Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study

Michela Botta, Anissa M Tsonas, Janesh Pillay, Leonoor S Boers, Anna Geke Algera, Lieuwe D J Bos, Dave A Dongelmans, Marcus W Hollmann, Janneke Horn, Alexander P J Vlaar, Marcus J Schultz, Ary Serpa Neto, Frederique Paulus, PRoVENT-COVID Collaborative Group, Jesse P van Akkeren, Anna Geke Algera, Cheetel K Algoe, Rombout B van Amstel, Onno L Baur, Pablo van de Berg, Alida E van den Berg, Dennis C J J Bergmans, Dido I van den Bersselaar, Freke A Bertens, Alexander J G H Bindels, Milou M de Boer, Sylvia den Boer, Leonoor S Boers, Margriet Bogerd, Lieuwe D J Bos, Michela Botta, Jennifer S Breel, Hendrik de Bruin, Sanne de Bruin, Caro L Bruna, Laura A Buiteman-Kruizinga, Olaf L Cremer, Rogier M Determann, Willem Dieperink, Dave A Dongelmans, Hildegard S Franke, Michal S Galek-Aldridge, Mart J de Graaff, Laura A Hagens, Jasper J Haringman, Sebastiaan T van der Heide, Pim L J van der Heiden, Nanon F L Heijnen, Stephan J P Hiel, Lotte L Hoeijmakers, Liselotte Hol, Markus W Hollmann, Marga E Hoogendoorn, Janneke Horn, Robrecht van der Horst, Evy L K Ie, Dimitri P Ivanov, Nicole Juffermans, Eline Kho, Eline S de Klerk, Ankie W M M Koopman-van Gemert, Matty Koopmans, Songul Kucukcelebi, Michael A Kuiper, Dylan W de Lange, Niels van Mourik, Sunny G L H Nijbroek, Marisa Onrust, Evelien A N Oostdijk, Frederique Paulus, Charlotte J Pennartz, Janesh Pillay, Luigi Pisani, Ilse M Purmer, Thijs C D Rettig, Jan-Paul Roozeman, Michiel T U Schuijt, Marcus J Schultz, Ary Serpa Neto, Mengalvio E Sleeswijk, Marry R Smit, Peter E Spronk, Willemke Stilma, Aart C Strang, Anissa M Tsonas, Pieter R Tuinman, Christel M A Valk, Felicia L Veen-Schra, Lars I Veldhuis, Patricia van Velzen, Ward H van der Ven, Alexander P J Vlaar, Peter van Vliet, Peter H J van der Voort, Louis van Welie, Henrico J F T Wesselink, Hermien H van der Wier-Lubbers, Bas van Wijk, Tineke Winters, Wing Yi Wong, Arthur R H van Zanten, Michela Botta, Anissa M Tsonas, Janesh Pillay, Leonoor S Boers, Anna Geke Algera, Lieuwe D J Bos, Dave A Dongelmans, Marcus W Hollmann, Janneke Horn, Alexander P J Vlaar, Marcus J Schultz, Ary Serpa Neto, Frederique Paulus, PRoVENT-COVID Collaborative Group, Jesse P van Akkeren, Anna Geke Algera, Cheetel K Algoe, Rombout B van Amstel, Onno L Baur, Pablo van de Berg, Alida E van den Berg, Dennis C J J Bergmans, Dido I van den Bersselaar, Freke A Bertens, Alexander J G H Bindels, Milou M de Boer, Sylvia den Boer, Leonoor S Boers, Margriet Bogerd, Lieuwe D J Bos, Michela Botta, Jennifer S Breel, Hendrik de Bruin, Sanne de Bruin, Caro L Bruna, Laura A Buiteman-Kruizinga, Olaf L Cremer, Rogier M Determann, Willem Dieperink, Dave A Dongelmans, Hildegard S Franke, Michal S Galek-Aldridge, Mart J de Graaff, Laura A Hagens, Jasper J Haringman, Sebastiaan T van der Heide, Pim L J van der Heiden, Nanon F L Heijnen, Stephan J P Hiel, Lotte L Hoeijmakers, Liselotte Hol, Markus W Hollmann, Marga E Hoogendoorn, Janneke Horn, Robrecht van der Horst, Evy L K Ie, Dimitri P Ivanov, Nicole Juffermans, Eline Kho, Eline S de Klerk, Ankie W M M Koopman-van Gemert, Matty Koopmans, Songul Kucukcelebi, Michael A Kuiper, Dylan W de Lange, Niels van Mourik, Sunny G L H Nijbroek, Marisa Onrust, Evelien A N Oostdijk, Frederique Paulus, Charlotte J Pennartz, Janesh Pillay, Luigi Pisani, Ilse M Purmer, Thijs C D Rettig, Jan-Paul Roozeman, Michiel T U Schuijt, Marcus J Schultz, Ary Serpa Neto, Mengalvio E Sleeswijk, Marry R Smit, Peter E Spronk, Willemke Stilma, Aart C Strang, Anissa M Tsonas, Pieter R Tuinman, Christel M A Valk, Felicia L Veen-Schra, Lars I Veldhuis, Patricia van Velzen, Ward H van der Ven, Alexander P J Vlaar, Peter van Vliet, Peter H J van der Voort, Louis van Welie, Henrico J F T Wesselink, Hermien H van der Wier-Lubbers, Bas van Wijk, Tineke Winters, Wing Yi Wong, Arthur R H van Zanten

Abstract

Background: Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak.

Methods: PRoVENT-COVID is a national, multicentre, retrospective observational study done at 18 intensive care units (ICUs) in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The primary outcome was a combination of ventilator variables and parameters over the first 4 calendar days of ventilation: tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and ICU complications. Patient-centred outcomes were ventilator-free days at day 28, duration of ventilation, duration of ICU and hospital stay, and mortality. PRoVENT-COVID is registered at ClinicalTrials.gov (NCT04346342).

Findings: Between March 1 and April 1, 2020, 553 patients were included in the study. Median tidal volume was 6·3 mL/kg predicted bodyweight (IQR 5·7-7·1), PEEP was 14·0 cm H2O (IQR 11·0-15·0), and driving pressure was 14·0 cm H2O (11·2-16·0). Median respiratory system compliance was 31·9 mL/cm H2O (26·0-39·9). Of the adjunctive treatments for refractory hypoxaemia, prone positioning was most often used in the first 4 days of ventilation (283 [53%] of 530 patients). The median number of ventilator-free days at day 28 was 0 (IQR 0-15); 186 (35%) of 530 patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation.

Interpretation: In patients with COVID-19 who were invasively ventilated during the first month of the outbreak in the Netherlands, lung-protective ventilation with low tidal volume and low driving pressure was broadly applied and prone positioning was often used. The applied PEEP varied widely, despite an invariably low respiratory system compliance. The findings of this national study provide a basis for new hypotheses and sample size calculations for future trials of invasive ventilation for COVID-19. These data could also help in the interpretation of findings from other studies of ventilation practice and outcomes in invasively ventilated patients with COVID-19.

Funding: Amsterdam University Medical Centers, location Academic Medical Center.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Study profile Follow-up to 90 days was completed in 495 patients.
Figure 2
Figure 2
Ventilation parameters Cumulative frequency distribution of tidal volume, PEEP, driving pressure, and respiratory system compliance. Vertical dotted lines represent the median on the first calendar day of ventilation for each variable, and horizontal dotted lines show the respective proportion of patients reaching each cutoff. PEEP=positive end-expiratory pressure.
Figure 3
Figure 3
Cumulative incidence of extubation with death before extubation as a competing risk (A) and 28-day survival (B) in the overall cohort (n=530)

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Source: PubMed

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