Acute hypoxaemic respiratory failure after treatment with lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal: long-term outcomes from the REST randomised trial

Abstract

Introduction: Lower tidal volume ventilation, facilitated by veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R), does not improve 90-day mortality in patients with acute hypoxaemic respiratory failure (AHRF). The aim of this analysis was to evaluate the effect of this therapeutic strategy on long-term outcomes.

Methods: This was a prespecified analysis of the REST trial, a UK-wide multicentre randomised clinical trial that compared lower tidal volume ventilation, facilitated by vv-ECCO2R (intervention), with standard care in the treatment of patients with moderate-to-severe AHRF. Mortality to 2 years was assessed, while respiratory function, post-traumatic stress disorder, cognitive function and health-related quality of life were evaluated in survivors at 1 year using standardised questionnaires.

Results: Of 412 patients enrolled into the REST trial, 391 (95%) had 2-year mortality outcome data available. There was no difference in the time to death between intervention and standard care (HR 1.08 (0.81, 1.44); log-rank test p=0.61). 161 patients alive at 1 year provided at least one questionnaire response. There was no difference in respiratory function, post-traumatic stress disorder, cognitive dysfunction or health-related quality of life between patients allocated to intervention or standard care.

Conclusion: Lower-tidal volume ventilation facilitated by vv-ECCO2R does not affect 1-year mortality in patients with moderate-to-severe AHRF. Of the patients who provided questionnaire responses, there was no treatment effect on long-term respiratory function, post-traumatic stress disorder, cognitive dysfunction or health-related quality of life.

Trial registration number: ClinicalTrials.gov identifier: NCT02654327.

Keywords: ARDS.

Conflict of interest statement

Competing interests: AJB received grants from the Northern Ireland Health and Social Care Research and Development Agency to undertake a clinical trial of extracorporeal carbon dioxide removal, grants from the NIHR HTA Programme for a clinical trial of extracorporeal carbon dioxide removal (13/143/02). CM, AA, DL, CJ and JM reported the Northern Ireland Clinical Trials Unit receiving funds from the NIHR HTA Programme for its involvement during the conduct of the study. JJM reported receiving grants from the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme during the conduct of the study and speaking fees from Baxter outside the submitted work. DFM reported receiving grants from the NIHR HTA Programme during the conduct of the study, and DFM has received funding to his institution for studies outside of this submitted work from the NIHR, Wellcome Trust, Innovate UK, Northern Ireland Health and Social Care Research and Development Office and Randox. DFM has a patent application issued to his institution. Outside of the submitted work DFM has received fees for consultancy from Bayer, GSK, Boehringer Ingelheim, Eli Lilly and Novartis and SOBI and for being a member of the data monitoring and ethics committee for Vir Biotechnology and Faron studies and as an educational seminar speaker for GSK.

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