Lung protection in acute respiratory distress syndrome: what should we target?

Most clinical trials of lung-protective ventilation have tested one-size-fits-all strategies with mixed results. Data are lacking on how best to tailor mechanical ventilation to patient-specific risk of lung injury.

Risk of ventilation-induced lung injury is determined by biological predisposition to biophysical lung injury and physical mechanical perturbations that concentrate stress and strain regionally within the lung. Recent investigations have identified molecular subphenotypes classified as hyperinflammatory and hypoinflammatory acute respiratory distress syndrome (ARDS), which may have dissimilar risk for ventilation-induced lung injury. Mechanically, gravity-dependent atelectasis has long been recognized to decrease total aerated lung volume available for tidal ventilation, a concept termed the 'ARDS baby lung'. Recent studies have demonstrated that the aerated baby lung also has nonuniform stress/strain distribution, with potentially injurious forces concentrated in zones of heterogeneity where aerated alveoli are adjacent to flooded or atelectatic alveoli. The preponderance of evidence also indicates that current standard-of-care tidal volume management is not universally protective in ARDS. When considering escalation of lung-protective interventions, potential benefits of the intervention should be weighed against tradeoffs of accompanying cointerventions required, for example, deeper sedation or neuromuscular blockade. A precision medicine approach to lung-protection would weigh.

A precision medicine approach to lung-protective ventilation requires weighing four key factors in each patient: biological predisposition to biophysical lung injury, mechanical predisposition to biophysical injury accounting for spatial mechanical heterogeneity within the lung, anticipated benefits of escalating lung-protective interventions, and potential unintended adverse effects of mandatory cointerventions.