Association of intensity of ventilation with 28-day mortality in COVID-19 patients with acute respiratory failure: insights from the PRoVENT-COVID study
Authors: Schuijt Michiel T. U. , Schultz Marcus J. , Paulus Frederique , Serpa Neto Ary ,   for the PRoVENT–COVID Collaborative Group, van Akkeren J. P. , Algera A. G. , Algoe C. K. , van Amstel R. B. , Baur O. L. , van de Berg P. , Bergmans D. C. J. J. , van den Bersselaar D. I. , Bertens F. A. , Bindels A. J. G. H. , de Boer M. M. , Boer S.den , Boers L. S. , Bogerd M. , Bos L. D. J. , Botta M. , Breel J. S. , de Bruin H. , de Bruin S. , Bruna C. L. , Buiteman-Kruizinga L. A. , Cremer O. , Determann R. M. , Dieperink W. , Dongelmans D. A. , Franke H. S. , Aldridge M. S. Galek , de Graaff M. J. , Hagens L. A. , Haringman J. J. , Heijnen N. F. L. , Hiel S. , van der Heide S. T. , van der Heiden P. L. J. , Hoeijmakers L. L. , Hol L. , Hollmann M. W. , Hoogendoorn M. E. , Horn J. , van der Horst R. , Ie E. L. K. , Ivanov D. , Juffermans N. P. , Kho E. , de Klerk E. S. , Koopman A. W. M. , Koopmans M. , Kucukcelebi S. , Kuiper M. A. , de Lange D. W. , van Meenen D. M. , Martin-Loeches Ignacio , Mazzinari Guido , van Mourik N. , Nijbroek S. G. , Onrust M. , Oostdijk E. A. N. , Paulus F. , Pennartz C. J. , Pillay J. , Pisani L. , Purmer I. M. , Rettig T. C. D. , Roozeman J. P. , Schuijt M. T. U. , Schultz M. J. , Neto A. Serpa , Sleeswijk M. E. , Smit M. R. , Spronk P. E. , Stilma W. , Strang A. C. , Tsonas A. M. , Tuinman P. R. , Valk C. M. A. , Veen F. L. , Vlaar A. P. J. , Veldhuis L. I. , van Velzen P. , van der Ven W. H. , van Vliet P. , van der Voort P. , van der Wier H. H. , van Welie L. , Wesselink H. J. F. T. , van Wijk B. , Winters T. , Wong W. Y. , van Zanten A. R. H. 
Published: August 2021

Abstract
Background
The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure.

Methods
We aimed to investigate the impact of intensity of ventilation on patient outcome. The PRoVENT-COVID study is a national multicenter observational study in COVID-19 patients receiving invasive ventilation. Ventilator parameters were collected a fixed time points on the first calendar day of invasive ventilation. Mean dynamic ΔP and MP were calculated for individual patients at time points without evidence of spontaneous breathing. A Cox proportional hazard model, and a double stratification analysis adjusted for confounders were used to estimate the independent associations of ΔP and MP with outcome. The primary endpoint was 28-day mortality.

Results
In 825 patients included in this analysis, 28-day mortality was 27.5%. ΔP was not independently associated with mortality (HR 1.02 [95% confidence interval 0.88–1.18]; P = 0.750). MP, however, was independently associated with 28-day mortality (HR 1.17 [95% CI 1.01–1.36]; P = 0.031), and increasing quartiles of MP, stratified on comparable levels of ΔP, had higher risks of 28-day mortality (HR 1.15 [95% CI 1.01–1.30]; P = 0.028).

Conclusions
In this cohort of critically ill invasively ventilated COVID-19 patients with acute respiratory failure, we show an independent association of MP, but not ΔP with 28-day mortality. MP could serve as one prognostic biomarker in addition to ΔP in these patients. Efforts aiming at limiting both ΔP and MP could translate in a better outcome.
Trial registration Clinicaltrials.gov (study identifier NCT04346342).