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

Purpose To investigate whether respiratory system elastance (E-RS) modifies the associations of tidal volume (V-T) and respiratory rate with clinical outcomes in mechanically ventilated patients with acute brain injury. Methods In this post hoc analysis of the VENTIBRAIN study,E(RS)was computed as the ratio of driving pressure (Delta P) toV(T)/PBW. Effect modification byE(RS)on outcome associations was assessed. Results In 1158 patients, V(T )was similar across E(RS )tertiles (median 7.9, 7.6 and 7.1 mL/kg), resulting in a marked Delta Pgradient across tertiles (median 5, 9, and 12 cmH(2)O). Higher V(T)was associated with lower ICU mortality in patients with low E-RS(OR 0.52, 95%CI 0.36-0.74) but not in those with high E-RS(OR 1.16, 95% CI 0.89-1.51;P-int< 0.001). Higher respiratory rate was associated with worse outcomes, particularly at low E-RS, with the association attenuating at higher E-RS. The Bayesian optimal V-T/PBW decreased continuously with E-RS, from 11.4 mL/kg atE(RS)0.5 cmH(2)O/(mL/kg) (approximate to Delta P6 cmH(2)O) to 4.4 mL/kg atE(RS)2.5 cmH(2)O/(mL/kg) (approximate to Delta P11 cmH(2)O), while the optimal respiratory rate increased from 15 to 19 breaths/min. At constant alveolar ventilation, 1-cmH(2)O Delta Pincrease had comparable prognostic impact to approximate to 3 breaths/min respiratory rate increases. These results were consistent irrespective of ARDS diagnosis. Conclusions The impact of ventilator settings is modulated by E-RS. A physiological framework for V(T )adjustment could consider Delta Palong with the respiratory rate required to maintain isocapnia, with outcome effects governed by a trade-off of approximate to 3 breaths/min per 1-cmH(2)O change in Delta P.