Oxygenation and ventilatory variables in ARDS: time to revise our definitions of severity?

Hypoxaemia is a defining criterion for acute respiratory distress syndrome (ARDS) [1], but not the main cause of death among affected patients [2, 3]. Most deaths are instead attributed to systemic inflammation and multiple organ failure [4], propagated in part by ventilation-induced lung injury (VILI) [5]. A few interventions for ARDS reduce mortality (e.g. low tidal volume ventilation, prone position, extracorporeal membrane oxygenation (ECMO)) [6–9], but accumulating evidence suggests their benefit is mediated primarily by mitigating VILI rather than improving hypoxaemia [8, 10]. Despite the critical impact of VILI on outcome pathways of ARDS patients, clinical trials have largely focused on oxygenation parameters as criteria for inclusion and intervention [7, 11, 12].