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

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

CHEST Critical Care (Jun 2025)

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

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

Affiliations

Robin L. Goossen, MD: Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; CORRESPONDENCE TO: R. L. Goossen, MD
Daan F.L. Filippini, MD: Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Relin van Vliet, MD: Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Laura A. Buiteman-Kruizinga, RN, PhD: Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Intensive Care, Reinier de Graaf Hospital, Delft, The Netherlands
Markus W. Hollmann, MD, PhD: Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Sheila N. Myatra, MD: Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
Ary Serpa Neto, MD, PhD: Australian 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, Brazil
Peter E. Spronk, MD, PhD: Department of Intensive Care, Gelre Hospitals, Apeldoorn, The Netherlands
Meta C.E. van der Woude, MD, PhD: Department of Intensive Care, Zuyderland Medical Centre, Heerlen, The Netherlands
Marcus J. Schultz, MD, PhD: Department 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, Austria
David M.P. van Meenen, MD, PhD: Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Frederique Paulus, PhD: Department 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 Netherlands
Lieuwe D.J. Bos, MD, PhD: Department 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 Netherlands

Journal volume & issue: Vol. 3, no. 2
p. 100145

Abstract

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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

Published in CHEST Critical Care

ISSN: 2949-7884 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://www.sciencedirect.com/journal/chest-critical-care

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