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ARDS is characterized by hypoxemic respiratory failure, which can be refractory and life-threatening. Modifications to traditional mechanical ventilation and nontraditional modes of ventilation are discussed in Part 1 of this two-part series. In this second article, we examine nonventilatory strategies that can influence oxygenation, with particular emphasis on their role in rescue from severe hypoxemia. A literature search was conducted and a narrative review written to summarize the use of adjunctive, nonventilatory interventions intended to improve oxygenation in ARDS. Several adjunctive interventions have been demonstrated to rapidly ameliorate severe hypoxemia in many patients with severe ARDS and therefore may be suitable as rescue therapy for hypoxemia that is refractory to prior optimization of mechanical ventilation. These include neuromuscular blockade, inhaled vasoactive agents, prone positioning, and extracorporeal life support. Although these interventions have been linked to physiologic improvement, including relief from severe hypoxemia, and some are associated with outcome benefits, such as shorter duration of mechanical ventilation, demonstration of survival benefit has been rare in clinical trials. Furthermore, some of these nonventilatory interventions carry additional risks and/or high cost; thus, when used as rescue therapy for hypoxemia, it is important that they be demonstrated to yield clinically significant improvement in gas exchange, which should be periodically reassessed. Additionally, various management strategies can produce a more gradual improvement in oxygenation in ARDS, such as conservative fluid management, intravenous corticosteroids, and nutritional modification. Although improvement in oxygenation has been reported with such strategies, demonstration of additional beneficial outcomes, such as reduced duration of mechanical ventilation or ICU length of stay, or improved survival in randomized controlled trials, as well as consideration of potential adverse effects should guide decisions on their use. Various nonventilatory interventions can positively impact oxygenation as well as outcomes of ARDS. These interventions may be considered for use, particularly for cases of refractory severe hypoxemia, with proper appreciation of potential costs and adverse effects. [ABSTRACT FROM AUTHOR]

Approximately 16% of deaths in patients with ARDS results from refractory hypoxemia, which is the inability to achieve adequate arterial oxygenation despite high levels of inspired oxygen or the development of barotrauma. A number of ventilator-focused rescue therapies that can be used when conventional mechanical ventilation does not achieve a specific target level of oxygenation are discussed. A literature search was conducted and narrative review written to summarize the use of high levels of positive end-expiratory pressure, recruitment maneuvers, airway pressure-release ventilation, and high-frequency ventilation. Each therapy reviewed has been reported to improve oxygenation in patients with ARDS. However, none of them have been shown to improve survival when studied in heterogeneous populations of patients with ARDS. Moreover, none of the therapies has been reported to be superior to another for the goal of improving oxygenation. The goal of improving oxygenation must always be balanced against the risk of further lung injury. The optimal time to initiate rescue therapies, if needed, is within 96 h of the onset of ARDS, a time when alveolar recruitment potential is the greatest. A variety of ventilatory approaches are available to improve oxygenation in the setting of refractory hypoxemia and ARDS. Which, if any, of these approaches should be used is often determined by the availability of equipment and clinician bias. [ABSTRACT FROM AUTHOR]