Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.
BACKGROUND
Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support.


METHODS
In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0 or pH <7.20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>30 cm H(2)O of peak inspiratory pressure) or high FiO(2) (>0.8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827.


RESULTS
766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622-59 200) at a discount rate of 3.5%.


CONCLUSIONS
We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK.


BACKGROUND
UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.
Peek
Giles J
GJ
Department of Cardiothoracic Surgery, Glenfield Hospital, Leicester, UK. giles.peek@uhl-tr.nhs.uk
Mugford
Miranda
M
Tiruvoipati
Ravindranath
R
Wilson
Andrew
A
Allen
Elizabeth
E
Thalanany
Mariamma M
MM
Hibbert
Clare L
CL
Truesdale
Ann
A
Clemens
Felicity
F
Cooper
Nicola
N
Firmin
Richard K
RK
Elbourne
Diana
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D003362:Cost-Benefit Analysis; D015199:Extracorporeal Membrane Oxygenation / Q000191:economics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012121:Respiration, Artificial / Q000191:economics; D012131:Respiratory Insufficiency / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult