Congenital diaphragmatic hernia: experience with preoperative stabilization and delayed surgery without ECMO and inhaled nitric oxide

Despite many advances in the management of congenital diaphragmatic hernia (CDH), the condition carries a mortality rate of 40-50% usually consequent to pulmonary hypoplasia and/or persistent pulmonary hypertension. Several centers have reported improved survival with preoperative stabilization and delayed surgery, which is now an accepted method of management. This is a retrospective analysis of all neonates with respiratory distress at birth due to CDH who were treated at our institution with neither extracorporeal membrane oxygenation nor nitric oxide being used. The medical records of all neonates with CDH and respiratory distress at birth who were treated at this institution from August 1, 1992 through March 1, 1997 were reviewed. There were 21 patients, 11 male and 10 female. There were 17 full-term and 4 premature infants; two premature infants at 30 and 34 weeks' gestation were not resuscitated because of severe associated congenital anomalies. Surgery was performed from 5 to 144 hr (mean 45 hr) in 18 infants. One infant died during preoperative stabilization from severe pulmonary hypoplasia and pulmonary hypertension and one infant died postoperatively from the same conditions. Seventeen of 19 infants (89.5%) survived and were discharged home. Three infants (17.6%) who failed to thrive due to severe gastroesophageal reflux (GER) required fundoplication. Eleven infants (64.7%) who had sepsis proven by blood culture responded satisfactorily to appropriate antibiotics. Preoperative stabilization and delayed surgery has been a satisfactory form of management in our series. The significant complication was sepsis, which must be addressed.     

Improved results in patients who have congenital diaphragmatic hernia using preoperative stabilization, extracorporeal membrane oxygenation, and delayed surgery

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia. The pulmonary vascular bed may be extremely reactive to various stimuli, and in the treatment it is important to avoid pulmonary vasospasm. The strategy in our institution since 1990 has involved a prolonged preoperative stabilization with gentle mechanical ventilation. Pressures have been kept as low as possible, and slight hypercarbia has been accepted. Peak inspiratory pressures exceeding 35 cm H2O have been avoided. Extracorporeal membrane oxygenation (ECMO) has been used according to standard inclusion criteria. Nitric oxide and high-frequency oscillation have been added to the therapeutic modalities during the study period. When the patient was considered stabilized, surgical repair was undertaken after a delay of 24 to 96 hours. In patients on ECMO who could not be decannulated, surgical repair was undertaken while on ECMO. From 1990 through 1995, 52 patients were admitted with a diagnosis of CDH. Forty-three of these were risk group patients presenting with respiratory distress within 6 hours after birth. A total of 48 patients survived (survival rate 92%), and 39 of the risk group patients (survival rate 91%). There were only four hospital deaths, all with contraindications to ECMO. It is suggested that the adopted protocol is beneficial in the treatment of CDH and that the fraction of patients who have pulmonary hypoplasia incompatible with life is smaller than previously believed.     

Maternal treatment with indomethacin and severe neonatal pulmonary hypertension (author's transl)

The authors report five cases of premature newborns whose mothers had been treated with indomethacin. In all patients, clinical and biological symptoms were those of pulmonary hypertension with persistence of the fetal circulation. In two cases, autopsy showed an important reduction of the lumen of pulmonary arterioles due to a thickening of the tunica media. The role of indomethacin in such respiratory syndrome is very likely. Therefore, indications for that treatment in pregnant women should be reduced.     

Surfactant decreases pulmonary vascular resistance and increases pulmonary blood flow in the fetal lamb model of congenital diaphragmatic hernia

INTRODUCTION: Experiments using animal models of neonatal respiratory distress syndrome have shown a decrease in pulmonary vascular resistance (PVR) with surfactant replacement, whereas studies with the lamb model of congenital diaphragmatic hernia (CDH) have demonstrated improvement in oxygenation and lung mechanics with this therapy. The aim of the present study was to measure the effects of surfactant replacement therapy on the pulmonary hemodynamics of the lamb model of CDH. METHODS: Ten lambs with surgically created CDH and five control lambs were instrumented at term, with the placental circulation intact. Ultrasonic flow probes were positioned around the main pulmonary artery and the common origin of the left and right pulmonary arteries to record total lung and main pulmonary artery blood flow. Catheters were inserted to record systemic, pulmonary, and left atrial pressure. Five CDH animals received 50 mg/kg of surfactant by tracheal instillation just before delivery. All 15 animals were then ventilated for 4 hours. RESULTS: Correcting the surfactant deficiency in the CDH lamb resulted in a significant increase in pulmonary blood flow, a decrease in PVR, and a reduction in right-to-left shunting. These improvements in hemodynamics were associated with a significant improvement in gas exchange over 4 hours. CONCLUSION: The fetal lamb model of CDH has elevated PVR in comparison to controls. Prophylactic surfactant therapy reduces this resistance and dramatically increases pulmonary blood flow while reducing extrapulmonary shunt. A surfactant deficiency may be partially responsible for the persistent pulmonary hypertension in neonates with CDH.     

Spiral computed tomographic scanning of the chest with three dimensional imaging in the diagnosis and management of paediatric intrathoracic airway obstruction

BACKGROUND: The usefulness of spiral computed tomographic (CT) scans of the chest with three dimensional imaging (3D-CT) of intrathoracic structures in the diagnosis and management of paediatric intrathoracic airway obstruction was assessed. METHODS: A retrospective review was made of five consecutive cases (age range six months to four years) admitted to the paediatric intensive care unit and paediatric radiology division of a tertiary care children's hospital with severe respiratory decompensation suspected of being caused by intrathoracic large airway obstruction. Under adequate sedation, the patients underwent high speed spiral CT scanning of the thorax. Non-ionic contrast solution was injected in two patients to demonstrate the anatomical relationship between the airway and the intrathoracic large vessels. Using computer software, three-dimensional images of intrathoracic structures were then reconstructed by the radiologist. RESULTS: In all five patients the imaging results were useful in directing the physician to the correct diagnosis and appropriate management. In one patient, who had undergone repair of tetralogy of Fallot with absent pulmonary valve, the 3D-CT image showed bilateral disruptions in the integrity of the tracheobronchial tree due to compression by a dilated pulmonary artery. This patient underwent pulmonary artery aneurysmorrhaphy and required continued home mechanical ventilation via tracheostomy. In three other patients with symptoms of lower airway obstruction the 3D-CT images showed significant stenosis in segments of the tracheobronchial tree in two of them, and subsequent bronchoscopy established a diagnosis of segmental bronchomalacia. These two patients required mechanical ventilation and distending pressure to relieve their bronchospasm. In another patient who had undergone surgical repair of intrathoracic tracheal stenosis three years prior to admission the 3D-CT scan ruled out restenosis as the reason for her acute respiratory decompensation. CONCLUSIONS: 3D-CT scanning is a useful additional diagnostic tool for intrathoracic airway obstruction in paediatric patients.     

Correction of congenital diaphragmatic hernia in utero VIII: Response of the hypoplastic lung to tracheal occlusion

Most fetuses with congenital diaphragmatic hernia (CDH) diagnosed before 24 weeks' gestation die despite optimal postnatal care. In fetuses with liver herniation into the chest, prenatal repair has not been successful. In the course of exploring the pathophysiology of CDH and its repair in fetal lambs, the authors found that obstructing the normal egress of fetal lung fluid enlarges developing fetal lungs, reduces the herniated viscera, and accelerates lung growth, resulting in improved pulmonary function after birth. They developed and tested experimentally a variety of methods to temporarily occlude the fetal trachea, allow fetal lung growth, and reverse the obstruction at birth. The authors applied this strategy of temporary tracheal occlusion in eight human fetuses with CDH and liver herniation at 25 to 28 weeks' gestation. With ongoing experimental and clinical experience, the technique of tracheal occlusion evolved from an internal plug (two patients) to an external clip (six patients), and a technique was developed for unplugging the trachea at the time of birth (Ex Utero Intrapartum Tracheoplasty [EXIT]). Two fetuses had a foam plug placed inside the trachea. The first showed dramatic lung growth in utero and survived; the second (who had a smaller plug to avoid tracheomalacia) showed no demonstrable lung growth and died at birth. Two fetuses had external spring-loaded aneurysm clips placed on the trachea; one was aborted due to tocolytic failure, and the other showed no lung growth (presumed leak) and died 3 months after birth. Four fetuses had metal clips placed on the trachea. All showed dramatic lung growth in utero, with reversal of pulmonary hypoplasia documented after birth. However, all died of nonpulmonary causes. Temporary occlusion of the fetal trachea accelerates fetal lung growth and ameliorates the often fatal pulmonary hypoplasia associated with severe CDH. Although the strategy is physiologically sound and technically feasible, complications encountered during the evolution of these techniques have limited the survival rate. Further evolution of this technique is required before it can be recommended as therapy for fetal pulmonary hypoplasia.     

Hemoglobin sickle-lepore: an unusual case of sickle cell disease

We report the case of a newborn with a large left-sided congenital diaphragmatic hernia (CDH) who required extra corporeal membrane oxygenation (ECMO) for severe respiratory insufficiency. CDH repair had to be performed on bypass circulation. Intraoperatively, an atypical hemihepatectomy of the herniated lobe was conducted, because reposition of the liver led to a kinking of the vena cava and to a torsion of the right lobe, resulting in ischemia and compromised venous flow. The extraordinary anatomical indication and the potential danger of uncontrollable bleeding are discussed.     

Osteoclastic resorption of bone-like apatite formed on a plastic disk as an in vitro assay system

Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We previously reported altered distribution of CGRP-positive PNEC in full-term rats with CDH, that may lead to an imbalance in vasoactive mediators. In the present study we examined the expression of CGRP-positive PNEC during lung development in rats with CDH induced by 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen). Cesarean sections were performed on Days 16, 18, 20, or 22, and the lungs were immunostained for CGRP and immunoreactive cells were quantitated through image analysis. On Day 16, CGRP-immunoreactive staining was negative; on Day 18, CGRP-immunoreactive cells were found in all controls (not exposed to Nitrofen), whereas in CDH pups, CGRP-positive cells were present in only four of six cases. On Day 20, CGRP immunoreactivity was similar in CDH pups, Nitrofen-exposed pups without CDH, and controls. On Day 22 (term), significantly more CGRP-positive cells (i.e., number of positive cells per surface area [mm2] or lung volume [mm3]) were found in ipsilateral lungs of CDH pups than in controls (P < 0.05). The difference was even more striking in contralateral lungs of CDH pups (P < 0.001), ruling out nonspecific effects of Nitrofen. In CDH lungs, the proportion of immunostained epithelium and the size of the neuroendocrine cell clusters (neuroepithelial bodies [NEB]) were not significantly different from those of controls. On Day 22, supraoptimal dilution immunocytochemistry yielded similar results in CDH pups and controls. We conclude that in CDH, CGRP expression in PNEC and NEB is delayed during early stages of lung development. Because CGRP also exhibits growth factor-like properties for endothelium and epithelial cells, the lack of this factor during a crucial developmental stage (canalicular period) may be causally related to lung hypoplasia.     

Identification of an HLA-C variant allele, Cw*0805, by sequencing based typing

CASE REPORT: Oleic acid and oleate are pulmonary toxins used to create laboratory models of acute respiratory distress syndrome, but there is little information on human toxicity. We report the intentional ingestion of 50 mL sodium oleate 20% by a 22-year-old woman with no symptoms for the first 2 days after ingestion. Her respiratory status deteriorated rapidly on day 3 progressing to acute respiratory distress syndrome (PaO2/FIO2 < 100 mm Hg) on day 4. Treatment with high-dose steroids and intensive respiratory support including high-frequency jet ventilation were associated with gradual but complete recovery by day 39. The delayed onset of symptoms suggested that the lung injury was due to the systemic circulation of oleate to the lungs rather than to direct aspiration. In oral poisoning by sodium oleate, the lung is the first and most lethally affected target organ in humans. This case demonstrates that ingestion of a relatively small amount of sodium oleate can cause delayed, progressively severe, lung injury.     

Varied presentations of unilateral lung hypoplasia and agenesis: a report of four cases

Unilateral lung hypoplasia or agenesis can be asymptomatic or present with recurrent respiratory symptoms. The latter may be amenable to surgical treatment in selected cases. Of four children in this report, two are being managed without surgery. A third was relieved of his symptoms by pneumonectomy. The fourth presented with acute foreign-body inhalation into the healthy right main bronchus, and coexistent left pulmonary agenesis was discovered at bronchoscopy. Bronchoscopy and computed tomography were found to be the most useful investigations in management.     

Distribution of hematopoietic stem cells in the mononuclear fraction of human umbilical cord blood]

Specific features of intrathoracic tuberculosis course, outcomes and treatment are outlined for 109 children. In 59 of them tuberculosis was associated with nonspecific respiratory diseases (NRD). 28.8%, 25.4%, 18.6, 27.2% of patients had cystic hypoplasia, chronic hypoplasia, recurrent pneumonia, recurrent bronchitis, respectively. Complicated course of tuberculosis occurred 2 times more frequently in its combination with NRD (71.2%). Destruction and discharge of bacteria were recorded in 49.2 and 47.5% of patients, respectively. Undulating running was 3.4 and side effects 1.6 times more frequent. Tuberculous children with NRD need longer antituberculous therapy using wide-spectrum antibiotics, symptomatic and exercise treatment, massage, surgical intervention if necessary. Complete resolution of lung lesions in NRD children were seen 4.8 times less frequently. In case of late diagnosis 54% of them retained residual changes in the form of lung tissues fibrosis, calcified foci in the lungs and lymph nodes.     

Sudden cardiac death in hypertrophic cardiomyopathy: risk evaluation

The pathophysiology of the lamb model of congenital diaphragmatic hernia (CDH) involves pulmonary hypoplasia, pulmonary hypertension, and surfactant deficiency. Inhaled nitric oxide (NO) is a highly selective pulmonary vasodilator. The aim of this study was to determine the effects of inhaled NO on pulmonary gas exchange, acid-base balance, and pulmonary pressures in a lamb model of CDH with or without exogenous surfactant therapy. At the gestational age of 78 days (full term, 145 days) 11 lamb fetuses had a diaphragmatic hernia created via a left thoracotomy and then were allowed to continue development in utero. After cesarean section, performed at term, six lambs received exogenous surfactant therapy (50 mg/kg, Infasurf) and five served as controls. All animals were pressure-ventilated for 30 minutes and then received 80 ppm of inhaled NO at an F1O2 of .9 for a 10-minute interval. Compared with the control lambs, the lambs with exogenous surfactant therapy had higher pH (7.17 +/- .06 v 6.96 +/- .07; P < .05), lower PCO2 (73 +/- 8 v 122 +/- 20, p < .05), and higher PO2 (153 +/- 38 v 50 +/- 23; P < .05). In control CDH lambs (without surfactant), inhaled NO did not improve pH, PCO2, or PO2, or decrease pulmonary artery pressure. In CDH lambs given exogenous surfactant, NO decreased pulmonary artery pressures (42 +/- 4 v 53 +/- 5; P < .005) and further improved PCO2 and PO2. NO also made the difference between pulmonary and systemic artery pressures more negative in the surfactant-treated lambs (-15 +/- 4 v -2.3 +/- 2.4; P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Antenatal diagnosis and surgical management of congenital cystic adenomatoid malformation of the lung

We experienced 12 cases of congenital cystic adenomatoid malformation of the lung (CCAM) including 6 cases diagnosed antenatally. They were classified into three groups according to the clinical manifestations. Group A was associated with hydrops fetalis (n = 3), group B presented with respiratory distress symptoms after birth (n = 6), and group C showed no respiratory symptoms (n = 3). All cases of group A were lost because of hydrops and respiratory failure due to pulmonary hypoplasia. Because a compression of the mass is thought to be a cause of hydrops, this group is considered to be a good indication for fetal treatment. All cases of group B showed progressive respiratory symptoms a few days after birth which were successfully treated surgically. In 2 of 3 cases of group C, the lesions decreased in size both antenatally and postnatally. We conclude that serial sonographic evaluations for fetal CCAM are important. If the fetus develops hydrops, fetal surgery is to be considered. If not, however, fetal surgery should not be done, because some lesions can shrink in size, or even disappear, while others can be treated successfully after birth by lobectomy or even segmentectomy.     

Neonatal detection of developmental dysplasia of the hip (DDH)

Congenital diaphragmatic hernia (CDH) may be associated with other anomalies, most frequently cardiovascular in nature. Despite fetal echocardiography, diagnosis of an accompanying cardiac malformation often is not made until after birth and sometimes not until after extracorporeal membrane oxygenation (ECMO) has been instituted. Aortic coarctation associated with CDH may occur as an isolated, surgically correctable malformation or it may be a component of the usually fatal left heart "hypoplasia" or "smallness" syndrome. The authors present two cases of aortic coarctation associated with CDH requiring ECMO that illustrate the management challenges of these coincident diagnosis. In one case, the accompanying coarctation was suspected and required precannulation angiography for confirmation, whereas in the other case, the diagnosis of coarctation was not made until after ECMO cannulation. Depending on its anatomic location and severity, an aortic coarctation associated with life-threatening CDH may limit the physiological efficacy of venoarterial ECMO. Furthermore, arterial cannulation for extracorporeal support requires that flow through the remaining carotid artery be maintained during aortic reconstruction, which may prove difficult for lesions best treated by subclavian flap angioplasty. When the diagnosis of coincident aortic coarctation and CDH is suspected or proven before institution of extracorporeal support, serious consideration should be given to venovenous bypass, because this may provide better postductal oxygenation and facilitate aortic repair with the option of left carotid artery inflow occlusion.     

New interpretation and management of dry lung syndrome: a case report

A premature female infant with life-threatening respiratory distress which was diagnosed as 'dry lung syndrome' is reported. The mother had 4 weeks of large volume leakage of the amniotic fluid due to premature rupture of the fetal membranes (PROM) at 23 weeks' gestation. The infant was born after 27 weeks' gestation (birthweight, 1016 g) and was suffering severe respiratory distress. Although a chest radiogram and gastric juice microbubble test did not improve the possibility of respiratory distress syndrome (RDS), very high ventilator settings did not improve her respiratory disorders. Considering the infant's deteriorating respiratory status and the prolonged leakage of the amniotic fluid, we suspected the presence of pulmonary hypoplasia. Although an attempt at high frequency oscillation (HFO) to rescue this infant had no effect, intratracheal instillation of epinephrine (EP) showed dramatic improvement of her respiratory status. This clinical course showed that the patient did not have pulmonary hypoplasia but might have severe airway obstruction and this airway obstruction may be the major cause of 'dry lung syndrome'. We postulate that when a newborn with suspected pulmonary hypoplasia is unresponsive to respiratory support. HFO should be administered. If HFO is ineffective in relieving the respiratory distress, one should suspect the presence of airway collapse and administer a bronchodilator such as EP. If the infant improves, a diagnosis of 'dry lung syndrome' may be assumed.     

Pulmonary reactions after exposure to 3-methylfuran vapour, a fungal metabolite

A case of obstructive pulmonary reaction with flu-like symptoms after exposure to 3-methylfuran is described. This compound is produced by fungi, and can be found in buildings with mould growth. Previous studies have shown that exposure to the substance might increase the prevalence of respiratory symptoms, and is pneumotoxic to animals at high concentrations.     

Multidisciplinary treatment of chronic pulmonary insufficiency. 4. The influence of intrathoracic pressure variations on increases in pulmonary vascular pressure during exercise in patients with chronic obstructive pulmonary disease

In the present era of direct monitoring of pressure in patients with chronic obstructive pulmonary disease (COPD), an appreciation of all factors that may influence the observed pulmonary vascular pressures is essential. Our study examines the impact of respiratory variations in intrathoracic pressure on the recorded pulmonary vascular pressures in 28 patients with COPD. Althouth pulmonary hypertension was present in only nine subjects at rest, all had an abnormal increase in the mean pulmonary arterial pressure during supine exercise. In 15 subjects, this abnormal response was, in part, related to an increase in pulmonary arterial wedge pressure to 15 mm Hg or more. The increase in pulmonary arterial wedge pressure was directly related to the amplitude of the peak-to-peak respiratory variation of such wedge pressure. This variation correlated with the specific airway resistance but was not related to the arterial oxygen pressure or pulmonary vascular resistance. These findings indicate the important influence of exaggerated respiratory effort on the measurement of pulmonary arterial wedge pressure and mean pulmonary arterial pressure in patients with chronic obstructive pulmonary disease.     

Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia

BACKGROUND/PURPOSE: Pulmonary hypertension plays a significant role in the pathophysiology of congenital diaphragmatic hernia (CDH). Although there has been an intensive research effort directed at mediators that may cause pulmonary vasoconstriction, no single agent has been identified. The authors hypothesize that there may be an alteration in the cGMP-nitric oxide (NO) pathway of vasodilatation contributing to the pulmonary hypertension observed in CDH. The purpose of these studies is to begin to elucidate vasoactive properties of pulmonary vessels with particular attention to the cGMP-NO pathway of vasodilatation in fetal lambs with CDH. METHODS: Fourth-generation pulmonary arteries and pulmonary veins were dissected from both right and left lungs of eight, 139-day gestational fetuses with surgically created CDH. Vessels were studied with standard isolated tissue bath techniques. Experiments examined basal release of NO in endothelium-intact PVs and PAs of both right and left lungs by measuring the contractile force of vessels constricted with norepinephrine (NE) in the presence and absence of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (L-NA). Concentration-response curves to the vasodilating agents zaprinast and A23187 were also obtained in vessels contracted by NE. RESULTS: Left and right pulmonary artery responses to NE are enhanced over those of historic controls. Pretreatment of left pulmonary arteries with L-NA enhances the vasoconstrictor response to NE, whereas right PAs show no increased response. Relaxation responses to A23187 and zaprinast, in both left and right pulmonary arteries were not different from control lambs. Relaxation responses of both left and right pulmonary veins to A23187 and zaprinast are blunted compared with controls. This blunting is significantly more in left pulmonary veins than right. Further, right but not left pulmonary veins display enhanced vasoconstrictive response to NE after L-NA pretreatment. CONCLUSIONS: The NO-cGMP pathway of vasodilatation is abnormal in the near term, fetal lamb with CDH. These abnormalities were most apparent in pulmonary veins and may reflect abnormal NOS activity or content between left and right lungs of the fetal lamb with CDH. Pulmonary arteries from CDH lambs have basal and stimulated NO release equal to that of historic controls but appear to be hypersensitive to exogenous vasoconstrictors.     

Specific sensitization of lymphocytes to tumor antigens by co-cultivation with peritoneal cells exposed to such antigens

Twenty-seven cases of congenital posterolateral diaphragmatic hernia past infancy are reviewed in tabular form and discussed as to presenting symptoms, physical and radiographic findings, operative treatment, and final outcome. A ten year old male treated by us is presented as a detailed case report. A great contrast is noted between the acute respiratory symptoms which threaten life in the infant hernia compared with the more chronic and recurrent gastrointestinal and respiratory symptoms in pateints past infancy. Onset of symptoms did not correlate with age or sex. Chest x-ray films and gastrointestinal contrast studies were most helpful in diagnosis. Abdominal and thoracic approaches were equally effective in reducing the herniated viscera and closing the diaphragmatic defect. We believe that long-term survival of patients with congenital posterolateral diaphragmatic hernia may be due to persistence of a confining pleuroperitoneal sac. Rupture of this sac in later life may coincide with onset of the characteristic symptoms which in turn prompt diagnostic studies. Congenital diaphragmatic hernia must be considered in the differential diagnosis of patients with both recurrent gastrointestinal and respiratory complaints. Plain radiographs of the chest and contrast studies of the gastrointestinal tract are necessary to confirm diagnosis preoperatively.