Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.
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.
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ABSTRACT: Ventilatory management of acute respiratory distress syndrome has evolved significantly in the last few decades. The aims have shifted from optimal gas transfer without concern for iatrogenic risks to adequate gas transfer while minimizing lung injury. This change in focus, along with improved ventilator and multiorgan system management, has resulted in a significant improvement in patient outcomes. Despite this, a number of patients develop hypoxemic respiratory failure refractory to lung-protective ventilation (LPV). The intensivist then faces the dilemma of either persisting with LPV using adjuncts (neuromuscular blocking agents, prone positioning, recruitment maneuvers, inhaled nitric oxide, inhaled prostacyclin, steroids, and surfactant) or making a transition to rescue therapies such as high-frequency oscillatory ventilation (HFOV) and/or extracorporeal membrane oxygenation (ECMO) when both these modalities are at their disposal. The lack of quality evidence and potential harm reported in recent studies question the use of HFOV as a routine rescue option. Based on current literature, the role for venovenous (VV) ECMO is probably sequential as a salvage therapy to ensure ultraprotective ventilation in selected young patients with potentially reversible respiratory failure who fail LPV despite neuromuscular paralysis and prone ventilation. Given the risk profile and the economic impact, future research should identify the patients who benefit most from VV ECMO. These choices may be further influenced by the emerging novel extracorporeal carbon dioxide removal devices that can compliment LPV. Given the heterogeneity of acute respiratory distress syndrome, each of these modalities may play a role in an individual patient. Future studies comparing LPV, HFOV, and VV ECMO should not only focus on defining the patients who benefit most from each of these therapies but also consider long-term functional outcomes.Journal of critical care 07/2013; 28(5). DOI:10.1016/j.jcrc.2013.04.009
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ABSTRACT: Microfabrication techniques are attractive for constructing artificial lungs due to the ability to create features similar in size to those in the natural lung. However, a simple and intuitive mathematical model capable of accurately predicting the gas exchange performance of microchannel artificial lungs does not currently exist. Such a model is critical to understanding and optimizing these devices. Here, we describe a simple, closed-form mathematical model for gas exchange in microchannel artificial lungs and qualify it through application to experimental data from several research groups. We utilize lumped parameters and several assumptions to obtain a closed-form set of equations that describe gas exchange. This work is intended to augment computational models by providing a more intuitive, albeit potentially less accurate, understanding of the operation and trade-offs inherent in microchannel artificial lung devices.Biomedical Microdevices 01/2013; DOI:10.1007/s10544-013-9736-1
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ABSTRACT: Extracorporeal membrane oxygenation (ECMO) is a form of prolonged cardiopulmonary bypass used to temporarily sustain cardiac and/or respiratory function in critically ill patients. Extracorporeal membrane oxygenation further complicates the management of critically ill patients who already have profound physiologic derangements with consequent altered pharmacokinetics. The purpose of this study is to identify and critically review the published literature describing pharmacokinetics in the presence of ECMO. This review revealed a dearth of data describing pharmacokinetics during ECMO in critically ill adults, with most of the available data originating in neonates. Of concern, the present data indicate substantial variability and a lack of predictability in drug behavior in the presence of ECMO. The most common mechanisms by which ECMO affects pharmacokinetics are sequestration in the circuit, increased volume of distribution, and decreased drug elimination. While lipophilic drugs and highly protein-bound drugs (eg, voriconazole and fentanyl) are significantly sequestered in the circuit, hydrophilic drugs (eg, β-lactam antibiotics, glycopeptides) are significantly affected by hemodilution and other pathophysiologic changes that occur during ECMO. Although the published literature is insufficient to make any meaningful recommendations for adjusting therapy for drug dosing, this review systematically describes the available data enabling clinicians to make conclusions based on available data. Furthermore, this review serves to highlight the need for well-designed and conducted clinical and laboratory-based studies to provide the data from which robust dosing guidance can be developed to improve clinical outcomes in this most unwell cohort of patients.Journal of critical care 04/2012; 27(6). DOI:10.1016/j.jcrc.2012.02.013