Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study

Martin Urner; Adrian G Barnett; Gianluigi Li Bassi; Daniel Brodie; Heidi J Dalton; Niall D Ferguson; Silver Heinsar; Carol L Hodgson; Giles Peek; Kiran Shekar; Jacky Y Suen; John F Fraser; Eddy Fan; COVID-19 Critical Care Consortium Investigators

doi:10.1136/bmj-2021-068723

Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study

BMJ. 2022 May 4:377:e068723. doi: 10.1136/bmj-2021-068723.

Authors

Martin Urner^{1

2

3}, Adrian G Barnett⁴, Gianluigi Li Bassi^{5

6

7

8

9}, Daniel Brodie^{10

11}, Heidi J Dalton^{12

13}, Niall D Ferguson^{1

2

3

14

15

16}, Silver Heinsar^{5

6

8

17}, Carol L Hodgson^{18

19}, Giles Peek²⁰, Kiran Shekar^{5

6

9}, Jacky Y Suen^{5

6}, John F Fraser^{5

6

8}, Eddy Fan^{21

2

3

14

16}; COVID-19 Critical Care Consortium Investigators

Collaborators

COVID-19 Critical Care Consortium Investigators:
Tala Al-Dabbous, Huda Alfoudri, Subbarao Elapavaluru, Ashley Berg, Christina Horn, Stephan Schroll, Jorge Velazco, Wanda Fikes, Ludmyla Ploskanych, Dan Meyer, Maysoon Shalabi-McGuire, Trent Witt, Ashley Ehlers, Lorenzo Grazioli, E Wilson Grandin, Jose Nunez, Tiago Reyes, Mark Joseph, Brook Mitchell, Martha Tenzer, Ryuzo Abe, Yosuke Hayashi, Hwa Jin Cho, In Seok Jeong, Nicolas Brozzi, Jaime Hernandez-Montfort, Omar Mehkri, Stuart Houltham, Jerónimo Graf, Rodrigo Perez, Roderigo Diaz, Camila Delgado, Joyce González, Maria Soledad Sanchez, Diego Fernando Bautista Rincón, Melissa Bustamante Duque, Angela Maria Marulanda Yanten, Desy Rusmawatiningtyas, Gabrielle Ragazzo, Azhari Taufik, Margaretha Gunawan, Vera Irawany, Muhammad Rayhan, Elizabeth Yasmin Wardoyo, Mauro Panigada, Silvia Coppola, Sebastiano Colombo, Giacomo Grasselli, Michela Leone, Alberto Zanella, Massimo Antonelli, Simone Carelli, Domenico Grieco, Motohiro Asaki, Kota Hoshino, Leonardo Salazar, Laura Duarte, Joseph McCaffrey, Allison Bone, David Thomson, Christel Arnold-Day, Jerome Cupido, Zainap Fanie, Malcom Miller, Lisa Seymore, Dawid van Straaten, Ibrahim Hassan, Ali Ait Hssain, Jeffrey Aliudin, Al-Reem Alqahtani, Khoulod Mohamed, Ahmed Mohamed, Darwin Tan, Joy Villanueva, Ahmed Zaqout, Ethan Kurtzman, Arben Ademi, Ana Dobrita, Khadija El Aoudi, Juliet Segura, Gezy Giwangkancana, Shinichiro Ohshimo, Koji Hoshino, Saito Hitoshi, Yuka Uchinami, Javier Osatnik, Anne Joosten, Antoni Torres, Ana Motos, Minlan Yang, Carlos Luna, Francisco Arancibia, Virginie Williams, Alexandre Noel, Nestor Luque, Trieu Huynh Trung, Sophie Yacoub, Marina Fantini, Ruth Noemi Jorge García, Enrique Chicote Alvarez, Anna Greti, Oscar Lomeli, Adrian Ceccato, Angel Sanchez, Ana Loza Vazquez, Ferran Roche-Campo, Divina Tuazon, Toni Duculan, Hiroaki Shimizu, Marcelo Amato, Luciana Cassimiro, Flavio Pola, Francis Ribeiro, Guilherme Fonseca, Mehul Desai, Erik Osborn, Hala Deeb, Antonio Arcadipane, Claudia Bianco, Raffaele Cuffaro, Gennaro Martucci, Giovanna Occhipinti, Matteo Rossetti, Chiara Vitiello, Sung-Min Cho, Kate Calligy, Glenn Whitman, Naoki Moriyama, Jae-Burm Kim, Nobuya Kitamura, Takashi Shimazui, Abdullah Al-Hudaib, Alyaa Elhazmi, Johannes Gebauer, Toshiki Yokoyama, Abdulrahman Al-Fares, Esam Alamad, Fatma Alawadhi, Kalthoum Alawadi, Sarah Buabbas, Hiro Tanaka, Satoru Hashimoto, Masaki Yamazaki, Tak-Hyuck Oh, Mark Epler, Cathleen Forney, Jared Feister, Katherine Grobengieser, Louise Kruse, Joelle Williamson, Eric Gnall, Mara Caroline, Sasha Golden, Colleen Karaj, Sherry McDermott, Lynn Sher, Timothy Shapiro, Lisa Thome, Mark Vanderland, Mary Welch, Luca Brazzi, Tawnya Ogston, Dave Nagpal, Karlee Fischer, Roberto Lorusso, Maria de Piero, Mariano Esperatti, Diarmuid O'Briain, Edmund G Carton, Ayan Sen, Amanda Palacios, Deborah Rainey, Cassandra Seefeldt, Lucia Durham, Octavio Falcucci, Amanda Emmrich, Jennifer Guy, Carling Johns, Emily Neumann, Nina Buchtele, Michael Schwameis, Stephanie-Susanne Stecher, Delila Singh, Michaela Barnikel, Lukas Arenz, Akram Zaaqoq, Lan Anh Galloway, Caitlin Merley, Marc Csete, Luisa Quesada, Isabela Saba, Daisuke Kasugai, Hiroaki Hiraiwa, Taku Tanaka, Eva Marwali, Yih-Sharng Chen, John Laffey, Marlice VanDyk, Sarah MacDonald, Ian Seppelt, Indrek Ratsep, Lauri Enneveer, Kristo Erikson, Getter Oigus, Andra-Maris Post, Piret Sillaots, Effe Mihelis, Mamoru Komats, S Veena Satyapriya, Amar Bhatt, Marco Echeverria, Juan Fiorda, Alicia Gonzalez, Nahush A Mokadam, Johnny McKeown, Joshua Pasek, Haixia Shi, Alberto Uribe, Rita Moreno, Bishoy Zakhary, Hannah Johnson, Nolan Pow, Marco Cavana, Alberto Cucino, Giuseppe Foti, Marco Giani, Vincenzo Russotto, Davide Chiumello, Valentina Castagna, Andrea Dell'Amore, Hoi-Ping Shum, Alain Vuysteke, Asad Usman, Andrew Acker, Blake Mergler, Nicolas Rizer, Federico Sertic, Benjamin Smood, Alexandra Sperry, Madhu Subramanian, Navy Lolong, Ernita Akmal, Erlina Burhan, Menaldi Rasmin, Bhat Naivedh, Peter Barrett, Julia Daugherty, David Dean, Antonio Loforte, Irfan Khan, Olivia DeSantis, Mohammed Abraar Quraishi, Gavin Salt, Dominic So, Darshana Kandamby, Jose M Mandei, Hans Natanael, Eka Yudha Lantang, Anastasia Lantang, Anna Jung, Terese Hammond, George Ng, Wing Yiu Ng, Pauline Yeung, Shingo Adachi, Pablo Blanco, Ana Prieto, Jesús Sánchez, Meghan Nicholson, Michael Farquharson, Warwick Butt, Alyssa Serratore, Carmel Delzoppo, Pierre Janin, Elizabeth Yarad, Richard Totaro, Jennifer Coles, Robert Balk, Samuel Fox, James Hays, Esha Kapania, Pavel Mishin, Andy Vissing, Garrett Yantosh, Saptadi Yuliarito, Kohar Hari Santoso, Susanthy Djajalaksana, Arie Zainul Fatoni, Masahiro Fukuda, Keibun Liu, Paolo Pelosi, Denise Battaglini, Juan Fernando Masa Jiménez, Sérgio Gaião, Roberto Roncon-Albuquerque, Jessica Buchner, Young-Jae Cho, Sang Min Lee, Su Hwan Lee, Tatsuya Kawasaki, Pranya Sakiyalak, Prompak Nitayavardhana, Tamara Seitz, Rakesh Arora, David Kent, Swapnil Parwar, Andrew Cheng, Jennene Miller, Daniel Marino, Jillian E Deacon, Shigeki Fujitani, Naoki Shimizu, Jai Madhok, Clark Owyang, Hergen Buscher, Claire Reynolds, Olavi Maasikas, Aleksandr Beljantsev, Vladislav Mihnovits, Takako Akimoto, Mariko Aizawa, Kanako Horibe, Ryota Onodera, Meredith Young, Timothy Smith, Cheryl Bartone, Timothy George, Kiran Shekar, Niki McGuinness, Lacey Irvine, Brigid Flynn, Abigail Houchin, Keiki Shimizu, Jun Hamaguchi, Leslie Lussier, Grace Kersker, John Adam Reich, Gösta Lotz, Maximilian Malfertheiner, Esther Dreier, Lars Maier, Neurinda Permata Kusumastuti, Colin McCloskey, Al-Awwab Dabaliz, Tarek B Elshazly, Josiah Smith, Konstanty S Szuldrzynski, Piotr Bielański, Yusuff Hakeem, Keith Wille, Rebecca Holt, Ken Kuljit S Parhar, Kirsten M Fiest, Cassidy Codan, Anmol Shahid, Mohamed Fayed, Timothy Evans, Rebekah Garcia, Ashley Gutierrez, Tae Song, Rebecca Rose, Suzanne Bennett, Denise Richardson, Dalia Lopez-Colon, Lovkesh Arora, Kristina Rappapport, Kristina Rudolph, Zita Sibenaller, Lori Stout, Alicia Walter, Daniel Herr, Nazli Vedadi, Lace Sindt, Cale Ewald, Julie Hoffman, Sean Rajnic, Shaun Thompson, Ryan Kennedy, Matthew Griffee, Anna Ciullo, Yuri Kida, Ricard Ferrer Roca, Cynthia Alegre, Sofia Contreras, Jordi Riera, Christy Kay, Irene Fischer, Elizabeth Renner, Hayato Taniguci, Gabriella Abbate, Halah Hassan, Varun A Karnik, Katrina Ki, Hollier F O'Neill, Nchafatso Obonyo, Leticia Pretti Pimenta, Janice D Reid, Kei Sato, Aapeli Vuorinen, Karin S Wildi, Emily S Wood, Stephanie Yerkovich

Affiliations

¹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
² Department of Medicine, University of Toronto, Toronto, ON, Canada.
³ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁴ Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, School of Public Health and Social Work, Queensland University of Technology, Brisbane, QLD, Australia.
⁵ Critical Care Research Group, Adult Intensive Care Services, Prince Charles Hospital, Brisbane, QLD, Australia.
⁶ Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
⁷ Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
⁸ Intensive Care Unit, St Andrew's War Memorial Hospital and The Wesley Hospital, Uniting Care Hospitals, Brisbane, QLD, Australia.
⁹ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
¹⁰ Department of Medicine, Columbia College of Physicians and Surgeons, New York, NY, USA.
¹¹ Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, NY, USA.
¹² Pediatric Critical Care Medicine, Inova Fairfax Hospital, Falls Church, VA, USA.
¹³ Heart and Vascular Institute, Inova Fairfax Hospital, Falls Church, VA, USA.
¹⁴ Toronto General Hospital Research Institute, Toronto, ON, Canada.
¹⁵ Department of Physiology, University of Toronto, Toronto, ON, Canada.
¹⁶ Division of Respirology, Department of Medicine, University Health Network, Toronto, ON, Canada.
¹⁷ Department of Intensive Care, North Estonia Medical Centre, Tallinn, Estonia.
¹⁸ Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
¹⁹ Department of Intensive Care, Alfred Health, Melbourne, VIC, Australia.
²⁰ Congenital Heart Center, University of Florida, Gainesville, FL, USA.
²¹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada [email protected].

Abstract

Objective: To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure.

Design: Observational study.

Setting: 30 countries across five continents, 3 January 2020 to 29 August 2021.

Participants: 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection.

Interventions: ECMO in patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FiO₂) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO.

Main outcome measure: The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding.

Results: 844 of 7345 eligible patients (11.5%) received ECMO at any time point during follow-up. Adherence adjusted mortality was 26.0% (95% confidence interval 24.5% to 27.5%) for a treatment strategy that included ECMO if the PaO₂/FiO₂ ratio decreased <80 mm Hg compared with 33.2% (31.8% to 34.6%) had patients received conventional treatment without ECMO (risk difference -7.1%, 95% confidence interval -8.2% to -6.1%; risk ratio 0.78, 95% confidence interval 0.75 to 0.82). In secondary analyses, ECMO was most effective in patients aged <65 years and with a PaO₂/FiO₂ <80 mm Hg or with driving pressures >15 cmH₂O during the first 10 days of mechanical ventilation.

Conclusions: ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and intensity of mechanical ventilation were found to be modifiers of treatment effectiveness and should be considered when deciding to initiate ECMO in patients with covid-19.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
COVID-19* / therapy
Extracorporeal Membrane Oxygenation*
Humans
Oxygen
Respiratory Distress Syndrome*
Respiratory Insufficiency* / etiology
Respiratory Insufficiency* / therapy
SARS-CoV-2

Substances

Oxygen