Respiratory mechanics modifies the impact of ventilator settings on clinical outcome in patients with acute brain injury

Purpose: To investigate whether respiratory system elastance (ERS) modifies the associations of tidal volume (VT) and respiratory rate with clinical outcomes in mechanically ventilated patients with acute brain injury. Methods: In this post hoc analysis of the VENTIBRAIN study, ERS was computed as the ratio of driving pressure (ΔP) to VT/PBW. Effect modification by ERS on outcome associations was assessed. Results: In 1158 patients, VT was similar across ERS tertiles (median 7.9, 7.6 and 7.1 mL/kg), resulting in a marked ΔP gradient across tertiles (median 5, 9, and 12 cmH2O). Higher VT was associated with lower ICU mortality in patients with low ERS (OR 0.52, 95%CI 0.36-0.74) but not in those with high ERS (OR 1.16, 95% CI 0.89-1.51; Pint < 0.001). Higher respiratory rate was associated with worse outcomes, particularly at low ERS, with the association attenuating at higher ERS. The Bayesian optimal VT/PBW decreased continuously with ERS, from 11.4 mL/kg at ERS 0.5 cmH2O/(mL/kg) (≈ ΔP 6 cmH2O) to 4.4 mL/kg at ERS 2.5 cmH2O/(mL/kg) (≈ ΔP 11 cmH2O), while the optimal respiratory rate increased from 15 to 19 breaths/min. At constant alveolar ventilation, 1-cmH2O ΔP increase had comparable prognostic impact to ≈ 3 breaths/min respiratory rate increases. These results were consistent irrespective of ARDS diagnosis. Conclusions: The impact of ventilator settings is modulated by ERS. A physiological framework for VT adjustment could consider ΔP along with the respiratory rate required to maintain isocapnia, with outcome effects governed by a trade-off of ≈ 3 breaths/min per 1-cmH2O change in ΔP.