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Extracorporeal membrane oxygenation probably does not significantly reduce mortality in severe ARDS
Clinical Question
Is extracorporeal membrane oxygenation effective for patients with severe acute respiratory distress syndrome?
Bottom line
This is a challenging study to interpret because of the large number of crossovers (which would tend to dilute or dampen the benefit of extracorporeal membrane oxygenation); the early stopping of the trial; and the clear benefit based on treatment failure, rather than mortality, as the outcome. It would be helpful to have longer term outcomes and outcomes regarding post-treatment exercise capacity and quality of life. This seems like a good opportunity for a meta-analysis, perhaps using patient-level data, which could help provide clarity given the modest sizes of all of the studies on this topic. 1b-
Reference
Study design: Randomized controlled trial (nonblinded)
Funding: Government
Setting: Inpatient (ICU only)
Synopsis
Extracorporeal membrane oxygenation (ECMO) is often used as a last-ditch treatment for adults with severe acute respiratory distress syndrome (ARDS), but its efficacy remains uncertain despite 3 previous trials. This study included adults with severe ARDS who had been using mechanical ventilation for less than 1 week and who were not responding despite maximal ventilator settings for at least 6 hours. The study was powered to require up to 331 patients to detect a difference of 40% vs 60% survival. Ultimately, the study was stopped after 249 patients were randomized to receive either ECMO or usual best care (including prone positioning and use of neuromuscular blocking agents) based on a prespecified definition of futility. Groups were balanced at the beginning of the study with a mean age of 53 years; 71% were men. The median time from intubation was 34 hours in both groups. During the study, there were a large number of crossovers from the usual care group to the ECMO group because of failing standard therapy (35/125 [28%]). The primary outcome was 60-day mortality, which did not differ significantly between groups (35% vs 46%; P = .09; relative risk 0.76; 95% CI 0.55 - 1.04). However, the secondary outcome of treatment failure (defined as death for patients in the ECMO group and death or crossover to ECMO in the control group) was significantly lower in the ECMO group (35% vs 58%; P < .001; number needed to treat = 4). The 90-day mortality was lower, as well, in the ECMO group, but did not achieve statistical significance (37% vs 47%). Harms of ECMO include a significantly longer hospital stay (36 vs 18 days), severe thrombocytopenia (27% vs 16%), and significant bleeding events (46% vs 28%). Rates of pneumothorax, dialysis, and hemorrhagic stroke were similar between groups. Finally, it is not stated whether the outcomes were assessed by investigators masked to treatment assignment.
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Comments
Useless study and an unhelpful review. I cant' imagine that anyone would expect that ECMO would result in a 20% absolute increase in survival (a 50% relative increase in this study). The absolute difference in survival quoted in the abstract was 9% (in favour of ECMO I presume although it is not exactly clear in the abstract). Well if this were true then I would say a 9% absolute increase in survival is amazing and the the problem with the study it that it was underpowered (obviously) to show this. I suspect this was related to a funding issue. Drug companies spend 100's of millions$ to demonstrate a 1% increase in survival using their newest wonder drug requiring 10 of thousand of patients be put into at trial yet this one was abandoned at about 250 pt?? I don't get it.
As for the review it really addressed no substantive issues and really the reviewer just said, "I can't make any sense of this". No wonder. If so the either don't review it, find someone else to do it or be more substantive in why it doesn't make any sense. Maybe my comments will help other bewildered readers.
It is disappointed to learn there is still no clear evidence of timing in indication, efficacy and overall outcome after more than thirty years of ECMO in clinical practise.
A solid study should be able to give us more clearance in this respect
I thought this issue was settled long ago.