![]() Most ARDS patients improve their oxygenation, as assessed by the ratio between the arterial partial pressure of oxygen (PaO 2) and FiO 2 (PaO 2/FiO 2), disease-specific treatment and the application of adequate levels of PEEP. These essential elements are the main components of the framework for lung-protective MV. Since the publication in 2000 of the milestone paper by the ARDS Network ( Acute Respiratory Distress Syndrome Network, Brower et al., 2000), the aim of MV is to achieve adequate gas-exchange avoiding damaging the lungs by using physiological tidal volumes (VT) of 4–8 ml/kg predicted body weight (PBW), preventing alveolar collapse with positive end-expiratory pressure (PEEP), limiting end-inspiratory plateau pressure (Pplat) to less than 30 cmH 2O, and limiting FiO 2 to maintain an adequate PaO 2. The use of mechanical ventilation (MV) is the standard supportive therapy of patients with ARDS. Caused by an intense direct (pulmonary) or indirect (systemic) inflammatory insult to the alveolar-capillary membrane, it is characterized by the presence of diffuse, non-cardiogenic, high-permeability, protein-rich pulmonary edema, and hypoxemia unresponsive to the application of high inspiratory concentrations of oxygen (FiO 2) ( Villar, 2011). The acute respiratory distress syndrome (ARDS) is a severe form of acute hypoxemic respiratory failure. We will briefly comment physiology-based gaps of negative trials and highlight the possible needs to address in future clinical trials in ARDS. Those trials tested the effects of adjunctive therapies (neuromuscular blocking agents, prone positioning), methods for selecting the optimum positive end-expiratory pressure (after recruitment maneuvers, or guided by esophageal pressure), high-frequency oscillatory ventilation, extracorporeal oxygenation, and pharmacologic immune modulators of the pulmonary and systemic inflammatory responses in patients affected by ARDS. In this article, we review 14 major successful and unsuccessful randomized controlled trials conducted in patients with ARDS on a series of techniques to improve oxygenation and ventilation published since 2010. The adverse effects of mechanical ventilation are direct consequences of the changes in pulmonary airway pressures and intrathoracic volume changes induced by the repetitive mechanical cycles in a diseased lung. Mechanical ventilation provides time for the specific therapy to reverse the disease-causing lung injury and for the recovery of the respiratory function. For decades, mechanical ventilation was the only standard support technique to provide acceptable oxygenation and carbon dioxide removal. However, in some patients hypoxemia persisted because the lungs are markedly injured, remaining unresponsive to increasing the inspiratory fraction of oxygen and positive end-expiratory pressure. ![]() Most ARDS patients improve their systemic oxygenation, as assessed by the ratio between arterial partial pressure of oxygen and inspired oxygen fraction, with conventional intensive care and the application of moderate-to-high levels of positive end-expiratory pressure. The acute respiratory distress syndrome (ARDS) is a severe form of acute hypoxemic respiratory failure caused by an insult to the alveolar-capillary membrane, resulting in a marked reduction of aerated alveoli, increased vascular permeability and subsequent interstitial and alveolar pulmonary edema, reduced lung compliance, increase of physiological dead space, and hypoxemia.
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