Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDSTake-Home Points

Background: In patients with ARDS, positive end-expiratory pressure (PEEP) titration remains a challenge and recommendations are not in agreement. In mechanically ventilated patients with COVID-19, subphenotypes based on different respiratory trajectories have been identified, but their heterogeneit...

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Main Authors: Robin L. Goossen, MD, Daan F.L. Filippini, MD, Relin van Vliet, MD, Laura A. Buiteman-Kruizinga, RN, PhD, Markus W. Hollmann, MD, PhD, Sheila N. Myatra, MD, Ary Serpa Neto, MD, PhD, Peter E. Spronk, MD, PhD, Meta C.E. van der Woude, MD, PhD, Marcus J. Schultz, MD, PhD, David M.P. van Meenen, MD, PhD, Frederique Paulus, PhD, Lieuwe D.J. Bos, MD, PhD
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:CHEST Critical Care
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949788425000188
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author Robin L. Goossen, MD
Daan F.L. Filippini, MD
Relin van Vliet, MD
Laura A. Buiteman-Kruizinga, RN, PhD
Markus W. Hollmann, MD, PhD
Sheila N. Myatra, MD
Ary Serpa Neto, MD, PhD
Peter E. Spronk, MD, PhD
Meta C.E. van der Woude, MD, PhD
Marcus J. Schultz, MD, PhD
David M.P. van Meenen, MD, PhD
Frederique Paulus, PhD
Lieuwe D.J. Bos, MD, PhD
author_facet Robin L. Goossen, MD
Daan F.L. Filippini, MD
Relin van Vliet, MD
Laura A. Buiteman-Kruizinga, RN, PhD
Markus W. Hollmann, MD, PhD
Sheila N. Myatra, MD
Ary Serpa Neto, MD, PhD
Peter E. Spronk, MD, PhD
Meta C.E. van der Woude, MD, PhD
Marcus J. Schultz, MD, PhD
David M.P. van Meenen, MD, PhD
Frederique Paulus, PhD
Lieuwe D.J. Bos, MD, PhD
author_sort Robin L. Goossen, MD
collection DOAJ
description Background: In patients with ARDS, positive end-expiratory pressure (PEEP) titration remains a challenge and recommendations are not in agreement. In mechanically ventilated patients with COVID-19, subphenotypes based on different respiratory trajectories have been identified, but their heterogeneity in response to PEEP/Fio2 strategy remains understudied. Research Question: Can these previously determined subphenotypes be detected early in the course of mechanical ventilation, and do these subphenotypes moderate the association between PEEP and Fio2 ventilation strategy and mortality? Study Design and Methods: Retrospective analysis of invasively ventilated patients with COVID-19. Patients were categorized into 2 treatment groups: high PEEP/low Fio2 strategy and low PEEP/high Fio2 strategy. To replicate previously described longitudinal respiratory subphenotypes, hereafter named the low-power or high-power subphenotype, a prediction model was created. The primary outcome was the interaction between PEEP/Fio2 strategy and subphenotype, with mortality as the dependent variable. Results: Of the 1,464 patients included in this analysis, 361 patients (25%) were allocated into the high PEEP/low Fio2 strategy and 1,103 patients (75%) were allocated into the low PEEP/high Fio2 strategy. A prediction model consisting of respiratory data of the first 2 days of invasive ventilation (area under the receiver operating characteristics curve, 0.88) assigned 908 patients (62%) to the low-power subphenotype and 556 patients (38%) to the high-power subphenotype. The high-power subphenotype was characterized by higher minute volume, mechanical power, ventilatory ratio, and driving pressure. The association between PEEP/Fio2 ventilation strategy and ICU mortality was moderated by the subphenotype (P = .03), with high PEEP/low Fio2 ventilation being associated with lower mortality in the low-power subphenotype (OR, 0.46; 95% CI, 0.31-0.67; P < .001) and not in the high-power subphenotype (OR, 0.85; 95% CI, 0.57-1.28; P = .44). Interpretation: In this study, high PEEP/low Fio2 ventilation was associated with improved mortality only in one of the subphenotypes, suggesting that such subphenotypes influence heterogeneity of PEEP and Fio2 effect and should be considered in personalized ventilation strategies. Clinical Trial Registry: ClinicalTrials.gov; No.: NCT05954351; URL: www.clinicaltrials.gov
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spelling doaj-art-d9b88075c1e84a4a80b90718bd3e7cd52025-08-20T03:22:23ZengElsevierCHEST Critical Care2949-78842025-06-013210014510.1016/j.chstcc.2025.100145Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDSTake-Home PointsRobin L. Goossen, MD0Daan F.L. Filippini, MD1Relin van Vliet, MD2Laura A. Buiteman-Kruizinga, RN, PhD3Markus W. Hollmann, MD, PhD4Sheila N. Myatra, MD5Ary Serpa Neto, MD, PhD6Peter E. Spronk, MD, PhD7Meta C.E. van der Woude, MD, PhD8Marcus J. Schultz, MD, PhD9David M.P. van Meenen, MD, PhD10Frederique Paulus, PhD11Lieuwe D.J. Bos, MD, PhD12Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; CORRESPONDENCE TO: R. L. Goossen, MDDepartment of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Intensive Care, Reinier de Graaf Hospital, Delft, The NetherlandsDepartment of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, IndiaAustralian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia; Department of Critical Care, Melbourne Medical School, University of Melbourne, Austin Hospital, Melbourne, VIC, Australia; Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, BrazilDepartment of Intensive Care, Gelre Hospitals, Apeldoorn, The NetherlandsDepartment of Intensive Care, Zuyderland Medical Centre, Heerlen, The NetherlandsDepartment of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Nuffield Department of Medicine, University of Oxford, Oxford, England; Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, AustriaDepartment of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Centre for Innovative Health Practice (ACHIEVE), Faculty of Health, Amsterdam University of Applied Sciences, Amsterdam, The NetherlandsDepartment of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Pulmonology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam, The NetherlandsBackground: In patients with ARDS, positive end-expiratory pressure (PEEP) titration remains a challenge and recommendations are not in agreement. In mechanically ventilated patients with COVID-19, subphenotypes based on different respiratory trajectories have been identified, but their heterogeneity in response to PEEP/Fio2 strategy remains understudied. Research Question: Can these previously determined subphenotypes be detected early in the course of mechanical ventilation, and do these subphenotypes moderate the association between PEEP and Fio2 ventilation strategy and mortality? Study Design and Methods: Retrospective analysis of invasively ventilated patients with COVID-19. Patients were categorized into 2 treatment groups: high PEEP/low Fio2 strategy and low PEEP/high Fio2 strategy. To replicate previously described longitudinal respiratory subphenotypes, hereafter named the low-power or high-power subphenotype, a prediction model was created. The primary outcome was the interaction between PEEP/Fio2 strategy and subphenotype, with mortality as the dependent variable. Results: Of the 1,464 patients included in this analysis, 361 patients (25%) were allocated into the high PEEP/low Fio2 strategy and 1,103 patients (75%) were allocated into the low PEEP/high Fio2 strategy. A prediction model consisting of respiratory data of the first 2 days of invasive ventilation (area under the receiver operating characteristics curve, 0.88) assigned 908 patients (62%) to the low-power subphenotype and 556 patients (38%) to the high-power subphenotype. The high-power subphenotype was characterized by higher minute volume, mechanical power, ventilatory ratio, and driving pressure. The association between PEEP/Fio2 ventilation strategy and ICU mortality was moderated by the subphenotype (P = .03), with high PEEP/low Fio2 ventilation being associated with lower mortality in the low-power subphenotype (OR, 0.46; 95% CI, 0.31-0.67; P < .001) and not in the high-power subphenotype (OR, 0.85; 95% CI, 0.57-1.28; P = .44). Interpretation: In this study, high PEEP/low Fio2 ventilation was associated with improved mortality only in one of the subphenotypes, suggesting that such subphenotypes influence heterogeneity of PEEP and Fio2 effect and should be considered in personalized ventilation strategies. Clinical Trial Registry: ClinicalTrials.gov; No.: NCT05954351; URL: www.clinicaltrials.govhttp://www.sciencedirect.com/science/article/pii/S2949788425000188COVID-19critical careFio2PEEPpneumonia, viralrespiration, artificial
spellingShingle Robin L. Goossen, MD
Daan F.L. Filippini, MD
Relin van Vliet, MD
Laura A. Buiteman-Kruizinga, RN, PhD
Markus W. Hollmann, MD, PhD
Sheila N. Myatra, MD
Ary Serpa Neto, MD, PhD
Peter E. Spronk, MD, PhD
Meta C.E. van der Woude, MD, PhD
Marcus J. Schultz, MD, PhD
David M.P. van Meenen, MD, PhD
Frederique Paulus, PhD
Lieuwe D.J. Bos, MD, PhD
Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDSTake-Home Points
CHEST Critical Care
COVID-19
critical care
Fio2
PEEP
pneumonia, viral
respiration, artificial
title Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDSTake-Home Points
title_full Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDSTake-Home Points
title_fullStr Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDSTake-Home Points
title_full_unstemmed Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDSTake-Home Points
title_short Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDSTake-Home Points
title_sort longitudinal respiratory subphenotypes and differences in response to positive end expiratory pressure and fio2 ventilation strategy in covid 19 ardstake home points
topic COVID-19
critical care
Fio2
PEEP
pneumonia, viral
respiration, artificial
url http://www.sciencedirect.com/science/article/pii/S2949788425000188
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