Tracheal resection and reanastomosis in the neonatal period.

BACKGROUND/PURPOSE: Severe congenital tracheal stenosis is rare. Most of these can be managed conservatively before elective repair. Focal tracheal stenosis has been treated with resection of the involved trachea and primary reanastomosis in older infants. The authors found no reports of repair of this lesion in neonates. Two patients are presented with severe respiratory failure on the first day of life that required extracorporeal life support (ECLS) who underwent successful tracheal resection and reanastomosis (TRR) during the first week of life. METHODS: A retrospective review was conducted. RESULTS: Both babies had severe pulmonary hypertension and carbon dioxide retention despite maximal therapy and were placed on ECLS shortly after transfer. One had an isolated stenosis of the upper trachea, and the other had agenesis of the right lung, esophageal atresia with tracheoesophageal fistula, and a tracheal stenosis at the end of a short trachea with a long, narrow left bronchus. Both underwent diagnostic studies and had surgical repair while on ECLS at day 3 and 7 of life without bleeding complications. They were weaned off ECLS 1 and 8 days after surgery. One patient was extubated and did well. The other was extubated transiently, but required a tracheostomy because of left mainstem bronchomalacia. Both are alive and well at 18 and 38 months of age, with no narrowing of the repairs. CONCLUSION: In the setting of severe respiratory failure requiring ECLS support, TRR can be performed safely and successfully in the neonate with focal tracheal stenosis.

Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension associated with pulmonary hypoplasia.

BACKGROUND/PURPOSE: Recurrent pulmonary hypertension in the neonatal population is an unusual event with dire consequences. Pulmonary hypertension seen in association with pulmonary hypoplasia may be refractory to conventional medical management. The effect of the calcium channel antagonist diltiazem was studied in five patients with severe pulmonary hypertension. METHODS: A retrospective review of the hospital records was performed to determine the efficacy of diltiazem for refractory pulmonary hypertension. All five patients experienced and did not respond to maximal conventional therapy, which included inhaled nitric oxide, intravenous nitrates, and extracorporeal membrane oxygenation (ECMO). Right ventricular pressures were determined by transthoracic echocardiograms and were used to document improvement in the pressure gradients. Statistical analyses were performed using a paired Student's ttest. A P value of less than .05 was considered significant. RESULTS: Diltiazem significantly reduced the right ventricular systolic pressure (RVSP) from 82 +/- 8.4 mm Hg to 58.4 +/- 7 mm Hg (P = .008). Two patients died; one had a large ventricular septal defect, and the other suffered multisystem organ failure secondary to sepsis. The surviving patients were weaned off diltiazem and did not experience recurrent pulmonary hypertension. CONCLUSIONS: In cases of pulmonary hypoplasia with recurrent pulmonary hypertension, diltiazem may be considered as a therapy. A multicenter prospective trial is advocated.

Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure.

HYPOTHESIS: Extracorporeal membrane oxygenation (ECMO) is effective in nonneonatal acute respiratory failure under certain circumstances. DESIGN: Retrospective medical record review. SETTING: The intensive care unit of a tertiary care hospital. PATIENTS: Thirty-four nonneonatal patients (mean age, 22 years; range, 8 days to 56 years), with ratios of the PaO2 to the fraction of inspired oxygen persistently below 70, who were treated with ECMO after maximal ventilator therapy had failed (mean time of ventilator therapy, 6.9 days; range, 1-41 days). The mean ECMO duration was 304 hours (range, 56-934 hours). Patients were grouped into 7 categories based on their diagnosis: sepsis or sepsis syndrome (n = 3), bacterial or fungal pneumonia (n = 10), viral pneumonia (n = 5), trauma or burn (n = 2), inhalation injury without burn (n = 1), immunocompromised state (due to transplantation or chemotherapy) (n = 8), and acute respiratory failure of unknown origin (n = 5). MAIN OUTCOME MEASURE: Survival to hospital discharge following ECMO therapy. RESULTS: Overall survival was 53% (18 patients). All 6 patients (100%) with viral pneumonias or isolated inhalation injuries survived. Of 13 patients with bacterial pneumonia, sepsis, or sepsis syndrome not complicated by multiorgan failure, 10 (77%) survived. In contrast, all but 1 of the immunocompromised patients died. Survival in patients who were intubated for less than 9 days before ECMO was 64%, whereas survival fell precipitously to 22% for patients who experienced mechanical ventilation for 9 or more days before the implementation of ECMO. Finally, the proportion of patients who died while receiving ECMO therapy was greater when the ECMO duration exceeded 300 hours (62% vs. 38%; P<.05). CONCLUSIONS: Nonneonatal survival with ECMO therapy is strongly dependent on the diagnosis. Pre-ECMO intubation for less than 9 days had little effect on survival. Survival rates decreased when the length of time of receiving ECMO exceeded 300 hours.

Prenatal glucocorticoids improve pulmonary morphometrics in fetal sheep with congenital diaphragmatic hernia.

PURPOSE: Prenatal glucocorticoids reverse pulmonary immaturity in rodents with pharmacologically induced congenital diaphragmatic hernia (CDH). The authors applied quantitative stereologic morphometric techniques to test whether these effects could be reproduced in large animals (sheep) with surgically created CDH. METHODS: Diaphragmatic hernias were created surgically in fetal lambs at gestational day 80. The fetuses were treated with intravenous cortisol (n = 6) or normal saline control (n = 5) from days 133 to 135. Lungs distended at 15 cm pressure from each group were harvested at day 136, processed histologically, and studied by brightfield microscopy at 400 x using a 42-point equidistant counting grid. Ten morphometric parameters (Mean +/- SEM) were measured by point-counting 60 fields/lung, and analysis of variance was performed. RESULTS: The CDH-cortisol-treated lungs showed striking significant maturational improvements when compared with lungs of CDH-normal saline controls by seven of ten morphometric parameters. CONCLUSIONS: (1) Prenatal glucocorticoids accelerate lung maturity in fetal lambs with CDH by seven quantitative morphometric parameters. (2) The observation that prenatal glucocorticoid therapy improves measures of maturity for both CDH rodent and sheep models encourages proceeding with a Phase I human clinical trial in ultrasound-confirmed CDH.

Infantile intestinal leiomyosarcoma: surgical resection (without adjuvant therapy) for cure.

A 7-week-old boy presented with a 6-week history of failure to thrive, acute intestinal obstruction, and an apparently irreducible intussusception (noted on contrast enema). He underwent abdominal exploration, during which a cecal mass was identified and resected. The mass proved to be a leiomyosarcoma. Histologically, it was an intermediate-grade malignancy with a predicted 5-year survival rate of 16% to 23% based on data from the adult experience. Three years after resection and without having received adjuvant therapy, he is healthy and free of disease. A review of the literature showed that in infants these tumors are predominantly colonic, compared with the predilection for small intestinal lesions found in the older pediatric and adult populations. Infantile intestinal leiomyosarcomata are rare malignancies that do well if complete surgical excision of the disease can be accomplished. The histological prognostic indicators proposed for intestinal leiomyosarcomas in the adult population cannot be extrapolated to infants because when they occur in infants, they appear to be less aggressive, and these patients do well without adjuvant therapy.

Prenatal glucocorticoid therapy reverses pulmonary immaturity in congenital diaphragmatic hernia in fetal sheep.

OBJECTIVE: To assess the feasibility of conducting clinical trials of prenatal steroid therapy for congenital diaphragmatic hernia (CDH) in humans, the authors tested whether prenatal glucocorticoid, currently the standard treatment to minimize respiratory distress syndrome in premature infants, might improve the pulmonary immaturity in severe CDH in a large animal model. SUMMARY BACKGROUND DATA: The authors have used the nitrofen-induced rat model of CDH, which demonstrates immature lungs by biochemical, morphometric, and molecular biologic criteria. They also have shown that the lethally immature lungs of the full-term CDH rats can be improved by biochemical, morphometric, physiologic, and molecular criteria by treating the mothers with parenteral steroids at doses extrapolated from the current therapy used to accelerate lung development of premature human babies. METHODS: During a 3-year period in 88 fetal sheep, 1) left-sided diaphragmatic hernias were created surgically at varying gestational ages (day 78-90; term = 142-145 days) and size to maximize severity (n = 45), 2) placement and design of indwelling fetal intravenous catheters were optimized (n = 13), and 3) timing and dosage of cortisol administration were determined (n = 17). As a result, diaphragmatic hernias were created on day 80, intravenous catheters were placed on day 120, and twice-daily intravenous cortisol injections (n = 8) or saline as the control (n = 5) were administered (days 133-135). Lambs were delivered on day 136 via cesarean section to avoid steroid-induced abortion; vascular access was obtained, and the fetuses were ventilated at standard settings. Physiologic data were collected, and lungs were harvested for biochemical and histologic analysis. RESULTS: Significant improvements were measured in postductal arterial oxygen pressure ([PaO2] 38 +/- 6 mmHg after cortisol therapy compared with 20 +/- 3 mmHg for saline controls; p = 0.002) and in dynamic compliance (0.42 +/- 0.05 mL/cm H2O vs. 0.29 +/- 0.01 mL/cm H2O; p = 0.01). Lung glycogen levels in the right lung of the cortisol group were significantly better than controls (4.6 +/- 0.3 mg/g lung vs. 6.8 +/- 0.4 mg/g; p = 0.002), as were protein/DNA levels (8.3 +/- 0.9 mg/mg vs. 14.5 +/- mg/mg; p < 0.05). Striking morphologic maturation of airway architecture was observed in the treated lungs. CONCLUSIONS: Prenatal glucocorticoids correct the pulmonary immaturity of fetal sheep with CDH by physiologic, biochemical, and histologic criteria. These data, combined with previous small animal studies, have prompted the authors to initiate a prospective phase I/II clinical trial to examine the efficacy of prenatal glucocorticoids to improve the maturation of hypoplastic lungs associated with CDH.

Surgical evaluation and management of refractory constipation in older children.

Chronic constipation is a common childhood problem that accounts for 3% to 5% of pediatric visits and 10% to 25% of referrals to pediatric gastroenterologists. The etiology of constipation can be elusive, and extensive investigation often fails to identify a specific cause. The authors conducted a 5-year retrospective review of the patients referred for deep transanal rectal biopsy to determine the usefulness of this procedure in the evaluation and subsequent surgical management of refractory constipation. Specimens obtained by transanal rectal biopsy established a diagnosis for 30 of the 70 patients, and 17 of these 30 had subsequent procedures in the treatment of their constipation. The authors conclude that transanal rectal biopsy identifies a significant number of patients with previously unidentified neuroenteric disorders who may benefit from additional surgery in the treatment of constipation refractory to medical management.

Type IV laryngotracheoesophageal clefts: surgical management for long-term survival.

Complete laryngotracheoesophageal clefts (types III and IV) are rare congenital anomalies that occur when the primitive foregut fails to separate into the tracheobronchial tree and the esophagus. This article summarizes a 10-year institutional experience with six infants who had type IV clefts, presents a modification of the authors' surgical approach, and identifies pitfalls in the management of these infants. Three of the six children are long-term survivors. The recognition of specific complicating issues leads to a standardized approach, which can result in successful repair and long-term survival.

Permissive hypercapnia as a ventilatory strategy in burned children: effect on barotrauma, pneumonia, and mortality.

OBJECTIVE: To document the incidence of barotrauma, pneumonia, and respiratory death associated with a mechanical ventilation protocol based on permissive hypercapnia in pediatric burn patients. DESIGN: Retrospective review. MATERIALS AND METHODS: Patients were managed using a mechanical ventilation protocol based on permissive hypercapnia, tolerating moderate (pH > 7.20) respiratory acidosis to keep inflating pressures below 40 cm H2O. MAIN RESULTS: Over a 2.5-year interval, 54 burned children (11% of 495 acute admissions) with an average age of 6.5 years (range 5 weeks to 17 years), average burn size of 44% (range 0 to 98%), and median burn size of 46% required mechanical ventilatory support for an average of 12.5 days (range 1 to 56 days). Inhalation injury was diagnosed in 34 (63%) of the children and 72% percent were admitted within 24 hours of injury. Overt barotrauma occurred in 5.6% of the patients, pneumonia in 32%, and respiratory death in 0%. CONCLUSIONS: A conventional ventilation protocol based on permissive hypercapnia is associated with acceptable rates of barotrauma and pneumonia. The low incidence of respiratory death associated with this strategy suggests that it also minimizes ventilator-induced lung injury.

Left ventricular failure complicating severe pediatric burn injuries.

PURPOSE: Despite improvements in the overall survival rates for critically burned children, failed resuscitation may account for 54% of deaths following burn injuries. Clinical and experimental studies have implicated failure of the right side of the heart in adults, biventricular failure in elderly patients, and inadequate resuscitation as causes of refractory burn shock. This retrospective study of resuscitation at a tertiary pediatric burn center showed that myocardial depression is a complicating factor in the treatment of the pediatric burn victim. METHODS: From 1989 to 1992, 28 critically burned children (> or = 60% total burn surface area) were resuscitated primarily at our center (admission within 24 hours of injury). Twenty-seven children had central lines, nine of whom underwent pulmonary artery catheterization for intensive hemodynamic monitoring because standard resuscitative therapy had failed. The average amount of fluid received at 8 and 24 hours after injury was within 10% of the calculated volume based on the Parkland formula. RESULTS: Indexes of a failing rescue attempt included respiratory distress (PaO2/FlO2 < or = 200), central venous pressure of greater than 10 mm Hg, and urine output of less than 1 mL/kg/h. Filling pressures were found to be normal or elevated in all children, indicating adequate volume replacement. Evaluation of cardiac function was performed using a thermodilution technique and showed that 100% of the study group had depressed left ventricular function, with an average left ventricular stroke work index (LVSWI) of 19.9 g.m/m2 (normal, 44 to 68 g.m/m2), whereas only 38% had concomitant right ventricular failure. This left-sided dysfunction persisted throughout the acute resuscitation period but was improved after appropriate modification of fluid resuscitation and initiation of vasopressors (average final LVSWI, 38.0 g.m/m2). There were no complications from placement of the Swan-Ganz catheters in this group. CONCLUSION: Cardiogenic failure is a major determinant of a failing pediatric burn resuscitation, and, contrary to the adult burn patient, the myocardial depression is predominantly left-sided. Information from pulmonary artery catheters can help direct therapy by providing indications for vasopressors and modifying fluid resuscitation.

The burn unit as a resource for the management of acute nonburn conditions in children.

Burn units bring together resources to manage large complex wounds, organ failures, and the hypermetabolic response to injury. These resources can also facilitate management of other problems such as purpura fulminans, toxic epidermal necrolysis, staphylococcal scalded skin syndrome, and major mechanical soft-tissue injuries. During a recent 10-year interval 2.4% of all acute admissions to a regional pediatric burn facility were in this category and form the basis for this review.

Immunologically nonspecific mechanisms of tissue destruction in the rejection of skin grafts.

When mice are lethally irradiated and reconstituted with allogeneic bone marrow cells, their skin is repopulated over a period of several months with Langerhans cells (LC) of marrow donor origin. Skin from such mice, when transplanted to unirradiated syngeneic recipients, became in many cases the sites of intense inflammatory responses that led to varying degrees of destruction of the transplanted skin and in some instances, to rejection of the entire graft. The frequency and intensity of these responses were influenced by the nature of the immunogenetic disparity between the donors and recipients of the marrow cells. Chimeric skin placed on hybrid mice derived from crosses between the marrow donors and recipients behaved in all respects as syngeneic grafts or autografts. When the recipients of the chimeric skin were presensitized to the antigens of the marrow donor, the responses were especially intense, and resulted in all cases in complete rejection. Thus the immunologically mediated attack on the allogeneic LCs was accompanied by widespread and nonspecific destruction of bystander cells. In all cases, the inflammation and tissue damage were confined sharply to the grafted skin, showing clearly that nonspecific or indirect tissue destruction is entirely consistent with highly selective destruction of grafted tissues. This finding removes a major objection to postulated mechanisms of rejection that involve indirect destruction of grafted tissues.

Mortality and respiratory failure in a pediatric burn population.

A 9-year retrospective review of 1,242 admissions to a tertiary burn center identified 137 patients who were intubated and ventilated for a critical airway or pulmonary problem. These patients varied in age from 2 months to 18 years with an average total body surface area (TBSA) burn of 55%. We evaluated this group for evidence of respiratory failure (ARF) as defined by the respiratory failure index (RFI) (PaO2/FIO2 < or = 300). While only 23% of admissions to the burn center were related to flame burns, these injuries accounted for 82% of children who had ARF. Forty-two percent of these intubated children had abnormalities on their admission chest x-ray and 61% of this cohort developed evidence of ARF as defined by the RFI. The development of sepsis along with ARF regardless of TBSA involvement doubles the mortality of ARF alone. Early burn wound excision and grafting is critically important to prevent the late complication of sepsis. We carefully monitor ventilator settings to insure low peak inspiratory pressures, allowing relative hypercapnia and avoiding hyperoxia. Despite an increased number of admissions and critically injured children, we have not seen an increase in morbidity and have had a 53% reduction in mortality in the last 2 years with these techniques. We believe this management offers the best outcome for the pediatric burn victim and would recommend this strategy to other centers dealing with these severely injured children.

A case of a closed partial cloacal septation defect with a patent urachus.

A boy with a closed partial cloacal septation defect with a patent urachus is reported. He had an intact abdominal wall, a patent urachus, a colovesical fistula, intact genitalia and urethra, imperforate anus, and a lipomyelocystocoele. Patients with similar constellation of findings have been reported as cloacal exstrophy variants. What distinguishes this case from the other reported variants is the intact abdominal wall with the patent urachus, the small and normally formed phallus and urethra, and the presence of a lipomyelocystocoele. We discuss the possible embryologic mechanism responsible for this boy's findings and possible relationship with the cloacal exstrophy spectrum. We also discuss new terminology for the epispadias-exstrophy spectrum. Furthermore this case reminds us that there is considerable variability within the epispadias-exstrophy spectrum.

Treatment of acute pulmonary failure with extracorporeal support: 100% survival in a pediatric population.

Since February 1990, five children, aged 10 days to 6.5 years, were treated with extracorporeal lung support at our hospital for acute, unrelenting pulmonary failure. Two had viral pneumonia: one with respiratory syncytial virus (RSV) bronchiolitis, and one with herpes simplex virus pneumonia, encephalitis, and disseminated intravascular coagulation. One presented with a febrile illness followed by a pulmonary hemorrhage. Two patients had adult respiratory distress syndrome (ARDS) complicating severe systemic illnesses, toxic epidermal necrolysis in one and cat scratch disease with encephalitis in the other. All children had diffuse parenchymal lung disease by chest x-ray. On maximum medical management all patients were developing carbon dioxide retention and progressive hypoxemia, exceeding previously established NIH study criteria for extracorporeal treatment. Three children (10 days, 2 months, 13 months) were placed on venoarterial support and two children (20 months and 6.5 years) were placed on venovenous extracorporeal support (ECCO2R). Three of the five had open lung biopsies performed, which showed findings consistent with a moderate to severe cellular phase of ARDS. No viral inclusions were found in the patient with RSV infection. One hundred percent immediate survival was achieved in this patient population. Average duration of support was 330 hours (range, 89 to 840). Following completion of extracorporeal support, all children were successfully weaned from the ventilator with an average time to extubation of 23.2 days (range, 2 to 58 days). One child died of congestive heart failure following palliative surgery for a complex noncyanotic congenital cardiac lesion 35 days after successfully weaning from extracorporeal support for an acute febrile illness and pulmonary hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Ectopic class II major histocompatibility antigens in Hirschsprung's disease and neuronal intestinal dysplasia.

Although the etiology of Hirschsprung's disease and neuronal intestinal dysplasia remains obscure, both have histological abnormalities involving ganglion cells and neuronal elements. Searching for a common pathway that may inhibit normal maturation of neurogenic precursors, we examined the possible role of an immune mechanism in the maldevelopment of the enteric neural network. Six patients with Hirschsprung's disease were studied by comparing biopsy specimens from diseased colon with ones taken from proximal ganglionic colon in the same patients. These were similarly compared with colonic biopsy specimens from patients studied with chronic constipation or bowel removed at the time of operation for other disorders. Biopsies were taken from four other patients with neuronal intestinal dysplasia. Each was examined by hematoxylin & eosin staining, acetylcholinesterase histochemistry, and immunohistochemistry of major histocompatibility complex (MHC) class I and class II antigens. All rectal samples from Hirschsprung's disease patients exhibited elevated acetylcholinesterase histochemistry and absent ganglia to confirm the diagnosis. These findings were correlated with marked elevation of class II MHC in the aganglionic area, whereas the proximal normal ganglionic segments showed no elevation. Rectal biopsy specimens from patients with chronic constipation exhibited no such elevation. A similar elevation of class II MHC was detected in the mucosa and submucosa of all four patients with the rare neuronal intestinal dysplasia disorder whose diagnosis was confirmed by giant ganglia in Auerbach's plexuses, aberrant Meissner's ganglia in the lamina propria mucosa, and giant neurofibrils in the mucosa and submucosa. The correlation of elevated class II MHC in these two neuronal dysfunction disorders may indicate an underlying autoimmune mechanism as is seen in thyroiditis and insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Laryngotracheoesophageal cleft (type IV): management and repair of lesions beyond the carina.

Since the first successful repair of a complete laryngotracheoesophageal cleft (LTEC) to the carina in 1982, three newborn infants were observed with a particularly difficult variant in which the cleft extends beyond the carina into the mainstem bronchi. This type IV LTEC creates a long common tracheoesophagus, whose successful separation requires meticulous preoperative, operative, and postsurgical care. Three infants had complete surgical repair at our institution at 29, 49, and 225 days old and survived a minimum of 8 months. Recurrent tracheoesophageal fistulae at the thoracic inlet occurred in two infants, but was not observed in one patient when sternocleidomastoid muscle was interposed between the trachea and esophagus in the neck. Microgastria is an associated finding in each infant with the tracheoesophageal cleft extending beyond the carina. The small stomach is problematic as it is anatomically inadequate for any antireflux procedure and has not grown well, even with prolonged feeding. Early cleft repair is essential to prevent the development of chronic lung disease secondary to recurrent aspiration. The techniques to make the diagnosis, the preferred treatment to initially protect the airway, a single-stage operation performed simultaneously through the chest and neck to definitively repair the cleft, and finally the intraoperative and postoperative management critical for an optimal outcome are described.

Aberrant colonic expression of MHC class II antigens in Hirschsprung's disease.

The major histocompatibility complex (MHC) Class I and II cell surface antigens responsible for the recognition of self vs non-self were studied in patients with documented Hirschsprung's disease. Monoclonal antibodies reactive with monomorphic determinants of human lymphocyte antigen (HLA)-A,B,C (Class I) and HLA-DR (Class II) were used to demonstrate immunohistochemically the expression of MHC antigens in 27 biopsy specimens from a variety of colorectal disorders. The rectal specimens examined from patients with Hirschsprung's disease showed an unexpected, marked elevation of Class II antigens with abnormal localization in the mucosa and lamina propria. This ectopic expression was not seen in any portion of the small or large bowel of patients who did not have Hirschsprung's disease. Furthermore, proximal normal colon of children with Hirschsprung's disease failed to show increased expression of Class II antigen. In an attempt to better define the effector arm at a cellular level, the distribution of helper T cells (CD4+), cytotoxic/suppressor T cells (CD8+) and natural killer cells (NK; CD16+) was examined in 5 cases. In Hirschsprung's disease, rectal infiltration of CD8+ and CD16+ cells was found, but not CD4+ cells. Ectopic expression of Class II antigen with increased numbers of rectal T cells and NK cells suggested that an early immunologic event may be causal in Hirschsprung's disease.