31 research outputs found
Elective high-frequency oscillatory ventilation in preterm infants with respiratory distress syndrome: an individual patient data meta-analysis
<p>Abstract</p> <p>Background</p> <p>Despite the considerable amount of evidence from randomized controlled trials and meta-analyses, uncertainty remains regarding the efficacy and safety of high-frequency oscillatory ventilation as compared to conventional ventilation in the early treatment of respiratory distress syndrome in preterm infants. This results in a wide variation in the clinical use of high-frequency oscillatory ventilation for this indication throughout the world. The reasons are an unexplained heterogeneity between trial results and a number of unanswered, clinically important questions. Do infants with different risk profiles respond differently to high-frequency oscillatory ventilation? How does the ventilation strategy affect outcomes? Does the delay – either from birth or from the moment of intubation – to the start of high-frequency oscillation modify the effect of the intervention? Instead of doing new trials, those questions can be addressed by re-analyzing the individual patient data from the existing randomized controlled trials.</p> <p>Methods/Design</p> <p>A systematic review with meta-analysis based on individual patient data. This involves the central collection, validation and re-analysis of the original individual data from each infant included in each randomized controlled trial addressing this question.</p> <p>The study objective is to estimate the effect of high-frequency oscillatory ventilation on the risk for the combined outcome of death or bronchopulmonary dysplasia or a severe adverse neurological event. In addition, it will explore whether the effect of high-frequency oscillatory ventilation differs by the infant's risk profile, defined by gestational age, intrauterine growth restriction, severity of lung disease at birth and whether or not corticosteroids were given to the mother prior to delivery. Finally, it will explore the importance of effect modifying factors such as the ventilator device, ventilation strategy and the delay to the start of high-frequency ventilation.</p> <p>Discussion</p> <p>An international collaborative group, the PreVILIG Collaboration (Prevention of Ventilator Induced Lung Injury Group), has been formed with the investigators of the original randomized trials to conduct this systematic review. In the field of neonatology, individual patient data meta-analysis has not been used previously. Final results are expected to be available by the end of 2009.</p
Meta-regression analysis of high-frequency ventilation vs conventional ventilation in infant respiratory distress syndrome
K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport
<p>Abstract</p> <p>Background</p> <p>Lung epithelial Na<sup>+ </sup>channels (ENaC) are regulated by cell Ca<sup>2+ </sup>signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K<sup>+ </sup>channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K<sup>+ </sup>channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC) by up-regulating both apical and basolateral ion transport.</p> <p>Methods</p> <p>Verapamil-induced depression of heterologously expressed human αβγ ENaC in <it>Xenopus </it>oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441), and <it>in vivo </it>alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca<sup>2+ </sup>signal in H441 cells was analyzed using Fluo 4AM.</p> <p>Results</p> <p>The rate of <it>in vivo </it>AFC was reduced significantly (40.6 ± 6.3% of control, <it>P </it>< 0.05, n = 12) in mice intratracheally administrated verapamil. K<sub>Ca3.1 </sub>(1-EBIO) and K<sub>ATP </sub>(minoxidil) channel openers significantly recovered AFC. In addition to short-circuit current (Isc) in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca<sup>2+ </sup>signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca<sup>2+ </sup>in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, K<sub>V </sub>(pyrithione-Na), K <sub>Ca3.1 </sub>(1-EBIO), and K<sub>ATP </sub>(minoxidil) channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na<sup>+ </sup>and K<sup>+ </sup>transport pathways.</p> <p>Conclusions</p> <p>Our observations demonstrate that K<sup>+ </sup>channel openers are capable of rescuing reduced vectorial Na<sup>+ </sup>transport across lung epithelial cells with impaired Ca<sup>2+ </sup>signal.</p
Bronchopulmonary dysplasia: clinical aspects and preventive and therapeutic strategies
Abstract Background Bronchopulmonary dysplasia (BPD) is the result of a complex process in which several prenatal and/or postnatal factors interfere with lower respiratory tract development, leading to a severe, lifelong disease. In this review, what is presently known regarding BPD pathogenesis, its impact on long-term pulmonary morbidity and mortality and the available preventive and therapeutic strategies are discussed. Main body Bronchopulmonary dysplasia is associated with persistent lung impairment later in life, significantly impacting health services because subjects with BPD have, in most cases, frequent respiratory diseases and reductions in quality of life and life expectancy. Prematurity per se is associated with an increased risk of long-term lung problems. However, in children with BPD, impairment of pulmonary structures and function is even greater, although the characterization of long-term outcomes of BPD is difficult because the adults presently available to study have received outdated treatment. Prenatal and postnatal preventive measures are extremely important to reduce the risk of BPD. Conclusion Bronchopulmonary dysplasia is a respiratory condition that presently occurs in preterm neonates and can lead to chronic respiratory problems. Although knowledge about BPD pathogenesis has significantly increased in recent years, not all of the mechanisms that lead to lung damage are completely understood, which explains why therapeutic approaches that are theoretically effective have been only partly satisfactory or useless and, in some cases, potentially negative. However, prevention of prematurity, systematic use of nonaggressive ventilator measures, avoiding supraphysiologic oxygen exposure and administration of surfactant, caffeine and vitamin A can significantly reduce the risk of BPD development. Cell therapy is the most fascinating new measure to address the lung damage due to BPD. It is desirable that ongoing studies yield positive results to definitively solve a major clinical, social and economic problem
Mechanisms of T cell organotropism
F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation
Diffusion tensor imaging in extremely low birth weight infants managed with hypercapnic vs. normocapnic ventilation
The Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits
<div><p>Background</p><p>Permissive hypercapnia has been shown to reduce lung injury in subjects with surfactant deficiency. Experimental studies suggest that hypercapnic acidosis by itself rather than decreased tidal volume may be a key protective factor.</p><p>Objectives</p><p>To study the differential effects of a lung protective ventilatory strategy or hypercapnic acidosis on gas exchange, hemodynamics and lung injury in an animal model of surfactant deficiency.</p><p>Methods</p><p>30 anesthetized, surfactant-depleted rabbits were mechanically ventilated (FiO<sub>2</sub> = 0.8, PEEP = 7cmH<sub>2</sub>O) and randomized into three groups: Normoventilation-Normocapnia (NN)-group: tidal volume (Vt) = 7.5 ml/kg, target PaCO<sub>2</sub> = 40 mmHg; Normoventilation-Hypercapnia (NH)-group: Vt = 7.5 ml/kg, target PaCO<sub>2</sub> = 80 mmHg by increasing FiCO<sub>2</sub>; and a Hypoventilation-Hypercapnia (HH)-group: Vt = 4.5 ml/kg, target PaCO<sub>2</sub> = 80 mmHg. Plasma lactate and interleukin (IL)-8 were measured every 2 h. Animals were sacrificed after 6 h to perform bronchoalveolar lavage (BAL), to measure lung wet-to-dry weight, lung tissue IL-8, and to obtain lung histology.</p><p>Results</p><p>PaO<sub>2</sub> was significantly higher in the HH-group compared to the NN-group (p<0.05), with values of the NH-group between the HH- and NN-groups. Other markers of lung injury (wet-dry-weight, BAL-Protein, histology-score, plasma-IL-8 and lung tissue IL-8) resulted in significantly lower values for the HH-group compared to the NN-group and trends for the NH-group towards lower values compared to the NN-group. Lactate was significantly lower in both hypercapnia groups compared to the NN-group.</p><p>Conclusion</p><p>Whereas hypercapnic acidosis may have some beneficial effects, a significant effect on lung injury and systemic inflammatory response is dependent upon a lower tidal volume rather than resultant arterial CO<sub>2</sub> tensions and pH alone.</p></div
The Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits
Effect of permissive hypercapnia on background cerebral electrical activity in premature babies
Factors effecting adoption of new neonatal and pediatric respiratory technologies
OBJECTIVE: There remains significant variation in the level and rate of adoption of new pediatric respiratory technologies, in spite of two decades of focus on "evidence-based medicine". Nearly 50 years ago Rogers introduced a rubric for understanding issues that effect the adoption of technologies that included four factors plus evidence of advantage. We sought to determine whether Rogers' factors were useful in understanding contrasts between clinical utilization of technology and evidence of advantage. DESIGN, SETTING, PARTICIPANTS: We conducted a written survey at two international neonatal/pediatric respiratory conferences. We asked about use of four specific indications for high-frequency ventilation (HFV) and nasal continuous positive airway pressure (nCPAP). RESULTS: These four specific respiratory therapies were aggressively used by most, despite significant differences in the evidence supporting their utility: elective use of HFV (57.4%); HFV to treat ARDS (62.7%); nCPAP for weaning following extubation (83.9%); and nCPAP to avoid intubation (82.1%). CONCLUSIONS: Evidence of outcomes advantage should be the key factor in assessing potentially beneficial technologies. However, we suggest that understanding the influence of observe-ability, complexity and subjectivity of relative advantage explains much of the contrast between adoption level and outcome evidence. These factors described by Rogers, that encourage adoption of mediocre technologies or that retard adoption of potentially beneficial technologies, should be understood and acknowledged. This perspective can be applied not only to national adoption patterns, but also to adoption of best practices within an individual unit