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One of the great disappointments during the past decades has been the failure to convert advances in our understanding of the biologic features of sepsis into new therapies. Although numerous multicenter, randomized controlled trials have been conducted in the last 30 years, no reduction of septic shock mortality was achieved [1] [2]. [3] Taking together available evidence suggests that no sepsis specific therapies are available until today, although a roadmap on the way to a specific septic shock therapy might be on the horizon [3] [4] including artificial intelligence [5]. [6]. Interestingly, in the Surviving Sepsis Campaign guidelines [7] ECMO (Extra Corporal Membrane Oxygenation) is not mentioned as a treatment option. ECMO has been a standard treatment for cardiac and respiraory failure in neonates and children for decades, [8] in contrast to adults where the debate about the benefit of ECMO still is ongoing. A systematic review and meta-analysis showed that the use of veno-arterial life support (ECLS) in cardiac arrest was associated with a higher survival (NNT [number needed to treat] 7.7) as well as a better neurological outcome, in the setting of cardiogenic shock there was a higher survival with ECLS compared with IABP (NNT 3) [9]. Since even the efficacy of venovenous extracorporal membrane oxygenation with severe respiratory distress syndrome (ARDS) has been disputed controversially until today a randomized controlled trial comparing vvECMO with conventional treatment was initiated with the results published recently (EOLIA trial) [10]. The main causes of ARDS were bacterial pneumonia in 45% and viral pneumonia in 18% of the patients, 78% of the patients had severe sepsis or septic shock. Primary end point was mortality at 60 days. No difference was found in the initial intention-to-treat analysis. However, 35 patients (28%) in the control group crossed over to ECMO. In fact, reanalysis including crossover patients as treatment failure and comparing death/crossover to ECMO of the control group vs death in the ECMO group showed a 23% lower mortality in the ECMO group (NNT 5). In addition, Robert Bartlett in an editorial in CCM argued that the difference of the intention to treat vs treatment failure analysis results from 35 patients in the conventional care group who crossed over to the ECMO group as rescue treatment when conventional care was failing. Accordingly, the study had become a study of early versus late ECMO. Therefore, the EOLIA trial had shown that ECMO should be used promptly when highrisk criteria are met, rather than as late rescue therapy when death from ARDS or multiple organ failure is imminent [11]. What about the use of va-ECMO in the treatment of septic shock? To date, ECMO is suggested only as rescue therapy [12] and only observational case series with some promising results have been published (for overview see Table 1). However, the impression is not unequivocal. Thus, in a commentary discussing the results of Ro et al. the question is asked whether ECMO therapy in septic shock is a heroic futility or not [27]. The

Septic shock: ECMO beyond ARDS? Introducing the Simon two-stage protocol when randomisation is considered unethical