Oxygen and pulmonary vasodilation: The role of oxidative and nitrosative stress.

Respiratory failure complicates up to 2% of live births and contributes significantly to neonatal morbidity and mortality. Under these conditions, supplemental oxygen is required to support oxygen delivery to the brain and other organs, and to prevent hypoxic pulmonary vasoconstriction. However, therapeutic oxygen is also a source of reactive oxygen species that produce oxidative stress, along with multiple intracellular systems that contribute to the production of free radicals in pulmonary endothelium and vascular smooth muscle. These free radicals cause vasoconstriction, act on multiple sites of the nitric oxide pathway to reduce cGMP-mediated vasodilation, and nitrate and inactivate essential proteins such as surfactant. In addition to oxygen, antenatal stressors such as placental insufficiency, maternal diabetes, and fetal growth restriction increase pulmonary and vascular oxidant stress and may amplify the adverse effects of oxygen. Moreover, the effects of free radical damage may extend well beyond infancy as suggested by the increased risk of childhood malignancy after neonatal exposure to hyperoxia. Antioxidant therapy is theoretically promising, but there are not yet clinical trials to support this approach. Targeting the abnormal sources of increased oxidant stress that trigger abnormal pulmonary vascular responses may be more effective in treating disease and preventing long term consequences.

Respiratory failure secondary to congenital pulmonary arterial thrombus with lung dysplasia.

Respiratory failure requiring extracorporeal membranous oxygenation in the newborn is commonly seen secondary to severe pathology such as congenital diaphragmatic hernia, meconium aspiration syndrome, pulmonary hypertension and pulmonary hypoplasia. However, atypical causes of respiratory failure, such as pulmonary arterial thrombi, are often refractory to traditional management and require careful multidisciplinary evaluation. We report a case of respiratory failure secondary to congenital pulmonary arterial thrombosis of unknown aetiology in an otherwise healthy neonate. We discuss the abnormal anatomy and pathophysiology that presented in our patient secondary to this condition and discuss our diagnostic process, management and outcomes. Additionally, we review the literature for reported cases and discuss current hypotheses on the development of congenital pulmonary arterial thrombi. Given the rare occurrence of this event, we hope to contribute to the understanding of future similar cases and emphasise the importance of keeping pulmonary arterial thrombi in the clinical differential.

Extracorporeal membrane oxygenation support in a newborn with lower urinary tract obstruction and pulmonary hypoplasia: a case report.

BACKGROUND: Survival of neonates with intrauterine renal insufficiency and oligo- or anhydramnios correlates with the severity of secondary pulmonary hypoplasia. Early prenatal diagnosis together with repetitive amnioinfusions and modern intensive care treatment have improved the prognosis of these neonates. Extracorporeal membrane oxygenation is an established treatment option, mainly applied to neonates with pulmonary hypoplasia caused by congenital diaphragmatic hernia. However, a few case reports of extracorporeal membrane oxygenation in neonates with lower urinary tract obstruction have been published. CASE PRESENTATION: We describe a case of a Caucasian male infant with prenatally diagnosed lower urinary tract obstruction and secondary pulmonary hypoplasia who was delivered spontaneously at 36 + 2 weeks of gestation. Venovenous extracorporeal membrane oxygenation was initiated on the first day of life for severe respiratory failure and consecutive hypoxemia despite treatment with inhaled nitric oxide and high-frequency oscillation. The patient was supported by extracorporeal membrane oxygenation for 10 days and extubated 6 weeks later. Hemofiltration was required on the second day of life because of renal insufficiency and was later replaced by peritoneal dialysis. The child was discharged after 4 months with nasal high-flow mild oxygen therapy and peritoneal dialysis. CONCLUSION: Neonatal extracorporeal membrane oxygenation support is a possible treatment option for neonates with lower urinary tract obstruction and pulmonary hypoplasia.

Histerectomía radical en paciente con enfermedad de Steinert: raquianestesia, ketamina y bloqueos TA P y de la vaina de los rectos / Radical hysterectomy in a patient with Steinert disease: spinal anaesthesia, ketamine and TAP and rectus sheath blocks

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Quistes pulmonares congénitos / Congenital lung cysts

Las malformaciones pulmonares congénitas constituyen una alteración en el desarrollo embriológico y fetal de las distintas estructuras pulmonares y una rara expresión de estas son los quistes pulmonares congénitos.Se presenta un recién nacido a término, de buen peso, asintomático y estable hasta el tercer día de vida al debutar con un estado de shock séptico secundario, de bronconeumonía complicada con derrame pleural derecho. En los estudios evolutivos hacia el cuarto de día de vida se le diagnostica como hallazgo radiológico la presencia de quistes pulmonares que evolucionan de forma asintomática. Después de una valoración multidisciplinaria es egresado con un seguimiento por su condición de alto riesgo. Actualmente saludable y con buen desarrollo psicomotor.La importancia del tema que se presenta es que se describe una presentación rara de quistes pulmonares congénitos en un recién nacido que desarrolló un estadio avanzado de sepsis(AU)

Congenital lung malformations constitute an alteration in the embryonic and fetal development of the different lung structures and a rare expression of these congenital lung cysts.Termed newborn, good weight, evolving asymptomatic and stable until the third day of life to debut a state of septic shock secondary to complicated bronchopneumonia with right pleural effusion. In evolutionary studies by the fourth day of life it is diagnosed, as radiological finding, the presence of lung cysts evolving asymptomatically. After a multidisciplinary assessment there is a graduate tracking of their status, with high risk. Currently healthy and good psychomotor development.The importance of the issue presented is a rare presentation of congenital lung cysts in a newborn who developed an advanced stage of sepsis was described.

Use of a continuous glucose sensor in an extracorporeal life support circuit.

BACKGROUND: Standard care for infants on extracorporeal life support (ECLS) relies on intermittent measurement of blood glucose (BG); however, this can lead to significant changes in BG that go unrecognized for several hours. The present study was designed to assess performance and clinical applicability of a subcutaneous glucose sensor technology modified for use as a blood-contacting sensor within the ECLS circuit. METHODS: Twelve children, aged 3 years or less, requiring ECLS support were studied. Three continuous glucose sensors (Medtronic MiniMed) were inserted into hubs placed in line with the ECLS circuit. Blood glucose was assessed with a laboratory analyzer (BG(LAB); Bayer Rapidlab 860) approximately every 5 h (mean 4.9 ± 3.3 h) with more frequent samples obtained with a bedside monitor (HemoCue) as needed. Sensor current (I(SIG)) was transmitted to a laptop computer and retrospectively calibrated using BGLAB. Sensor performance was assessed by mean absolute relative difference (MARD), linear regression slope and intercept, and correlation, all with BGLAB as reference. RESULTS: The BGLAB averaged 107.6 ± 36.4 mg/dl (mean ± standard deviation) ranging from 58 to 366 mg/dl. The MARD was 11.4%, with linear regression slope (0.86 ± 0.030) and intercept (9.0 ± 3.2 mg/dl) different from 1 and 0, respectively (p < .05), and correlation (r² = 0.76; p < .001). The system was not associated with any adverse events, and placement and removal into the hubs was easily accomplished. Instances in which more frequent BG values were obtained using a bedside HemoCue (BGHEMO) monitor showed the sensor to respond rapidly to changes. CONCLUSIONS: We conclude that continuous sensors can be adapted for use in an ECLS circuit with accuracy similar to or better than that achieved with the subcutaneous site. Continuous glucose monitoring in this population can rapidly detect changes in BG that would not otherwise be observed. Further studies will be needed to assess the benefit of continuous glucose monitoring in this population.

A 20-year experience on neonatal extracorporeal membrane oxygenation in a referral center.

OBJECTIVE: Advances in treatment of neonatal respiratory failure are responsible for a decline in the number of newborns treated with extracorporeal membrane oxygenation (ECMO). The aim of this study are to determine demographic changes, focusing on time of referral, diagnosis, and respiratory parameters in neonates put on ECMO. DESIGN: Retrospective review. SETTING: Tertiary ECMO center. PATIENTS: A total of 321 neonates were treated with ECMO from January 1987 to December 2006. RESULTS: Overall number of patients increased with every 5-year period, whereby congenital diaphragmatic hernia (CDH) was the most common diagnosis (53%), followed by meconium aspiration syndrome (MAS) (21%), sepsis and/or pneumonia (13%), and others such as persistent pulmonary hypertension of the newborn (PPHN), respiratory distress syndrome (RDS), or hypoplasia of the lung (13%). Worsening severity of illness as measured by ECMO duration and days on ventilator has to be stated for all diagnoses. Nevertheless, survival rate remained stable; both overall and diagnosis-specific mortality rates did not change significantly. Of all children, 67% survived to discharge or transfer, while best rates were seen for MAS (94%), followed by sepsis and/or pneumonia (69%), CDH (62%), and other diagnoses (43%). Concerning survival rate, no difference between inborn and outborn children occurred. However, between early- and late-referred children, a referral to the ECMO center during the first 24 h of life was associated with a significantly higher rate of survival (77% versus 54%, p = 0.0004), predominantly seen for CDH (67% versus 35%, p = 0.02). CONCLUSION: We strongly recommend timely transfer to an ECMO center in patients with CDH who are at risk of circulatory failure.

Pulmonary pathology in thyroid transcription factor-1 deficiency syndrome.

Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12-21.3 haploid deletion encompassing the TTF-1 gene locus who had cerebral dysgenesis, thyroidal dysfunction, and respiratory insufficiency. The clinical course was notable for mild hyaline membrane disease, continuous ventilatory support, and symmetrically distributed pulmonary cysts by imaging. He developed pneumonia and respiratory failure and died at 8 months. Pathologically, the lungs had grossly visible emphysematous changes with "cysts" up to 2 mm in diameter. The airway generations and radial alveolar count were diminished. In addition to acute bacterial pneumonia, there was focally alveolar septal fibrosis, pneumocyte hypertrophy, and clusters of airspace macrophages. Ultrastructurally, type II pneumocytes had numerous lamellar bodies, and alveolar spaces contained fragments of type II pneumocytes and extruded lamellar bodies. Although immunoreactivity for surfactant protein SP-A and ABCA3 was diminished, that for SP-B and proSP-C was robust, although irregularly distributed, corresponding to the distribution of type II pneumocytes. Immunoreactivity for TTF-1 protein was readily detected. In summation, we document abnormal airway and alveolar morphogenesis and altered expression of surfactant-associated proteins, which may explain the respiratory difficulties encountered in TTF-1 haploinsufficiency. These findings are consistent with experimental evidence documenting the important role of TTF-1 in pulmonary morphogenesis and surfactant metabolism.

Spine deformities in rare congenital syndromes: clinical issues.

STUDY DESIGN: A focused review of the literature with regard to the important system abnormalities of patients with spinal deformities associated with exotic congenital syndromes with additional data from the author's own experience in assessment of patients with rare syndromes treated for thoracic insufficiency syndrome. OBJECTIVES: The objectives of this study are to emphasize important medical considerations that influence the choice of surgical treatment of spinal deformity in patients with exotic congenital syndromes and point out preoperative strategies that reduce treatment morbidity and mortality of these patients. SUMMARY OF BACKGROUND DATA: Individual experience is limited in the treatment of spine abnormality in rare exotic syndromes and the medical aspects of these syndromes that may impact spinal treatment are seldom discussed in detail in the orthopedic literature. For a successful outcome in the treatment of spinal deformity in these unique patients, a working knowledge of the unique pitfalls in their medical care is necessary in order to avoid morbidity and mortality during their treatment. METHODS: The literature was reviewed for 6 exotic congenital syndromes with known or unreported spinal abnormalities and the author's personal 22-years experience of the treatment of thoracic insufficiency syndrome in the relevant congenital syndromes was summarized. RESULTS: Children with Marfan syndrome and spinal deformity may have serious cardiac abnormalities. Spontaneous dissection of the aortic root is a clear danger and patients should be monitored by serial echocardiograms. Prophylactic cardiac surgery may be necessary before spinal surgery is to be performed. Patients with Jeune syndrome have a high rate of proximal cervical stenosis and should undergo screening with cervical spine films at birth. Significant stenosis or instability may require decompression and cervical-occipital fusion. Arthrogryposis may be associated with a severe scoliosis and jaw contracture may make intubation difficult. Larsen syndrome may have early onset scoliosis that is very rigid and requires early intervention. Cervical kyphosis and subluxation may be lethal in these patients and screening radiographs are important. Upper airway abnormalities are an anesthesia concern. Jarcho-Levin syndrome is a thoracic volume depletion deformity due to shortness of the thorax, either a spondylocostal dysostosis variant or spondylothoracic dysplasia. The former has a chaotic congenital scoliosis with varied combination of missing and fused ribs. Although spondylocostal dysostosis has a benign reputation in the literature for respiratory complications, respiratory insufficiency is nevertheless common and 1 death is known from respiratory failure. Spondylothoracic dysplasia seldom has significant scoliosis, but has a mortality rate approaching 50% from respiratory complications due to thoracic insufficiency syndrome. In spite of severe restrictive respiratory disease, adult survivors of spondylothoracic dysplasia appear to do well clinically for unknown reasons. Cerebrocostomandibular syndrome has scoliosis, micrognathia, and thoracic insufficiency syndrome, due to an "implosion" deformity of the thorax from congenital pseudarthrosis of the posterior ribs. CONCLUSION: For optimal patient care, it is necessary to have a clear understanding of exotic congenital syndromes and how they may impact on both the presentation of spinal deformity and the response to treatment, as well as how they may introduce additional morbidity into standard treatment plans. It is clear that with this understanding that preoperative strategies can be employed to enhance the safety of spinal treatment for these unique children.

Congenital muscle fiber-type disproportion in a patient with congenital central hypoventilation syndrome due to PHOX2B mutations.

Increasing numbers of genetic origins are being reported for congenital muscle fiber-type disproportion. Most of these identified disorders are genetic myopathies. This is the first case report (to our knowledge) demonstrating congenital central hypoventilation syndrome due to PHOX2B mutations with congenital muscle fiber-type disproportion. The muscle histopathologic findings in the patient showed no changes of disuse atrophy and suggest that PHOX2B mutations may have an additional role in muscle development, contributing to respiratory failure in congenital central hypoventilation syndrome.

Hipoplasia pulmonar infantil / Lung hypoplasia in childhood

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Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies.

Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies in type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns.

[Congenital nasal pyriform aperture stenosis: an uncommon, potentially fatal cause of inhibition of nasal breathing in neonates]. / Kongenitale Stenose der Apertura piriformis: Seltene, potenziell lebensbedrohliche Ursache einer Nasenatmungsbehinderung bei Neugeborenen.

Congenital nasal pyriform stenosis can be a life threatening emergency in neonates which must be included in the differential diagnosis of nasal airway obstruction. We describe the case of a male child who developed symptoms 36 h after birth. As the conservative therapy was not successful surgery became necessary.

[Tracheotomy in children of the Pediatric ENT Department in years 1995-2005]. / Tracheotomia u dzieci--na podstawie materialu Kliniki Otolaryngologii Dzieciecej w Poznaniu w latach 1995-2005.

INTRODUCTION: In the nineteenth century tracheotomy was performed in case of diphtheria. In 1869 Trousseau presented data on 215 cases of this disease treated this way and it became an operation that was reserved for life threatening conditions. In 1907 Jackson presented his experience with tracheotomy and provided information on equipment and techniques that are still used nowadays. MATERIAL AND METHODS: A retrospective analysis was performed on 79 patients undergoing tracheotomy at Pediatric ENT Dept in Poznañ from 1995-2005. Charts were reviewed with respect to primary diagnosis and indication for tracheotomy. RESULTS: Approximately 56% of the tracheotomies were performed in infants, 18%--in neonates and 26% in children over 1 years old. The most common indication for this procedure in neonates was prolonged intubation--43% in neonates and 25% in infants. Congenital laryngotracheal anomalies were the second group of indications in neonates--28.5% cases and congenital heart anomalies in infants--22.7%. In children over 1 year of age the most common indication were respiratory failure--52.,4% and prolonged intubation in 14.3%. CONCLUSIONS: Obvious anatomical differences between the larynx and trachea of the adult and the child necessitate different surgical techniques. It is important to perform tracheotomy over a bronchoscope or endotracheal tube when possible because of the malleability of the trachea in the child. After the tracheotomy tube is placed it is necessary to check its position and level with flexible bronchoscope.

Neonatal extracorporeal life support: impact of new therapies on survival.

OBJECTIVE: To evaluate the effects of pre-extracorporeal life support (ECLS) management with nitric oxide (NO), high frequency ventilation (HFV), and surfactant on mortality among neonates supported with ECLS. STUDY DESIGN: Extracorporeal Life Support Organization (ELSO) data on 7017 neonates cannulated for respiratory reasons between 1996 and 2003 were analyzed using chi2, analysis of variance, and logistic regression. RESULTS: The use of ECLS declined by 26.6% over the study period with no significant change in mortality. Unadjusted ECLS mortality for NO-treated patients was lower than for infants not treated with NO (25.1% vs 28.6%, P = .0012) and for infants treated with surfactant than for infants not treated with surfactant (18.7% vs 30.3%, p <.0001.) Unadjusted mortality for HFV-treated patients was no different than for non-HFV-treated patients (26.0% vs 26.6%, P = .56). After adjusting for confounders (primary diagnosis, age at cannulation, ECMO year 1996-1999 vs 2000-2003), surfactant use was associated with decreased mortality. NO-treated neonates were less likely to have a pre-ECLS cardiopulmonary arrest than infants not treated with NO. NO, HFV, and surfactant were not associated with prolongation of ECLS or mechanical ventilation. CONCLUSIONS: NO, HFV, and surfactant were not associated with increased mortality in neonates who require ECLS for hypoxic respiratory failure.

New approaches to managing congenital diaphragmatic hernia.

A number of new techniques have been studied for managing newborns with congenital diaphragmatic hernia and respiratory insufficiency. Among these have been the techniques of delayed approach to the repair of the diaphragmatic hernia; permissive hypercapnia; nitric oxide and surfactant administration; intratracheal pulmonary ventilation; liquid ventilation; perfluorocarbon-induced lung growth; and lung transplantation. These interventions are at various stages of development and evaluation of effectiveness. All, however, are being explored in the hopes of improving outcome in patients with congenital diaphragmatic hernia who continue to have significant morbidity and mortality in the newborn period.

Surfactant protein B deficiency in infants with respiratory failure.

Surfactant Protein B (SP-B) deficiency has been recently identified as an uncommon, autosomal recessive lung disorder in term infants. This inability to produce SP-B leads to progressive, lethal, hypoxemic respiratory failure in the first year of life. A frameshift mutation (121 ins 2) is the predominant but not exclusive cause. The clue to diagnosis is to have a high suspicion of SP-B deficiency in any term infant with severe respiratory distress without any apparent cause. SP-B deficiency can be diagnosed prenatally or postnatally. The only current treatment options available include lung transplantation or compassionate care. Current developments in gene therapy offer hope for future treatment.

Impact of ECMO on neonatal mortality in Michigan (1980-1999).

PURPOSE: Although extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving intervention, the effect of ECMO on neonatal mortality has never been evaluated. In this study, we examined the relationship between increased ECMO utilization and its effect on the neonatal mortality rate in the state of Michigan. METHODS: Neonatal mortality data were obtained from the Michigan State Department of Community Health. Data included total annual live births, total neonatal deaths, and deaths from respiratory causes in neonates > or =35 weeks' gestational age (ie, potential ECMO candidates). Pooled ECMO patient data from Michigan's 3 ECMO centers were obtained from the Extracorporeal Life Support Organization (ELSO) Registry. Associations between ECMO volume and neonatal mortality rates were assessed using simple linear regression. A scatterplot of ECMO volume and mortality rates was created, and the resulting fitted regression lines were superimposed on the plots. Statistical significance of the associations (ie, difference in slope of the regression line from zero) were based on a standard 2-sided Wald test for the regression slope parameter. RESULTS: From 1980 through 1999, 1,061 neonates were treated with ECMO in Michigan, and 875 (82.5%) survived. When annual neonatal mortality rate (from all causes) and the rate from respiratory causes versus ECMO volume (cases per year) are superimposed with fitted regression lines, both are significantly different from zero (P =.041 and P =.002, respectively). The model predicts that for every 100 neonates treated with ECMO in Michigan, 38 lives are saved. The model also can be used to predict the annual neonatal mortality rate in Michigan if ECMO had not been utilized. CONCLUSIONS: A strong association exists between ECMO volume and observed reductions in neonatal mortality seen in Michigan over the last 2 decades. This is the first study to show an association between ECMO and neonatal mortality rate at the population level.