Lung Protective One-lung Ventilation With Fix and Variable Tidal Volume
HypoxemiaPulmonary Sepsis3 moreDuring One-lung ventilation, the use of lower tidal volumes (VT) is helpful to avoid over-distension, provide sufficient oxygenation, but can result in increased atelectasis. Nevertheless, it is not known if, during one-lung ventilation with constant low VT, moderate levels of PEEP combined with lung recruitment maneuvers are superior to variable low tidal volume for intraoperative oxygenation and protection against PPCs. Aim of the study is to compare a strategy using constant tidal volume with recruitment maneuvers versus variable tidal volume with recruitment maneuvers during thoracic surgery in adults. We hypothesize that in adult, non-obese patients undergoing thoracic surgery under standardized OLV with variable tidal volumes, modearte PEEP and recruitment maneuvers as compared to constant without recruitment maneuvers prevent PPCs. Patients will be randomly assigned to one of two groups: FIX TIDAL VOLUME GROUP (Groupfix): mechanical ventilation with constant (6 ml/kgIBW) tidal volume and PEEP of 5 cmH2O with recruitment maneuvers VARIABLE TIDAL VOLUME GROUP (Groupvar): mechanical ventilation with variable (6 ml/kgIBW ± 33%) tidal volume with variable respiratory rate to maintain constant minute ventilation and PEEP of 5 cmH2O with recruitment maneuvers.
ART-3 Pilot - Driving Pressure Limited Ventilation for Patients Without ARDS (ART3pilot)
Mechanical VentilationAcute Respiratory Distress SyndromeThis is a multicenter randomized controlled pilot trial to investigate the feasibility of a driving pressure limited mechanical ventilation strategy compared to a conventional strategy in patients without acute respiratory distress syndrome (ARDS).
Ganciclovir/Valganciclovir for Prevention of CMV Reactivation in Acute Injury of the Lung and Respiratory...
Acute Lung InjuryAcute Respiratory Distress Syndrome1 moreTo evaluate whether administration of ganciclovir reduces serum IL-6 levels (i.e. reduction between baseline and 14 days post-randomization) in immunocompetent adults with severe sepsis or trauma associated respiratory failure. Primary Hypotheses: - In CMV seropositive adults with severe sepsis or trauma , pulmonary and systemic CMV reactivation amplifies and perpetuates both lung and systemic inflammation mediated through specific cytokines, and contributes to pulmonary injury and multiorgan system failure, AND - Prevention of CMV reactivation with ganciclovir decreases pulmonary and systemic inflammatory cytokines that are important in the pathogenesis of sepsis and trauma related complications.
Safety and Efficacy Study of Acthar in Subjects With ARDS
Acute Respiratory Distress SyndromeThis study is being performed to evaluate the potential efficacy and safety of Acthar as a treatment for moderate-severe Acute Respiratory Distress Syndrome (ARDS). Approximately 210 subjects will be randomized to 1 of 6 possible treatment groups in a 3:2:3:2:3:2 ratio. Study medication (SM) will be administered via subcutaneous (SC) injection for 4 weeks using a blinded gradually tapering regimen, and subjects will be followed for 60 days post-randomization.
Inhaled Nitric Oxide (iNO) as an Adjunct to Neonatal Resuscitation
Respiratory Distress Syndrome in Premature InfantsVery Low Birth Weight BabyThis study hopes to determine whether nitric oxide along with oxygen during the first 20 minutes of life in infants needing help with breathing will reduce the percentage and total exposure to oxygen during that time frame. Although the use of oxygen in management of breathing is an important part of supporting baby immediately after delivery, there is more evidence that too much exposure to oxygen may lead to potential problems for your baby later. Oxygen exposure can be harmful to premature babies developing lungs.
Airway Pressure Release Ventilation (APRV) Compared to ARDSnet Ventilation
Acute Lung InjuryAdult Respiratory Distress Syndrome1 moreTraditional modes of ventilation have failed to improve patient survival. Subsequent observations that elevated airway pressures observed in traditional forms of ventilation resulted in barotrauma and extension of ALI lead to the evolution of low volume cycled ventilation as a potentially better ventilatory modality for ARDS. Recent multicenter trials by the NIH-ARDS network have confirmed that low volume ventilation increases the number of ventilatory free days and improves overall patient survival. While reducing mean airway pressure has reduced barotrauma and improved patient survival, it has impaired attempts to improve alveolar recruitment. Alveolar recruitment is important as it improves V/Q mismatch, allows reduction in FIO2 earlier, and decreases the risk of oxygen toxicity. Airway pressure release ventilation (APRV) is a novel ventilatory modality that utilizes controlled positive airway pressure to maximize alveolar recruitment while minimizing barotrauma. In APRV, tidal ventilation occurs between the increase in lung volumes established by the application of CPAP and the relaxation of lung tissue following pressure release. Preliminary studies have suggested that APRV recruits collapsed alveoli and improves oxygenation through a restoration of pulmonary mechanics, but there are no studies indicating the potential overall benefit of APRV in recovery form ALI/ADRS.
Early Insulin and Development of ARDS
Respiratory Distress SyndromeAdult2 moreAcute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is a severe lung condition that causes respiratory failure. Symptoms usually develop within 24 to 48 hours of an original injury or illness, and people with ALI/ARDS typically require care in the intensive care unit (ICU). Little is known about how to prevent the onset of ALI/ARDS. The purpose of this study is to examine if early infusions of insulin, known as intensive insulin therapy (IIT), can help prevent ALI/ARDS in hospitalized patients with high levels of blood sugars and severe infections.
Effect of Low Tidal Volume Ventilation in Improving Oxygenation and Thus Reducing Acute Lung Injury...
Acute Respiratory Distress SyndromeWe propose that as low tidal volume ventilation has proven to be beneficial in patients with established ARDS it may have a role in preventing the onset of acute lung injury in the cardiac surgical population. Institution of low tidal volume ventilation in the operating room may reduce the release of the cytokines and interleukins that have been known to contribute to the development of acute lung injury. In this study, we propose that the institution of low tidal volume ventilation in the operating room will reduce the incidence of acute lung injury. Measurement of PaO2 to FiO2 ratio twenty four and forty eight hours post operatively will help determine if there is a difference in oxygenation between the two groups. Chest X-ray findings, time to extubation and length of ICU stay will also determine if there is a role for low tidal volume ventilation in the operating room. We will also attempt to establish a causative mechanism by measuring plasma levels of cytokines known to be associated with the development of ARDS.
Prevention of Neonatal Respiratory Distress Syndrome With Antenatal Steroid Administration
Lung DiseasesRespiratory Distress SyndromeTo determine the effect of corticosteroids, administered 24 to 48 hours before parturition, on the incidence of neonatal respiratory distress syndrome (RDS) and to determine whether the therapy has any adverse short- or long-term (up to 36 months) effects on the infant. Secondarily, to determine whether the therapy has any adverse short-term effects on the mother and to determine whether morbidity rates for neonatal respiratory distress syndrome as well as total and cause-specific infant mortality rates differ between mothers who received antenatal steroids and those who received conventional medical care.
CORONA: A Study Using DeltaRex-G Gene Therapy for Symptomatic COVID-19
COVID-19Cytokine Storm1 moreCOVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. COVID-19 causes life threatening complications known as Cytokine Release Syndrome or Cytokine Storm and Acute Respiratory Distress Syndrome. These complications are the main causes of death in this global pandemic. Over 1000 clinical trials are on-going worldwide to diagnose, treat, and improve the aggressive clinical course of COVID-19. The investigators propose the first, and so far, only gene therapy solution that has the potential to address this urgent unmet medical need. Rationale There are striking similarities between the damaged lung environment of COVID-19 induced ARDS and the tumor microenvironment (exposed collagen from tissue destruction by invading tumor or by the virus-induced immune response, and presence of activated proliferative cells (cancer cells and tumor associated fibroblasts or activated T cells, macrophages and pulmonary fibroblasts in COVID-19); DeltaRex-G is a disease-seeking retrovector encoding a cytocidal dominant negative human cyclin G1 as genetic payload). When injected intravenously, the DeltaRex-G nanoparticles has a navigational system that targets exposed collagenous proteins (XC proteins) in injured tissues (e.g. inflamed lung, kidney, etc.), thus increasing the effective drug concentration at the sites of injury, in the vicinity of activated/proliferative T cells evoked by COVID-19. Our hypothesis is that DeltaRex-G then enters the rapidly dividing T cells and kills them by arresting the G1cell division cycle, hence, reducing cytokine release and ARDS; Intravenous DeltaRex-G has minimal systemic toxicity due to its navigational system (targeting properties) that limits the biodistribution of DeltaRex-G only to areas of injury where exposed collagenous (XC) proteins are abnormally found; and DeltaRex-G is currently available in FDA approved "Right to Try" or Expanded Access Program for Stage 4 cancers for an intermediate size population. To gain this approval, FDA requires DeltaRex-G to have demonstrated safety and efficacy in early clinical trials.