COVID-19; SARS-CoV-2; acute respiratory distress syndrome; emulated target trial; extracorporeal membrane oxygenation; Adult; Cohort Studies; Humans; Retrospective Studies; Treatment Outcome; COVID-19/complications; COVID-19/therapy; Extracorporeal Membrane Oxygenation; Respiratory Distress Syndrome/etiology; Respiratory Distress Syndrome/therapy; Respiratory Distress Syndrome; Pulmonary and Respiratory Medicine; Critical Care and Intensive Care Medicine
Abstract :
[en] Rationale: Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. Objectives: To estimate the effect of ECMO on 90-day mortality versus IMV only. Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 80 or PaCO2 ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. Measurements and Main Results: A total of 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0-9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, -2%; 95% confidence interval, -10 to 5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic. Conclusions: In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Hajage, David; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP
Combes, Alain; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMRS) 1166, Institute of Cardiometabolism and Nutrition, Paris, France ; Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Pitié-Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie, Paris, France
Guervilly, Christophe; Medecine Intensive Réanimation, Centre hospitalier Universitaire L'Hôpital Nord, Assistance Publique hôpitaux de Marseille, Marseille, France ; Aix-Marseille Université, Faculté de Médecine Centre d'Études et de Recherches sur les Services de Santé et qualité de vie EA 3279, Marseille, France
Lebreton, Guillaume; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMRS) 1166, Institute of Cardiometabolism and Nutrition, Paris, France ; Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Pitié-Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie, Paris, France ; Medecine Intensive Réanimation, Centre hospitalier Universitaire L'Hôpital Nord, Assistance Publique hôpitaux de Marseille, Marseille, France ; Aix-Marseille Université, Faculté de Médecine Centre d'Études et de Recherches sur les Services de Santé et qualité de vie EA 3279, Marseille, France ; Department of Cardiovascular and Thoracic Surgery, Pitié-Salpêtrière Hospital, APHP- Sorbonne University, Paris, France
Mercat, Alain; Département de Médecine Intensive - Réanimation et Médecine Hyperbare, CHU d'Angers, Faculté de Santé, Université d'Angers, Angers, France
Pavot, Arthur; Université Paris-Saclay, AP-HP, Service de médecine intensive-réanimation, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS, Le Kremlin-Bicêtre, France
Nseir, Saad; Médecine Intensive-Réanimation, CHU Lille, Inserm U1285, University of Lille, CNRS, UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France
Mekontso-Dessap, Armand; AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpitaux universitaires Henri Mondor, DMU Médecine, Service de Médecine Intensive Réanimation, INSERM Unité U955, Créteil, France ; UPEC (Université Paris Est Créteil), Faculté de Santé de Créteil, IMRB, GRC CARMAS, Créteil, France
Mongardon, Nicolas; Service d'Anesthésie-Réanimation Chirurgicale, Hôpitaux Universitaires Henri Mondor, DMU CARE, Assistance Publique-Hôpitaux de Paris, Inserm U955 équipe 3, Faculté de Santé, Université Paris-Est Créteil, Créteil, France
Mira, Jean Paul; Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Universitaire de Paris Centre, Hôpital Cochin, Médecine Intensive Réanimation, Paris Descartes Sorbonne Paris Cité University, Paris, France, Department of Infection, Immunity and Inflammation, Cochin Institute, Inserm U1016, Paris, France
Ricard, Jean-Damien; Université de Paris, APHP, Hôpital Louis Mourier, DMU ESPRIT, Service de Médecine Intensive Réanimation, Colombes, France
Beurton, Alexandra; AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, site Pitié-Salpêtrière, Service de Médecine Intensive et Réanimation (Département R3S), and Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France
Tachon, Guillaume; Service de Médecine Intensive Réanimation, Hôpital Foch, Suresnes, France
Kontar, Loay; Department of Intensive Care Medicine, CHU Amiens-Picardie, avenue Laennec, Amiens, France
Le Terrier, Christophe; Division of Intensive Care, Geneva University Hospitals, Geneva, Switzerland ; Faculty of Medicine, University of Geneva, Geneva, Switzerland
Richard, Jean Christophe; Service de Médecine Intensive-Réanimation, Hôpital de la Croix-Rousse-Hospices Civils de Lyon, Lyon, France
Mégarbane, Bruno; Department of Medical and Toxicological Critical Care, Lariboisière Hospital, APHP, INSERM UMRS-1144, Paris University, Paris, France
Keogh, Ruth H; Department of Medical Statistics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom, and
Belot, Aurélien; Inequalities in Cancer Outcomes Network, London School of Hygiene and Tropical Medicine, London, United Kingdom
Maringe, Camille; Inequalities in Cancer Outcomes Network, London School of Hygiene and Tropical Medicine, London, United Kingdom
Leyrat, Clémence ; Department of Medical Statistics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom, and
Schmidt, Matthieu ; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMRS) 1166, Institute of Cardiometabolism and Nutrition, Paris, France ; Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Pitié-Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie, Paris, France
AP-HP - Fondation de l’AP-HP French Ministry of Social Affairs and Health
Funding text :
Supported by the Foundation APHP (Assistance Publique des Hôpitaux de Paris) and its donators through the program “Alliance Tous Unis Contre le Virus”, the Direction de la Recherche Clinique et du Développement, and the French Ministry of Health and the foundation of the University Hospitals of Geneva, Geneva, Switzerland. This research was funded in whole or in part by the United Kingdom Medical Research Council, MR/ T032448/1. The funder had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. C.L. is supported by the United Kingdom Medical Research Council (Skills Development Fellowship MR/T032448/1). R.H.K. is funded by a UKRI Future Leaders Fellowship (MR/S017968/1). C.M. and A. Belot are funded by a Cancer Research United Kingdom program grant (C7923/A29018).Supported by the Foundation APHP (Assistance Publique des Hôpitaux de Paris) and its donators through the program “Alliance Tous Unis Contre le Virus”, the Direction de la Recherche Clinique et du Developpement, and the French Ministry of Health and the foundation of the University Hospitals of Geneva, Geneva, Switzerland. This research was funded in whole or in part by the United Kingdom Medical Research Council, MR/ T032448/1. The funder had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. C.L. is supported by the United Kingdom Medical Research Council (Skills Development Fellowship MR/T032448/1). R.H.K. is funded by a UKRI Future Leaders Fellowship (MR/S017968/1). C.M. and A. Belot are funded by a Cancer Research United Kingdom program grant (C7923/A29018).
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