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Background/purpose: Despite improvements in the surgical management of biliary atresia, the long-term incidence of progressive liver failure remains high. Because chronic inflammation involving both bile ducts and liver parenchyma contributes to the pathology, the authors have hypothesized that the liver damage may be altered using immunosuppressive therapy. The aim of this study was to examine the safety and efficacy of long-term steroid therapy in patients with biliary atresia., Methods: A retrospective analysis of all patients with biliary atresia treated with an hepatoportoenterostomy and postoperative steroid therapy at our 3 institutions was undertaken. Patients were treated uniformly with immunosuppressive doses of oral steroids for a minimum of 6 weeks after surgery., Results: Twenty-five infants with biliary atresia were treated with steroid therapy. Overall survival rate was 22 patients (88%) with a mean follow-up period of 50 months. Nineteen patients (76%) became jaundice free with native liver function. Four patients (16%) did not respond to treatment and required transplantation. Age less than 12 weeks was a crucial predictor of success of adjuvant steroid therapy. Cholangitis developed in 8 patients (32%). There were no complications caused by steroid therapy., Conclusions: Steroid administration at immunosuppressive doses markedly improves the clinical outcome within the first 5 years after surgery as measured by jaundice-free status and survival without liver transplantation when compared with concurrent reports. These results suggest that immunosuppressive therapy is safe and has a positive impact on the clinical course of this disease. However, a randomized study is needed to ultimately prove such an hypothesis.

Background/purpose: The mechanisms by which static airway pressures in the developing lung affect development are unknown. The in vitro murine fetal lung model with airway ligation reproduces the phenomenon of intraluminal airway pressure in developing lungs. We have applied the technique of differential display of mRNAs to fetal murine lungs that were maintained in organ culture with and without tracheal ligation. The goal of this investigation was to identify genes that are induced or enhanced by airway pressure during lung development., Methods: Fetuses were harvested from CD-1 mice on gestational day (Gd) 14. The lungs were removed and trachea either transected or ligated and organ cultured for 7 days. Total RNA was extracted from cultured unligated controls and ligated lungs. Reverse transcription (RT) of the purified total RNA from each pooled sample was performed with anchor primer H-T11G or C and one of 24 arbitrary primers followed by polymerase chain reaction (PCR) of the RT mixtures. PCR products were electrophoresed on a DNA sequencing gel. Differentially expressed cDNA bands of interest were cut from the dried gel. Each cDNA was then reamplified. Reamplified cDNAs were extracted, PCR amplified, cloned, and sequenced for homology to existing sequences in the GenBank database., Results: Sequencing identified 4 differentially expressed genes enhanced by tracheal ligation: hepatoma-derived growth factor (HDGF), ribosomal protein S24, stathmin, and parathyroid hormone (PTH)., Conclusions: Genes enhanced by airway pressure or tracheal ligation are mitogenic for fibroblasts, correlate with cell proliferation, regulate cell proliferation and differentiation, and may play a role in growth in distal lung and type II cell differentiation. Further work is necessary to identify the mechanisms by which these genes influence lung maturational processes.

Background/purpose: The addition of growth factors EGF (epidermal growth factor) plus TGFbeta1 (transforming growth factor beta1; E + T) or dexamethasone (DEX) to normal murine fetal lungs in culture enhances lung development. In addition, ligation of the airway in lungs in organ culture, enhances lung development. Nitrofen (2,4-dichlorophenyl-p-nitrophenylether) administration to pregnant mice results in pulmonary hypoplasia in the offspring with many similarities to human hypoplastic lung conditions. This study investigates the effects of growth factors, dexamethasone, and airway ligation on the development of hypoplastic fetal murine lungs in whole-organ culture. We hypothesized that E+T, DEX, or airway ligation will enhance the development and maturation of hypoplastic murine fetal lungs in vitro., Methods: Time-dated pregnant CD-1 mice were given nitrofen, 25 mg, intragastrically at gestational day (Gd) 8. The dams were killed on Gd 14, and the fetuses were removed. The hypoplastic fetal lungs were excised, and the tracheae were transected. The lungs were cultured in serum-free BGJb media in the presence or absence of E+T (10 ng/mL + 2 ng/mL, respectively) or DEX (10 nmol/L). Some lungs were cultured for 7 days with the tracheae ligated., Results: Gross morphology under a dissecting stereomicroscope showed that the lungs were larger after E+T, DEX, or tracheal ligation. Histologically, the untreated lungs had progressed from the pseudoglandular stage to a canalicular-like stage with poorly differentiated airways. The E+T-treated lungs had better developed airway branching and small acini; however, thick mesenchyme persisted. The ligated lungs had well-developed airway branching and acinar structures. After DEX treatment the lungs were most developed with very well defined airway branching and expanded acinar structures; however, there was no secondary septation. Ultrastructurally, the hypoplastic lungs at Gd 14 and after 7 days in culture had no glycogen in their epithelial cells, no defined acinar formation, and had damaged mitochondria. The E+T-treated or tracheally ligated lungs had abundant type II cells, secreted lamellar bodies (LBs), and showed infrequent tubular myelin. Mitochondrial damage was noted in these lungs as in the untreated lungs. DEX-treated hypoplastic lungs showed large acini. The acinar walls were thick; however, they had type II cells with abundant LBs and intact mitochondria. The airways were noted to have differentiated cell types. Surfactant secretions in acinar spaces showed tubular myelin structures., Conclusions: E+T, tracheal ligation, or DEX accelerates lung development and maturation of hypoplastic fetal murine lungs compared with untreated controls. DEX had a greater effect with special reference to repair of mitochondrial damage. DEX not only accelerated lung development, but it may have reversed some of the effects nitrofen.

Background: Pulmonary hypertension (PH) after congenital diaphragmatic hernia (CDH) repair remains a significant cause of morbidity and mortality. Although treatment advances have improved overall survival, a new cohort of patients is surviving with PH beyond the postnatal period. Because the clinical entity of postnatal persistent pulmonary hypertension (PPHTN) in CDH patients has not been published, the authors undertook a retrospective study of our neonatal CDH experience to characterize this group of infants., Methods: Charts of all infants with CDH treated at this institution from January 1991 to June 1997 were reviewed (n = 51). Persistent pulmonary hypertension by echocardiographic (Echo) measurements at the time of discharge identified PPHTN patients. Control survivors had normal pulmonary artery pressures at discharge. Physiological parameters and the results of therapeutic interventions were analyzed to predict PPHTN., Results: Seven infants (four boys, three girls) had PPHTN at discharge. Significant differences with the control group were noted in length of stay, duration of intubation, and duration of nitric oxide therapy. Extracorporeal membrane oxygenation (ECMO) duration was not significantly different between the groups. By 12 months of age, PPHTN resolved in six patients (87%), and one died at 13 months. Regardless of therapy, two parameters showed 100% positive predictive value for identifying patients with PPHTN (P < .001): an Echo demonstrating PH at 2 months of age or continued oxygen requirement at 3 months. Oxygen requirement at 2 months had a 67% predictive value of PPHTN., Conclusions: With current treatment strategies for CDH, infants can survive with persistent pulmonary hypertension beyond the newborn period. The long-term survival rate is excellent, and normalization of pulmonary artery pressures can be expected. PPHTN can be predicted in those infants with Echo-defined pulmonary hypertension at 2 months.

Purpose: The authors hypothesized that increased intraluminal pressure in the fetal stomach would enhance development in a murine organ culture model., Methods: Gestation day 14 (Gd14) fetal stomachs from time-dated pregnant CD-1 mice (term, 20 days) were maintained in organ culture for 7 days. Some stomachs were ligated at the gastroesophageal (GE) and pyloroduodenal (PD) junctions. Others were left unligated. Gd14, Gd16, and Gd18 stomachs were taken as well to compare organogenesis in vivo. Tissues were processed for histological, morphometric, and immunohistochemical analysis, as well as total protein and DNA determination., Results: The ligated stomachs were visibly distended compared with unligated stomachs in organ culture after 7 days. The length and width of the 7-day in vitro ligated stomachs were significantly increased compared with unligated (2.97+/-0.04 mm v 2.48+/-0.05 mm and 2.14+/-0.04 mm v 1.57+/-0.08 mm, respectively, P < .05). Mucosal epithelial cells showed nuclear polarization, and there was a distinct outer muscle layer in the ligated stomachs, but not in the unligated stomachs, which demonstrated pseudostratified epithelial cells in the mucosa. The ligated stomachs had increased in mucosal thickness compared with unligated (31.4+/-1.3 microm vs 24.9+/-0.9 microm, p < 0.05). The ligated stomachs also had significantly increased protein and DNA content when compared with unligated stomachs (65.8+/-3.1 microg and 23.3+/-1.2 microg v 55.0+/-2.7 microg and 19.0+/-1.2 microg, respectively, P < .05). However, there were no significant differences noted between the protein to DNA ratios. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, demonstrated increased proliferative activity of the mucosal epithelial cells in the ligated stomachs., Conclusions: Esophageal and pyloric ligation enhanced the development of the fetal stomach in vitro in comparison with unligated stomachs cultured under similar conditions. Developmental characteristics of the ligated stomachs paralleled that of Gd16 stomachs in vivo.

The authors have previously shown that murine fetal lungs can be maintained in serum-free whole organ culture and that airway ligation accelerates lung development. In spite of extensive use of lung organ culture systems, the vasculature of the unperfused lung in organ culture has not been studied. The aim of the present study was to compare organ cultures of heart-lung blocks with continuous perfusion of the pulmonary vasculature to those without perfusion, ie, whole lungs cultured without the attached heart. Time-dated pregnant CD-1 mice were killed on gestational day (Gd) 14. The fetuses were removed via laparotomy. Heart-lung blocks and whole lungs without the heart were excised under sterile conditions and cultured in BGJb media. Some of the heart-lungs and whole lungs underwent tracheal ligation whereas others were left with the trachea unligated allowing free egress of airway fluid. After 7 days, the cultured organs were processed for histology, ultrastructural analysis, and immunohistochemistry. (1) Lungs were fixed in 10% formalin, paraffin embedded, and processed for routine H&E staining. (2) Lungs were fixed in 2.5% glutaraldehyde in cacodylate buffer and processed for transmission electron microscopy. (3) Lungs were embedded in CRYOform and flash frozen for immunohistochemical localization of PECAM-1 (CD31) (PECAM-1, Platelet endothelial cell adhesion molecule-1, a selective endothelial cell marker). Our daily observations of the cultured organs showed that the heart maintained synchronized beating for all 7 days in culture. Perfusion of the pulmonary microvasculature was demonstrated. Light microscopically, H&E sections showed that fresh fetal Gd14 pseudoglandular lungs (time-zero) had a defined capillary network, which was more centrally localized and peripherally less developed. The presence of more numerous lung capillaries in the cultured heart-lung blocks was noted when compared with cultured lungs alone. Ultrastructurally, endothelial cells with intact structural integrity were identified only in cultured whole lungs with hearts. Immunohistochemical staining of the whole lungs with rat antimurine PECAM-1 monoclonal antibody performed on cryosections showed the presence of vasculature by specific PECAM-1 localization on endothelial cells. PECAM-1 labeling of capillaries was noted in Gd14 (time-zero) lungs. In addition, the lungs cultured with hearts, ie, perfused lungs, showed more well defined, distinct capillary networks stained with PECAM-1 antibody than unperfused lungs without hearts. Our results showed that microvasculature is present in murine fetal lungs at Gd14. After 7 days in organ culture, the maintenance of lung microvasculature was confirmed histologically, ultrastructurally, and immunohistochemically. The microvasculature in whole lungs cultured as perfused/beating heart-lung blocks was better maintained than the microvasculature of unperfused whole lungs cultured without hearts. A perfused whole lung organ culture model is attractive because the lung architecture is better maintained and may be useful in lung developmental studies as it mimics the in situ heart-lung functional physiological relationship.

Evidence exists from both congenital anomalies and animal models that normal fetal lung development is dependent on maintenance of fluid pressure within the developing "airways." Fetal tracheostomy, allowing free egress of airway fluids, results in lung hypoplasia, indicating that some airway distending pressure is required for normal lung development to occur. In contrast, fetal tracheal ligation, which increases fetal airway pressure, reverses lung hypoplasia in animal models. The authors' experiments test the hypothesis that large airway obstruction accelerates the development of murine lungs in vitro in whole-organ culture. Fetuses from time-dated pregnant CD-1 mice at day 14 of gestation were removed (term, 20 days), and the lungs were excised. The left bronchus of each lung was ligated (n = 26), after which the left lung was isolated and cultured at 37 degrees C (95% air, 5% CO2) in BGJb media supplemented with vitamin C and antibiotics. Some fetal lungs were cultured under similar conditions without bronchial ligation (n = 11). After 7 days in culture, the lungs were taken for various analyses. The lungs were fixed in either formaldehyde and processed for paraffin embedding for light microscopic evaluation and morphometric data collection, or were freshly minced and aliquots taken for total protein and DNA content. Several more ligated and unligated lungs were processed for ultrastructural analysis. Morphometric analysis on transverse sections of lungs showed significant differences in the lung tissue size, thickness, epithelial cell height, luminal areas, perimeters, and total number of airspaces (airway + primordial alveolar airspaces). It was evident that bronchial ligation promoted lung development. The ligated lungs displayed thinning of the primordial alveolar walls with cuboidal epithelial cells. The total number of airspaces per field was lower for better developed ligated lungs because of the increased area of airspaces compared with that of the unligated lungs. The dorsoventral tissue thickness (in micrometers) of the ligated lungs was significantly greater than that of the unligated lungs (124.1 +/- 7.0 v 89.6 +/- 8.0); the average outer perimeter of the primordial alveolar airspaces was greater for ligated lungs (404.56 +/- 19.0 microns v 256.85 +/- 17.0 microns). Similarly, the luminal diameter of the spaces of ligated lungs was almost double that of the unligated lungs (38.0 +/- 2.0 microns v 20.3 +/- 2.0 microns), as was the luminal surface area. The morphometric data, which suggest enhanced maturation of the ligated lungs, are supported by results of ultrastructural studies. Ligated lungs had significantly more lamellar bodies. Although total protein and DNA content were greater among the ligated lungs, the protein/DNA ratios did not differ among the groups. The intraluminal pressure (airway pressure) of ligated lungs was 2.9 mm Hg and 3.1 mm Hg at 2 and 4 days in organ culture; the respective pressures for unligated lungs were 1.0 mm Hg and 0.8 mm Hg. These data support the hypothesis that mechanical distending pressure resulting from airway obstruction not only improves pulmonary architecture but also accelerates lung development in vitro. Although these effects have been seen in in vivo models, this is the first proposed in vitro organ culture model. This model may prove to be a powerful tool for the study of molecular mechanisms of mammalian lung development with respect to mechanical and chemical (cytokines, hormones) stimuli.

Although fetal dermal repair is known to be fundamentally different from adult healing, the response to wounding in other organs is less well characterized. Scarless repair in mid-gestation dermis with a transition to adult-type healing at term has been shown in fetal organ culture. A lung explant culture system was used to investigate whether wound repair in the fetal lung shows characteristics similar to those found in fetal dermis. Lungs from 14-day and 18-day Cd-1 murine fetuses and 2-day-old newborns, (term = 20 days, n = 24) were wounded by linear incision and incubated at 37 degrees C, in a 21% O2, 5% CO2 environment, in BGJb supplemented with vitamin C and antibiotics. Medium was changed daily. Samples were fixed at 7 days and embedded in paraffin. Sections were stained with hematoxalyn-eosin and Masson Trichrome. Additional 14-day and 18-day samples were frozen in freon and immunohistochemical staining for TGF-beta performed. Other frozen tissues from each time point were homogenized and used to assay for endogenous TGF-beta levels by Western blot analysis. Histology showed reconstitution of tissue architecture across the wound in 14-day and 18-day specimens. In representative histological sections, intact bronchial architecture developed across the previous wound site. No cellular inflammatory response was observed, and collagen deposition was undetectable at the site of the wound by Trichrome staining. By 22 days the lung explants showed a much less ordered repair, including disorganized collagen deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide (NO) represents a new therapeutic modality for treating neonatal pulmonary hypertension and may obviate the need for extracorporeal membrane oxygenation (ECMO) in a number of cases of neonatal respiratory failure. Recently, the authors treated an infant with a congenital diaphragmatic hernia and pulmonary hypertension with NO on two separate occassions. During the initial period of stabilization, NO failed to reverse the pulmonary hypertension and prevent the development of progressive respiratory failure. After a successful course of ECMO, recurrent pulmonary hypertension developed that was successfully treated with continuous low-dose NO therapy for over 1 month. Prolonged administration of NO in varying doses titrated to clinical and echocardiographic parameters was well tolerated by the infant and prevented the need for a second run of ECMO.

Anterior gastric fundoplication (AGF) has been performed at the University of Michigan since 1988. To objectively evaluate the long-term efficacy of the AGF, the authors performed a study of children who had undergone AGF between June 1988 and June 1990 (n = 46). Six of them died of unrelated causes. Twenty-two consented to follow-up evaluation that included parental interview, physical examination, upper gastrointestinal series (UGI), 24-hour esophageal pH probe monitoring (EpH), and a liquid-phase gastric emptying study. Twenty patients (74%) remained asymptomatic, and only one child required reoperation. Four asymptomatic patients exhibited gastroesophageal reflux (GER) by UGI, and three others by EpH. Three children were noted to have delayed gastric emptying. These results compare favorably with data previously reported from this institution of a 5-year follow-up of children after Nissen fundoplication. There is a trend toward improved efficacy (87% v 74%; P = .12), decreased reoperation rate (4% v 14%; P = .11), and less severe complications. The present study shows that AGF is effective treatment for GER when evaluated by objective studies and is comparable in therapeutic efficacy and safety to the Nissen fundoplication.

This study was undertaken to evaluate factors predictive of postoperative outcome after general surgical (GS) procedures in patients with congenital heart disease (CHD). All patients with a diagnosis of CHD who underwent a GS procedure under general anesthesia during a consecutive 10-year period were considered eligible for the study The congenital heart defect was classified as either simple (ASD, VSD, PDA) or complex (endocardial cushion defects, transposition of the great vessels, tetralogy of Fallot), and the GS procedure as either major (intraperitoneal, intrathoracic, or vascular reconstructive) or minor (inguinal herniorrhaphy, vascular access). The overall mortality rate for the patient population was 12% (27 deaths among 226 procedures), minor procedures being associated with a 3% mortality rate (2 of 70 procedures), and major procedures with a 16% mortality rate (25 of 156 procedures). Incremental risk factors for mortality included a preoperative American Society of Anesthesiologists' (ASA) physical status class of IV or higher (P = .0003), a preoperative in-hospital stay of 10 or more days (P = .004), birth at a tertiary care center (P = .04), and emergency operations (P = .05). In the subgroup of patients less than 6 months old, weight of less than 2.4 kg at the time of surgery and a 1-minute Apgar score of less than 4 were additional independent risk factors (P = .04 and .01, respectively). By logistic analysis, previous corrective cardiac procedures, whether complete or palliative, did not significantly alter the postoperative outcome. The authors conclude that physiologically well-compensated patients with CHD can undergo elective operations at a low operative risk; however, poorly compensated patients undergoing urgent or emergent operations are at high risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Complications after nonoperative management of hepatic trauma are rare but include persistent biliary fistula in 4% of cases. Therapy usually involves surgical drainage or hepatic resection to control the fistula. The authors present a case of hepatic biliary fistula treated nonoperatively with percutaneous drainage and endoscopic sphincterotomy. A 16-year-old girl suffered a grade III parenchymal liver fracture to the right lobe in an automobile accident. She was hemodynamically stable with no coexistent injuries and was treated nonoperatively. Over 2 weeks her total bilirubin rose to 3.2 mg/dL, and alkaline phosphatase was 463 U/L. Ultrasound showed free intraperitoneal fluid, and 2 L of bilious fluid were retrieved by paracentesis. A radionuclide scan confirmed massive extravasation of isotope from the right lobe. Two drains percutaneously placed over the parenchymal fracture produced 500 to 600 mL of bile daily. Endoscopic retrograde cholangiopancreatography (ERCP) 1 week later showed a normal extrahepatic biliary system. A 1-cm sphincterotomy was performed without difficulty. Within 72 hours, percutaneous drains produced only 35 mL per day. The follow-up radionuclide scan showed no evidence of extrahepatic biliary extravasation, and 3 weeks later the drains were removed. Six months after the accident, results of the computerized tomography scan and liver function tests were normal. It was believed that endoscopic sphincterotomy reduced fistula output by decreasing the intrabiliary pressure caused by the ampulla, thus favoring internal drainage. This case demonstrates the effectiveness of endoscopic sphincterotomy as an alternative to direct surgical intervention for the management of posttraumatic biliary fistula.

In models using both intact animals and isolated lungs of rats, rabbits, lambs, and dogs, application of high airway pressure and resultant lung overdistension has been shown to cause lung injury. Under pathological conditions, the more normal portions of the lung may be subjected to relative overdistension when supranormal airway pressures are used. A small animal model of lung overdistension is presented here to demonstrate that lung injury can be caused by moderate lung overdistension. Rats were anesthetized with Ketamine and pentobarbital. A tracheostomy was performed and arterial and central venous catheters placed. The animal was placed in a plethysmograph and an infant ventilator was used to provide mechanical ventilation. In the first experiment, animals in group A (n = 6, control) were ventilated at tidal volume (TV) of 5 mL/kg for 5 hours. Animals in group B (n = 6) were ventilated at TV 15 mL/kg for 60 minutes and then were returned TV of 5 mL/kg for the remainder of the experiment. Animals in group C (n = 5) were ventilated at TV 20 mL/kg for 60 minutes and then returned to TV 5 mL/kg. Static lung compliance and arterial blood gasses were measured. Wet and dry lung weight were obtained after sacrifice. In the second experiment, animals in group D (n = 4, control) were ventilated at TV 5 mL/kg for 240 minutes and killed. Animals in group E (n = 4) were ventilated at TV 20 mL/kg for 60 minutes, returned to TV 5 mL/kg, and killed at 240 minutes. Fluorescein-labeled albumin was administered to each animal prior to mechanical ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

A compact closed-circuit gas exchange monitor (GEM) was built for measurement of oxygen consumption (VO2) in ventilated infants. The GEM includes a ventilator-driven slave bellows, a CO2 scrubber, one-way valves to ensure unidirectional flow, and tubing to complete the small-volume low-compliance system, which fits easily between the ventilator (VENT) and the endotracheal tube (ETT). Oxygen consumption is measured by volume loss from a spirometer attached by a one-way valve. Pressure is monitored at the airway, and the VENT is adjusted to attain the desired pressure pattern. The system was leak tested by placing a 3-kg weight on the spirometer bell (continuous positive airway pressure = 20 cm H2O) and then ventilating with peak inspiratory pressures (PIP) of 60 cm H2O without leak. Bench testing for accuracy of volume loss was checked by ventilating the device into another calibrated spirometer and achieving equal volumes. First, four rabbits were studied to determine the range of ventilator backup rates (BUR = 0 to 60), inspiratory times (IT = .2 to .6 seconds), and airway pressures (up to 40/8 cm H2O) attainable by this device. Then six fasted rabbits weighing 2.2 to 4.0 kg were anesthetized with a ketamine-rompun mixture, underwent tracheostomy, and were placed on a pressure VENT. The BUR was set at 20/min and the IT at .5 seconds. The GEM was placed between the VENT and the ETT, and the PIP was adjusted to maintain PaCO2 between 30 and 40 torr, eliminating spontaneous respiration. Oxygen consumption was measured at five-minute intervals for one hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Closed-circuit spirometry techniques were used to study gas exchange (oxygen and carbon dioxide transport) across the native lung and membrane lung in ten neonates treated with extracorporeal membrane oxygenation (ECMO). Initially there was negligible oxygen transport across the native lung (0.4 +/- 0.4 mL/kg/min). An increase in native lung oxygen transport (2.0 +/- 1.5 mL/kg/min) at low ventilator settings and high levels of extracorporeal support heralded recovery of the native lung and predicted weaning from ECMO. Measurement of oxygen consumption and carbon dioxide production permitted the energy expenditure to be calculated in these critically ill neonates. The metabolic rates varied widely in each neonate over time and among neonates. (mean 57 +/- 11 kcal/kg/d, range 38 to 80 kcal/kg/d). This emphasizes the need to determine energy expenditure in order to guide nutritional support.

Extracorporeal membrane oxygenation (ECMO) has been successful (greater than 80% survival) in 35 centers in greater than 900 newborns with severe respiratory failure having an estimated mortality of greater than 80% on conventional management. During the last 3 years we have treated 79 newborns with 74 survivors (94%). Their diagnoses included meconium aspiration, persistent fetal circulation, respiratory distress syndrome, congenital diaphragmatic hernia, and sepsis. Seven patients (9%) had life-threatening intrathoracic complications requiring emergent intervention while on ECMO: tension hemothorax (3), tension pneumothorax (2), and pericardial tamponade (2). Pericardial tamponade and tension hemothorax and pneumothorax show a similar pathophysiology of increasing intrapericardial pressure and decreasing venous return. Perfusion is initially maintained by the nonpulsatile flow of the ECMO circuit before further decrease in venous return results in decreasing ECMO flow and progressive hemodynamic deterioration. Each of the seven patients demonstrated a clinical triad that includes increasing PaO2 and decreasing peripheral perfusion (as evidenced by decreasing pulse pressure and decreasing SvO2) followed by decreasing ECMO flow with progressive deterioration. The diagnoses were confirmed by transillumination, chest x-ray, or cardiac echocardiogram. Initial emergent placement of a percutaneous drainage catheter was temporizing in all seven cases. However, four patients required emergent thoracotomy for definitive treatment while still on ECMO. All seven patients were weaned from ECMO and are short-term survivors (6 months to 3.5 years). As use of ECMO for newborn severe respiratory failure increases, responsible physicians must be familiar with life-threatening intrathoracic complications and appropriate treatment strategies.