restrict diaphragmatic excursion, possibly compress the lungs, and may produce abdominal compartment syndrome (ACS). ACS not only impairs respiratory function, but the high intraabdominal pressure can diminish blood flow to the kidneys and other viscera, impair venous return, and even increase intracranial pressure via effects on intrathoracic pressure (Rosenthal et al., 1998). Thus, during abdominal closure, the anesthesiologist must monitor airway pressures to identify decreased pulmonary compliance, as well as observe for evidence of decreased perfusion to the lower extremities (evidence of ACS). The surgeon and the anesthesiologist should cooperate to assess the feasibility of a primary closure. Yaster et al. (1988) noted that an increase in intragastric pressure of greater than 20 mm Hg and CVP of more than 4 mm Hg above baseline were often associated with reductions in venous return and cardiac index, requiring surgical decompression of the abdomen. The impact of ACS on hemodynamic function and its treatment with percutaneous drainage of the peritoneal cavity has been described in adults and older children, especially in the setting of trauma, and recently in a low–birth-weight infant with a sepsis and an intestinal perforation (Hunter and Damani, 2004; Hunter, 2008, Rasner et al., 2008).

An arterial catheter facilitates blood sampling and continuous monitoring of blood pressure. However, a CVP catheter might be equally valuable for evaluating changes in blood volume and the degree of visceral compression during abdominal closure, and to allow metabolic monitoring (e.g., serial intraoperative glucose levels in infants with Beckwith-Wiedemann syndrome) (Yaster et al., 1988). Intravenous fluids often consist of 5% to 10% dextrose in 0.2% saline to deliver the maintenance therapy and lactated Ringer’s solution (8 to 15 mL/kg, or more, per hour) for third-space loss. Vigilant efforts at preventing heat loss should be sustained (see Chapter 6, Thermoregulation: Physiology and Perioperative Disturbances).

After decompression of the stomach, anesthesia may be induced with inhalation or intravenous agents. Because it distends the bowel, nitrous oxide is avoided. In most cases, neuromuscular blockade facilitates the abdominal decompression or closure. Ventilation with an air (or nitrogen) and oxygen mixture with low concentrations of an inhalation anesthetic plus intravenous opioids are titrated in response to the hemodynamic status. In neonates who have received transfusions of adult blood, the inspired oxygen concentration must be adjusted to maintain oxygen saturation between 85% and 95% and lower in the preterm infant (See Chapter 17, Neonatology for Anesthesiologists). In infants who have not received adult hemoglobin transfusions, the oxygen saturation should be maintained at 90% to 97%, and in preterm infants it should be kept at between 90% and 95%. In the infant who has had no transfusion, this assumes a P₅₀ of 19 mm Hg, and an O₂ saturation between 90% and 97% results in a Pao₂ of 40 to 64 mm Hg. In the preterm infant, an O₂ saturation of 90% to 95% results in a Pao₂ of 40 to 52 mm Hg (See Chapter 3, Respiratory Physiology, Table 3-3). Vane et al. (1994) demonstrated that spinal anesthesia can be an effective anesthetic for the repair of gastroschisis in selected patients. Evaluating for associated intraabdominal anomalies (e.g., atresia) is worthwhile, but especially in the setting of gastroschisis the “matted” bowel is difficult to examine thoroughly for other malformations.

Postoperative Care

Postoperatively, after an uncomplicated primary closure of an abdominal wall defect, mechanical ventilation is usually required for 24 to 48 hours or longer; thereafter, respiratory compliance usually improves dramatically (Nakayama et al., 1991, 1992). Clearly, infants undergoing a gradual reduction after placement of a silo or similar device should be mechanically ventilated during this process. Infants with a small defect can sometimes be extubated at the conclusion of surgery. All patients must be carefully monitored for respiratory and infectious complications in an intensive care unit after closure of an abdominal wall defect. Inferior vena caval compression (evident by blueish lower limbs) or bowel ischemia (necrotizing enterocolitis) can occur as a result of increased abdominal pressure and may require surgical decompression.

The onset of peristalsis after repair of omphalocele or gastroschisis is usually delayed, and the resulting ileus may be prolonged so that total parenteral nutrition is generally required for days to weeks postoperatively (O’Neil and Grosfeld, 1974). Bowel hypomotility is most common in infants with gastroschisis. In anticipation of this, most infants with large lesions and especially gastroschisis should have appropriate intravenous access established in the OR to facilitate early postoperative nutritional support, which is essential for healing and recovery. Prolonged feeding intolerance should precipitate an evaluation for an associated intestinal atresia or other intestinal lesion.

Outcome

Survival of infants born with anterior abdominal wall defects has improved dramatically as a result of prenatal diagnosis; improved surgical, anesthetic, and perioperative intensive care; and nutritional support. The advent of accurate prenatal imaging has allowed termination of a pregnancy when a fetus with multiple anomalies, chromosomal lesions, or a huge defect is identified. When the defect exists in isolation from other anomalies or malformations, 95% to 97% survival is expected. Mortality and long-term outcome are related to associated anomalies (e.g., cardiac malfunction or intestinal atresia); complications of treatment (e.g., bowel perforation, necrotizing enterocolitis, sepsis, or short bowel syndrome); and the side effects of intravenous alimentation (e.g., liver failure or sepsis). In a single institutional report by Phillips et al. (2008), of the patients with gastroschisis and intestinal atresia about one third have significant intestinal dysmotility without short bowel syndrome or obstruction. Although specific data have been collected to stratify and predict outcomes of patients with abdominal wall defects, an obvious observation is that infants with a simple defect (i.e., no atresias, no extraintestinal anomalies, and defect smaller than 5 or 6 cm) and no postoperative complications (e.g., obstruction, necrotizing enterocolitis, or short gut syndrome) have a better prognosis than those with a complex lesion or difficult postoperative course (Molik et al., 2001; Henrich et al., 2008). Of course, outcomes in the setting of a giant omphalocele (i.e., a liver-containing lesion through an abdominal defect wider than 5 cm) are overshadowed by a significant incidence of long-term respiratory insufficiency that may be related to sequelae of abnormal chest wall development (Tsakayannis et al., 1996; Biard et al., 2004).

In a follow-up study of 23 infants born with gastroschisis between 1972 and 1984 and who survived more than 1 year (older than 16 years of age at the time of study), Davies and Stringer (1997) reported that 22 of these 23 infants were in good health and that their overall growth was normal. About one third of the patients with gastroschisis had undergone additional surgery for adhesions, bowel obstruction, or scar complications related to their defect. In a 30-year review of morbidity related to adhesions after an abdominal wall defect in the neonatal period, van Eijck et al. (2008) reported an incidence of small bowel obstruction of 25% in the gastroschisis group, but only 13% in the patients who had had an omphalocele. Of all the patients, 88% required a laparotomy, and 85% occurred in the first year of life. A history of sepsis or wound dehiscence was a factor for predicting the development of a small bowel obstruction. The authors suggest that pediatric surgeons should evaluate the relevance of adhesion-prevention techniques and materials at the time of the initial surgical treatment of abdominal wall defects (e.g., component separation technique or hyaluronate-based barrier) (van Eijck et al., 2008).

Of note, in 25% to 60% of patients with anterior wall defects, the absence of an umbilicus was a distressing physical sign, especially during adolescence (Tunell et al., 1995; Davies and Stringer, 1997). Studies involving shorter follow-up periods have noted patients with chronic abdominal pain and gastroesophageal reflux (Fasching et al., 1996). Recently, economic analysis of care of infants with gastroschisis emphasized that the cost of care is high and that on average 47 days of hospitalization were needed in order to establish full feeds (Sydorak et al., 2002).

Embryology

The diaphragm, lungs, and gastrointestinal tract develop synchronously. The lungs begin as a ventral bud of the foregut. Airway development and branching begin between the fourth and fifth weeks of gestation and progress until the terminal bronchioles are formed by the seventeenth week. The ventral (membranous) component of the diaphragm is formed between the third and fourth weeks of gestation. At about the eighth week of gestation, this portion envelops the esophagus, inferior vena cava, and aorta and fuses with the foregut mesentery to form the posterior and medial (membranous) portions of the diaphragm. The lateral margins of the diaphragm are considered to be derived from the muscular components of the body wall (recent investigations in rats have questioned the contribution of the body wall). The pleuroperitoneal canals close when all the membranous portions of the diaphragm fuse together, and by the ninth week of gestation, diaphragmatic closure is usually complete (Wells, 1954). If the closure (obliteration) of the pleuroperitoneal canals is delayed beyond the ninth to tenth weeks of development, or if the normal rotation and settling of the midgut occur before the tenth week or before the obliteration of the pleuroperitoneal canals, the midgut (abdominal viscera) herniates into the thoracic (pleural) cavity.

In the past, this defect has been attributed to an abnormal closure of the pleuroperitoneal canal, but investigations using the nitrofen-induced CDH model in the rat have used an innovative approach to reexamining the etiology of this lesion. CDH seems to be linked to a disordered formation of the pleuroperitoneal fold—a much earlier event (fourth week of gestation). An abnormal formation of the framework of mesenchyme, which inhibits muscular development of the diaphragm, has been linked to abnormalities in the retinoid signaling pathway. This suggests that vitamin A may play a role in the pathophysiology of CDH (Greer et al., 2003; Holder et al., 2007). CDH was found in 20% to 40% of offspring of rodents (dams) deficient in vitamin A, suggesting a critical role of the retinoid pathway. In addition, exposure to nitrofen (inhibitor of a key enzyme responsible for conversion of retinal to retinoic acid) was associated with development of CDH.

Preoperative Management

Diagnosis and Treatment

Diagnostic and therapeutic modalities have been developed for both the prenatal and postnatal periods.

Postnatal Diagnosis and Treatment

Clinical Presentation

Infants who are born with bilateral lung hypoplasia or severe unilateral hypoplasia exhibit symptoms immediately at birth. In the setting of a prenatal diagnosis, the delivery is deferred to a high-risk center with access to pediatric surgeons, NO, extracorporeal oxygenation, HFOV, and other advanced neonatal therapies.

The classic triad of CDH consists of cyanosis, dyspnea, and apparent dextrocardia. Physical examination reveals a scaphoid abdomen, bulging chest, decreased breath sounds, distant or right-displaced heart sounds, and bowel sounds in the chest. Radiographic examination of the chest shows a bowel gas pattern in the chest, mediastinal shift, and little lung tissue at the right costophrenic sulcus (Fig. 18-15).

FIGURE 18-15 CDH. A, Chest x-ray showing small bowel. B, Laparoscopic view of herniated small bowel. C, Laparoscopic view of colon and intestine. D, Laparoscopic view of reduced abdominal contents. E, Laparoscopic view with completed repair.

Infants who weigh 1000 g, are born before 33 weeks’ gestation, or who have an alveolar-to-arterial oxygen gradient (P[A-a]o₂) of more than 500 seldom survive (Raphaely and Downes, 1973). On the other hand, over the last two decades, antenatal diagnosis, neonatal stabilization and delayed surgery, and (most importantly) the avoidance of ventilator-induced lung injury have resulted in significant improvement in morbidity and mortality of infants with severe CDH.

Timing of Surgery

In the past, CDH was considered a neonatal emergency, and surgery to reduce the hernia was performed urgently. The infant’s lungs were hyperventilated with 100% oxygen in an attempt to produce pulmonary vasodilation with hyperoxia and respiratory alkalosis. Although the combination of hyperoxia and respiratory alkalosis may produce transient pulmonary vasodilation, mechanical ventilation results in overdistension and damage to the alveolar and capillary membranes (volutrauma, previously called barotrauma), which induces an inflammatory reaction and the associated release of vasoactive mediators. Eventually, pulmonary vasoconstriction and hypertension occur, as the balance between vasodilation (oxygen plus alkalosis) and vasoconstriction (inflammatory mediators) shifts and secondary lung injury increases.

The goal of the initial management of CDH is to avoid a surgical intervention when the infant is hypoxic and acidotic and the cardiorespiratory status is labile. Optimizing hemodynamic and respiratory support rather than the specific timing of surgery contributes to improving outcome (Migliazza et al., 2007). Thus, medical management is directed to stabilizing the cardiorespiratory function by improving oxygenation to achieve a preductal saturation more than 90%, correcting any metabolic acidosis, reducing right-to-left shunting and increasing pulmonary perfusion using the least aggressive ventilation possible (Hazebroek et al., 1988). These goals underlie the rationale for some centers initiating HFOV immediately and introducing ECMO to allow pulmonary rest. Unfortunately, these maneuvers have not been predictably effective.

Surgery affects the respiratory system’s compliance. Sakai et al. (1987) reported that the postoperative compliance of the respiratory system (Crs), as measured with a noninvasive, passive mechanic’s technique, immediately decreased 10% to 77% from the preoperative value, suggesting that pulmonary dynamics often deteriorate after surgical repair of the hernia (Lesouef et al., 1984). These observations prompted a reevaluation of the practice of urgent surgery. Instead, surgery is delayed to allow transition to a stable postnatal cardiorespiratory status.

Nakayama and others (1991) evaluated pulmonary function and outcome of 22 infants with severe CDH treated either with traditional emergency repair or with preoperative stabilization for 2 to 11 days. Of 13 infants who underwent immediate repair of CDH, nine received ECMO support postoperatively, and six of the 13 infants (two after ECMO) survived (46% survival). Of nine infants whose surgery was delayed for preoperative stabilization, six immediately received ECMO support for 4 to 10 days; one with extreme lung hypoplasia died before surgery after an intraventricular hemorrhage. The other eight infants survived after surgery (89% survival). Seven days after surgery, Crs of infants in the immediate repair group did not improve from the preoperative values. In contrast, C_rs increased more than 60% from their baseline values in the infants who underwent preoperative stabilization. Although the duration of mechanical ventilation was similar in the survivors of the two groups, the preoperative stabilization group had higher postductal Pao₂, lower respiratory rates, lower peak and mean airway pressures, and lower fraction of inspired oxygen values (Fio₂). Based on the physiologic and clinical evidence, these researchers concluded that preoperative stabilization is beneficial before the repair of CDH. Surgery should be delayed as long as 5 to 15 days until PVR has decreased and ventilation can be maintained with a low peak inspiratory pressure (less than 25 cm H₂O) and Fio₂ (about 0.50).

Preoperative care of an infant with severe CDH should start in the delivery room. Positive pressure ventilation by mask and bag has risks, because attempting to expand the noncompliant lungs may damage the hypoplastic lung by overdistention, as well as distend the stomach and intestines (which are in the left hemithorax), further decreasing chest compliance (Wada et al., 1997; Björklund et al., 1997). If spontaneous ventilatory efforts are inadequate, early intubation of the trachea and decompression of the stomach are important initial steps to prevent further distension of and pulmonary compression by the displaced abdominal viscera.

However, after intubation of the trachea, minimizing the trauma from positive pressure ventilation is an important ventilatory intervention. Björklund et al. (1997) found that six manual inflations with a tidal volume of 35 to 40 mL/kg in preterm lambs resulted in persistent respiratory failure and pneumothorax despite surfactant treatment. Wada and colleagues (1997) also found that ventilation of premature lambs at birth with a tidal volume of 20 mL/kg for only 30 minutes resulted in marked decreases in Crs, along with the development of poor gas exchange. In comparison, premature lambs ventilated with 5 or 10 mL/kg of tidal volumes maintained high Crs and normal gas exchange. Although most infants with CDH are born at term or near term, these data may be relevant in CHD where the pulmonary development is abnormal.

Animal studies suggest that ventilatory strategies that employ small tidal volumes maintain high Crs and better gas exchange (Björklund et al., 1997; Wada et al., 1997). Thus, current ventilatory strategies for an infant with CDH incorporate lower peak and end expiratory airway pressures and accept hypercapnea (Wung et al., 1985, 1995; Boloker et al., 2002). In general, HFOV serves as a rescue therapy; however, others advocate respiratory support with HFOV immediately at birth (Migliazza et al., 2007). Ventilation and Fio₂ are adjusted to maintain a preductal saturation of 90% to 95%. The Paco₂ is allowed to remain as high as 60 to 65 mm Hg (permissive hypercapnea). Crystalloid and blood products are administered to maintain intravascular volume and red–blood-cell mass. Adequate sedation is administered in efforts to minimize increase in PVR. Periods of right-to-left shunting are tolerated if the patient’s underlying hemodynamic status is stable, and vasopressors (e.g., dopamine or milrinone) are infused to maintain hemodynamic stability. In the immediate postnatal period, some infants initially respond to stabilizing maneuvers (e.g., gentle ventilation or hemodynamic support), but in some cases this early stability represents a “honeymoon period” that is followed by a sudden, often unexplained return to a state of persistent pulmonary hypertension and clinical deterioration (e.g., acidosis, hypoxemia, severe hypercapnia, pulmonary hypertension, and right-to-left shunting through the foramen ovale, and patent ductus arteriosus). If a reversion to a state of persistent pulmonary hypertension occurs, then trials of NO and HFOV are initiated and ECMO is considered.

Nitric Oxide

NO is a free radical with a short half-life, produced endogenously but often administered as an inhaled agent to take advantage of its effects as a selective pulmonary vasodilator. Although a role for NO in the treatment of pulmonary hypertension with CDH is a logical extension from its effectiveness in infants with pulmonary hypertension associated with meconium aspiration, sepsis, or congenital heart disease, clear cut effectiveness in the setting of CDH has not been demonstrated (Kinsella et al., 1992; Roberts et al., 1992; Bloch et al., 2007).

NO diffuses across the alveolar capillary membranes and binds to and thereby stimulates enzymes with transition metal centers (e.g., heme), such as cyclic guanylate cyclase. This increases cyclic GMP, activates protein kinase, and causes vascular smooth muscle to relax (see Chapters 3, 4, and 17, Respiratory Physiology in Infants and Children, Cardiovascular Physiology, and Neonatology for Anesthesiologists). Phosphodiesterases quickly metabolize NO, thereby limiting its half-life. In addition to cyclic guanosine monophosphate (cGMP)-mediated action, NO also has non-cGMP actions. For example, NO interacts directly with proteins with active thiol groups, such as those in the heart. NO’s modification of various myocardial proteins has been linked to regulation of contractility, but this action has not been well defined in the setting of CDH and neonatal pulmonary hypertension (Zimmet and Hare, 2006).

Toxic effects of NO are primarily attributed to its interaction with superoxide and the production of the highly reactive oxidant peroxynitrite. In addition, NO reacts with oxygenated hemoglobin to form methemoglobin. Although monitoring the concentration of methemoglobin is recommended if NO is administered for prolonged periods, significant methemoglobinemia is not commonly encountered during common clinical scenarios.

In a small series, Shah et al. (1994) noted that patients with CDH may be more resistant to the effects of inhaled NO, whereas Karamanoukian et al. (1994) noted that NO was effective in patients with hypoplastic lungs only after extracorporeal membrane oxygenation. In a study of patients treated with HFOV from birth, only 28% of those with severe pulmonary hypertension achieved reversal after NO. In general, most patients with intractable pulmonary hypertension plus lung hypoplasia do not have a predictable, dramatic response to NO. Nonetheless, because some patients do respond and the drug has limited toxicity in lower doses, NO is often used in infants with CDH who require therapy beyond gentle conventional ventilatory support (e.g., HFOV).

Even in the setting of respiratory failure without CDH, the long-term benefits of NO compared with other therapeutic interventions remain controversial. In a follow-up study of infants (with fewer and more than 34 weeks’ gestation, treated and not treated with NO) who had been enrolled in the INNOVA trial (15 neonatal units in the United Kingdom, Republic of Ireland, Finland, and Belgium), respiratory morbidity was similar when the impact of NO was analyzed. For example, wheezing and rehospitalization were common in both term and preterm infants who received and did not receive NO (Hoo et al., 2009). Clearly, neonates with severe respiratory compromise are at high risk for long-term pulmonary dysfunction.

Extracorporeal Membrane Oxygenation

A notable series of 400 patients were reported in two manuscripts by Azarow et al. (1997) in Toronto and Wilson et al. (1997) in Boston. ECMO was used as rescue therapy in Boston, and HFOV was used in Toronto. Survival in the two cities was nearly identical (53% and 55%). A 2008 Cochrane review concluded that in spite of short-term efficacy, improved long-term survival without major sequelae was not apparent with ECMO (Mugford et al., 2008). Thus, many centers now reserve ECMO as a rescue therapy for infants who have persistent preductal hypoxemia in spite of inotropic and ventilatory support (including HFOV and NO) (Bohn, 2002, 2006).

A common set-up for ECMO is a venoarterial circuit where the patient’s internal jugular vein and common carotid artery are cannulated. In this system, blood is drained by gravity from the right atrium, oxygenated through the membrane oxygenator, and returned to the patient through the arterial cannulae. During venovenous bypass, the patient’s blood returns to the membrane oxygenator by gravity, is oxygenated in the membrane oxygenator, and is then returned to the venous system. Thus, in venovenous ECMO, adequate systemic oxygen delivery depends on an effective cardiac output, whereas in infants undergoing venoarterial ECMO the bypass system can compensate for both pulmonary and myocardial dysfunction. Significant risks are associated with ECMO, including bleeding at surgical or chest tube insertion sites, intracranial hemorrhage, sepsis, hypertension, and brain death. Clearly, the underlying disease (e.g., meconium aspiration without pulmonary hypoplasia vs. CDH with pulmonary hypoplasia) influences the success rates of ECMO (Dalton and Thompson, 1992). In general, because the mortality and the likelihood of intracranial hemorrhage are higher in low–birth-weight infants, ECMO is limited to infants weighing more than 2 kg and with more than 35 weeks’ gestation, and to infants who have no evidence of prior intracranial hemorrhage.

The criteria for instituting ECMO vary, but guidelines generally include P(A-a)o₂ of greater than 600 mm Hg for more than 6 to 8 hours or an oxygen index (Fio₂ × mean airway pressure/Pao₂) of 51 for 5 hours. Nonetheless, no selection criteria appear to be accurate in predicting survival (Newman et al., 1990; Van Meurs, 1990; Steimle et al., 1994; Bohn, 2006; Mugford et al., 2008). In view of the improved survival with gentle ventilation (including HFOV), coupled with the significant morbidity associated with ECMO, ECMO intervention has been relegated a less central role in the setting of CDH.

Embryology

The embryogenesis of TEF/EA remains incompletely defined, but several theories have been proposed (Ioannides and Copp, 2009). It is known that the trachea and esophagus develop from the foregut in the first 4 to 5 weeks of gestation. One theory suggests that the respiratory system results from a rapid outgrowth from the foregut. That is, the tracheal primordium buds off the foregut and remains a separate structure during subsequent development. Another theory focuses on active growth of mesenchymal septum that divides the foregut into ventral (respiratory) and dorsal (gastrointestinal) structures. The septum has been considered to begin at the distal site (bronchopulmonary buds), but in fact such a structure has not been clearly identified in studies of tracheoesophageal development. Other theories seem to combine segments of each of these two theories, proposing that the trachea and esophagus separate as a result of foregut folds. Ioannides et al. (2002) suggested that the physical separation of the original foregut is a critical component of the organogenesis of the esophagus and trachea. On the other hand, differentiation of both respiratory and esophageal components usually does not occur in the setting of TEF/EA.

At the molecular level, aberrant signaling in the sonic hedgehog pathways and other regulatory genes has been linked to TEF/EA in several studies (Veraksa et al., 2000).

Hedgehog proteins are signaling glycoproteins involved in many processes of early development, including embryogenesis of the foregut as well as development of the craniofacial structures, heart, and great vessels. Of the multiple hedgehog proteins, only sonic hedgehog (Shh) is expressed in mammalian gut and lung. Mutants for Shh and for the Gli proteins (transcription factors) have been noted with tracheoesophageal malformations and various other well-described associated anomalies (e.g., VACTERL) (Kim et al., 2001).

In studies examining the expression of thyroid-transcription factor-1 (TTF-1) known to be specific to the respiratory tract, the distal esophagus in TEF/EA was proposed to be of tracheal origin. TTF-1 expression localizes to the lung bud but not to the esophagus early in gestation. TTF-1 is expressed in the fistula tract throughout gestation. Based on this work, the distal “esophagus” might be of embryonic lung origin. This finding, in part, could explain the pathophysiology and clinical findings of TEF/EA: poor esophageal motility, gastroesophageal reflux, esophageal stenosis, and pseudostratified columnar (respiratory epithelium) rather than squamous epithelium (esophageal epithelium) (Crisera et al., 1999a, 1999b). Other explanations for abnormal esophageal motor function in TEF/EA focus on the abnormal innervation of the esophagus. For example, dysplasia of both Meissner’s plexus (submucosal nerves) and Auerbach’s plexus (myenteric) occur along with an abnormal distribution of mitochondria, and high levels of vasoactive intestinal polypeptide and NO synthase (NOS) (Li et al., 2007).

Anatomy of TEF

The anatomic variations of TEF have been well described and, in most cases TEF and EA occur together (Types B, C, E) (Fig. 18-16). The most common lesion (more than 90% of cases) is type C, in which a fistula exists between the trachea and the lower esophageal segment at a point slightly above the carina, and the upper esophageal segment ends blindly in the mediastinum at the level of the second or third thoracic vertebra.

FIGURE 18-16 Types of congenital abnormalities of the esophagus. A, EA, no esophageal communication with the trachea. B, EA, upper segment communicating with the trachea. C, EA, lower segment communicating with the back of the trachea. More than 90% of all esophageal malformations fall into this group. D, EA, both segments communicating with the trachea. E, Esophagus has no disruption of its continuity but has a TEF. F, Esophageal stenosis.

(From Gross RE: The surgery of infancy and childhood, Philadelphia, 1953, WB Saunders.)

Prenatal Diagnosis and Clinical Presentation

TEF should be suspected in the presence of maternal polyhydramnios, which may result from esophageal obstruction that prevents the swallowing of amniotic fluid. Preterm labor may then develop as a result of the excessive intrauterine volume. However, in most cases polyhydramnios is a nonspecific sign and develops idiopathically; congenital anomalies account for only 10% to 20% of cases (Dashe et al., 2002). For example, polyhydramnios can develop secondary to impaired fetal swallowing because of abnormal central nervous system function, including weakness associated with neuromuscular dysfunction. Unfortunately, polyhydramnios and small or absent fetal stomach bubble are the most common ultrasound findings associated with TEF/EA. These have a low positive predictive value, and false positives are common (Houben and Curry, 2008). Similarly, when TEF accompanies EA, amniotic fluid can pass into the stomach from the trachea, usually enough to form a stomach bubble but not enough to prevent polyhydramnios. In addition, polyhydramnios is rarely identified before about 24 weeks’ gestation (Pretorius et al., 1987). A dilated blind-ending upper pouch of the esophagus (upper pouch sign) has been described on ultrasound, but as with MRI studies, it has not been deemed an accurate prenatal method for diagnosing TEF/EA (Houben and Curry, 2008). Overall, the prenatal detection rate is 40% to 50%. The significant incidence of coexisting abnormalities and syndromes (e.g., Trisomy 18) implies that an in utero diagnosis should precipitate karyotyping and an intense search for other structural anomalies. As with other severe congenital anomalies, prenatal diagnosis of TEF/EA may improve outcome by allowing optimal prenatal counseling and postnatal treatment. Unlike with CDH, supportive interventions for TEF/EA are less urgent and the implications of birth outside a major medical center are less risky, so prenatal diagnosis, although ideal, is of somewhat less critical significance.

Postnatal diagnosis depends on the specific anatomy of the TEF/EA, except in the case of an H-fistula, when the newborn infant exhibits excessive salivation, drooling, cyanotic spells, swallowing problems, and coughing, which is relieved to some extent by suctioning. The diagnosis of EA can be confirmed in the delivery room by the inability to pass a catheter down the esophagus into the stomach. When a radiopaque catheter is used, a radiograph reveals the catheter in the blind upper pouch. If a TEF is present, a plain radiograph of the chest and abdomen reveals air or gas bubbles in the stomach and intestines that have entered through the fistula (Fig. 18-17). Ultrasonography is important in the diagnosis of any associated cardiac, renal, or genitourinary abnormalities. Often, H-type fistulas escape diagnosis until an infant, child, or adult is evaluated for recurrent pneumonia.

FIGURE 18-17 Gastric distention in type C lesion, may require prompt relief. Note blindly ending esophagus on lateral view.

(Courtesy of Dr. Arnold Colodny, Boston, Mass.)

Preoperative Management

The ligation of a TEF is urgent, but not emergent, except in the setting of respiratory insufficiency severe enough to require ventilatory support. In that setting, the presence of a TEF and poor lung compliance often prevent delivery of adequate tidal volumes (ventilation escapes into the esophagus and stomach via the fistula). In such cases, the dilation of the stomach may add to the respiratory compromise by elevating the diaphragm and worsening pulmonary compliance. Preoperatively, several interventions are undertaken promptly to protect the lungs from aspiration pneumonia, including:

Intraoperative Management

Airway Management

The awake intubation technique is considered by some to be the safest approach to secure the airway in infants with TEF. It allows appropriate positioning of the endotracheal tube without positive pressure ventilation, as well as minimizes the risk of gastric distention from inspired gases passing through the fistula. Often, titrating small doses of fentanyl (0.2 to 0.5 mcg/kg) or morphine (0.02 to 0.05 mg/kg) allows intubation of the trachea without excessive hemodynamic stimulation or depression. An alternative induction technique includes an inhalation anesthetic with or without muscle relaxation and with cautious, gentle positive pressure ventilation as needed.

Evaluating the upper airway via rigid or fiberoptic bronchoscopy remains integral to the presurgical planning of TEF/EA repair. Although some surgeons and anesthesiologists consider the procedure a fundamental part of the preoperative or intraoperative assessment (e.g., ensure that only one fistula is present, assess for tracheomalacia and other anomalies, and position the endotracheal tube), others reserve bronchoscopy for cases where the clinical status suggests that anatomy must be further defined. In fact, fistulas may be difficult to identify via bronchoscopy. In addition, if the bronchoscopy is conducted to ensure a precise positioning of an endotracheal tube, this goal may be difficult to sustain after the bronchoscopy (even with careful marking of the endotracheal tube, attention to flexion and extension of the neck, and other precautions) because of subsequent repositioning for surgery and normal movement of the endotracheal tube during positive pressure ventilation and repeated suctioning during surgery. Furthermore, the TEF is often located close to the carina, and attempts to position the endotracheal tube below the fistula may precipitate one-lung ventilation (intentional or unintentional).

A key decision for the surgeon and anesthesiologist involves whether one-lung ventilation would facilitate the surgical procedure, and if so, appropriately select those patients who are likely to tolerate the technique (see Minimal-Access Surgery in the Neonate, p. 561). If tolerated, collapse of the lung may improve surgical exposure, but in some cases an unacceptable fall in oxygen saturation (in spite of high Fio₂ and continuous positive airway pressure [CPAP] to the nonventilated lung) requires a return to two-lung ventilation. Thus, it may be illogical to commit significant time to bronchoscopy, and in some cases doing so may needlessly prolong the operative time. Finally, even with initial ideal positioning of the endotracheal tube, in some patients ventilation through the fistula still occurs, especially if high peak airway pressures are required.

After the endotracheal tube is in its “assigned” position (i.e., one- or two-lung ventilation), end-tidal carbon dioxide and oxygen saturation should be monitored, and the stomach and chest should be auscultated to ensure that the lung(s) are adequately ventilated. Ideally, the stomach is not distended with inspired gases (i.e., ventilation does not enter the stomach via the fistula, or the fistula itself has not been intubated). Salem et al. (1973) suggested distal positioning of the endotracheal tube, with the bevel facing anteriorly and the posterior wall of the endotracheal tube occluding the fistula, but this maneuver is challenging to achieve and maintain.

Although precordial stethoscopes have been relegated to secondary rank because monitoring oxygen saturation and end-tidal carbon dioxide have become standards of care, a precordial stethoscope can contribute importantly to intraoperative care during repair of TEF. The precordial stethoscope can be positioned in the left axilla (i.e., during a right thoracotomy) to allow breath-to-breath monitoring of adequate ventilation to the dependent lung. Ideally, in infants with unstable cardiorespiratory status or congenital heart disease, an arterial catheter (umbilical or radial) should be available. In the setting of right-to-left shunting via a patent ductus arteriosus, pre- and postductal oxygen saturation monitoring with two pulse oximeters may provide critical data about shunting and pulmonary hypertension (see Congenital Diaphragmatic Hernia, p. 567).

Few patients have a gastrostomy at the time of presentation for surgery for EA/TEF, but if one is present, the gastrostomy tube could be submerged in a container of water after the trachea is intubated to observe for gas bubbles, which would be evident during ventilation of the fistula. If bubbling occurs, the endotracheal tube should be repositioned. Alternatively, the gastrostomy tube can be connected to a capnograph. When the endotracheal tube is proximal to the fistula, carbon dioxide might be detected. When the endotracheal tube is distal to the fistula, no expiratory gases would be detected.

A gastrostomy may serve as a low-resistance vent through which some of the tidal volume escapes, especially if high peak airway pressures are needed to ventilate noncompliant lungs and the chest wall. Although inserting a Fogarty catheter (or other ballooned device) retrograde via the gastrostomy or via a bronchoscope into the TEF has been reported, this technique is often impractical in the setting of small infants (Filston et al., 1982; Karl, 1985). Precise positioning of a catheter so that the balloon is occluding only the fistula is difficult to achieve, and even if the positioning is perfect on initial attempt, maintaining this precise position of the catheter for any length of time is almost impossible. Furthermore, displacement of the balloon can be disastrous (e.g., occluding the trachea). Finally, a high-pressure balloon may impinge on small pulmonary vessels or airways, compromising pulmonary blood flow or ventilation.

Once satisfactory ventilation is assured, the chest is opened and the lungs are retracted. Lung retraction (or one-lung ventilation) may dramatically change oxygenation and ventilation, especially in infants with respiratory dysfunction from immature lungs, pneumonia, or congenital heart disease. Intermittent release of pressure by the surgeon to allow reinflation of the lungs often improves oxygenation and ventilation. Blood clots or secretions may block the endotracheal tube, and repeated endotracheal suctioning may be required. Because the trachea is a soft structure in the newborn, surgical manipulation may kink the airway and further obstruct the airway. Thus, interference with adequate oxygenation and ventilation can occur as a result of the patient’s anatomy, operative positioning, and surgical manipulations. In many cases, the inspired concentration of oxygen and mechanical ventilation (sometimes manual ventilation) must be adjusted often, balancing the risks of oxygen toxicity and barotrauma with those of hypoxia. Of course, the surgeon and anesthesiologist must constantly communicate to minimize avoidable events.

Diaz et al. (2005) reported the incidence of intraoperative critical events (as well as overall survival) in open-surgical TEF/EA repair in patients with and without congenital heart disease (excluding patent ductus and or patent foramen ovale). In this report, all patients with ductus-dependent lesions were mechanically ventilated preoperatively, and the incidence of clinically important events was higher in this group, even when compared with infants who had less significant heart anomalies. Difficulty with intubation and oxygen saturation secondary to lung retraction, plugging of the endotracheal tube, and hypotension dominated the events. Perioperative mortality in the highest risk group was 23%, consistent with the survival rates (82% survival, even with a major cardiac lesion) as reported by Lopez et al. (2006), using a three-tiered risk assignment.

After the TEF is ligated and if primary esophageal anastomosis is planned, the anesthesiologist passes a catheter through the nose or mouth into the blind upper pouch to identify the upper esophageal structure. The surgeon passes a catheter into the lower part of the esophagus, and the anastomosis is made over the catheter. When the anastomosis is complete, the catheter is withdrawn just above the suture line, and the proximal end of the catheter is marked at the mouth. The distance from the mouth to the distal tip is noted to guide suctioning in the postoperative period.

Postoperative Management

Some full-term infants are extubated after simple ligation of a TEF, but this is rare. Tracheomalacia or a defective tracheal wall at the site of the fistula can cause collapse of the airway and preoperative aspiration may compromise pulmonary function. Treatment of postoperative pain, when combined with the host of other cardiorespiratory problems of the newborn, often requires a period of postoperative ventilation for at least 24 to 48 hours. Opioid infusions and regional anesthetic techniques have been successfully used for pain management. Most surgeons request that ventilation with a mask and bag be avoided for at least several days postoperatively, especially if the esophagus has been anastomosed. Infants who have had a “long-gap” atresia repaired often have tension at the anastomotic site that may be better protected with postoperative ventilatory support for 5 to 7 days. Deep sedation or neuromuscular blockade to eliminate spontaneous ventilation (i.e., eliminate negative intrapleural pressure transmitted to the anastomosis) are maintained as a function of the status of the infant, as well as bias of the surgeon or neonatologist. Babies whose lungs were contaminated preoperatively or intraoperatively, whose intraoperative course was complicated (e.g., trachea perforation), or whose underlying lung disease is associated with prematurity or other lesions are also mechanically ventilated postoperatively. In these cases, the approach to postoperative ventilatory support is often defined more by the pulmonary status than the surgical events. In part, the intraoperative anesthetic plan is tailored to meet the postoperative ventilatory requirements.

Outcomes

TEF/EA cannot be considered a simple anatomic problem that is easily cured by a surgical intervention. After surgery, structural and functional abnormalities commonly persist long term, even into adulthood. The design of the initial neonatal surgery must focus on the goal of achieving physiologically normal function, but this is difficult. To avoid the psychological overlay of “chronic disease,” early repair is obviously ideal. In reality, multiple significant long-term problems should be anticipated in survivors of TEF/EA.

Early complications primarily consist of anastomotic leaks and strictures. Some anastomotic leaks spontaneously seal; others may require intensive medical or even surgical treatment. Strictures at the site of esophageal anastomosis or the fistula may develop in as many as 30% to 40% of infants, but early lesions often respond to two or three dilations. More significant strictures often develop in response to gastroesophageal reflux (GER) and are associated with a history of significant anastomotic leaks in the immediate postoperative period and after repair of long-gap lesions.

GER is probably the most common and significant long-term problem after TEF/EA. GER is recognized in at least 40% of patients (35% to 58%), and is more common after anastomosis under tension, after gastrostomy, and after delayed primary repair (Kovesi and Rubin, 2004; Spitz, 2006). GER seems to correlate with many of the long-term problems associated with TEF/EA: strictures; pulmonary disease (e.g., recurrent aspiration pneumonia, reactive airways disease, and parenchymal disease); feeding problems and oral aversion; and poor growth. Follow up and evaluation of GER are critical for all survivors of TEF/EA.

Esophageal dysmotility/disordered peristalsis and abnormal lower esophageal sphincter function is recognized in at least 75% of patients with EA and in all children who have undergone delayed repair with interposition procedures. In childhood, choking episodes are common. Many children eat slowly and often compensate by drinking water and other liquids during meals. Choking episodes may be associated with apnea and cyanotic spells. Esophageal obstruction may develop, and some patients require removal of impacted material. Although dysphagia may persist into adulthood in 10% to 30% of patients, symptoms seem to dissipate after the first decade of life (Kovesi and Rubin, 2004).

Symptoms of dysmotility correlate with reduced intrinsic innervation (e.g., myenteric plexus or Auerbach’s plexus), disorganized muscle layers in the esophagus, tracheobronchial remnants, and a shortened intraabdominal segment of the esophagus (secondary to anastomosis). Feeding aversion develops more commonly in those with pure EA and in those who are exclusively fed via gastrostomy early in life. Feeding aversion, esophageal dysmotility, and GER may lead to growth failure. Furthermore, without aggressive medical or surgical therapy, esophagitis and eventually Barrett’s esophagus, a precancerous lesion, may develop. Approaches toward performing antireflux surgery (e.g., Nissen fundoplication) vary from center to center, but surgery clearly plays a role in treating severe GER. Some surgeons recommend aggressive surgical intervention within the first 6 to 24 months of life to minimize the secondary complications of severe GER.

Tracheomalacia and other abnormalities of the trachea also define long-term outcome after TEF/EA. Although common, tracheomalacia appears to be clinically significant in only about 10% of patients (Spitz, 2007). Tracheomalacia tends to improve after the first 3 to 5 years of life, and is rare in isolated EA. Tracheomalacia is generally identified at or just above the site of the TEF, and therefore is most prominent in the lower one third of the trachea. The trachea seems to have an excessive membranous portion that is prone to instability. A brassy cough (“TEF cough”) is common in infants and children but rarely persists into adulthood. When symptoms are severe, stridor may develop. Treatment for tracheomalacia is required only in patients with severe symptoms (e.g., apnea, recurrent pneumonia, or worsening stridor) and usually involves an aortopexy (i.e., suturing the aorta to the posterior surface of the sternum), which draws the anterior trachea forward as the posterior aspect of the aorta adheres to the trachea. Recently, a stenting procedure has been effective in treating tracheomalacia and may be less invasive than aortopexy (Kovesi and Rubin, 2004).

In addition to the major structural abnormalities, the epithelium at the site of the TEF (but at times in all the major airways) can be abnormal, lacking both cilia and goblet cells, and thereby decreasing mucociliary clearance (Goyal et al., 2006). This lesion may be exacerbated by or be secondary to GER. Rarely, secretions may be retained to the point of inducing tracheal metaplasia. A blind pouch at the site of the former TEF can be a nidus for trapping secretions.

Recurrent upper and lower respiratory infections occur in 35% to 75% of infants and children, especially throughout the first 3 to 4 years of life, and they may be related to GER or impaired mucociliary clearance secondary to the abnormal tracheal epithelia (Dudley and Phelan, 1976; Spitz, 2007). Wheezing commonly accompanies these infections (Chetcuti and Phelan, 1993). Even with decreased symptoms over time, pulmonary function studies 6 to 37 years after repair show a high incidence of obstructive and restrictive forms of lung disease (Chetcuti et al., 1992; Robertson et al., 1995). Specifically, abnormal expiratory flow rates (e.g., low forced expiratory volume at 1 second [FEV₁] in 25%, low forced expiratory flow 25%-75% [FEF_25%-75%] in 14%), reduced lung volume (e.g., low vital capacity in 15%), and airway hyperreactivity have been documented in survivors.

Open posterolateral thoracostomy in infants has been associated with musculoskeletal malformations, including “winged” scapula and chest-wall asymmetry (see Minimal-Access Surgery in the Neonate, p. 561). Scoliosis has been attributed to both the thoracostomy and associated vertebral anomalies. Scoliosis would predictably reduce total lung capacity, so in survivors of TEF/EA, compromise may be exaggerated when a structural chest-wall deformity is added to other sources of pulmonary dysfunction.

As with other congenital anomalies, survivors of TEF/EA encounter lifelong disorders that require multidisciplinary, long-term supportive care and meticulous follow-up care to minimize complications induced by and secondary to their primary lesions.

Pathophysiology

NEC is a paradoxical disease. Infants with milder disease usually recover with outcomes similar to those of other infants of the same gestational age, but severely affected infants who require surgery have high mortality, and those who survive usually develop significant gastrointestinal and neurodevelopmental morbidity. Although miniepidemics do occur, most cases of NEC are sporadic and cannot be correlated with any specific infectious agent. The disease only occurs postnatally (not in stillborns), and it is rare in full-term infants and infants who have never been fed (Hsueh et al., 2002). The full-term infant who does develop NEC tends to display symptoms and signs in the first 1 to 3 days of life, sometimes before feeding has been initiated. There is usually a history of a hypoxic and ischemic events such as perinatal asphyxia, respiratory distress, or congenital heart disease. In contrast, the preterm infant tends to develop symptoms and signs after 2 to 3 weeks of life after feeding has been initiated, often without any preceding dramatic cardiorespiratory event.

Intestinal mucosal injury from ischemia caused by reduced mesenteric blood flow is commonly proposed as a physiologic mechanism for NEC. Mesenteric blood flow may be compromised by a decreased cardiac output in the presence of fetal asphyxia, a patent ductus arteriosus, apnea or bradycardia, heart failure, arrhythmia, severe cardiorespiratory instability, or hypoxemia. Immature regulation and autoregulation of the mesenteric circulation in response to a primary event (e.g., apnea, or patent ductus arteriosus) probably factors into the pathogenesis of NEC. Specific clinical events that seem to contribute to the pathogenesis of NEC include enteral feeding of small preterm infants, use of a hyperosmolar formula, bacterial infection, intestinal dysfunction (e.g., feeding intolerance or slow transit), infection, polycythemia, congenital heart disease, and a history of umbilical arterial catheterization or exchange transfusion.

The most common anatomic site for NEC is the ileocolic region. However, NEC is often discontinuous, with patchy distribution in both the small and large intestines in as many as 50% of cases (Fig. 18-19). Large bowel involvement is most common in the full-term infant. Perforations often are multiple and although commonly identified at the junction of a necrotic and normal bowel, perforations are also found within the affected areas.

The primary pathologic findings in NEC are coagulative or ischemic necrosis, as well as inflammation. The inflammatory response seems to be unique in that abscesses do not form, as seen in inflammatory bowel disease, infectious colitis, or acute arterial occlusion (Hsueh et al., 2002). The combination of ischemia and bacteremia seems to underline the pathophysiology of the disease. For example, NEC does not evolve after an episode of vascular injury in utero, when the bowel is sterile (Musemeche et al., 1986). Instead, an intestinal atresia or stenosis may develop. The formation of gas bubbles (pneumatosis intestinalis) reflects fermentation of an intraluminal substrate by bacteria; however, NEC is not associated with a specific organism or with particularly virulent bacteria. A wide range of organisms have been identified in the stool of infants with NEC, some who also have a bacteremia with the same organism: Escherichia coli; various strains of Enterobacter, Klebsiella, and Pseudomonas; coagulase-negative Staphylococci; and others. Viral agents have been associated with NEC but are not considered a major infectious etiology.

Classically, although the hypothesis for the etiology of NEC has focused on circulatory insufficiency or infection, the pathophysiology of NEC in the preterm infant also involves an exaggerated inflammatory response in the setting of abnormal bacterial colonization, an inadequate epithelial barrier (e.g., defects in mucus or immature tight junctions), an immature intestinal motility (e.g., disordered peristalsis), and an immature gastrointestinal immunity (Hunter et al., 2008). In fact, the immature gastrointestinal tract is characterized by inadequate secretion and production of mucin, which may predispose it to increased permeability to and adherence of bacteria. The immature immunity of the preterm intestine increases the susceptibility of an inadequate barrier to injury from uncontrolled inflammatory responses.

Activation of inflammatory and apoptotic pathways and antiapoptotic mechanisms relies on the interaction of systems in the invading organism with specific receptors in the host. So-called microbial-associated molecular patterns (MAMPs) interact with a specific pattern-recognition receptor (PRR) on host cells. A well-known PRR is the human toll-like receptor 4 (TLR4), a receptor for lipopolysaccharide (LPS), a substance in the cell walls of some bacteria. Of relevance to the preterm infant, hypoxia and exposure to infant formula may exaggerate expression of this receptor. Adult human intestine is characterized by minimal TLR4 expression, but expression in fetal intestine is high. The overexpression of the normal TLR4 receptor may predispose the immature intestine to enhanced proinflammatory injury; interaction with MAMPs of pathogenic bacteria leads to apoptosis and inhibition of healing from injury (Leaphart et al., 2007). Apoptosis of the intestinal epithelia has been noted in human infants with NEC (Ford et al., 1997). Thus the preterm infant may be predisposed to NEC via an inability to maintain adequate inflammatory responses while avoiding overactivation of proinflammatory responses (e.g., via TLR4 receptors), which lead to injury.

Although multiple inflammatory markers and various cytokines (IL-8, IL-10, liver and intestine fatty acid binding protein) have been associated with NEC, no single marker has been identified that allows early diagnosis and management of NEC (Young et al., 2009). Several “models” of NEC, emphasizing the role of inflammatory and vasoactive mediators, platelet-activating factor (PAF), and tumor necrosis factor-α (TNF α) have been developed (Fong et al., 1990; Sun and Hsueh, 1991; Sun et al., 1996; Wand et al., 1997; Tan et al., 2000). However, no experimental approach has been ideal, because models for this disease do not exactly mimic the clinical disease (Sodhi et al., 2008).

Nonetheless, by correlating clinical studies to experimental models, it appears that similar to sepsis, NEC is driven by the pathway of activation of cytokines, prostaglandins, and NO, which interact to initially induce intestinal injury via polymorphonuclear neutrophil (PMN) activation and PMN adhesion (Fig. 18-20). PAF and TNF α seem to play a central role in inducing intestinal injury.

FIGURE 18-20 Schematic representation of the pathophysiology of NEC. GI, Gastrointestinal; IL-1, interleukin 1; PAF, platelet-activating factor; TNF, tumor necrosis factor.

One theory is that PAF induces cell injury after inducing production of various reactive oxygen species (ROS), but the precise mechanism is unclear. Of note, the xanthine dehydrogenase/xanthine oxidase system is abundant in the intestine and seems to generate superoxide during ischemia. Elevated levels of PAF have been measured in infants with NEC.(Rabinowitz et al., 2001). In addition, premature infants have low levels of the PAF-degrading enzyme acetylhydrolase (Caplan et al., 1990). Exactly how other mechanisms included in the pathogenesis of NEC (e.g., immature immunologic mechanisms, abnormal patterns of bacterial overgrowth, and deficient mesenteric blood flow regulation) interact with the intense inflammatory response is not completely understood. Finally, differences in the content of sialic acid and N-acetylglucosamine residues of the mucosa may affect anatomy and function of the microvilli, leading to certain types of bacterial colonization, bacterial adhesion, and eventually, permeation of the gastrointestinal tract (Claud and Walker, 2001).

Another pathway that plays a critical role in the pathophysiology of NEC centers on the interaction of NO, prostaglandins, and epidermal growth factor (EGF) in regulating epithelial function. Prostaglandins function in maintaining tight junctions. Normal low levels of NO regulated by endothelial nitric oxide synthase (NOS) activity enhance blood flow to the mucosa and maintain microvascular flow. However, high levels of NO in response to stimulation of inducible NOS may cause cytotoxicity as a result of damage to the epithelial barrier (disrupting epithelial tight junctions) and excessive apoptosis, as seen in early NEC (Ford et al., 1997; Chokshi et al., 2008). Thus, although NO seems to be critical in maintaining mucosal blood flow, high levels may have injurious effects, disrupting the tight junctions of the epithelium and inducing abnormal apoptosis. In addition, endothelin (a vasoconstrictor) is released in response to various pathologic conditions, such as NEC. EGF seems to induce migration and proliferation of epithelial cells in response to injury, but levels of this mediator are low in some preterm infants, specifically those with NEC. The cytoprotective effect of EGF, which is found in high levels in breast milk, may eventually be incorporated into nutritional strategies to prevent and treat NEC (Guner et al., 2008b; Nair et al., 2008).

Finally, various genetic factors (i.e., prematurity, respiratory distress syndrome, and periventricular leukomalacia) may interact either directly or indirectly in the development of NEC. For example, recent analyses of preterm twins uncovered a familial origin for NEC, as well as for intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD) (Bhandari et al., 2006). That is, 52% of the variance for NEC could be explained by genetic and shared environmental factors. The TLR4 gene and its products have been reported to be higher in an animal model of NEC, and the risk for NEC has been associated with a specific genotype of interleukin (CPS1 T1405N polymorphism, IL-18[607]) (Jilling et al., 2006). The incidence of the genotype was significantly higher in those with stage III compared with those who had stage I or II NEC (Moonen et al., 2007).

The observation that inflammation is the result of NEC, rather than the cause, has prompted a variety of interventions aimed at enhancing epithelial integrity, such as human milk feeds, various amino acid supplementations, and various probiotics, prebiotics, and postbiotics (Lin et al., 2008a). Although a specific role for any agents other than human milk remains unclear, any introduction of pharmacologic agents may have dramatic effects on other therapeutic agents used in the NICU and the operating room.

Preoperative Management

A typical infant with NEC is a preterm baby weighing less than 1500 g and often less than 1000 g. Some infants have had perinatal asphyxia or other respiratory complications in the early postnatal period. Prenatal complications associated with NEC may include events that are associated with asphyxia or prematurity, such as premature rupture of the membrane, placenta previa, maternal sepsis, toxemia, breech delivery, or cesarean section for fetal distress.

In “classic NEC,” gastrointestinal signs appear between the first and tenth days of life in more than 90% of cases, and they include abdominal distention, retained gastric secretions and high gastric residuals after feeding (may be bile-tinged), vomiting, bloody or mucoid diarrhea, and occult blood in stools. Figure 18-21 shows the probability of a patient experiencing intramural gas, bloody stools, or portal venous gas when diagnosed with NEC vs. gestational age. In some cases, these signs are preceded by nonspecific abnormalities such as apnea, bradycardia, thermal instability, or lethargy, with a gradual development of gastrointestinal problems. In other infants, the course is fulminant with rapid onset of abdominal signs with acidosis, hemodynamic instability, and disseminated intravascular coagulation (i.e., septic shock), often with bowel perforation. In infants with acute onset of advanced NEC, surgical intervention is emergent. Many infants with obvious NEC have decreased platelet counts (50,000 to 75,000/mm³ or lower) and prolonged prothrombin and partial thromboplastin times. Some infants have leukocytosis with a high percentage of bands, but others develop profound leukopenia and neutropenia. Early in the disease process, abdominal radiographs may reveal dilated, fixed (adynamic ileus) loops of bowel, but in advanced NEC, pneumatosis (intramural air in the intestine), gas in the portal venous system, and pneumoperitoneum develop.

FIGURE 18-21 Probability curves for symptoms of bloody stools, intramural gas, or portal venous air in babies with NEC.

(From Sharma R et al.: Clinical manifestations of rotavirus infection in the neonatal intensive care unit, Pediatr Infect Dis J 21:1099, 2002.)

Without evidence of intestinal necrosis or perforation, the initial treatment for NEC is nonoperative. Decompressing the stomach with an orogastric tube, no feeding, administering fluid and electrolyte therapy (including parenteral nutrition), delivering broad-spectrum antibiotics after obtaining cultures of blood and urine, and correcting hematologic abnormalities are the main components of medical therapy. Supportive hemodynamic therapy, including inotropic agents and steroids, may be needed to treat septic shock. Bowel perforation is the only generally accepted indication for surgery, but relative indications may include peritonitis, air in the portal system, bowel wall edema, ascites, and a progressively deteriorating cardiorespiratory status (Box 18-2).

The role for primary peritoneal drainage in the surgical treatment of NEC and IP has been scrutinized. Peritoneal drainage was initially proposed as a method to treat the most unstable infants with NEC, usually ELBW infants (Ein et al., 1977). Some have reported that this intervention provides advantages in the ELBW infants but not in those weighing more than 1500 g (Azarow et al., 1997). Theoretically the ELBW infant may benefit from such a temporizing procedure that would allow resuscitation and stabilization. However, the effectiveness of peritoneal lavage in “buying time” for an infant to achieve hemodynamic, acid/base, and hematologic stability is actively debated.

In a prospective cohort of 16 NICUs (NICHD Neonatal Research Network), the overall in-hospital mortality associated with NEC in this group of ELBW infants was 49%. Poor prognosis was associated with lower gestational age and birth weight, preoperative vasopressors, and HFOV support. Mortality was 55% for patients with NEC and 38% for those with IP. However, in this study, initial treatment with a peritoneal drain vs. laparotomy was at the discretion of the surgeon (i.e., subject to bias), therefore mortality could not be accurately correlated with surgical management (Blakely et al., 2005). Subsequently, a multicentered randomized trial compared outcome of primary peritoneal drainage with laparotomy in another group of preterm infants. In this study, the infants were lighter than 1500 g and had fewer than 34 weeks’ gestation (compared with a weight of less than 1000 g in the earlier study), who had free intraperitoneal air either on abdominal radiograph or by clinical examination (by both the surgeon and neonatologist), or had stool, bile, or pus on paracentesis. Because of clinical deterioration, 5 of the 55 (9%) in the peritoneal drainage group underwent laparotomy. Because of stricture, obstruction, or feeding intolerance, another 16 (29%) underwent laparotomy. Mortality at 90 days was similar (peritoneal drainage, 34.5%; laparotomy, 35.5%), as was dependence on intravenous nutrition (peritoneal drainage, 47.2%; laparotomy, 40%). Length of hospitalization did not differ between the groups. Of note, the investigators did not uncover a difference in mortality when outcome was stratified according to gestational age subsets (younger than 24, 25 to 26, 27 to 30, and 30 to 34 weeks’ gestation) (Moss et al., 2006).

In a multicenter randomized trial including 31 NICUs in 13 European countries, ELBW infants with pneumoperitoneum on radiograph either underwent laparotomy or placement of an intraperitoneal drain. Survival at 6 months was similar (51.4%, intraperitoneal drain; 63.6%, laparotomy). In contrast to Moss et al.’s (2006) study, 74% of infants underwent laparotomy between 0.4 and 21 days. These investigators suggest that peritoneal drainage is ineffective as a temporizing measure or as a definitive treatment. That is, if a drain is placed, a laparotomy should be performed soon afterward (Rees et al., 2008).

The preoperative assessment of infants with NEC focuses on evaluating and correcting the respiratory, circulatory, metabolic, and hematologic disorders. Trends in blood gases, glucose, electrolytes, hematocrit, and coagulation status (including platelet count) should be noted. Increased colloid and crystalloid therapy may be needed in hypovolemic infants with massive third-space fluid losses, bleeding, and disseminated intravascular coagulation. Electrolyte disturbances (including acidosis) are exaggerated in the setting of acute renal failure, which may evolve secondary to shock or abdominal compartment syndrome.

Respiratory support often must be increased as abdominal distention or metabolic and respiratory acidosis worsen. Thus, the anesthesiologist must decide whether a ventilator from the NICU would provide advantages, whether manual ventilation is necessary (possible need for more personnel), or whether the ventilator associated with the anesthesia machine is adequate. If the infant’s status is so unstable that transport to the operating room seems too risky, a surgical procedure in the NICU should be considered.

Intraoperative Management

Intraoperative monitoring ideally includes arterial and central venous cannulae for continuous monitoring and blood gas and metabolic analysis. Fresh frozen plasma, platelets, and red blood cells may be administered early in surgery in response to clinical and laboratory evidence of coagulopathy. Inspired oxygen concentration should be adjusted to produce an arterial oxygen saturation of 85% to 90%. Nitrous oxide must be avoided, especially in the presence of free air in the gastrointestinal and portal venous systems.

Potent inhalation agents are often poorly tolerated and often are only introduced in low concentrations to supplement narcotics. High doses of fentanyl (e.g., 50 mcg/kg) or other narcotic can be slowly delivered, as tolerated hemodynamically, or delivered as an infusion to provide infants with analgesia and amnesia. Neuromuscular blocking agents facilitate surgical interventions. Inotropic agents are often needed to support the cardiovascular system when fluid therapy alone fails to maintain adequate perfusion. Glucose intolerance is common in septic infants. In all cases, fluid that does not contain glucose should be delivered to provide crystalloid resuscitation. Of note, the high glucose content of red blood cell products may eliminate any need for other glucose delivery. Ideally, glucose can be measured intraoperatively, especially in procedures longer than 45 to 60 minutes that require large quantities of blood, and in infants with major glucose instability preoperatively.

Because of the large fluid requirements, hypothermia is a common intraoperative complication. The operating room and infused fluids are warmed to assist in maintaining adequate body temperature. In the surgical treatment of NEC, necrotic bowel is resected, and usually, the marginally viable ends are exteriorized. The cardinal principles of surgery for NEC are to excise all necrotic bowel but preserve as much bowel length as possible by leaving “marginal” appearing bowel in place, decompressing the bowel, and removing pus, stool, and necrotic debris from the peritoneal cavity. Preserving the bowel may require multiple segmental resections and second-look operations to reassess bowel viability. Select patients may tolerate resection and primary reanastomosis. Bowel strictures may develop within days to months after the initial surgery, often necessitating further surgical intervention. Often enterostomies are closed within 4 weeks to 6 months after the initial surgery.

Postoperative Management

Postoperatively, mechanical ventilation and cardiovascular support are universally required in these infants. Central venous parenteral nutrition is essential after sepsis is controlled and metabolic stability is established.

Outcome

Mortality from NEC is high, ranging between 10% and 30% (or higher in surgically treated ELBW infants). Regardless of treatment (medical or surgical), approximately 30% of patients develop strictures. Recurrence of NEC is rare. Infants who initially respond to placement of an intraperitoneal drain may eventually require surgery, but some do not. Infants who develop an isolated intestinal perforation may be distinct from those with NEC and have a more benign course. The hospital course for preterm infants with NEC can be prolonged and characterized by repeated episodes of sepsis and long-term requirements for intravenous alimentation as enteral feedings are introduced slowly.

A devastating complication in survivors of NEC is short bowel syndrome, which develops in as many as 20% to 25% of surgically treated patients (Rees et al., 2008). In these cases, the bowel resection is so extensive that the infant is unable to establish enteral feedings, implying a need for long-term intravenous alimentation despite its high-risk morbidity (e.g., sepsis and hepatic failure). Although site and amount of resection seem to correlate with the development of short bowel syndrome, diffuse mucosal injury may persist in areas of bowel injured by NEC but not resected. Current interventions include intestinal lengthening procedures or even bowel transplantation. The use of tissue-engineered small intestine is under intense investigation (Guner et al., 2008b). Evidence suggests that breast milk decreases the incidence of NEC and its complications. The roles for treatment with probiotics, nonspecific (steroids, indomethacin, magnesium, copper) and specific antiinflammatory agents (PAF receptor blockers), growth factors (erythropoietin), or antibiotics remain speculative (Millar et al., 2003).

Beyond the gastrointestinal outcome, the risk for long-term neurodevelopmental problems was first reported in 50% of survivors almost three decades ago (Stevenson et al., 1980). Deficits in psychomotor and mental development have been confirmed in the VLBW survivors of NEC, especially those who have undergone surgery (Vohr et al., 2000; Stoll et al., 2004; Hintz et al., 2005; Rees et al., 2007; Schulzke et al., 2007). The risk for those treated surgically is approximately twice that of those treated medically. In fact, those treated medically have outcomes similar to those of the same gestational age without a history of NEC (see Chapter 17, Neonatology for Anesthesiologists).

Prevention strategies are now focused on feeding techniques and manipulating gut flora. However, definitive approaches for introducing probiotics, various amino acids, or agents such as epidermal growth factor have not been established. Clearly, identifying infants at risk to prevent progression to a disease that requires surgery may be critical in minimizing gastrointestinal and neurodevelopmental complications from NEC.

Intraoperative Management

Anesthetic requirements vary depending on the severity of the abdominal distention and complexity of the surgery: a simple perineal anoplasty, a temporary colostomy, or an extensive abdominoperineal repair. Anorectal malformation can be classified by the presence or absence of a fistula and by the fistula’s location (Pena and Hong, 2000) (Box 18-3). Perineal fistulas in both male and female infants represent the simplest defect, and treatment generally consists of an anoplasty performed in the neonatal period. Imperforate anus with no fistula is the least common, presentation, whereas rectourethral fistulas are the most common, with the exception of the perineal fistula. The standard surgical approach has generally involved the following three steps:

Surgical trends, however, have been aimed at performing the primary repair without a colostomy. The primary repair involves a posterior surgical approach. Laparoscopic techniques have been used to assist in the pull-through technique (Georgeson, 2000).

Anesthetic considerations for neonates with intestinal obstruction from any etiology include airway management of a full stomach, assessment of fluid status, correction of electrolyte disturbances, treatment of sepsis, and cardiorespiratory evaluation. Marked abdominal distention secondary to intestinal obstruction can impede diaphragmatic excursion and impair ventilation. Gastric (or lower intestinal) contents often are incompletely emptied with nasogastric suction, so that the risk of aspiration is significant, especially during induction of general anesthesia.

Intubation of the trachea of infants with an apparently normal upper airway can be accomplished with an awake or rapid-sequence technique. If the anesthesiologist suspects that the upper airway will be difficult to visualize, the usual airway precautions should be observed. That is, neuromuscular blocking agents, deep sedation, and general anesthesia are avoided and an awake technique is attempted. Supplemental support systems for the difficult airway (e.g., neonatal bronchoscopes, light wand, and LMA) should be available (see Chapter 10, Equipment).

Anesthesia during the surgery can include potent inhalation anesthetics, narcotics, or both. In general, nitrous oxide is avoided because of the risk for increasing bowel distention. Intermediate-acting or long-acting nondepolarizing muscle relaxants often improve surgical conditions at lower inhaled anesthetic concentrations. If early postoperative extubation is planned, narcotics should be judiciously administered, but in many cases postoperative mechanical ventilation is required.

Imperforate anus is usually recognized early in the postnatal period, and massive distention may not develop in the group of infants without total bowel obstruction. Therefore the complications associated with intestinal obstruction are minimized, as are the complications from bowel ischemia, third-space fluid loss, electrolyte disturbances, and sepsis. Imperforate anus without a fistula can be associated with the development of total intestinal obstruction in utero, leading to severe abdominal distention, bowel perforation, sepsis, or a combination. In addition, other congenital anomalies often have a dramatic effect on the management of these infants. For example, imperforate anus is associated with TEF, renal anomalies, and heart disease (VACTERL Association).

During surgery, the management of fluids, blood replacement, and electrolyte delivery are similar to the principles discussed for NEC and for intestinal obstruction. As with any intraabdominal surgery in the newborn, a major challenge is maintaining an adequate intravascular volume. The presence of radiopaque contrast agents, bowel manipulation, and peritonitis increases third-space fluid requirements. In such cases, 10 mL/kg per hour (or more) of isotonic saline solution or colloid is generally needed intraoperatively. Monitoring urine output, quality of heart tones, heart rate, and blood pressure is a basic requirement to assess continuing fluid needs. Invasive monitors such as an arterial catheter and a CVP catheter generally are reserved for those with marked cardiorespiratory instability.

Postoperative Management

The preoperative and intraoperative courses and the effects of associated congenital anomalies set the stage for the postoperative course. Many infants require postoperative ventilatory support, total parenteral alimentation, cardiovascular support, and treatment of sepsis. The function and recovery of the gastrointestinal system vary enormously among infants with imperforate anus and seem to be related to whether the lesion is isolated and whether the complications of total bowel obstruction have developed.

Outcome

Intestinal obstruction has historically been one of the major causes of death after neonatal surgery. With more skilled pediatric management and the development of parenteral alimentation, mortality is now limited primarily to infants whose condition is diagnosed late and who require extensive excision of the small and large bowels. Long-term complications from anorectal malformations, especially a high imperforate anus, can be lifelong and involve sequelae related to fecal soiling, constipation, and sexual inadequacy.

Duodenal Obstruction

The incidence of duodenal obstruction in the neonate is 1:10,000 to 1:40,000 births and is often associated with other congenital anomalies such as Down syndrome, cystic fibrosis, renal anomalies, intestinal malrotation, and especially midline defects such as esophageal atresia and imperforate anus. An intraluminal diaphragm, a membranous web, or an annular pancreas can also be associated with obstruction of the duodenum. The degree of obstruction varies from severe or complete atresia to incomplete obstruction or stenosis (Mustafawi and Hassan, 2008). Air contrast films reveal a dilated stomach and a dilated proximal duodenum, resulting in the “double-bubble” appearance (Fig. 18-22).

FIGURE 18-22 Duodenal obstruction. A, The classic plain-film sign of duodenal atresia. B, The endoscopic view of a duodenal web.

(From Barksdale EM, Jr: Surgery. In Zitelli BJ, Davis HW, editors: Atlas of pediatric physical diagnosis, ed 4, St. Louis, 2002, Mosby, p 572.)

Infants with complete obstruction exhibit copious vomiting of bile or bile-stained gastric contents and minimal abdominal distention. The infant may or may not pass meconium in the first day of life. Infants who have incomplete obstruction have intermittent bile-stained vomiting and usually pass meconium. A delay in the treatment of this condition can result in dehydration, weight loss, and hypochloremic alkalosis.

Jejunoileal Atresia

Jejunoileal atresia causes complete obstruction in 1:5000 live births. In contrast to duodenal atresias, jejunoileal atresias are associated with few other anomalies. Prematurity is associated with 50% of cases, polyhydramnios with 25%, and cystic fibrosis with 20%.

The etiology of jejunoileal atresia is uncertain but is thought to involve intrauterine vascular accidents. Four types of atresia have been identified (Fig. 18-23). Type I is not a true atresia but actually is a membranous obstruction of the lumen in an intestine of otherwise normal length and diameter. Type II, a true atresia, consists of two blind ends that are often connected by a fibrous strand with slightly shortened intestinal length. Type IIIA lesions have blind ends separated by a mesenteric defect. The type IIIB lesion is also called “apple peel” or “Christmas tree” deformity and consists of a long jejunal atresia with a very short remaining ileum. The superior mesenteric artery is missing, and the blood supply to the ileum is by retrograde flow via a branch of the ileocolic artery. Type IIIB lesions are rare but have a very high mortality rate. Type IV lesions involve multiple intestinal atresias.

FIGURE 18-23 The various types of jejunal atresia.

(From Grosfeld JL: Jejunoileal atresia and stenosis. In Welch KJ et al., editors: Pediatric surgery, ed 4, Chicago, 1986, Year Book.)

Meconium Ileus

Meconium ileus is a luminal obstruction of the distal small bowel by abnormal meconium. Meconium ileus is found almost exclusively in patients with cystic fibrosis, but only 20% of patients with cystic fibrosis have meconium ileus. Because meconium ileus manifests in the neonatal period, respiratory symptoms of cystic fibrosis generally are not present. Both surgical and nonsurgical therapies are used to relieve the obstruction. The nonsurgical approach involves diatrizoate meglumine enemas, which can be both diagnostic and therapeutic. Diatrizoate meglumine, a water-soluble contrast agent, loosens and softens the meconium, thereby facilitating its evacuation. When medical management does not succeed, surgery is performed. After the peritoneal cavity is entered and the obstruction is located, diatrizoate meglumine or acetylcysteine is injected into the bowel lumen and allowed to mix with the meconium. When the meconium has loosened, it is massaged into the colon. If this is unsuccessful, an enterostomy is performed, and the sterile meconium is evacuated from the small bowel (Fig. 18-24).

FIGURE 18-24 Thick tenacious meconium in a patient with meconium ileus.

Malrotations and Volvulus

Malrotations are rare and generally result from abnormalities in the rotation of the bowel, which usually occur during the tenth to twelfth weeks of gestation. Consequently, areas of ischemia and atresia develop, along with volvulus, resulting in strangulation of bowel, bloody stools, abdominal distention, peritonitis, and hypovolemic shock (Fig. 18-25). Nonrotation or malrotation is twice as common in boys as in girls and often produces symptoms of intestinal obstruction in the first 1 to 2 months after birth. In other cases, symptoms do not appear until later, even adulthood. The diagnosis of malrotation cannot be excluded if diarrhea is present, if clinical symptoms are mild, or if x-rays are normal (Miller et al., 2003). In patients with intestinal malrotation without volvulus, surgery often involves Ladd’s procedure, which can be performed either open or laparoscopically (Draus et al., 2007). Malrotations are often associated with duodenal stenosis or atresia or small intestinal atresia, as well as with cardiac, esophageal, urinary, and anal anomalies. Major anatomic defects of the abdominal wall (e.g., gastroschisis and omphalocele) and CDH universally have intestinal malrotation or nonrotation.

FIGURE 18-25 Malrotation with midgut volvulus without ischemia (A) and with infarction (B).

(From Barksdale EM, Jr: Surgery. In Zitelli BJ, Davis HW, editors: Atlas of pediatric physical diagnosis, ed 4, St. Louis, 2002, Mosby, p 572.)

The operative procedure for a nonrotation complicated by volvulus consists of untwisting the intestine and then a short intraoperative period of observation to evaluate recovery of vascular perfusion to the involved intestine. Areas of frank necrosis are excised, and a primary anastomosis is performed. If the patient has peritonitis or poor perfusion of the remaining bowel, proximal and distal enteral stomas are formed. The surgical operation, Ladd’s procedure, involves the following five steps: eviscerating the midgut, derotating the volvulus in a counterclockwise direction, lysis of Ladd’s peritoneal band, appendectomy, and placing the caecum in the left lower quadrant.

Children with less than 30 to 40 cm of small bowel generally develop short-gut syndrome and ultimately require TPN. If marginal areas of intestinal viability are present at the operation, they may be left unresected in the hope that postoperative resuscitation improves the perfusion. Under these circumstances, a “second-look” operation usually is performed 24 to 48 hours later.

Embryology and Diagnosis

The tumor is derived from pleuripotential cell lines and contains components consisting of all three germ layers. Perinatal mortality is high when the tumor is diagnosed antenatally. Postulated causes of death include high output cardiac failure, preterm delivery secondary to polyhydramnios, anemia from hemorrhage into the tumor, dystocia, and tumor rupture.

Sacrococcygeal teratomas receive their blood supply from the middle sacral artery and branches of the internal iliac artery. A steal syndrome can shunt blood from the placenta and lead to high output cardiac failure and hydrops. Approximately 2% to 10% of sacrococcygeal tumors are malignant before the infant reaches 2 months of age, and 50% are malignant by 1 year of age. Serum α-fetoprotein levels are elevated in 70% of children with malignant tumors.

Sacrococcygeal tumors generally arise from the tip of the coccyx and vary with the amount of internal and external extension. These tumors are classified into four types according to their locations (Box 18-4; Fig. 18-26).

FIGURE 18-26 A, In utero diagnosis by MRI. B, Sacrococcygeal teratoma.

(From Avni FE, Guibaud L, Robert Y, et al.: MR imaging of fetal sacrococcygeal teratoma: diagnosis and assessment, Am J Roentgenol 178(1):179–183, 2002.)

Intraoperative Management

Surgical treatment involves complete resection of both the tumor and coccyx. Failure to remove the coccyx completely can result in local recurrence. In utero treatment options include open fetal surgery, endoscopic laser ablation, and radiofrequency ablation (Bullard and Harrison, 1995; Hecher and Hackeloer, 1996; Paek et al., 2001) (see Chapter 19, Anesthesia for Fetal Surgery).

Anesthetic management for removal of tumors in the neonatal period requires an understanding of neonatal physiology and an appreciation for the possibility of cardiovascular instability, massive blood transfusion requirements, hypothermia, and coagulation dysfunction. Death during resection is often related to hemorrhage, hypothermia, coagulopathy, and the inability to provide adequate cardiopulmonary support during the intraoperative manipulation of the tumor. For large tumors, adequate venous access, central venous access, and invasive arterial pressure monitoring are essential.

Outcome

Predictors of poor outcome have been associated with diagnosis before 20 weeks’ gestation, delivery before 30 weeks’ gestation, development of hydrops, low birth weight, and a 5-minute Apgar score of less than 7 (Chisholm et al., 1999). Long-term issues involve urologic complications, urinary incontinence, problems with defecation, and cosmetically unacceptable scars (Derikx et al., 2007; Tailor et al., 2009). Associated congenital anomalies are common in patients with congenital anorectal malformations (Stoll et al., 2007).