Management strategies for ARDS are centered on treatment of the underlying clinical disorder while providing supportive care that minimizes ventilator-induced lung injury (VILI).
The majority of patients with ARDS develop respiratory failure severe enough to necessitate mechanical ventilation. While positive-pressure ventilation helps to ensure adequate oxygenation, our understanding of the potential harms of mechanical ventilation has evolved over the last decade. There are four potential mechanisms of alveolar damage in ventilated patients with ARDS: (1) barotrauma caused by excessive airway pressures, (2) volutrauma caused by over distension of alveoli from high tidal-volume ventilation, (3) atelectrauma caused by shearing forces on alveoli from inspiratory opening and expiratory collapse, and (4) biotrauma caused by the release of proinflammatory cytokines from excessive mechanical forces on the lung.13
A substantial amount of basic and clinical research has been devoted to understanding optimal ventilator strategies to reduce VILI, which are summarized as follows.
Low Tidal-Volume Ventilation
One strategy for reducing lung injury during mechanical ventilation is the use of low tidal-volume (Vt) ventilation. This became the standard of care following the landmark National Heart, Lung, and Blood Institute's ARDS Network (ARDSNet) trial in 2000, in which a lower Vt (goal 6 mL/kg ideal body weight) with lower plateau-pressure (< 30 cm H2O) was compared to a higher Vt and plateau-pressure (12 mL/kg ideal body weight and < 50 cm H2O). Patients randomized to the low Vt/low plateau-pressure group had a reduced 28-day mortality and developed fewer instances of organ failure.14 These findings have been confirmed by additional work showing increased intensive care unit and hospital mortality in patients ventilated with higher Vt.15
Positive End-Expiratory Pressure
Another strategy used to reduce injury during mechanical ventilation is the application of positive end-expiratory pressure (PEEP) to reduce cyclical alveolar opening/collapse. However, the optimal level of PEEP in ventilated patients with ARDS remains controversial given the opposing risks of alveolar overdistension and hemodynamic compromise. In a meta-analysis of trials comparing high-PEEP and low-PEEP strategies (14 cm H2O vs ~8 cm H2O), patients with moderate to severe ARDS (PaO2/FiO2 ≤ 200) showed a small but significant improvement in survival among the higher PEEP group. However, this mortality benefit did not exist when all ARDS patients (PaO2/FiO2 ≤ 300) were included in the analysis.16 One possible explanation for these findings is that patients with moderate to severe ARDS (with more significant edema and potentially recruitable lung) may respond favorably to higher PEEP, whereas patients with mild ARDS (and less proportion of recruitable lung) may experience alveolar distension of their healthy, already-aerated lung tissue. At this time, clinical practice guidelines recommends titrating PEEP to maintain an oxygen saturation of 88% to 95% and a plateau pressure of 30 cm H2O or less to avoid barotrauma.
Fraction of Inspired Oxygen
While the use of high concentrations of inspired oxygen (FiO2) is commonly necessary, at least temporarily, for patients with severe ARDS, excessive use of high FiO2 can cause a spectrum of lung injury. Cellular injury appears to be related to increased production of reactive oxygen species, which impair intracellular molecule function and cause cell death.17 This can lead to damage of the airways and pulmonary parenchyma. Reducing the FiO2 to the lowest tolerable level is desirable for all critically ill patients and particularly in patients with ARDS who have already sustained some form of lung injury.
Novel Ventilation Strategies
Transpulmonary pressure-guided ventilation—Transpulmonary pressure-guided ventilation uses an esophageal balloon-catheter to estimate pleural pressure and titrate PEEP to each individual's lung and chest wall mechanics. This approach targets a positive transpulmonary pressure (PTP) to deliver enough PEEP to prevent repetitive airspace collapse yet avoiding alveolar overdistension. A preliminary single-centered trial showed that optimizing PTP significantly improved oxygenation and lung mechanics compared to a conventional ventilation strategy.18 Further investigations are being conducted to examine potential survival benefit.
High-frequency oscillation ventilation—High-frequency oscillation ventilation (HFOV) delivers very small tidal volumes at a high frequency (180-1800 per minute) in an effort to maintain a high mean airway pressure. The supporting theory is that sustaining a constant mean airway pressure during inspiration and expiration will prevent end-expiratory collapse. An initial randomized, controlled trial showed an early, transient improvement in oxygenation among patients ventilated with HFOV versus conventional ventilation.19 However, a subsequent trial showed no significant differences between both groups and was stopped prematurely due to low inclusion.20
Airway pressure release ventilation—Airway pressure release ventilation is a mode of pressure-controlled mechanical ventilation, which applies continuous positive airway pressure for a prolonged time, followed by a release phase to a lower pressure for a shorter period of time. The prolonged high-pressure phase allows for maintenance of adequate lung volume and alveolar recruitment while the shorter low-pressure phase provides the majority of ventilation and carbon dioxide removal.21 APRV was developed to provide lung recruitment while minimizing VILI. Several studies have shown APRV to improve clinical outcomes, such as oxygenation, lung recruitment, respiratory mechanics, and sedation requirement. However, thus far it has not been shown to improve mortality as compared to other lung protective ventilation strategies.22
Patients with ARDS require diligent supportive care, including judicious use of sedatives, appropriate fluid management, and adequate nutritional support.
The use of sedatives and analgesia in patients with ARDS improves ventilator tolerance23 and decreases oxygen consumption.24 However, given the significant morbidity associated with excessive sedation, judicious use of agents is recommended. Moreover, improved outcomes have been demonstrated through the application of strategies for frequent sedation liberation and awakening as well as early mobilization.25
Although the ARDS definition excludes patients with pulmonary edema exclusively due to volume overload or cardiogenic etiologies, an estimated 30% of patients with ARDS have an elevated pulmonary artery occlusion pressure less than 18 mm Hg. Even in patients without elevated filling pressures, a positive fluid balance is associated with poorer outcomes.26 Thus, conservative fluid management for patients with hemodynamic stability and adequate urine output may be beneficial in patients with ARDS.
Given the tremendously catabolic state present among patients with ARDS, nutritional support is advantageous. Enteral feedings are preferable if the gastrointestinal tract is acceptable for intake. Theoretically, enteral feeds with increased fat and decreased carbohydrates should result in less carbon dioxide production, thereby decreasing the degree of respiratory acidosis. The ARDSNet EDEN trial showed no difference in physical function, survival, or cognitive performance among patients receiving trophic versus full enteral feedings.27
Neuromuscular blocking agents are used to achieve paralysis and decrease ventilator dyssynchrony. Improved patient–ventilator synchrony is thought to reduce VILI by improving control of low tidal-volume ventilation and decreasing the inflammatory response.28 In patients with ARDS, early, short-term paralysis has been shown to improve mortality without a significant increase in development of muscle weakness.29
Prone positioning results in improved oxygenation through three primary mechanisms. First, redistribution of blood flow to healthier lung regions results in a decreased ventilation perfusion mismatch and recruitment of dependent lung units.30 Mechanically, lung tissue relieved of compression from anterior mediastinal and abdominal structures. Lastly, clearance of respiratory secretions is improved with an associated reduction in ventilator-associated pneumonia.31 For patients with severe ARDS (PaO2/FiO2 ≤ 100 mm Hg), early application of prone positioning has been shown to confer a survival benefit at 28 and 90 days.32
Extracorporeal Membrane Oxygenation
During extracorporeal membrane oxygenation (ECMO) blood is rerouted outside the body to an external membrane oxygenator, which acts as an artificial lung to facilitate adequate gas exchange. Major risks include bleeding due to anticoagulation (in particular, intracranial hemorrhage) and complications of large bore vascular access. While initial studies showed no improvement in mortality, a more recent trial suggested a potential survival benefit for patients put on ECMO,33 though other studies have not reproduced this benefit. Currently, ECMO is reserved as an option for rescue therapy for patients with severe ARDS and refractory hypoxemia.
Pulmonary Vasodilator Pharmacotherapy
Inhaled vasodilators, such as nitric oxide (NO) have been used in ARDS to improve oxygenation by selectively dilating pulmonary arterial vasculature and decreasing ventilation/perfusion mismatching. While inhaled NO has been shown to improve oxygenation in some ARDS patients with refractory hypoxemia, it has not shown a reduction in mortality.34 Thus, inhaled NO has not used routinely and is instead reserved for patients with intractable hypoxemia.