Association of intensity of ventilation with 28-day mortality in COVID-19 patients with acute respiratory failure: insights from the PRoVENT-COVID study

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

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).

Keywords: Acute respiratory failure; COVID-19; Coronavirus disease 2019; Driving pressure; ICU; Invasive ventilation; Mechanical power; Mechanical power of ventilation; Mortality; ΔP.

Conflict of interest statement

ASN reports personal fees from Dräger, outside of the submitted work. The other authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Association between driving pressure and mechanical power and 28-day mortality. A Kaplan–Meier curve comparing the 28-day mortality of patients ventilated with ΔP > 15 cmH2O vs. ΔP ≤ 15 cmH2O. B Kaplan–Meier curve comparing the 28-day mortality of patients ventilated with MP > 17 (J/min) versus ≤ 17 (J/min). C and D Effect of increasing levels of ΔP or MP on 28-day mortality. Circles and error bars are hazard ratio and 95% confidence interval for 5 quantiles of increasing ΔP or MP. Dashed lines and grey areas represent hazard ratio and 95% confidence interval for increasing values of ΔP or MP analyzed as a continuous variable and centralized in the mean of each variable. All models were adjusted for age, chronic obstructive pulmonary disease, pH, and heart rate. ΔP: driving pressure; MP: mechanical power
Fig. 2
Fig. 2
Hazard ratio for 28-day mortality across relevant quartiles of driving pressure and mechanical power. A (left) Comparable values of ΔP, but increasing values of MP across strata. Multivariable HR for increasing MP per stratum is presented below. B (right) Comparable values of MP, but increasing values of ΔP across strata. Multivariable HR for increasing ΔP per stratum is presented below. The Y1 axis is for airway pressure; the Y2 axis is for mechanical power. X axis reports cohort sample sizes. Circles and error bars in the lower panels are HR and 95% confidence interval for quartiles of increasing ΔP and matched MP or vice-versa. All models were adjusted for age, chronic obstructive pulmonary disease, pH, and heart rate

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