Extracorporeal membrane oxygenation for critically ill adults
Ralph Tramm, Dragan Ilic, Andrew R Davies, Vincent A Pellegrino, Lorena Romero, Carol Hodgson, Ralph Tramm, Dragan Ilic, Andrew R Davies, Vincent A Pellegrino, Lorena Romero, Carol Hodgson
Abstract
Background: Extracorporeal membrane oxygenation (ECMO) is a form of life support that targets the heart and lungs. Extracorporeal membrane oxygenation for severe respiratory failure accesses and returns blood from the venous system and provides non-pulmonary gas exchange. Extracorporeal membrane oxygenation for severe cardiac failure or for refractory cardiac arrest (extracorporeal cardiopulmonary resuscitation (ECPR)) provides gas exchange and systemic circulation. The configuration of ECMO is variable, and several pump-driven and pump-free systems are in use. Use of ECMO is associated with several risks. Patient-related adverse events include haemorrhage or extremity ischaemia; circuit-related adverse effects may include pump failure, oxygenator failure and thrombus formation. Use of ECMO in newborns and infants is well established, yet its clinical effectiveness in adults remains uncertain.
Objectives: The primary objective of this systematic review was to determine whether use of veno-venous (VV) or venous-arterial (VA) ECMO in adults is more effective in improving survival compared with conventional respiratory and cardiac support.
Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and EMBASE (Ovid) on 18 August 2014. We searched conference proceedings, meeting abstracts, reference lists of retrieved articles and databases of ongoing trials and contacted experts in the field. We imposed no restrictions on language or location of publications.
Selection criteria: We included randomized controlled trials (RCTs), quasi-RCTs and cluster-RCTs that compared adult ECMO versus conventional support.
Data collection and analysis: Two review authors independently screened the titles and abstracts of all retrieved citations against the inclusion criteria. We independently reviewed full-text copies of studies that met the inclusion criteria. We entered all data extracted from the included studies into Review Manager. Two review authors independently performed risk of bias assessment. All included studies were appraised with respect to random sequence generation, concealment of allocation, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias.
Main results: We included four RCTs that randomly assigned 389 participants with acute respiratory failure. Risk of bias was low in three RCTs and high in one RCT. We found no statistically significant differences in all-cause mortality at six months (two RCTs) or before six months (during 30 days of randomization in one trial and during hospital stay in another RCT). The quality of the evidence was low to moderate, and further research is very likely to impact our confidence in the estimate of effects because significant changes have been noted in ECMO applications and treatment modalities over study periods to the present.Two RCTs supplied data on disability. In one RCT survival was low in both groups but none of the survivors had limitations in their daily activities six months after discharge. The other RCT reported improved survival without severe disability in the intervention group (transfer to an ECMO centre ± ECMO) six months after study randomization but no statistically significant differences in health-related quality of life.In three RCTs, participants in the ECMO group received greater numbers of blood transfusions. One RCT recorded significantly more non-brain haemorrhage in the ECMO group. Another RCT reported two serious adverse events in the ECMO group, and another reported three adverse events in the ECMO group.Clinical heterogeneity between studies prevented meta-analyses across outcomes. We found no completed RCT that had investigated ECMO in the context of cardiac failure or arrest. We found one ongoing RCT that examined patients with acute respiratory failure and two ongoing RCTs that included patients with acute cardiac failure (arrest).
Authors' conclusions: Extracorporeal membrane oxygenation remains a rescue therapy. Since the year 2000, patient treatment and practice with ECMO have considerably changed as the result of research findings and technological advancements over time. Over the past four decades, only four RCTs have been published that compared the intervention versus conventional treatment at the time of the study. Clinical heterogeneity across these published studies prevented pooling of data for a meta-analysis.We recommend combining results of ongoing RCTs with results of trials conducted after the year 2000 if no significant shifts in technology or treatment occur. Until these new results become available, data on use of ECMO in patients with acute respiratory failure remain inconclusive. For patients with acute cardiac failure or arrest, outcomes of ongoing RCTs will assist clinicians in determining what role ECMO and ECPR can play in patient care.
Conflict of interest statement
Ralph Tramm (RT): none known.
Dragan Ilic (DI): none known.
Andrew R Davies (AD): none known.
Vincent A Pellegrino (VP): grant from Intensive Care Foundation (Australia and New Zealand), Effect of ECMO on long term disability in severe ARDS. Grant from Extracorporeal Life Support Organization (ELSO) (USA), Predictors of survival from VV and VA ECMO. ELSO is an international non‐profit organization of healthcare professionals and scientists who are dedicated to the development and evaluation of novel therapies for support of failing organ systems. The primary mission of the Organization is to maintain a registry of, at least, use of extracorporeal membrane oxygenation in active ELSO centres. Registry data are to be used to support clinical research, support regulatory agencies and support individual ELSO centres. ELSO provides educational programmes for active centres, as well as for the broader medical and lay communities. This grant was used to analyse data from adult patients with severe acute respiratory failure treated with ECMO from 2000 to 2012 using information derived from the ELSO international registry. VP is a co‐investigator who received funding. The grant has no relevance to the review because it developed a score from registry data, not from clinical trials. Travel/accommodations/meeting expenses: Maquet provided a travel fund for attendance at the 4th International Pediatric Symposium in Singapore, October 2013. The 4th International Pediatric Symposium was a Maquet‐sponsored scientific meeting held in Singapore that was dedicated to perfusion and ECMO (extracorporeal membrane oxygenation) matters in the care of paediatric patients. Marquet supplies extracorporeal life support (ECLS) equipment that is used to provide ECMO. This encompasses pumps (The CARDIOHELP System), circuits (HLS Set Advanced) and other supportive equipment.
Lorena Romero (LR): none known.
Carol Hodgson (CH): none known.
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Source: PubMed