James J McNamee1,2, Michael A Gillies3, Nicholas A Barrett4, Gavin D Perkins5,6, William Tunnicliffe7, Duncan Young8, Andrew Bentley9,10, David A Harrison11, Daniel Brodie12,13, Andrew J Boyle1,2, Jonathan E Millar14, Tamas Szakmany15,16, Jonathan Bannard-Smith17,18, Redmond P Tully19, Ashley Agus20, Clíona McDowell20, Colette Jackson20, Daniel F McAuley1,2. 1. Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom. 2. Regional Intensive Care Unit, Royal Victoria Hospital, Belfast, United Kingdom. 3. Department of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom. 4. Guy's and St Thomas' NHS Foundation Trust, King's College London, United Kingdom. 5. Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom. 6. Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 7. University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 8. Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom. 9. Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom. 10. Acute Intensive Care Unit, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 11. Clinical Trials Unit, Intensive Care National Audit & Research Centre (ICNARC), London, United Kingdom. 12. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York. 13. Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, New York. 14. Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom. 15. Department of Anaesthesia, Intensive Care and Pain Medicine, Division of Population Medicine, Cardiff University, Cardiff, United Kingdom. 16. Critical Care Directorate, Royal Gwent Hospital, Aneurin Bevan University Health Board, Newport, Gwent, United Kingdom. 17. Department of Critical Care, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 18. Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, United Kingdom. 19. Department of Anaesthetics and Intensive Care, Royal Oldham Hospital, Northern Care Alliance, Oldham, United Kingdom. 20. Northern Ireland Clinical Trials Unit, Belfast, United Kingdom.
Abstract
Importance: 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. Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants: 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. Interventions: 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). Main Outcomes and Measures: 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. Results: 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%]; P = .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]; P = .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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.
Importance: 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. Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants: 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. Interventions: 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). Main Outcomes and Measures: 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. Results: 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%]; P = .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]; P = .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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.
Authors: Alain Combes; Daniel Brodie; Nadia Aissaoui; Thomas Bein; Gilles Capellier; Heidi J Dalton; Jean-Luc Diehl; Stefan Kluge; Daniel F McAuley; Matthieu Schmidt; Arthur S Slutsky; Samir Jaber Journal: Intensive Care Med Date: 2022-08-09 Impact factor: 41.787
Authors: Leonardo Guidi; Alessandro Belletti; Diego Palumbo; Francesco De Cobelli; Michele De Bonis; Alberto Zangrillo Journal: Respir Investig Date: 2022-07-19
Authors: Peter T Graf; Christoph Boesing; Isabel Brumm; Jonas Biehler; Kei Wieland Müller; Manfred Thiel; Paolo Pelosi; Patricia R M Rocco; Thomas Luecke; Joerg Krebs Journal: J Intensive Care Date: 2022-03-07
Authors: Katherine D Wick; Daniel F McAuley; Joseph E Levitt; Jeremy R Beitler; Djillali Annane; Elisabeth D Riviello; Carolyn S Calfee; Michael A Matthay Journal: Crit Care Date: 2021-11-23 Impact factor: 19.334
Authors: Jesús Villar; Juan M Mora-Ordoñez; Juan A Soler; Fernando Mosteiro; Anxela Vidal; Alfonso Ambrós; Lorena Fernández; Isabel Murcia; Belén Civantos; Miguel A Romera; Adrián Mira; Francisco J Díaz-Domínguez; Dácil Parrilla; J Francisco Martínez-Carmona; Domingo Martínez; Lidia Pita-García; Denis Robaglia; Ana Bueno-González; Jesús Sánchez-Ballesteros; Ángel E Pereyra; Mónica Hernández; Carlos Chamorro-Jambrina; Pilar Cobeta; Raúl I González-Luengo; Raquel Montiel; Leonor Nogales; M Mar Fernández; Blanca Arocas; Álvaro Valverde-Montoro; Ana M Del Saz-Ortiz; Victoria Olea-Jiménez; José M Añón; Pedro Rodríguez-Suárez; Rosa L Fernández; Cristina Fernández; Tamas Szakmany; Jesús M González-Martín; Carlos Ferrando; Robert M Kacmarek; Arthur S Slutsky Journal: Crit Care Explor Date: 2022-04-29