Elsevier

The Lancet

Volume 374, Issue 9698, 17–23 October 2009, Pages 1351-1363
The Lancet

Articles
Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial

https://doi.org/10.1016/S0140-6736(09)61069-2Get rights and content

Summary

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 H2O of peak inspiratory pressure) or high FiO2 (>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.

Findings

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 treatment led to a gain of 0·03 quality-adjusted life-years (QALYs) at 6-month follow-up. A lifetime model predicted the cost per QALY of ECMO to be £19 252 (95% CI 7622–59 200) at a discount rate of 3·5%.

Interpretation

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.

Funding

UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.

Introduction

Despite advances in intensive care during the past 20 years, mortality and morbidity of patients with acute respiratory distress syndrome remains high; mortality for such patients is 34–58%.1, 2, 3, 4, 5, 6 Surviving patients could have clinically significant physical (respiratory and musculoskeletal) and neuropsychological (emotional and cognitive) disabilities.3 Such patients need inpatient rehabilitation and hospital readmissions, leading to high financial burden on carers and health-care systems.3

Conventional management is by intermittent positive-pressure ventilation, which can cause very high airway pressures and oxygen concentrations. The combination of barotrauma, volutrauma, biotrauma, and toxic effects of oxygen exacerbates lung injury from the primary illness. An alternative treatment, extracorporeal membrane oxygenation (ECMO), uses cardiopulmonary bypass technology to provide gas exchange so that ventilator settings can be reduced, which provides time for treatment and recovery.

Two previous randomised controlled trials have assessed adult extracorporeal life support.7, 8 Neither of these studies has relevance to modern ECMO because the case selection, ventilation strategies, extracorporeal circuit design, and disease management were completely different from modern protocols. Therefore observational studies provide the only relevant evidence. Case series of patients with severe respiratory failure report survival rates without ECMO of 18–44%6, 9 compared with up to 66% with ECMO (including full support of oxygenation and lung rest).10, 11, 12 To further define the safety, clinical efficacy, and cost-effectiveness of ECMO, we did the rigorous randomised controlled trial CESAR (Conventional ventilation or ECMO for Severe Adult Respiratory failure) in combination with an economic evaluation from the perspective of the health-care provider, the UK National Health Service (NHS).

Section snippets

Participants

Patients were enrolled from three types of centre: the ECMO centre at Glenfield Hospital, Leicester, which treated all patients who were randomly allocated for consideration to receive ECMO; tertiary intensive care units (conventional treatment centres); and referral hospitals, which sent patients to the conventional treatment centres if they were randomly allocated to receive continued conventional management.13 103 hospitals obtained ethics committee approval to collaborate in the study of

Results

Between July, 2001, and August, 2006, enquiries were made about 766 potentially eligible patients from 148 centres, of whom 180 were enrolled from 68 centres and randomly allocated (figure 1). Table 1 shows the demographic characteristics of these patients at baseline.

68 (75%) patients considered for treatment with ECMO actually had ECMO support, and most of the remaining patients (n=17) had conventional management (table 2); median duration of treatment was slightly shorter for patients

Discussion

This study shows a significant improvement in survival without severe disability at 6 months in patients transferred to a specialist centre for consideration for ECMO treatment compared with continued conventional ventilation. For patients allocated to receive conventional management, outcome at 6-month follow-up was better than predicted when planning the study. However, outcome was even better for patients allocated for consideration to receive ECMO than for those allocated to receive

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