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

ArticleinThe Lancet 374(9698):1351-63 · September 2009with69 Reads
Impact Factor: 45.22 · DOI: 10.1016/S0140-6736(09)61069-2 · Source: PubMed
Abstract

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

    • "In regard to the mortality data, one of the main questions that remains is how ECMO use has increased to such a high incidence? It is of note that the influenza A(H1N1) pandemic in 2009, the results of important landmark trials published in 2009 concerning H1N1 patients and non-H1N1 patients [5, 7], and technical improvements of ECMO available in 2010, respectively, occurred more or less simultaneously. This was followed by a steep increase in ECMO utilization between 2009 and 2012. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: The evolution of the epidemiology and mortality of extracorporeal membrane oxygenation (ECMO) remains unclear. The present study investigates the evolving epidemiology and mortality of various ECMO techniques in Germany over time, used for both severe respiratory and cardiac failure. Methods: Data on all patients receiving venovenous (vv-ECMO) and venoarterial (va-ECMO) ECMO as well as pumpless extracorporeal lung assist/interventional lung assist (PECLA/ILA) outside the operating room in Germany from 1 January 2007 through 31 December 2014 were obtained from the Federal Statistical Office of Germany and analyzed. Results: The incidence of vv-ECMO and va-ECMO in the population increased threefold from 1.0:100,000 inhabitants/year in 2007 to a maximum of 3.0:100,000 in 2012, and from 0.1:100,000 in 2007 to 0.7:100,000 in 2012 and to a maximum of 3.5:100,000 in 2014, respectively. The incidence of arteriovenous PECLA/ILA also increased from 0.4:100,000 to a maximum of 0.6:100,000 in 2011, but decreased thereafter to 0.3:100,000 in 2014. The relative proportion of older patients receiving ECMO is steadily increasing. In-hospital mortality decreased over time and reached 58 and 66 % for vv-ECMO and va-ECMO in 2014, respectively. In addition, mortality steadily increased with age and was especially high in the first 48 h of ECMO use. Conclusions: In a high-income country like Germany, the use of ECMO has been rapidly increasing since 2007 for both respiratory and cardiac support, with a recent plateau in vv-ECMO use. In-hospital mortality decreased with increasing ECMO utilization, but remains high, especially in older patients and in the first 48 h of use.
    No preview · Article · Mar 2016 · Intensive Care Medicine
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    • "The patients who died represented a category already with calculated poor outcome as seen by their very low RESP scores. Most of our respiratory cases fulfilled the criteria of severe ARDS with refractory hypoxemia that can benefit from ECMO support [1,3,24,34]. Patients were ventilated according to ARDS net [45] protocol with low tidal volume 4–6 ml/kg/breath PEEP was increased incrementally while the patients were sedated and paralyzed [46] and following increase in FiO 2 reaching 100% inhaled oxygen, the peak inspiratory pressure was set to keep plateau pressure maximum of 35 cm H 2 O [45]. Steroids were tested in several studies [47]. "
    [Show abstract] [Hide abstract] ABSTRACT: Extracorporeal membrane oxygenation (ECMO) is considered a rescue therapy in severe cases of acute cardiac and or respiratory failure.
    Full-text · Article · Mar 2016
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    • "Aufgrund der Datenlage zweier großer multizentrischer randomisierter Studien kann die HFOV bei akuten Lungenversagen nicht empfohlen werden (OSCILLATE, OSCAR; [5, 47] ). Die Rationale für die extrakoporale Membranoxygenierung (ECMO) als Ultima-Ratio-Therapie der Zentrumsmedizin besteht darin, die biophysikalischen Schädigungsmechanismen der Beatmung zu minimieren (Einschlusskriterien: p a O 2 < 50 mmHg oder S a O 2 < 85– 90 % bei F I O 2 1,0 und PEEP > 10cmH 2 O; [23] ). Dabei ist eine frühzeitige Entscheidung zur Implantation einer ECMO sicherlich von Vorteil. "
    [Show abstract] [Hide abstract] ABSTRACT: Both in the intensive care setting and during surgery, mechanical ventilation plays an important role in the treatment of critically ill patients with lung injury, but also in lung healthy patients. Mechanical ventilation is noncurative and is accompanied by various severe side effects. It is hypothesized that multiorgan failure can be induced by mechanical ventilation. Furthermore, there is evidence to suggest cross-talk between lungs and other organs. In particular, the activation of specific cells and cell programs in peripheral organs is an important step on the way to multiorgan failure. In addition to bidirectional connection between the lung and brain, nonprotective ventilation leads to cell apoptosis in the kidney and intestine and leads to an increase of biomarkers for organ dysfunction. It is believed that both inflammation mediators and pro-apoptotic factors are responsible for organ dysfunction.
    Full-text · Article · May 2015 · Medizinische Klinik - Intensivmedizin und Notfallmedizin
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