Airway Pressure Release Ventilation in Acute Hypoxemic Respiratory Failure: Curb Your Enthusiasm.

Critical Care Medicine www.ccmjournal. org 1817 Acute hypoxemic respiratory failure is prevalent among patients admitted to ICUs and often requires mechanical ventilatory support. Observational studies and clinical trials have demonstrated the benefit of lung-protective ventilatory strategies that avoid or mitigate ventilator-induced lung injury among patients with and without hypoxemia (1, 2). The most well-established lung-protective strategy is that promulgated by the acute respiratory distress syndrome (ARDS) Network in which tidal volume size and end-inspiratory plateau pressure are limited and oxygenation is managed using a table of positive end-expiratory pressure (PEEP) and Fio 2 parings (2). Although this strategy has improved important clinical outcomes, mortality remains high and many of those that survive suffer long-term adverse effects that compromise quality of life. For these reasons, there is continued interest in ventilation strategies that could further reduce ventilator-induced lung injury and improve patient outcomes. Since it was first described in the mid-1980s, airway pressure release ventilation (APRV) has been pursued by some as an alternate approach to conventional lung-protective ventilation strategies (3). APRV is a pressure-limited time-cycled mode of mechanical ventilation. In this mode, the ventilator cycles between what are effectively two levels of continuous positive airway pressure. As originally described, the majority of the respiratory cycle (T-high) is spent at a higher pressure (P-high) with interposed brief releases (T-low) to a lower pressure (P-low), which some set to 0 cm H 2 O (3). Cycling between pressures is independent of the patient’s respiratory efforts, which may continue without disrupting the ventilator cycle and vice versa. The potential benefits and harms of APRV in the setting of lung injury have recently been reviewed in detail (4). Briefly, advocates of APRV link many of its putative benefits to the preservation of spontaneous respiratory efforts, including decreased work of breathing and improved comfort as dyssynchrony should be minimal. It is argued that deep sedation and paralytics are therefore less often necessary. Further, the active diaphragm is thought to prevent atelectasis at the lung bases and improve hemodynamics by facilitating venous return, which together improve ventilation/perfusion matching. Oxygenation is further improved as a result of sustained higher airway pressures on recruitable lung parenchyma over time. Although released volumes during P-low can be large, it is argued that the transient nature of the release (if T-low is set correctly) creates auto-PEEP that prevents cyclic atelectotrauma. Skeptics of APRV make a similarly strong argument against its use (4). The large released volumes during T-low raise significant concern given that tidal volume reduction is known to improve outcomes. Although a short T-low and the associated auto-PEEP are touted as being protective against atelectotrauma, this argument assumes expiratory time-constants of injured and noninjured regions are similar. Markstaller et al (5) showed that this is not true. In a porcine model of lung injury, 94% of aerated injured lung derecruited with a time constant of 0.8 seconds, whereas collapse of healthy lung took many seconds. Although prolonged exposure to high airway pressure may recruit atelectatic parenchyma and improve oxygenation, this does not occur in all patients (6). Additionally, spontaneous respiratory efforts when lung volume is high may lead to important increases in transpulmonary pressure that could further exacerbate injury. Furthermore, prolonged periods of high airway pressure may suppress venous return and compromise right ventricular function via increased pulmonary vascular resistance. Last, although APRV is advertised as being more comfortable and requiring less sedation, this is not a consistent finding. Given this robust debate, and because APRV is available on most modern ventilators, many readers will be interested in the results of a systematic review and meta-analysis by Lim and Litton (7) in this issue of Critical Care Medicine. The study includes data from 412 patients with acute hypoxemic respiratory failure enrolled in seven randomized controlled trials conducted between 2000 and 2018 that compare APRV to more traditional ventilatory strategies. The analysis shows that patients randomized to APRV had a lower risk of death (relative risk, 0.67; 95% CI, 0.48–0.94) and improved day 3 Pao 2 / Fio 2 ratio. Lim and Litton (7) also report subgroup analyses that compare APRV to studies in which the control arm was ventilated using a low tidal volume strategy (n = 6 studies), studies using alternate modes of ventilation (n = 3 studies), studies limited to patients with ARDS (n = 4 studies), and those studies for which short term mortality (at ~30 d) was known (n = 6 studies). In each analysis, APRV either performed better or trended toward improved performance. Additionally, *See also p. 1794.