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Positive end-expiratory pressure (PEEP) has been used during mechanical ventilation since the first description of acute respiratory distress syndrome (ARDS). In the subsequent decades, many different strategies for optimally titrating PEEP have been proposed. Higher PEEP can improve arterial oxygenation, reduce tidal lung stress and strain, and promote more homogenous ventilation by preventing alveolar collapse at end expiration. However, PEEP may also cause circulatory depression and contribute to ventilator-induced lung injury through alveolar overdistention. The overall effect of PEEP is primarily related to the balance between the number of alveoli that are recruited to participate in ventilation and the amount of lung that is overdistended when PEEP is applied. Techniques to assess lung recruitment from PEEP may help to direct safer and more effective PEEP titration. Some PEEP titration strategies attempt to weigh beneficial effects on arterial oxygenation and on prevention of cyclic alveolar collapse with the harmful potential of overdistention. One method for PEEP titration is a PEEP/Fi table that prioritizes support for arterial oxygenation. Other methods set PEEP based on mechanical parameters, such as the plateau pressure, respiratory system compliance, or transpulmonary pressure. No single method of PEEP titration has been shown to improve clinical outcomes compared with other approaches of setting PEEP. Future trials should focus on identifying individuals who respond to higher PEEP with recruitment and on clinically important outcomes (e.g., mortality).

Diagnostic yield and number of lymph nodes sampled using deep sedation is superior to moderate sedation in patients undergoing EBUS-TBNA. Prospective studies accounting for other factors including patient selection and cost are needed.

Care for patients with acute respiratory distress syndrome (ARDS) has changed considerably over the 50 years since its original description. Indeed, standards of care continue to evolve as does how this clinical entity is defined and how patients are grouped and treated in clinical practice. In this narrative review we discuss current standards-treatments that have a solid evidence base and are well established as targets for usual care-and also evolving standards-treatments that have promise and may become widely adopted in the future. We focus on three broad domains of ventilatory management, ventilation adjuncts, and pharmacotherapy. Current standards for ventilatory management include limitation of tidal volume and airway pressure and standard approaches to setting PEEP, while evolving standards might focus on limitation of driving pressure or mechanical power, individual titration of PEEP, and monitoring efforts during spontaneous breathing. Current standards in ventilation adjuncts include prone positioning in moderate-severe ARDS and veno-venous extracorporeal life support after prone positioning in patients with severe hypoxemia or who are difficult to ventilate. Pharmacotherapy current standards include corticosteroids for patients with ARDS due to COVID-19 and employing a conservative fluid strategy for patients not in shock; evolving standards may include steroids for ARDS not related to COVID-19, or specific biological agents being tested in appropriate subphenotypes of ARDS. While much progress has been made, certainly significant work remains to be done and we look forward to these future developments.

Mechanical ventilation (MV) is critical in the management of many patients with acute respiratory distress syndrome (ARDS). However, MV can also cause ventilator-induced lung injury (VILI). The selection of an appropriate Vt is an essential part of a lung-protective MV strategy. Since the publication of a large randomized clinical trial demonstrating the benefit of lower Vts, the use of Vts of 6 ml/kg predicted body weight (based on sex and height) has been recommended in clinical practice guidelines. However, the predicted body weight approach is imperfect in patients with ARDS because the amount of aerated lung varies considerably due to differences in inflammation, consolidation, flooding, and atelectasis. Better approaches to setting Vt may include limits on end-inspiratory transpulmonary pressure, lung strain, and driving pressure. The limits of lowering Vt have not yet been established, and some patients may benefit from Vts that are lower than those in current use. However, lowering Vts may result in respiratory acidosis. Tactics to reduce respiratory acidosis include reductions in ventilation circuit dead space, increases in respiratory rate, higher positive end-expiratory pressures in patients who recruit lung in response to positive end-expiratory pressure, recruitment maneuvers, and prone positioning. Mechanical adjuncts such as extracorporeal carbon dioxide removal may be useful to normalize pH and carbon dioxide levels, but further studies will be necessary to demonstrate benefit with this technology.

Mechanical ventilation is critical for the survival of many patients with the acute respiratory distress syndrome (ARDS) but can also cause ventilator-induced lung injury (VILI). One form of VILI occurs when the lungs exhale to relatively low volumes and airway pressures. This may cause injurious tidal closing and reopening of small bronchioles and alveoli or excessive stress at the margins between aerated and atelectatic airspaces. 1,2 In animal studies, positive end-expiratory pressure (PEEP) reduced or prevented VILI from exhalation to low volumes and pressures. 1,[3][4][5] PEEP can also recruit some previously atelectatic or fluid-filled lung regions, allowing more of the lung to be available for inflation during inspiration. This could reduce VILI from overdistention of an otherwise reduced amount of aerated lung.In some early studies, the levels of PEEP that were applied for lung protection exceeded the levels that most clinicians use when managing patients with ARDS. This led to recommendations to use higher PEEP in patients with ARDS to minimize low volume and low pressure VILI and hopefully to improve clinical outcomes. The "open lung approach" (OLA) aims to achieve high levels of lung aeration in patients with ARDS by first conducting recruitment maneuvers (RMs) to reverse atelectasis and then applying high levels of PEEP to keep recruited alveoli open. 6 Recruitment maneuvers typically involve a ventilatory approach that transiently increases pulmonary airway pressure to reopen recruitable lung areas. For example, an RM can be conducted by raising inspiratory airway pressures to 50 cm of H 2 O for 1 or 2 minutes. However, 3 large randomized clinical trials of higher PEEP and RMs in patients with ARDS and a Pao 2 /Fio 2 ratio of 300 or less did not demonstrate significant reductions in mortality. [7][8][9] An individual patient data meta-analysis of these 3 clinical trials suggested that higher PEEP reduced mortality in patients with more severe hypoxemia (Pao 2 /Fio 2 ≤200), but this

BACKGROUND: Although specific interventions previously demonstrated benefit in patients with the ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown.RESEARCH QUESTION: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States? STUDY DESIGN AND METHODS: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and PaO 2 to FIO 2 ratio of # 150 with positive endexpiratory pressure of $ 5 cm H 2 O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed.RESULTS: A total of 2,466 patients were enrolled. Median baseline PaO 2 to FIO 2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, # 6.5 mL/kg predicted body weight; plateau pressure, peak inspiratory pressure, or both, # 30 mm H 2 O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR.

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