title: Extracorporeal membrane oxygenation for critically ill adults.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  METHODS
  We included randomized controlled trials (RCTs), quasi-RCTs and cluster-RCTs that compared adult ECMO versus conventional support.
  
  
  METHODS
  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.
  
  
  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).
  
  
  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.
authors.affiliation: Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Department of Epidemiology and Preventive Medicine, Monash University, Level 6 The Alfred Centre, 99 Commercial Road, Melbourne, Victoria, Australia, 3004.
authors.forename: Ralph
authors.initials: R
authors.lastname: Tramm
authors.forename: Dragan
authors.initials: D
authors.lastname: Ilic
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Davies
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Pellegrino
authors.forename: Lorena
authors.initials: L
authors.lastname: Romero
authors.forename: Carol
authors.initials: C
authors.lastname: Hodgson
mesh_terms: D000208:Acute Disease; D000328:Adult; D016638:Critical Illness / Q000401:mortality / Q000628:therapy*; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods* / Q000401:mortality; D006304:Health Status; D006801:Humans; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012131:Respiratory Insufficiency / Q000401:mortality / Q000628:therapy; D015983:Selection Bias