AUTHOR=Schuijt Michiel T. U. , van Meenen David M. P. , Martin–Loeches Ignacio , Mazzinari Guido , Schultz Marcus J. , Paulus Frederique , Serpa Neto Ary TITLE=Association of Time–Varying Intensity of Ventilation With Mortality in Patients With COVID−19 ARDS: Secondary Analysis of the PRoVENT–COVID Study JOURNAL=Frontiers in Medicine VOLUME=Volume 8 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.725265 DOI=10.3389/fmed.2021.725265 ISSN=2296-858X ABSTRACT=Background High intensity of ventilation has an association with mortality in patients with acute respiratory failure. It is uncertain whether similar associations exist in patients with acute respiratory distress syndrome (ARDS) patients due to coronavirus disease 2019 (COVID–19). We investigated the association of exposure to different levels of driving pressure (ΔP) and mechanical power (MP) with mortality in these patients. Methods PRoVENT–COVID is a national, retrospective observational study, performed at 22 ICUs in the Netherlands, including COVID–19 patients under invasive ventilation for ARDS. Dynamic ΔP and MP were calculated at fixed time points during the first 4 calendar days of ventilation. The primary endpoint was 28–day mortality. To assess the effects of time–varying exposure, Bayesian joint models adjusted for confounders were used. Results Of 1122 patients included in the PRoVENT–COVID study, 734 were eligible for this analysis. In the first 28 days, 29.2% of patients died. A significant increase in the hazard of death was found to be associated with each increment in ΔP (HR 1.04, 95% CrI 1.01–1.07) and in MP (HR 1.12, 95% CrI 1.01–1.36). In sensitivity analyses, cumulative exposure to higher levels of ΔP or MP resulted in increased risks for 28–day mortality. Conclusion Cumulative exposure to higher intensities of ventilation in COVID–19 patients with ARDS have an association with increased risk of 28–day mortality. Limiting exposure to high ΔP or MP has the potential to improve survival in these patients.