Abstract: 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). 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.

Plain-language summary: We found four studies that randomly allocated 389 patients to receive ECMO versus conventional lung support. All studies comprised patients with acute lung failure. We found no completed study in patients with acute heart failure or arrest. We found one ongoing study in patients with acute lung failure and two ongoing studies in patients with acute heart failure (arrest). The evidence is current to August 2014. Clinical differences in the care provided for patients with acute lung failure prevented us from combining the results of individual studies. Individual studies reported no differences in all-cause death at or before six months in patients given ECMO compared with those who were not. In one study survival was low in both groups but none of the patients who survived had limitations in their daily activities six months after discharge. Another study found improved survival without severe disability in patients transferred to an ECMO centre for consideration of ECMO six months after study entry. In three studies, patients in the ECMO group received greater numbers of blood transfusions. One study reported more non-brain bleeding in the ECMO group, and another study reported two serious adverse events in the ECMO group. Another study reported three adverse events in the ECMO group. Clinical practice, study planning and ways of using ECMO have varied considerably among studies. Technological developments (circuits, pumps and mechanical lungs) have improved performance and patient safety with ECMO applications over time. These clinical differences in the care provided for patients with acute lung failure prevented us from combining the results of individual studies. In critically ill adults, ECMO may or may not be more effective in improving survival compared with conventional lung support. Results from ongoing studies will help us better understand the role of ECMO and ECPR in the treatment of patients with acute lung or heart failure.