Exciting new ECMO technology awaits compelling scientific evidence for widespread use in adults with respiratory failure

MacLaren et al. [1] discuss the exciting potential offeredby extracorporeal support, including extracorporealmembrane oxygenation (ECMO). Many uses of ECMOhave recently been discussed. These include a technicallyadvanced means of transporting patients with severerespiratory failure [2] and a treatment for acute respira-tory distress syndrome (ARDS) following novel H1N1inﬂuenza infection [3]. Extracorporeal support remains anexciting domain of investigation, development and clini-cal application. Innovations, such as IVOX, aboundamong developers and practitioners of extracorporealsupport [4]. Dr. Bartlett has been a consistent leader andinnovator in this ﬁeld.MacLaren et al. [1] make impressive arguments, andtheir illustrations are clear and compelling. Their Fig. 6 isa striking example of the advances/changes in clinicalcare. The new extracorporeal circuits they nicely describeare clearly much simpler, easier to use, and appear moresafe than those used in the past. Importantly, they appearsafer than those used in the two past clinical trials thatadhered to accepted experimental standards [5, 6]. Thisraises legitimate questions about the current value of theresults of those two older clinical trials. These legitimatequestions should be answered with new clinical trials thatadhere to accepted experimental standards. The authorsclearly indicate that major advances in both extracorpo-real circuitry and clinical care have taken place, since thetechnology of these two older clinical trials was intro-matched by similar advances in extracorporeal clinicaltrials. Rigorous clinical trials with modern technologywill likely provide results that answer crucial questionsabout ‘‘in whom, how, and when’’ extracorporeal supportshould be applied.The experimental design of two-group randomizedcontrolled clinical trials has not changed substantiallysince the older trials were completed [5, 6]. In the absenceof credible new clinical trial results, we have no betterinformation to guide decisions about widespread use ofextracorporeal support than that provided by the two pastclinical trials that adhered to accepted experimentalstandards [5, 6]. Some clinicians hold strong beliefs in theefﬁcacy of ECMO support for patients with severe ARDS.Dr. MacLaren [7] articulately expressed these beliefs in arecent letter. Such strong beliefs are not new. In 1984 and1985 Gattinoni et al. [8] reported a dramatic increase insurvival with use of low frequency positive pressureventilation with extracorporeal carbon dioxide removal(LFPPV-ECCO2R) (using veno-venous support). Mycolleagues and I conducted a randomized controlledclinical trial with the expectation that LFPPV-ECCO2Rwas likely to be a signiﬁcant treatment advance (from ourpublished discussion: ‘‘...we concluded from publishedreports that there was about a 0.5 prior probability thatLFPPV-ECCO2R was a superior therapy for ARDS’’ [6]).However, we did not detect a survival advantage ofLFPPV_ECCO2R. Gattinoni et al., in a letter to the edi-tor, replied that the LFPPV_ECCO2R technique was notyet optimized and the technique not yet ready for aclinical trial (see letters to the editor in [6]). We asked, ina reply letter, how it could be known that the LFPPV-ECCO2R technique was beneﬁcial (the conclusion of thestrong believers) when the technique was not yet