Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure
Authors: James J. McNamee, Michael A. Gillies, Nicholas A. Barrett, Gavin D. Perkins, William Tunnicliffe, Duncan Young, Andrew Bentley, David A. Harrison, Daniel Brodie, Andrew J. Boyle, Jonathan E. Millar, Tamas Szakmany, Jonathan Bannard-Smith, Redmond P. Tully, Ashley Agus, Clíona McDowell, Colette Jackson, Daniel F. McAuley, Temi Adedoyin, Kayode Adeniji, Caroline Aherne, Gopal Anand Iyer, Prematie Andreou, Gillian Andrew, Ian Angus, Gill Arbane, Pauline Austin, Karen Austin, Georg Auzinger, Jonathan Ball, Dorota Banach, Jonathan Bannard-Smith, Leona Bannon, Lucy Barclay, Helena Barcraft-Barnes, Richard Beale, Sarah Bean, Andrew Bentley, Georgia Bercades, Colin Bergin, Sian Bhardwaj, Colin Bigham, Isobel Birkinshaw, Euan Black, Aneta Bociek, Andrew Bodenham, Malcolm G Booth, Christine Bowyer, David A Brealey, Stephen Brett, Jennifer Brooks, Karen Burt, Louise Cabrelli, Leilani Cabreros, Hazel Cahill, Aidan Campbell, Luigi Camporota, Sara Campos, Julie Camsooksai, Ronald Carrera, Joseph Carter, Jaime Carungcong, Anelise Catelan-Zborowski, Susanne Cathcart, Shreekant Champanerkar, Matthew Charlton, Shiney Cherian, Linsey Christie, Srikanth Chukkambotla, Amy Clark, Sarah Clark, Richard Clark, Ian Clement, Eve Cocks, Stephen Cole, Sonia Cole, Jade Cole, Nick Coleman, Emma Connaughton, Andrew Conway Morris, Lauren Cooper, Ian Cooper, Carolyn Corbett, Sarah Cornell, Carmen Correia, Victoria Cottam, Keith Couper, Laura Creighton, Maryam Crews, Neil Crooks, Jacqueline Curtin, Zoe Daly, Alan Davidson, Rhys Davies, Michelle Davies, Christopher Day, Mike Dean, Ged Dempsey, Anna Dennis, Susan Dermody, Liesl Despy, Murugesh Devaramani, Patricia Doble, Robert Docking, Adrian Donnelly, Natalie Dooley, Natalie Dormand, Andrew Drummond, Mark JG Dunn, Leigh Dunn, Christine Eastgate, Karen Ellis, Sarah Farnell, Helen Farrah, Emma Fellows, Timothy Felton, Helder Filipe, Clare Finney, Simon Finney, Jillian Fitchett, Brian Gammon, Saibal Ganguly, Minerva Gellamucho, Susan Gibson, Charles Gibson, Lynn Gilfeather, Michael A Gillies, Stuart Gillon, Shameer Gopal, Anthony Gordon, Stephanie Goundry, Lia Grainger, Neus Grau Novellas, Joanne Gresty, Mark Griffiths, Jamie Gross, Una Gunter, Karen Hallett, Samantha Harkett, Donna Harrison-Briggs, Louise Hartley, Ingrid Hass, Noel Hemmings, Steven Henderson, Helen Hill, Gemma Hodkinson, Kate Howard, Clare Howcroft, Ying Hu, Jonathan Hulme, Tariq Husain, Joanne Hutter, Dorothy Ilano, Richard Innes, Nicola Jacques, Sarah James, Sarah Jenkins, Paul Johnston, Brian Johnston, Colette Jones-Criddle, Santhana Kannan, Parminder Kaur Bhuie, Andrea Kelly, Sophie Kennedy-Hay, Liana Lankester, Susannah Leaver, Stephane Ledot, Rosario Lim, Lucie Linhartova, Fei Long, Niall S MacCallum, Sarah MacGill, Andrew Mackay, Sarah Maclean, Amber Markham, Daniel Martin, Tim Martin, Tracy Mason, Nick Mason, Justine McCann, Corrienne McCulloch, Christopher McGhee, Loren McGinley-Keag, Michael McLaughlin, Lia McNamee, Margaret McNeil, Laura Mee, Claire Mellis, Teresa Melody, Jeanette Mills, Esther Molina, Matt PG Morgan, Mushiya Mpelembue, Stephanie Muldoon, Sheila Munt, Nazril Nordin, Christopher Nutt, Sinead O'Kane, Aisling O'Neill, Valerie Page, Elankumaran Paramasivam, Dhruv Parekh, Sarah Patch, Sameer Patel, Lia Paton, Gavin Perkins, Manuel Pinto, David Pogson, Petra Polgarova, Jagtar Pooni, Martin Pope, Grant C Price, Jashmin Priya Maria, Lynda Purdy, Alex Puxty, John Rae, Mark Raper, Henrik Reschreiter, Steve Rose, Anthony Rostron, Alistair Roy, Christine Ryan, Jung Ryu, Kiran Salaunkey, Julia Sampson, Vivian Sathianathan, Lorraine Scaife, Simon WM Scott, Timothy E Scott, Sumant Shanbhag, David Shaw, Malcolm Sim, Suveer Singh, Andrew Smallwood, Hazel Smith, John Smith, Jayne Smith, Deborah Smyth, Catherine Snelson, Michael Spivey, Elaine Spruce, Charlotte Summers, Peter Sutton, Tamas Szakmany, Nicholas Talbot, Maie Templeton, Jessica Thrush, Redmond Tully, William Tunnicliffe, Ian Turner-Bone, Tonny Veenith, Alan Vuylsteke, Andrew Walden, Jonathan Walker, Kathryn Ward, Tim Walsh, Victoria Waugh, Colin Wells, Ingeborg Welters, Tony Whitehouse, Arlo Whitehouse, Christopher Whitton, Elizabeth Wilby, Danielle Wilcox, Laura Wilding, James Williams, Karen Williams, Sarah Winnard, Lindsey Woods, Chris Wright, Neil H Young, Xiaobei Zhao, Parjam Zolfaghari
Journal: JAMA (2021)

<h3>Importance</h3> In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. <h3>Objective</h3> To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. <h3>Design, Setting, and Participants</h3> This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. <h3>Interventions</h3> Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). <h3>Main Outcomes and Measures</h3> The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. <h3>Results</h3> Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%];<i>P</i> = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3];<i>P</i> = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. <h3>Conclusions and Relevance</h3> Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02654327