Table 1 Partial list of pivotal studies advancing precision ventilation for ARDS

Tidal volume

Hager et al. [92]

Reanalysis of the ARDSNet tidal volume trial demonstrated plateau pressure below 30 cm H₂O was associated with additional improvement in survival, raising the possibility of residual VILI despite current standard-of-care low tidal volume ventilation

Amato et al. [13]

Reanalysis of several clinical trials demonstrated changes in airway driving pressure mediated effects of tidal volume (and PEEP) on mortality, suggesting driving pressure may be a useful metric for individualizing tidal volume to patient-specific mechanics

Pereira Romano et al. [19]

Pilot clinical trial demonstrated feasibility of a driving pressure-limited strategy without ECMO, laying the groundwork for a future trial of individualized tidal volumes

PEEP

EPVent-1 and EPVent-2 trials [22, 93]

Single and multi-center trials, respectively, that demonstrated PEEP individualized to esophageal pressure, an estimate of pleural pressure, improved adjusted survival compared to an empirical low-PEEP strategy, but did not affect survival compared to an empirical high-PEEP strategy

Alveolar recruitment for ARDS trial (ART) [21]

Multicenter trial demonstrated a stepwise recruitment maneuver combined with PEEP titrated to highest respiratory system compliance, compared to an empirical low-PEEP strategy, increased mortality; interpretation of the PEEP effect is limited by the aggressive, prolonged exposure to extremely high airway pressures during the incremental/decremental recruitment maneuver

LIVE trial [23]

Multicenter trial demonstrated tailoring PEEP to radiographic findings (higher PEEP in patients with non-focal opacities, lower PEEP if focal opacities) did not improve survival compared to an empirical low-PEEP strategy, although misclassification of radiographs limits interpretation of findings

Weighting relative importance of ventilator parameters

Gattinoni et al. [27]

Cohort study proposed mechanical power delivered by the ventilator, combining several ventilator parameters into a unifying metric to quantify VILI risk

Costa et al. [29]

Cohort study that concluded driving pressure and respiratory rate were the key parameters of mechanical power that influence mortality, also suggesting the effect on mortality of each 1 cm H₂O increase in driving pressure was four times that of each 1 breath/min increase in respiratory rate