View clinical trials related to Acute Lung Injury.
Filter by:The purpose of this study is to show that inhaled steroids in patient with PARDS can decrease the days on mechanical ventilator measured by ventilator-free days,to improve the oxygenation index (OI) or oxygenation saturation index (OSI) in patients receiving inhaled steroids and to show the relevance and feasibility of a larger study by assessing the hypothesis in a small cohort of patients. Patient will be treated for a maximum of 10 days. Secondary objectives are to reduce the length of stay (LOS) in the pediatric intensive care unit (PICU) and hospital admissions; to show less inflammation in the patients receiving inhaled steroids by measuring inflammatory markers from tracheal aspirates like Interleukin (IL6, IL8, tumor necrosis factor (TNF) α, matrix metalloproteinase8 (MMP8) and matrix metalloproteinase9 (MMP9). Lastly, to show that inhaled steroids can improve residual lung disease evaluated by Pulmonary Function Test (PFTs) and Impulse Oscillometry (IOS).
Pulmonary recruitment maneuvers open these lung areas and appropriate adjustment of positive expiratory pressure (PEP) helps to stabilize recruitment and reduce the stress associated with alveolar opening and closing. Its beneficial effects in the lung affected by Acute Respiratory Distress Syndrome (ARDS) remain unclear. The hypothesis is that there is a heterogeneous effect of the recruitment maneuver according to the phenotype of ARDS. It is important to be able to define responder patients from non-responders to this recruiting maneuver.
The main objective of this study is to compare the pharmacokinetic models of sevoflurane-induced sedation during ARDS depending on the lung imaging phenotype (focal vs nonfocal phenotypes) The authors hypothesized that sevoflurane used for inhaled sedation could have distinct pharmacokinetic profiles depending on lung imaging phenotypes (focal vs nonfocal) during ARDS in ICU patients.
Sepsis leads to a deregulated host response that can lead to organ failure. During sepsis, experimental and clinical data suggest the occurrence of mitochondrial dysfunctions, particularly in circulating muscle and monocytes, which may contribute to organ failure and death. Lower respiratory infection is the leading cause of death from infectious causes. Mechanical ventilation (MV) is required in 20% of cases of bacterial pneumopathy with Streptococcus pneumoniae (S.p.) , with mortality reaching 50%. There are then frequently criteria for acute respiratory distress syndrome (ARDS), combining bilateral lung involvement and marked hypoxemia. Cyclic stretching of lung cells induced by MV causes sterile inflammation and tissue damage (i.e. ventilator-induced lung injury [VILI]), which can cause cellular dysfunction that alter the immune response, particularly during ARDS. This is why the application of a so-called protective MV is then required. However, this does not prevent about one-third of patients from showing signs of alveolar overdistension, as evidenced by an increase in motor pressure (MP) (MP≥ 15 cmH2O), associated with an increase in mortality. The deleterious effects of MV could be explained by the occurrence of mitochondrial abnormalities. Indeed, the cyclic stretching of lung cells leads to dysfunction in the respiratory chain and the production of free oxygen radicals (FOS), altering membrane permeability. These phenomena could promote VILI, facilitate the translocation of bacteria from the lung to the systemic compartment and lead to alterations in immune response. In our model of S.p. pneumopathy in rabbits, animals on MV develop more severe lung disorders (lack of pulmonary clearance of bacteria, bacterial translocation in the blood, excess mortality), compared to animals on spontaneous ventilation (SV). Intracellular pulmonary mitochondrial DNA (mtDNA) concentrations, a reflection of the mitochondrial pool, are significantly decreased in ventilated rabbits compared to SV rabbits and in infected rabbits compared to uninfected rabbits. At the same time, the mitochondrial content of circulating cells decreased early (H8) in all infected rabbits, but was only restored in rabbits in SV, those who survived pneumonia (Blot et al, poster ECCMID 2015, submitted article). These data suggest an alteration in the mechanisms that restore mitochondrial homeostasis (mitochondrial biogenesis and mitophagy) during the dual infection/MV agression, which may explain the observed excess mortality. Other work by our team illustrates the importance of these phenomena by showing in a mouse model of polymicrobial infection that inhibition of mitophagia in macrophages promotes survival (Patoli et al, in preparation). Human data on this subject are non-existent. The phenomena of mitochondrial dysfunction nevertheless deserve to be explored in humans during the combined MV/pneumopathy aggression in order to understand its possible impact on the effectiveness of the host's immune response. In a personalized medicine approach, these data would open up prospects for targeted therapies, capable of activating mitochondrial biogenesis and/or modulating mitophagia, to prevent organ dysfunction and mortality during severe CALs treated with antibiotic therapy.
Unresolved ARDS is defined by the persistence of ARDS criteria at the end of the first week of evolution despite an appropriate treatment of the cause of ARDS. A persistent ARDS is associated with an increased mortality and prolonged lengths of mechanical ventilation, ICU stay and hospitalization. Persistent ARDS is characterized by ongoing inflammation, parenchymal-cell proliferation, and fibroproliferation leading to disordered deposition of collagen. All of these pathways may be responsive to corticosteroid therapy. Only two randomized controlled double-blinded trials assessed the use of corticosteroids for persistent ARDS. In 24 patients, Meduri et al. reported an improvement of lung function and survival (1). In 180 patients, Steinberg et al showed no effect of corticosteroids on survival (2). A lower risk of death was observed when corticosteroids were started before 14 days after the onset of ARDS (2). Alveolar procollagen III is validated as a biomarker of active fibroproliferation. Alveolar procollagen III > 9 µg/L is associated to fibroproliferation (3). As mortality was lower in patients who received corticosteroids while presenting a high alveolar level of procollagen III on inclusion, Steinberg et al. showed that patients presenting with a low level of procollagen III and treated with corticosteroids had an increased risk of death (2). Investigatores hypothesize that the use of procollagen III could improve personalized decision-making regarding steroid treatment in patients presenting with persistent ARDS. The future of anti-fibrotic treatment, including corticosteroids, in persistent ARDS might propose to individualize the therapy according to the presence of an active fibroproliferative phase (precision or personalized medicine).
The purpose of this study is to assess whether circulating Angiotensin (Ang) II and Ang (1-7) levels are associated with right ventricular (RV) dysfunction in mechanically ventilated subjects. It is also designed to further characterize the subject population for severity of RV dysfunction. This study will investigate the association of renin-angiotensin system (RAS) peptides and markers of RV function, as measured by echocardiography, in subjects requiring acute mechanical ventilation. Maximum 150 subjects will be enrolled for the study and they will be evaluated over three days period using standard of care investigations, including trans-thoracic echocardiography (TTE) and/or trans-esophageal echocardiography (TOE) echocardiography. The maximum total duration of this study for subjects is 28 days.
Acute Respiratory Distress Syndrome (ARDS) still remains associated with a mortality rate of 30 - 45 % despite improvement in mechanical ventilation. Driving pressure, defined as the difference between the end-inspiratory and the end-expiratory airway pressure, appears as an important factor contributing to mortality in patients with the ARDS. In patients already receiving a conventional tidal volume of 6 ml/kg predicted body weight (PBW), a driving pressure ≥ 14 cmH2O increases the risk of death in the hospital. One mean to lower the driving pressure is to decrease the tidal volume such that from 6 to 4 ml/kg predicted body weight. However, this strategy promotes hypercarbia by reducing the alveolar ventilation, providing the respiratory rate is constant. In this setting, implementing an extracorporeal CO2 removal (ECCO2R) therapy may offset the associated hypercarbia. The investigators have previously demonstrated that combining a membrane oxygenator within an hemofiltration circuit provides efficacious low flow ECCO2R on a renal replacement therapy monitor. In this study, we thought to investigate the efficacy of the PrismaLung stand-alone therapy. Using a PrismaFlex monitor and a HP-X circuit, a neonatal membrane oxygenator (PrismaLung) is used to provide decarboxylation without renal replacement therapy. The study will consist in three periods: - The first period will address the efficacy of the PrismaLung device at tidal volume of 6 and 4 ml/kg PBW using an off-on-off design. - The second part of the study will investigate the effect of varying the sweep gas flow and the mixture of the sweep gas on the CO2 removal rate (random order). - The third part will compare three ventilatory strategies applied in a cross-over design : 1. Minimal distension: Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA). 2. Maximal recruitment: 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O. 3. Standard: Tidal volume 6 ml/kg and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA). Each strategies will be apply in a random order for a duration of 22 hours. Pulmonary inflammatory and fibrosis pathway will be assess before and after each period using bronchoalveolar lavage (BAL) samples. Systemic inflammatory cytokines will also be investigate. Main measurements will include respiratory mechanics, transpulmonary pressure, work of breathing, end-expiratory lung volume and tidal ventilation using electrical impedance tomography.
The aim of study is to determine if 99mTc Annexin V-128 (AxV- 128/Tc) single photon emission computed tomography (SPECT)-computed tomography (CT) can detect perioperative lung injury. The investigators will study patients undergoing major surgery, specifically Whipple procedures (pancreatico-duodenectomies) and compare AxV-128/Tc SPECT-CT scans before and after surgery in Chronic Obstructive Pulmonary Disease (COPD) and non-COPD patients.
Bleeding complications and thromboembolic complications are frequent during extracorporeal membrane oxygenation (ECMO). Retrospective data suggest that platelet inhibition using prostaglandins, in this case PGE1, may reduce thromboembolic complications without increasing the bleeding risk. This randomized, double-blind trial aims to investigate the effects of PGE1 on bleeding risk, thromboembolic complications and the function of the ECMO.
Acute respiratory distress syndrome (ARDS) is a widely prevalent and morbid disease for which the current standard treatment is supportive care and avoidance of complications with lung-protective ventilation. Lower-tidal volume ventilation has been largely accepted as a means of lung protective ventilation, but the mechanism for its effectiveness is not yet clear, and debate remains as to how best to choose positive end-expiratory pressure (PEEP). Reduction in driving pressure (plateau pressure minus PEEP) has been suggested as a possible means to minimize ventilator-induced lung injury. This protocol aims to identify the range of safe paired-settings of PEEP and tidal volume, with selection guided by driving pressure and the stress index, a tool to recognize potential lung hyperinflation during mechanical ventilation.