Congenital Diaphragmatic Hernia

Congenital Diaphragmatic Hernia

Congenital Diaphragmatic Hernia Marc L. Cullen, M.D.,* Michael D. Klein, M.D., t and Arvin I. Philippart, M .D .:f: HISTORY Congenital diaphragmatic...

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Congenital Diaphragmatic Hernia Marc L. Cullen, M.D.,* Michael D. Klein, M.D., t and Arvin I. Philippart, M .D .:f:

HISTORY

Congenital diaphragmatic hernia was originally described by Lazarus Riverius. His observations of the postmortem findings in a 24-year-old man were published in Bonetus' s Sepulchretum in 1679. 18 Charles Holt gave the first account of these findings in a child in 1701. 54 Morgagni described the congenital anterior diaphragmatic defect that bears his name in 1769. He credited Stehelinus with the observation of the small ipsilateral lung. 78 In 1848 Vincent Alexander Bochdalek described herniation of the bowel through a dorsal diaphragmatic split. He postulated that the bowel was forced through this lumbocostal triangle as a result of the inverted position of the fetus. 15 Despite the anatomic and etiologic inaccuracy of Bochdalek' s theory, congenital posterolateral diaphragmatic hernia is known as a Bochdalek hernia. The first collected series of congenital diaphragmatic hernia was reported by Bowditch in 1853. 20 He reported 26 cases with high early mortality. The first successful repair has been variously credited to both Aue 7 and Heidenhain in 1902. 52 The first successful repair of a diaphragmatic hernia in an infant less than 24 hours old was performed by Gross in 1946. 44 Since that time, the history of diaphragmatic hernia has been characterized by attempts to improve survival in symptomatic newborns. The use of endotracheal intubation, assisted ventilation, and early surgical reduction was advocated by many from 1950 to 1970. The presence of pulmonary hypoplasia was first described by Campanale and Rowland in 1953, 23 and its effect on survival was recognized by Areechon and Reid in 1963. 4 The pathologic consequences of pulmonary hypertension and venous admixture in diaphragmatic hernia were described by Murdoch and associ*Associate Chief Resident, Department of Pediatric General Surgery, Children's Hospital of Michigan, Detroit, Michigan t Associate Chief, Department of Pediatric General Surgery, Children's Hospital of Michigan; Associate Professor, Department of Surgery, Wayne State University, Detroit, Michigan *Chief, Department of Pediatric General Surgery, Children's Hospital of Michigan; Associate Professor, Department of Surgery, Wayne State University, Detroit, Michigan

Surgical Clinics of North America-Yo!. 65, No. 5, October 1985

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ates 79 and by Rowe and Uribe93 in 1971. Since then several new drugs have been introduced, such as the muscle relaxant pancuronium, which facilitates mechanical ventilation, and tolazoline, which decreases pulmonary vascular resistance. White and associates first achieved prolonged respiratory support in newborns with respiratory distress syndrome by using extracorporeal membrane oxygenation (ECMO). ll7 Bartlett and colleagues reported the first survivors of persistent fetal circulation treated with ECMO in 1976, 10 and German and associates soon after applied ECMO to infants with congenital diaphragmatic hernia and had one survivor. 37

ANATOMY The diaphragm in the newborn is a dome-shaped partition between the abdominal and thoracic cavities. It consists of four fibromuscular components and three permanent hiatuses. The central tendon is the first component. Its fibers are oriented in an anterior-posterior axis. The posterior fibers form a concave attachment to the vertebral column. Anteriorly, they interdigitate with the sternal portion. This second (sternal) component consists of two muscular slips that attach the xiphoid to the central tendon. The third, or costal, component arises bilaterally from the lower six costal cartilages and inserts on the anterior and lateral portions of the central tendon. The fourth, or lumbar, component arises from the first three lumbar vertebrae and defines the right and left crura, including the first two permanent diaphragmatic hiatuses: the aortic and the esophageal. The caval hiatus is in the central tendon to the right of the midline. Between the sternal and the costal portions of the diaphragm the superior epigastric artery and loose areolar tissue occupy Larrey' s space. This is the site of the Morgagni hernia. There is a second potential space filled by loose areolar tissue at the junction of the costal and lumbar portions of the diaphragm. It is known as the vertebrocostal trigone. This is the site of the embryonic pleuroperitonea! canal and the location of the posterolateral diaphragmatic hernia known as a Bochdalek hernia. The actual area described by Bochdalek as the site of the defect, however, is medial to this (Fig. 1). The phrenic nerve carries both sensory and motor fibers to the diaphragm. Its major branches are distributed around the central tendon.

EMBRYOLOGY The development of the diaphragm, lung, and gastrointestinal tract must be understood in order to appreciate the clinical spectrum and pathophysiology of diaphragmatic hernia. The diaphragm has four developmental components (Fig. 2). The ventral component is formed in the third to fifth week of gestation by the septum transversum, arising from a mesodermal plate of the cephalic fold that grows dorsally from the developing anterior body wall. It envelops the esophagus, inferior vena cava, and aorta and fuses with the foregut mesentery by the eighth week of development to form the posterior and medial portions of the diaphragm. The lateral mar-

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Figure 1. The diaphragm as seen from below. (A= aortic hiatus; E =esophageal hiatus; VC =vena caval hiatus; M =potential space for Morgagni hernia; B =site of Bochdalek hernia.)

gins of the diaphragm are then developed from muscular components of the body wall. The pleuroperitonea! canals are the last areas to close from fusion of the membranous portions of the components already discussed. Muscular fibers from the third, fourth, and fifth cervical myotomes reinforce these membranous folds, completing diaphragmatic closure by the ninth week of gestation. 115 During this time, the esophagus elongates, the stomach migrates distally, and the midgut herniates into the umbilical coelom. The midgut par-

Figure 2. Developmental components of the diaphragm. (l =anterior components from septum transversum; 2 =posterior component from foregut mesentery; 3 =lateral component from body wall muscle; 4 = pleuroperitonea] canals; A= aortic hiatus; E =esophageal hiatus; VC =vena caval hiatus.)

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tially rotates and returns at about the tenth week. If this event occurs prior to closure of the pleuroperitonea} canal, the abdominal viscera may herniate into the thoracic cavity. Whether this hernia results from premature return of the intestine or late closure of the pleuroperitonea} membranes remains uncertain. The timing of herniation accounts for variation in the associated malrotation of the intestine. Later herniation may explain the variable presence of a sac, indicating membranous closure of the canal without muscular ingrowth. The failure of muscular buttressing of the pleuroperitonea} membrane without early intestinal herniation results in various degrees of eventration. Synchronous with diaphragmatic and intestinal development, the lung begins as a ventral bud of the foregut. The airway develops by progressive dichotomous branching in the milieu of thoracic mesenchyme during the fourth to fifth weeks of gestation. 66 Subsequent airway division occurs until all the conducting and terminal bronchioles are established by the seventeenth week. 55 The third phase of lung development occurs between the seventeenth and twenty-fourth weeks, when the airways differentiate, the lumina widen, and the epithelium thins. 55 Alveolar development begins at 24 weeks and continues well after birth.

EPIDEMIOLOGY The incidence of congenital diaphragmatic hernia varies from 1 in 2000 to 1 in 5000 live births. 19• 51 This incidence is greater in stillbirths and abortions. 22 There is no sexual, racial, or geographic preference, and most maternal factors show no consistent relationship. Hydramnios is noted in 20 per cent of pregnancies resulting in the birth of a child with diaphragmatic hernia (50 per cent associated with stillbirths). 22 The presence of hydramnios may indicate poor outcome. 2 Fewer than 75 familial cases have been reported. 31, 32, 80 Andersen3 and Warkany and Roth 110 demonstrated that vitamin A deprivation in genetically predisposed rats increased the percentage of offspring with congenital diaphragmatic hernia. Other drugs that may induce congenital diaphragmatic hernia include phenmetrazine, 86 quinine, 63 thalidomide, 53 Bendectin, 21 and nitrophen. 56 Posterolateral defects account for 75 to 85 per cent of congenital diaphragmatic hernia. 51 • 75• 92 Left-sided posterolateral defects occur eight times more frequently than right-sided hernias in the newborn period. Rightsided hernias are more common in older children. 8 Bilateral hernias (Fig. 3) are rare (1 per cent) and usually fatal. 70 Morgagni hernias occur infrequently, representing 1 to 6 per cent of all congenital diaphragmatic defects. They occur more often on the right side (90 per cent) and bilaterally (7 per cent). There is a slight male predominance and an older age at presentation. 9· 30· 105 Excluding malrotation and patent ductus arteriosus, the incidence of associated anomalies is between 10 per cent and 20 per cent. 1· 57 This rises to 95 per cent in stillborn infants. 22 Infants born with congenital diaphragmatic hernia who survive 1 hour after birth rarely have severe associated

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Figure 3. Bilateral Bochdalek hernias. Bilateral thoracic opacification is seen with a small amount of aerated lung at both apexes. Nasogastric tube (arrows) indicates left-sided intrathoracic stomach.

anomalies. 48 • 81 A number of patients with anterior hernias have complex septum transversum defects, such as Cantrell's pentalogy (omphalocele, diaphragmatic hernia, pericardia} defect, intracardiac defect, and sternal cleft). 86• 116 Total diaphragmatic eventrations are associated with other malformations, including pulmonary sequestration and cardiac and vascular anomalies. 43 • m PATHOPHYSIOLOGY

Pulmonary arterial pressure in utero equals systemic arterial pressure. Venous blood returning to the heart is mixed with oxygenated blood from the umbilical vein. This admixture is diverted through the foramen ovale and the ductus arteriosus because of high pulmonary vascular resistance in the unexpanded lung, and only 10 per cent ultimately goes to the lung. 63 At birth the lungs expand and pulmonary vascular resistance decreases, thus increasing pulmonary blood flow. The increase in alveolar and arterial oxygen tension mediates the release of endogenous vasoactive compounds that stimulate a further decrease in pulmonary vascular tone as well as closure of the ductus arteriosus and foramen ovale. 6 When pulmonary vascular resistance remains elevated, the syndrome of primary pulmonary hypertension of the newborn results. 68 This is more commonly known as persistent fetal circulation. 38 Elevated pulmonary vas-

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cular resistance results in right-to-left shunting across the ductus arteriosus and foramen ovale as well as through intrapulmonary shunts. The resulting hypoxia and acidosis lead to a vicious circle of further increases in pulmonary vascular resistance that trigger more severe shunting and hypoxia. It is persistent fetal circulation that appears to limit survival in those patients with congenital diaphragmatic hernia who do not have severe pulmonary hypoplasia. In congenital diaphragmatic hernia, pulmonary hypoplasia is associated with decreased size and number of bronchi, lung saccules, and alveoli. There is also a corresponding decrease in the total size of the pulmonary vascular bed. 61 • 67 In addition, it has been suggested that the herniated viscera cause mediastinal compression and distortion, which decrease flow through the ductus arteriosus. Increased flow through the pulmonary vascular bed results in muscular hypertrophy of the pulmonary arteries and an exaggerated sensitivity to postnatal hypoxia, hypercarbia, and acidosis, which produce the clinical syndrome of persistent fetal circulation. 67 The stage of pulmonary development at which visceral herniation occurs may explain the clinical spectrum of the respiratory problems seen with congenital diaphragmatic hernia. Wiseman and MacPherson 118 used this hypothesis to divide patients with congenital diaphragmatic hernia into four groups. The first group experiences visceral herniation early in the course of bronchial branching. The result is severe bilateral pulmonary hypoplasia, which is uniformly fatal. Herniation at the stage of distal bronchial branching results in unilateral hypoplasia. Survival in this group depends on a delicate balance of pulmonary vascular and ductal resistances. A third group experiences herniation late in gestation. In this favorable group, respiratory distress follows air swallowing with compression of otherwise adequate lung. In the fourth group, herniation occurs postnatally. There is no attendant pulmonary pathology, and survival is excellent. CLINICAL PRESENTATION Infants in the first and second groups present in the first 8 hours of life, whereas those in the third group present by 24 hours of age. The postnatal group can present at any time into adulthood. 8• 42 • 94 In newborns with the common left congenital diaphragmatic hernia, cyanosis, dyspnea, and cardiac dextroposition are the classic triad. Physical examination reveals a scaphoid abdomen, decreased breath sounds, distant heart sounds, and bowel sounds in the chest. There is loss of abdominal tympany, and there is dullness to percussion in the chest. An anteroposterior film of the infant will reveal mediastinal shift, air-filled bowel loops in the chest, and a relatively gasless abdomen (Fig. 4). Positioning of a nasagastric tube prior to the radiographic examination may help demonstrate an intrathoracic stomach. Right-sided Bochdalek hernias (Fig. 5) may be asymptomatic because of tamponade of the defect by the liver. They are recognized later only when a roentgenogram reveals an intrathoracic mass or pleural effusion. 24 • 27 Group B streptococcal sepsis has been associated with congenital diaphrag-

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Figure 4. Left Bochdalek hernia. A classic example of a left posterolateral hernia with stomach and multiple bowel loops in the chest and a relatively gasless abdomen. Trachea and mediastinum are displaced to the right.

matic hernia, especially right-sided defects. 5• 47 Lung compression and diaphragmatic dysfunction are believed to make these children more susceptible to the ubiquitous group B streptococcus. Approximately 5 per cent of all cases of congenital diaphragmatic hernia present after the neonatal period. 84 Right-sided defects are twice as common as left-sided defects in this group. In older children, congenital diaphragmatic hernias may be free, unrestricted pleuroperitonea} defects without a sac or, more commonly, hernias with a pleuroperitonea} membrane or sac. The distinction between a hernia with a sac and an eventration may not be significant. The hernia with a sac has no muscular elements, but an eventration does. About 7 per cent of patients with congenital diaphragmatic hernia presenting after the newborn period have no symptoms, but the congenital diaphragmatic hernia is recognized on a roentgenogram obtained for an unrelated problem. Gastrointestinal complaints such as vomiting and abdominal pain and respiratory problems such as cough and chest pain usually bring the patient to medical attention. 84 Morgagni hernias and eventrations can also present late with respiratory symptoms (Figs. 6 and 7). Congenital eventration must be distinguished from the acquired variety, which is usually the result of phrenic nerve injury. The degree of muscular hypoplasia correlates with symptomatology. It varies from late presentation with minimal symptoms in partial or unilateral eventration to

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Figure 5. Right Bochdalek hernia. Right-sided intrathoracic displacement of aerated bowel is seen in the chest. Again, a paucity of abdominal gas and marked displacement of the heart and compression of the contralateral lung are apparent.

Figure 6. Morgagni hernia. A, Anteroposterior view of a right-sided intrathoracic mass compressing the right atrium. B, Lateral view confirms anterior retrosternallocation. Sharp demarcation suggests the sac.

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Figure 7. Eventration. A, Thoracic migration of abdominal viscera. The lung is compressed at the apex; the trachea and mediastinum are shifted. B, Lateral view confirms outline of elevated diaphragm.

severe respiratory distress simulating a Bochdalek hernia with total or bilateral eventrations noted on the first day of life. Partial eventrations are more common on the right, and total ab:o.:nce of muscle is more common on the left.m Clinical presentation predicts survival. Infants requiring endotracheal intubation in the delivery room 74 and those weighing less than 1000 gm or born before 33 weeks of gestation94 seldom survive. Children presenting after 8 hours of life usually have respiratory distress orr the basis of compression of adequate lung and thus have good survival. The availability of ultrasound and the theoretical consideration of fetal surgery have directed attention to the antenatal diagnosis of congenital diaphragmatic hernia. Adzick and associates noted that hydramnios was present in 76 per cent of the women whose fetuses were diagnosed as having congenital diaphragmatic hernia by ultrasound, amniography, or computed tomography. 2 The proposed advantage of antenatal diagnosis is the ability to deliver the infant electively at a medical center prepared to care for the complex problems of the infant as well as those of the mother. To date, however, this has had no apparent effect on survival. 2• 85 • 108 The important differential diagnoses of congenital diaphragmatic hernia associated with respiratory distress are space-occupying developmental anomalies that present with diminished breath sounds and contralateral mediastinal shift. 25• 76 Congenital lobar emphysema is not difficult to distinguish because of the even distribution of air in the affected lobe. The radiologic appearance of cystic adenomatoid malformation of the lung, however, includes multiple air- and fluid-filled cystic spaces that resemble the bowel loops in congenital diaphragmatic hernia (Fig. 8). In cystic adenomatoid malformation, the ipsilateral diaphragm is more easily identified and often

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Figure 8. Cystic adenomatoid malformation. Air-filled cystic spaces are seen in the left chest with cardiac displacement simulating a Bochdalek hernia. Barium enema reveals normal intraabdominal left colon. • Stomach bubble seen intra-abdominally confirms diagnosis of primary lung pathology.

appears flattened or even concave. Tachypnea results in air swallowing with dilated loops of intestine within the abdomen. In contrast, congenital diaphragmatic hernia is associated with a scaphoid abdomen, less abdominal gas, and a less clearly defined diaphragm. In an infant with minimal respiratory distress, gastrointestinal contrast studies may be helpful in differentiation (Fig. 9); however, in the critically ill newborn, such studies are not appropriate.

PREOPERATIVE EVALUATION AND PREPARATION

Once congenital diaphragmatic hernia is diagnosed, a 10-Fr sumped nasogastric tube is placed in the stomach and connected to suction to minimize further distention of the intestine within the thoracic cavity. An endotracheal tube is promptly inserted, as ventilating with a mask quickly fills the intestine with air, further compromising expansion of the lung. High concentrations of oxygen, rapid respiratory rates, and low tidal volumes are required to maintain relatively low pressures and avoid contralateral pneumothorax. In the past, this could be accomplished only with hand bagging, but modern neonatal ventilators using pressure limits and high respiratory rates (70 to 100) are acceptable. A tidal volume approximately 60 per cent

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Figure 9. Left Bochdalek hernia. A, Barium enema in anteroposterior projection. B, Lateral projection shows intrathoracic location of majority of colon. Nasogastric tube shows the stomach intra-abdominally. Barium contrast facilitated correct diagnosis.

of expected is a safe initial setting for ventilation in children who may have severe pulmonary hypoplasia. At any sign of deterioration, contralateral pneumothorax should be assumed and a chest tube placed. Radiographic confirmation is not required. Peripheral perfusion should be supported with intravenous fluid and dopamine as necessary. Acidosis should be aggressively treated with hyperventilation, sodium bicarbonate, or tromethamine (THAM). Monitoring includes a transcutaneous oxygen monitor placed on the right upper chest to record preductal Pa0 2 and to indicate peripheral tissue perfusion. An umbilical artery catheter with Pa0 2 or 0 2 saturation sensor records postductal Pa0 2 • End-tidal C0 2 monitoring, especially during anesthesia, gives a good indication of the ventilatory status. A urinary catheter, right radial artery cannula, and central venous cannula are helpful but may be placed postoperatively. A blood sample for typing and crossmatching should be sent, broad-spectrum antibiotics should be administered, and 1 mg of vitamin K should be given. Several studies of preoperative predictors of mortality in congenital diaphragmatic hernia have been published. 16• 74 • 75 • 90• 95 If the pH can be corrected preoperatively to greater than 7.2, the PaC0 2 to less than 50 mm Hg, and the Pa0 2 to greater than 100 mm Hg, the prognosis is excellent. When the pH cannot be brought above 7.0, the Pa0 2 cannot be brought

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above 80 mm Hg, and the PaC0 2 cannot be brought below 50 mm Hg, there is nearly uniform mortality. Good survival is predicted by an alveolararterial oxygen difference (A-aD0 2) of less than 500 mm Hg. 74 • 95 Efforts spent achieving these parameters appear to increase survival, 16 and do not adversely affect it. 94 We, however, strongly believe that stabilization and resuscitation must proceed expeditiously and simultaneously with preparations for surgical rt:duction. This can be accomplished in both the newborn unit and the operating room. Patients who present after the newborn period are managed according to their symptomatology. As with any hernia, life-threatening incarceration and strangulation can occur. OPERATIVE TECHNIQUE Some surgeons have approached congenital diaphragmatic hernia from the chest, 57 yet the experience described by Willis Potts on trying to reduce the intestinal content from a thoracic approach is suggestive of the difficulty: "It was like trying to stuff foam into a bottle with a tweezer. " 87 There are many advantages to an abdominal approach: The bowel is easily reduced, the defect can be repaired under direct vision, associated anomalies can be corrected, and the abdominal wall can be stretched to accommodate the intestines if necessary. On the right side, the abdominal approach requires some extra caution in avoiding the hepatic veins during the repair. The abdomen is explored through a subcostal incision and the hernia reduced by gentle traction on the intestine. Once the bowel is reduced, it is important to visualize the lung or chest wall clearly to determine if a sac is present. If present (10 to 20 per cent), a sac must be excised to avoid leaving a loculated space-occupying lesion in the chest. 59 One should also inspect the mediastinum for sequestered extralobar pulmonary segments that are occasionally seen with this lesion. Most defects can be closed by direct suture after mobilization. We use permanent horizontal mattress sutures and slightly overlap the edges. In some posterolateral defects, the posterior edge may be difficult to define but is usually present. Downward traction on the kidney often will reveal the rolled-up edge of diaphragm, and occasionally the peritoneum must be opened to define it. If no rim can be found, the suture material can be passed around a rib to anchor the repair firmly. Although composite chest wall flaps have been advocated for closure of large defects, 12• 97 we avoid them because of the time required, the extent of the procedure, and the subsequent deformity. In our experience, large defects are best closed with a prosthetic material such as Goretex that allows fibrous ingrowth and permanent healing. The use of prosthetic materials expedites the repair of a large defect and obviates excessive tension that can result in recurrence. Such patches become incorporated over time into a normal diaphragmatic configuration. Prosthetic materials such as Silastic that do not allow such ingrowth should not be used. If the patient's condition permits, a Ladd procedure is performed.

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Prior to diaphragmatic closure, a 12-Fr chest tube is placed in the pleural space and is connected to underwater seal but not to suction. The abdomen is closed as it would be for an abdominal wall defect, by placing permanent fascial sutures without tying them and then pulling the abdominal wall together while observing the blood pressure and lung compliance. If there appears to be obstruction to the vena cava with hypotension or difficulty in ventilation, a ventral hernia can be created by closing skin only. The fascial closure can be completed within 1 week. Silastic prostheses such as those used for abdominal wall defects can be used for difficult abdominal closures. 89 These two maneuvers should rarely be necessary. Unlike many, we do not use gastrostomy tubes. 51• 120 We prefer a thoracic approach for the operative repair of Morgagni hernias, but an abdominal approach may facilitate reduction in some cases. Many Morgagni hernias will have a sac that must be excised. Eventration must be managed individually. Many localized, asymptomatic eventrations do not require operation. In the newborn and older infant with respiratory embarrassment, surgical correction can be achieved by plication or sac excision and repair. We approach eventration from the chest to directly visualize and preserve the phrenic nerve. An ellipse of central redundant diaphragm is excised to allow accurate placement of horizontal mattress sutures without injury to the intestine. In both procedures, the redundancy is corrected to give a normal diaphragmatic contour.

POSTOPERATIVE CARE Following surgery, the patient remains intubated and is slowly weaned by reducing pressure, Fi02 , and respiratory rate and finally by discontinuing muscle paralysis. Frequent chest roentgenograms allow careful assessment of mediastinal position. The mediastinum usually is quite far to the right and should return to the midline slowly. The hypoplastic ipsilateral lung should not be expected to fill the hemithorax. If the mediastinum shifts too quickly, the chest tube can be opened to equalize intrathoracic pressures. The patient is left intubated for a minimum of 24 hours postoperatively and then extubat~d using standard criteria. There should be a low threshold for reintubation if gas exchange deteriorates. Pancuronium (0.1 mg .per kg intravenously) is used to paralyze the patient to allow adequate mechanical ventilation, and morphine (0.1 mg per kg intravenously) can be used for sedation.

COMPLICATIONS Barotrauma, most commonly represented by contralateral pneumothorax, has been reported in 7 to 20 per cent of patients and has been associated with considerable mortality. 39· 46 The hernia is reported to recur in 10 to 22 per cent. 28 • 92 and most require reoperation. More liberal use of prostheses for diaphragmatic repair might prevent this complication. Chylothorax following repair of congenital diaphragmatic hernia has been re-

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ported. 113 Injury to the spleen, kidneys, and adrenal glands have been reported, as have gastric anQ. midgut volvulus and adhesive intestinal obstruction. 114 These complications should occur infrequently. At present, the mortality rate for infants who become symptomatic within the first 24 hours of life varies from 25 to 75 per cent. 29• 92• 94• 112 Children symptomatic in the first 6 hours of life have the worst outcome, with an 80 per cent mortality rate. 51 This mortality is a consequence of the pulmonary hypoplasia and pulmonary artery hypertension that complicate diaphragma!ic hernia. Mortality is uncommon in infants who become symptomatic after 6 hours of life. RESPIRATORY F AlLURE

Persistent fetal circulation is the major complication following repair of diaphragmatic hernia and, together with pulmonary hypoplasia, accounts for most postoperative deaths. Primary myocardial failure has also been implicated. 82• 96 There is often a dramatic postoperative improvement (the honeymoon period) for 12 to 24 hours, followed by marked deterioration. This syndrome, characterized by intense pulmonary vasoconstriction resulting in elevated pulmonary artery and right ventricularend-diastolic pressures, produces right-to-left shunting at the level of the ductus arteriosus and often at the foramen ovale. 29• 34• 79 Attempts at ductal ligation have not improved survival29 and may cause right heart failure as ductal ligation does nothing to reduce pulmonary vascular resistance. Infants dying from congenital diaphragmatic hernia have increased muscle mass in the pulmonary vascular tree80 and a heightened sensitivity to vasospastic stimuli such as hypoxia and acidosis. 71 The vicious circle of pulmonary vasospasm with subsequent hypoxia and acidosis that further exacerbate pulmonary vasospasm can sometimes be reversed by tolazoline. Tolazoline, an alpha-adrenergic blocker, is an effective vasodilator. 35• 72• 102 In addition to its ability to relax vascular smooth muscle, 77 it appears to have a positive inotropic effect. 13• 35 We use tolazoline (intravenous bolus 1 to 2 mg per kg) when there is significant right-to-left ductal shunting. We consider ductal shunting to be significant when the difference between preductal and postductal Pa0 2 is greater than 25 per cent or when the postductal Pa02 is less than 80 mm Hg with an Fi02 of 1.0. Tolazoline therapy is maintained by a continuous infusion of 1 to 4 mg per kg per hour into a peripheral vein draining into the superior vena cava. Bloss and associates have described the variable responses to this drug as good (mean increase in Pa0 2 of 149 mm Hg), poor (mean increase in Pa0 2 of 33 mm Hg), and none (mean increase in Pa02 less than 20 mm Hg). Those who responded to tolazoline did so in 1 hour or less. Al\ nonresponders and 67 per cent of poor responders died. 14 In addition to variability in responsiveness, we have found that an initial response to tolazoline frequently is not sustained. Complications of tolazoline include thrombocytopenia, abdominal distention, and gastrointestinal and pulmonary hemorrhage. 109 Tolazoline acts as a vasodilator on both systemic and pulmonary circulation. Therefore, hy-

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potension may occur as a result of its use and should be treated with volume expansion and dopamine. Mter the bolus dose of tolazoline, there is frequently an intense cutaneous blush. Some authors have used a pulmonary artery catheter to administer tolazoline and to monitor pulmonary artery pressure. 29 • 35 We have found the use of a pulmonary artery catheter cumbersome and fraught with complications. Other drugs have been used or are under investigation as pulmonary vasodilators (Table 1). In vivo and in vitro studies have shown changes in pulmonary vascular resistance that correlate with changes in plasma levels of prostacyclin and thromboxane A2 • 36• 73 Prostaglandin E 1 has been demonstrated to decrease pulmonary vascular resistance independent of its effects on ductal patency. 41 Prostaglandin D 2 has been demonstrated to decrease pulmonary vascular resistance without decreasing systemic pressures. 99 Acidosis is a powerful stimulant of pulmonary vasospasm and must be treated vigorously with hyperventilation. We use respiratory rates of 80 to 120 and an inspiratory:expiratory ratio that is reversed from the normal (1 or even 1.3:1). If this is not effective, we will use tromethamine (THAM) (3 to 5 ml per kg per dose; 0.3 M solution). If acidosis persists despite adequate perfusion and hypocarbia (PaC0 2 less than 30 mm Hg), sodium bicarbonate (1 to 2 mg per kg per dose) is given to obtain slight alkalosis. If fluid alone is not effective in maintaining adequate perfusion, dopamine is administered at 2 to 10 j.Lg per kg per min intravenously. Patients who continue to show hypoxemia despite initiation of the preceding measures are considered candidates for ECMO. ECMO is essentially cardiopulmonary bypass such as that performed in the operating room for open heart surgery. It is employed to reverse hypoxemia and acidosis and to treat pulmonary hypertension as well as to support vital organs dur-

Table 1.

Drugs used in the Treatment of Respiratory Failure Complicating the Repair of Congenital Diaphragmatic Hernia

DEMONSTRATED CLINICALLY EFFECTIVE AS VASODILATOR

Tolazoline (Priscoline) 1-4 mg/kg/hr Chlorpromazine (Thorazine) Nitroprusside 60 f.Lg/kg/hr Nitroglycerin 7-30 f.Lg/kg/hr

Acetylcholine 50 mg/kg/hr

USED ALONE OR IN COMBINATION; NOT PROVED EFFECTIVE

Isoproterenol . J3-agonist and inotrope Methylprednisolone Decreases sensitivity to catecholamine Morphine sulfate Increases venous capacitance; sedation Bradykinin Vasodilator of pulmonary and systemic circuits Curare Paralysis and histamine release

EXPERIMENTAL APPLICATION

Arachidonic Acid Derivatives Prostaglandin E 1 Prostaglandin D 2 Prostaglandin 12 (prostacyclin) Leukotriene Antagonists Investigational compound

Calcium Channel Blockers Nifedipine Miscellaneous Dilantin Glucagon

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ing respiratory failure. ECMO has been applied in 44 published cases of congenital diaphragmatic hernia. Twenty-three of these patients have survived, although many show some degree of cerebral dysfunction. 100 ECMO is performed in the neonatal intensive care unit, where cannulas are placed using local anesthesia. Blood is drained from the cannula in the right atrium placed via the right internal jugular vein and is returned to the aortic arch by a catheter placed from the right carotid artery. Venous blood drains by gravity to a reservoir. A volume-sensitive solenoid interrupts the pump when venous return is insufficient. Flow is maintained by a roller pump, and venous blood is passed through a membrane oxygenator and heat exchanger before being returned to the patient (Fig. 10). Our criteria for selecting patients for ECMO are outlined in Figure 11. We have not found the neonatal pulmonary insufficiency index (NPII) useful, as contemporary management, including hyperventilation, sodium bicarbonate, and tromethamine, seldom allow the development of significant acidosis.U We insist that candidates for ECMO demonstrate a "honeymoon" period, characterized by a postductal P0 2 greater than 100 mm Hg,

Figure 10. Elements of venoarterial ECMO circuit are shown. Insets reveal details of catheter tip locations.

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I

STABILIZATION

OR REDUCTION

I I

IMPROVES

DETERIORATE EXPIRE-- PROGRESSIVELY

12"

pH Pre-Dp0 2 Post-Dp0 2 A-aD0 2 fi02

<

24"

> 7.45 > 150 > 100

< 400 < 80%

48"

Right to Left Shunt A-aD0 2 Post-Dp0 2 fi02

> 25% > 500 < 100

>

DETERIORATE

SUSTAINED--SURVIVE

= 100%

Maximum medical therapy, including hyperventilation, alkalosis, paralysis, and tolazoline

pH

<

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Post-Dp02 < 40 Pre-Dp0 2 < 80 A-aD02 > 600 Barotrauma

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Pre-Dp02 < 55 >DETERIORATE Post-Dp0 2 < 80 SLOWLY > 500 A-aD0 2

E X P I R E - - - - - - - - L - - - - - - - SURVIVE

Figure lL Management criteria for respiratory failure complicating the repair of congenital diaphragmatic hernia.

a pH greater than 7.45, and an A-aD0 2 less than 400 mm Hg on an Fi0 2 of less than 0.8, which indicates that pulmonary hypoplasia is not the underlying cause of the respiratory failure. After such a period of improvement, any acute deterioration evidenced by a postductal P0 2 less than 40 mm Hg, pH less than 7.15, and an A-aD0 2 greater than 600 mm Hg lasting for 2 to 3 hours despite maximal medical therapy is an indication for instituting ECMO. In patients initially responding to medical therapy but gradually failing, a postductal Pa0 2 less than 80 mm Hg, pH less than 7.4, and an A-aD0 2 greater than 500 mm Hg for 12 hours are also indications for ECMO support. Once ECMO is started, ventilatory assistance is decreased. This is beneficial in preventing barotrauma and oxygen toxicity. In patients on ECMO, the Pa0 2 is regulated by adjusting the blood flow through the oxygenator, and the PaC0 2 is regulated by adjusting the gas composition and its flow to the membrane lung. It should be noted that in

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patients on ECMO the right-to-left shunt is often quickly reversed physiologically whereas the ductus arteriosus fails to close anatomically. This can lead to severe left-to-right shunting with systemic hypoperfusion and oliguria after initial improvement. We have had to ligate a patent ductus arteriosus in several patients on ECMO, including one with congenital diaphragmatic hernia. Most of these patients responded appropriately with improved perfusion and increased urine output, but all eventually died. The major theoretic disadvantage of ECMO is ligation of the carotid artery, although to date there has been no documented morbidity or mortality directly related to this in almost 200 cases. The major practical disadvantage of ECMO is the need to totally heparinize the patient in order to prevent thrombosis and arterial emboli. These problems, together with the expense and logistic difficulty of assembling the equipment and a welltrained team, have limited the application of ECMO to patients who are already hypoxic and acidotic. One might expect better results if ECMO were applied earlier. Active investigation is being pursued in several laboratories to find alternatives to systemic heparinization. Modification of blood-contact surfaces such as wall-bonded heparin 107 and regional heparinization of the circuit65· 106 are areas of current interest. Attempts to avoid carotid artery cannulation by providing venous return of oxygenated blood through either a second vein or a double-lumen cannula are under trial but are not of established efficacy. 62 Various forms of high-frequency ventilation have been suggested for the treatment of respiratory failure complicating congenital diaphragmatic hernia. This modality provides gas exchange while reducing mean airway pressure. The reduction of peak airway pressure decreases the risk of barotrauma and may help lower pulmonary vascular resistance. There are three methods of delivering high-frequency ventilation. High-frequency positivepressure ventilation employs tidal volumes less than the dead-space volume delivered with positive pressure at rates of 60 to 180. High-frequency jet ventilation delivers tidal volumes less than the dead-space volume through a thin nozzle placed in the center of the endotracheal tube at rates of 240 to 720. The newest technique is high-frequency oscillation, which employs small volumes at frequencies of 240 to 2400 without a jet. 40 The mechanisms of gas transport are not completely understood, but entrainment and augmented diffusion are used to explain what occurs. 98 Karl and associates reported the clinical application of high-frequency oscillation in newborn infants with congenital diaphragmatic hernia who failed medical management. 58 They were able to achieve hypocarbia, alkalosis, and temporary improvement in oxygenation. The mortality rate has been nearly 100 per cent with this technique to date, but various modifications that are under way may improve outcome. LONG-TERM RESULTS

Most authors have found some respiratory abnormality in patients who survive repair of congenital diaphragmatic hernia. Reid and Hutcherson 91 demonstrated decreases in total lung capacity and vital capacity as well as

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increased residual volume. Chatrath and associates 26 demonstrated normal lung volumes but found that forced expiratory volume at 1 second and forced vital capacity were less than predicted. Chest roentgenograms were normal or showed some degree of hyperinflation, and radionuclide lung scans revealed reduction of pulmonary perfusion on the affected side. 119 These abnormal findings do not appear clinically significant. Boles and Anderson17 reviewed 58 patients at a symposium in 1979 with a minimum 5year follow-up. They found that weight and height were average for age and that the children were functioning at a normal school grade for age. They appeared active, vigorous, and healthy. Results were normal in four children in whom pulmonary function tests were performed. ANTENATAL DIAGNOSIS AND TREATMENT Considerable effort has been directed at elucidating the antepartum events in the development of congenital diaphragmatic hernia to determine where they might be reversible. The in utero creation of a diaphragmatic hernia in a fetal lamb was first achieved by de Lorimier and associates in 1967. 33 The hemodynamics of diaphragmatic hernias created in utero were studied by Kent and coworkers, 60 Starett and de Lorimier, 101 and Olivet and associates. 83 In 1976 Haller and colleagues simplified creation of a diaphragmatic hernia in utero by using an inflatable balloon to simulate the space-occupying intrathoracic viscera. 45 Harrison and associates, in a modification of Haller's technique, demonstrated that the inflated balloon created a profound decrease in pulmonary parenchymal mass and pulmonary vascular cross-sectional area. 50 Correction simulated in utero by deflation of the balloon has resulted in survivors with intermediate lung volumes. 49 Soper and colleagues created midgestational diaphragmatic hernias in fetal lambs, corrected them in the third trimester, and produced some longterm survivors. 100 Despite the eloquence of these and other investigations, three problems evade explanation. First, more than a simple reduction in total lung volume or weight must be achieved, as children have good survival after pneumonectomy. 103 Second, the experimental work emphasizes the compression of the lung during the third trimester, when growth is most rapid. This does not, however, correlate with the clinical spectrum of the disease; the effects of herniation are supposed to be most catastrophic when the herniation is presumed to occur early, whereas later compression of the lung does not produce severe respiratory distress. Third, work by Iritani in Japan demonstrated diaphragmatic hernias in 80 per cent of the offspring of mice that were fed nitrophen. 56 In reviewing these animals, he postulates that pulmonary hypoplasia may be a primary event, or at least the result of simultaneous inhibition of diaphragmatic and pulmonary precursors, and not the result of simple lung compression. Therefore, the application of antenatal surgery to the problem of diaphragmatic hernia remains theoretic. Increased accuracy of diagnosis, improved methodology for selecting patients at greatest risk, and solutions to complex ethical issues are required prior to transferral of the antenatal lamb experience to the human maternal-fetal unit.

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SUMMARY Congenital diaphragmatic hernia continues to be a critical problem in neonatal surgery. Despite the apparent simplicity of the anatomic defect, the physiology is complex, and survival remains uncertain. Surgical success has been achieved, but we recognize that the barrier to survival is pulmonary parenchymal and vascular hypoplasia as well as the complex syndrome of persistent fetal circulation. In many ways the problem of diaphragmatic hernia is as much of an enigma to today' s physician-scientist as it was to Bochdalek in the nineteenth century. The treatment of respiratory distress after repair of congenital diaphragmatic hernia has brought out the most creative and innovative efforts of pediatric surgeons in both the laboratory and the intensive care unit.

REFERENCES l. Adelman, S., and Benson, C. D.: Bochdalek hernias i.1 infants: Factors determining mortality. J. Pediatr. Surg., 11:569-573, 1973. 2. Adzick, N. S., Harrison, M. R., and Glick, P. L.: Diaphragmatic hernia in the fetus: Prenatal diagnosis and outcome in 94 cases. J. Pediatr. Surg., in press. 3. Andersen, D. H.: Effect of diet during pregnancy upon the incidence of congenital hereditary diaphragmatic hernia in the rat. Am. J. Pathol., 25:163-185, 1949. 4. Areechon, W., and Reid, L.: Hypolasia of the lung with congenital diaphragmatic hernia. Br. Med. J., 1:230-233, 1963. 5. Ashcraft, K. W., Holder, T. M., Amoury, R. A., eta!.: Diagnosis and treatment of right Bochdalek hernia associated with group B streptococcal pneumonia and sepsis in the neonate. J. Pediatr. Surg., 18:480-485, 1983. 6. Assali, N. S., Johnson, G. H., and Brinkman, C. R., III: Control of pulmonary and systemic vasomotor tone in the fetus and neonate. Am. J. Obstet. Gynecol., 108:761772, 1970. 7. Aue, 0.: Angeborene Zwerchfellhernien. Dtsch. Z. Chir., 160:14, 1920. 8. Ban, J. L., and Moore, T. C.: Intrathoracic tension incarceration in of stomach and liver through right-sided congenital posterolateral hernias. J. Tborac. Cardiovasc. Surg., 66:969-973, 1973. 9. Baran, E. M., Houston, H. E., Lynn, H. B., eta!.: Foramen of Morgagni hernias in children. Surgery, 62:1076--1081, 1967. 10. Bartlett, R. H., Gazzaniga, A. B., Jeffries, M. R., eta!.: Extracorporeal membrane oxygenation (ECMO): Cardiopulmonary support in infancy. Trans. Am. Soc. Artif. Intern. Organs, 22:80-90, 1976. 11. Bedard, M., Splittgerber, F., Cullen, M. L., eta!.: Selection of infants with persistent fetal circulation (PFC) for extracorporeal membrane oxygenation. Pediatr. Res., 19:338, 1985. 12. Bianchi, A., Doig, C. M., and Cohen, S. J.: The reverse latissimus dorsi flap for congenital diaphragmatic hernia repair. J. Pediatr. Surg., 18:560-563, 1983. 13. Bloss, R. S., Aranda, J. V., and Beardmore, H. E.: Congenital diaphragmatic hernia. Pathophysiology and pharmacologic support. Surgery, 89:518-524, 1981. 14. Bloss, R. S., Aranda, J. V., and Beardmore, H. E.: Vasodilator response and prediction of survival in congenital diaphragmatic hernia. J. Pediatr. Surg., 16:118-121, 1981. 15. Bochdalek, V. A.: Einige Betrachtungen iiber die Entstehung des angeborenen Zwerchfellbruches. Als Beitrag zur pathologischen Anatomie der Hernien. Vierteljahrschrift fiir die praktische Heilkunde, 19:89, 1848. 16. Boix-Ochoa, J., Natal, A., Canal, J., eta!.: The important influence of arterial blood gases on the prognosis of congenital diaphragmatic hernia. World J. Surg., 1:783-787, 1977. 17. Boles, E. T., Jr., and Anderson, G.: Diaphragmatic hernia in the newborn: Mortality,

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45. Haller, J. A., Jr., Signer, R. D., Golladay, E. S., et al.: Pulmonary and ductal hemodynamics in studies of simulated diaphragmatic hernia of fetal and newborn lambs. J. Pediatr. Surg., 117:67.'H380, 1976. 46. Hansen, J., Jones, S., Burrington, J., et al.: The decreasing incidence of pneumothorax and improving survival in infants with congenital diaphragmatic hernia. J. Pediatr. Surg., 19:385--388, 1984. 47. Harris, M. C., Moskovitz, N. B., Single, W. D., et al.: Group B streptococcal septicemia and delayed onset diaphragmatic hernia. Am. J. Dis. Child., 135:723--725, 1981. 48. Harrison, M. R., Bjordal, R. I., Langmark, F., eta!.: Congenital diaphragmatic hernia: The hidden mortality. J. Pediatr. Surg., 13:227-230, 1978. 49. Harrison, M. R., Bressack, M. A., Churg, A. M., eta!.: Correction of congenital diaphragmatic hernia in utero. II. Simulated correction permits fetal lung growth with survival at birth. Surgery, 88:260-268, 1980. 50. Harrison, M. R., Jester, J. A., and Ross, N. A.: Correction of congenital diaphragmatic hernia in utero. I. The model: Intrathoracic balloon produces fatal pulmonary hypoplasia. Surgery, 88:174-182, 1980. 51. Harrison, M. R., and de Lorimier, A. A.: Congenital diaphragmatic hernia. Surg. Clin. North Am., 61:1023--1035, 1981. 52. Heidenhain, L.: Geschichte ein Falles von chronischer Incarceration des Magens in einer angeborenen Zwerchfellhernie, welcher durch Laparotomie geheilt wurde, mit anschliessenden. Bemerkungen ueber die Miiglichkert, das Kardiocarcinom der Speiseriihre zu reseciren. Dtsch. Z. Chir., 76:394, 1905. 53. Hobolth, N.: Drugs and congenital abnormalities. Lancet, 2:1333--1334, 1962. 54. Holt, C.: Child that lived two months with congenital diaphragmatic hernia. Philos. Trans., 22:992, 1701. 55. Inselman, L. S.: Growth and development of lung. J. Pediatr., 98:1-15, 1981. 56. Iritani, I.: Experimental study on pathogenesis and embryogenesis of congenital diaphragmatic hernia. Anat. Embryo!., 169:133--139, 1984. 57. Johnson, D. G., Deamer, R. M., and Koop, C. E.: Diaphragmatic hernia in infancy: Factors affecting the mortality rate. Surgery, 62, 1082-1091, 1967. 58. Karl, S. R., Ballantine, T.V. N., and Snider, M. T.: High frequency ventilation at rates of 375--1800 cycles per minute in four neonates with congenital diaphragmatic hernia. J. Pediatr. Surg., 18:822-829, 1983. 59. Kenigsberg, K., and Gwinn, J. L.: The retained sac in repair of posterolateral diaphragmatic hernia in the newborn. Surgery, 57:894-897, 1965. 60. Kent, G. M., Olley, P. M., Creighton, R. E., eta!.: Hemodynamic and pulmonary changes following surgical creation of a diaphragmatic hernia in fetal lambs. Surgery, 72:427-433, 1972. 61. Kittagawa, M., Hislop, A., Boyder, E. A., et al.: Lung hypoplasia in congenital diaphragmatic hernia. A quantitative study of airway, artery and alveolar developments. Br. J. Surg., 58:342-346, 1971. 62. Klein, M. D., Andrews, A. F., Wesley, J. R., et al.: Venovenous perfusion in ECMO for newborn respiratory insufficiency: A clinical comparison with venoarterial perfusion. Ann. Surg., 201:520-526, 1985. 63. Krummel, T. M., Greenfield, L. J., Kirkpatrick, B. V., eta!.: Alveolar-arterial oxygen gradients versus the neonatal pulmonary insufficiency index for prediction of mortality in ECMO candidates. J. Pediatr. Surg., 19:380-384, 1984. 64. Kup, J.: Zwerchfelldefekt nach Abtreibungsversuch nit chinin. Munch. Med. Wochenschr., 27:2582-2583, 1967. 65. Langer, R., Linhardt, R. J., Hoflberg, S., et al.: An enzymatic system for removing heparin in extracorporeal therapy. Science. 217:261-263, 1982. 66. Langston, C.: Normal and abnormal structural development of the lungs. Prog. Clin. Bio. Res., 140:75--91, 1983. 67. Levin, D. L.: Morphologic analysis of the pulmonary vasculature in congenital left-sided diaphragmatic hernia. J. Pediatr., 92:805--809, 1978. 68. Levin, D. L., Heyman, M.A., Kitterman, J. A., eta!.: Persistent pulmonary hypertension of the newborn. J. Pediatr., 89:626-630, 1976. 69. Levin, D. L., Hyman, A. I., Heyman, M. A., eta!.: Fetal hypertension and the development of increased pulmonary vascular smooth muscles. A possible mechanism for

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72. 73. 74.

75. 76. 77.

78. 79.

80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96.

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97. Simpson, A. S., and Gossage, J. D.: Use of abdominal wall muscle flap in repair oflarge congenital diaphragmatic hernia. J. Pediatr. Surg., 6:42-44, 1971. 98. Sjostrand, J. H., and Ericksson, I. A.: High rates and low volumes-not just a matter of ventilatory frequency. Anesth. Analg., 59:567-576, 1980. 99. Soifer, S. J., Morin, F. C., III, and Heymann, M. A.: Prostaglandin D 2 reverses induced pulmonary hypertension in the newborn lamb. J. Pediatr., 100:458-463, 1982. 100. Soper, R. T., Pringle, R. C., and Scofield, J. C.: Creation and repair of diaphragmatic hernia in the fetal lamb: Techniques and survival. J. Pediatr. Surg., 19:33--40, 1984. 101. Starett, R. W., and de Lorimier, A. A.: Congenital diaphragmatic hernia in lambs: Hemodynamic and ventilatory changes with breathing. J. Pediatr. Surg., 10:575-582, 1975. 102. Stevens, D. C., Schreiner, R. L., Bill, M. J., et al.: An analysis of tolazoline therapy in the critically ill neonate. J. Pediatr. Surg., 15:964-970, 1980. 103. Stiles, Q. R., Meyer, B. W., Lundesmith, G. E., et al.: The effects of pneumonectomy in children. J. Thorac. Cardiovasc. Surg., 58:394-400, 1969. 104. Snyder, W. A., Jr., and Greaney, E. M., Jr.: Congenital diaphragmatic hernia: 77 consecutive cases. Surgery, 57:576-582, 1965. 105. Thomas, C. G., and Chilherow, N. R.: Herniation through the foramen of Morgagni in children. Br. J. Surg., 64:215-217, 1977. 106. Toguchi, K., Murashita, M., Mochizuki, T., et al.: Factors influencing survival and successful weaning from clinical ventricular bypass with local heparinization and blood filtration: An analysis of 21 consecutive patients. Trans. Am. Soc. Artif. Intern. Organs, 25:176-180, 1979. 107. Toomasian, J. M., Helmer, G. A., Zeme, M. I., et al.: Control of thrombosis in extracorporeal circulation: Variations of anticoagulation. Trans. Am. Soc. Artif. Intern. Organs, 29:206-209, 1983. 108. Touloukian, R. J., and Hobbins, J. C.: Maternal ultrasonography in the antenatal diagnosis of surgically correctable fetal abnormalities. J. Pediatr. Surg., 15:373--377, 1980. 109. Ward, R. M.: Pharmacology oftolazoline. Clin. Perinatal., 11:703-713, 1984. llO. Warkany, J., and Roth, C. B.: Congenital malformations induced in rats by maternal vitamin A deficiency. J. Nutr., 35:1-ll, 1948. lll. Wayne, E. R., Burrington, J.D., and Davis, W. S.: Eventration of the diaphram. Pediatr. Surg., 9:643-651, 1974. ll2. Weiner, E. S.: Congenital posterolateral diaphragmatic hernia: New dimensions in management. J. Pediatr. Surg., 12:149-156, 1982. ll3. Weiner, E. S., Owens, L., and Salzberg, A. M.: Chylothorax after Bochdalek herniorrhaphy in a neonate. Treatment with intravenous hyperalimentation. J. Thorac. Cardiavase. Surg., 65:200-205, 1973. ll4. Welch, K. J.: The thoracic parietes. In Complications of Pediatric Surgery. Philadelphia, W. B. Saunders Company, 1982, pp. 170-181. ll5. Wells, L. J.: Development of the human diaphragm and pleural sacs. Contrib. Embryol., 35:109-133, 1954. ll6. Wesselhoeft, C. W., and DeLuca, F. G.: Neonatal septum transversum defects. Am. J. Surg., 147:481-485, 1984. ll7. White, J. J., Andrews, H. G., Risenberg, H., et al.: Prolonged respiratory support in newborn infants with a membrane oxygenator. Surgery, 70:288-296, 1971. ll8. Wiseman, N. E., and MacPherson, R. I.: "Acquired" congenital diaphragmatic hernia. J. Pediatr. Surg., 12:657-665, 1977. ll9. Wohl, M. E. B., Griscom, N. T., Strider, D. J., et al.: The lung following repair of congenital diaphragmatic hernia. J. Pediatr., 99:405-414, 1977. 120. Woolley, M. M.: Congenital posterolateral diaphragmatic hernia. Surg. Clin. North Am., 56:317-327, 1976. 121. Zwishenberger, J., Toomasian, J., Draken, K., et al.: Total respiratory support with single cannula veno-venous ECMO: Double lumen continuous flow vs. single lumen tidal flow. TASAIO (Abstracts), 14:66, 1985. Michael D. Klein, M.D. Children's Hospital of Michigan 3901 Beaubien Boulevard Detroit, Michigan 48201