Extracorporeal carbon dioxide removal compared to ventilation alone in patients with acute hypoxaemic respiratory failure: cost-utility analysis of the REST RCT
Authors: Agus Ashley , McNamee James J. , Jackson Colette , McAuley Danny F. 
Published: July 2023

Background
Acute hypoxaemic respiratory failure requiring mechanical ventilation is a major cause of morbidity and mortality and has significant resource implications in terms of intensive care unit and hospital stay.

Objective
To assess the cost-effectiveness of extracorporeal carbon dioxide removal compared to ventilation alone in patients with acute hypoxaemic respiratory failure.

Design
A cost-utility analysis embedded within a pragmatic, multicentre, allocation-concealed, open-label, randomised controlled trial.

Participants
Four hundred and twelve (of a planned sample size of 1120) adult patients receiving mechanical ventilation for acute hypoxaemic respiratory failure, were recruited between May 2016 and December 2019 from 51 intensive care units in the UK.

Interventions
Participants were randomised (1 : 1) to receive extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with ventilation alone (n = 210).

Outcomes
Health-related quality of life via the EuroQol-5 Dimensions, five-level version, health resource use and associated costs were measured over the study period. The cost per quality-adjusted life-year was estimated at 12 months post randomisation.

Results
Mean EuroQol-5 Dimensions, five-level version utility scores were low and similar for each group. Quality-adjusted life-years were calculated for those patients with complete EuroQol-5 Dimensions, five-level version data (extracorporeal carbon dioxide removal n = 140, ventilation alone n = 143) and there was no discernible difference in quality-adjusted life-years at 12 months (mean difference –0.01; 95% confidence interval –0.06 to 0.05; 140). Total 12-month health resource use cost (including intervention costs) was calculated for those patients with complete cost data (extracorporeal carbon dioxide removal n = 125, ventilation alone n = 126) and costs were statistically significantly higher in the extracorporeal carbon dioxide removal group (mean difference £7668.76, 95% confidence interval 159.75, 15,177.77). Multiple imputation was used for missing total cost and quality-adjusted life-year data in the cost-utility analysis. Ventilation alone dominated extracorporeal carbon dioxide removal and there was 0% probability of extracorporeal carbon dioxide removal being cost-effective compared to ventilation alone for all willingness to pay thresholds per quality-adjusted life-year considered (£0–50,000).

Conclusions
Extracorporeal carbon dioxide removal was associated with significantly higher costs, but no benefit in health-related quality of life. Given the data, extracorporeal carbon dioxide removal is not considered to be a cost-effective approach to treating patients with acute hypoxaemic respiratory failure.

Limitations
These included the absence of a baseline healthy utility score, minor data loss related to not obtaining complete intensive care unit readmission data for Scottish participants, and not estimating long-term cost-effectiveness due to the study closing early.

Future work
Measuring baseline health-related quality of life in critical care studies is difficult; future economic evaluations in this setting should consider measuring health-related quality of life as soon as possible after the patients regain capacity.

Trial registration
This trial is registered as NCT02654327 and ISRCTN 31262122.

Funding
This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 13/143/02.