Dynamic driving pressure and clinical outcomes in mechanically ventilated patients with acute brain injury: a secondary analysis of the VENTIBRAIN study^*

Purpose: To investigate the association between dynamic driving pressure (ΔPdyn) and mortality in mechanically ventilated patients with acute brain injury (ABI), and to evaluate whether neurological and pulmonary injury severity modify this relationship. Methods: This prespecified secondary analysis of the VENTIBRAIN prospective study (NCT04459884) included mechanically ventilated adult patients with ABI (traumatic brain injury, subarachnoid hemorrhage, intracranial hemorrhage, or ischemic stroke). ΔPdyn was calculated daily over the first 14 days as peak inspiratory pressure minus positive end-expiratory pressure (PEEP). Bayesian joint models evaluated the time-varying association between ΔPdyn and mortality at ICU discharge, hospital discharge, and 6 months. Secondary analyses evaluated effect modification by baseline Glasgow Coma Scale (GCS), PaO₂/FiO₂, and ABI subtype. Results: Among 1,555 patients (median age 59 years, 34.5% female), higher time-varying ΔPdyn was associated with increased ICU mortality (hazard ratio [HR], 1.057 per daily 1cmH₂O; 95% credible interval, 1.037–1.078; posterior probability of HR > 1, 99.9%). Findings were consistent across all ABI subtypes and were similar for static ΔP (plateau pressure minus PEEP). The association was strongest in patients with severe ABI (GCS ≤ 8) and severe hypoxemia (PaO₂/FiO₂ ≤ 100). Results were robust across all outcome timepoints and multiple sensitivity analyses. Conclusion: Higher time-varying ΔPdyn was associated with increased mortality in this cohort of patients with ABI. Neurological injury severity independently modified the harm from ΔPdyn with a magnitude comparable to severe hypoxemia. Measurement of ΔPdyn may aid risk stratification and ventilation strategies in ABI; future trials should evaluate the effect of reducing ΔPdyn in this population.