the oxygenator. extracorporeal blood flow remains constant, but gas transfer does not occur. they are then observed for several hours, during which the ventilator settings that are necessary to maintain adequate oxygenation and ventilation off ecmo are determined as indicated by arterial and venous blood gas results. veno-arterial ecmo liberation trial va ecmo trials require temporary clamping of both the drainage and infusion lines, while allowing the ecmo circuit to circulate through a bridge between the arterial and venous limbs. this prevents thrombosis of stagnant blood within the ecmo circuit. in addition, the arterial and venous lines should be flushed continuously with heparinized saline or intermittently with heparinized blood from the circuit. in general, va ecmo trials are shorter in duration than vv ecmo trials because of the higher risk of thrombus formation. history ecmo was developed in the 1950s by john gibbon, and then by c. walton lillehei. the first use for neonates was in 1965. banning gray lary first demonstrated that intravenous oxygen could maintain life. his results were published in surgical forum in november 1951. lary commented on his initial work in a 2007 presentation wherein he writes, "our research began by assembling an apparatus that, for the first time, kept animals alive while breathing pure nitrogen. this was accomplished with very small bubbles of oxygen injected into the blood stream. these bubbles were made by adding a 'wetting agent' to oxygen being forced through a porcelain filter into the venous blood stream. shortly after its initial presentation to the american college of surgeons, this apparatus was reviewed by walton lillehei who with dewall made the first practical heartlung machine that employed a bubble oxygenator. with variations such machines were used for the next twenty years." manufacturers medtronic maquet (getinge group) xenios ag (fresenius medical care) sorin group terumo nipro microport availability by country country/territory continent hospitals equipped units united statesnorth america361 (in 2022) canadanorth america23 (in 2022) australiaoceania146 (in 2020) brazilsouth america21 (in 2021) england and waleseurope5 (in 2020)15 (in 2020) northern irelandeurope0 (in 2020)0 (in 2020) scotlandeurope1 (in 2020)6 (in 2020) germanyeurope214 (in 2020)779 (in 2021) polandeurope47 (in 2020) swedeneurope7 or more (in 2020) albaniaeurope0 (in 2020)0 (in 2020) russiaeurope124 + 17 (in 2020) moscoweurope16 (in 2020) saint petersburg, russiaeurope719 (in 2020) japanasia2208 (in 2020) mainland chinaasia400 (approx. in 2020) 2,857 (in 2023) taiwan asia 51 (in 2016) 105 (in 2016) 129 (including rental units, in 2016) sri lanka south asia 2 (in 2021) 2 (in 2021) research randomized controlled trials (rcts) four randomized controlled trials (rcts) have been conducted to evaluate the effectiveness of ecmo in respiratory failure patients. early trials conducted by zapol et al. and morris et al. were plagued by technical challenges related to the ecmo technology available in the 1970s and 1990s. the cesar and eolia trials utilized modern ecmo systems and are considered the central ecmo rcts. cesar trial (2009) the conventional ventilatory support vs. extracorporeal membrane oxygenation for severe adult respiratory failure (cesar) trial was a uk-based multicenter rct aiming to evaluate the safety, efficacy and cost effectiveness of ecmo compared to conventional mechanical ventilation in adults with severe but reversibly respiratory failure. death or severe disability at 6 months or prior to hospital discharge was the primary outcome. the primary outcome was analyzed by intention to treat only. economic analysis included quality-adjusted life-years (qalys), analysis of cost generating events, cost-utility 6-months post-randomization and modelling of life-time cost utility. the trial planned to enroll 180 patients; 90 to each arm. the trial met its enrollment goal of 180 patients. 68 of the 90 (75%) of the patients intended to be treated with ecmo were actually treated with ecmo. survival of patients allocated to the ecmo group (i.e. referred for consideration for treatment with ecmo) was significantly higher than patients allocated to the conventional ventilation group (63% vs 47%, p=0.03). the referral to ecmo group gained 0.03 qaly compared to the conventional ventilation group at the 6-month follow-up. the referral to ecmo group had longer lengths of stay and higher costs. no standardized treatment protocol for the conventional ventilation group is the main limitation of the cesar study. the trial authors note that this occurred due to the inability of enrolling sites to agree on a protocol. this resulted in control patients not receiving lung protective ventilation which is known to improve mortality in ards patients. the authors conclude that referral of patients with severe, potentially reversible respiratory failure to an ecmo center can significantly improve 6-month, severe disability free survival. the cesar trial results do provide a direct survival comparison for treatment with ecmo versus conventional mechanical ventilation alone since only 75% of the ecmo group were actually treated with ecmo. eolia trial (2018) the ecmo to rescue lung injury in severe ards (eolia) trial was designed to evaluate the effects of early ecmo initiation compared to continued standard of care (conventional mechanical ventilation) in severe ards patients. mortality at 60 days was the primary endpoint. the calculated sample size was 331 patients with an intent to show a 20% reduction in absolute mortality in the ecmo group. the main secondary endpoint was treatment failure – cross-over to ecmo due to refractory hypoxemia or death in the control group and death in the ecmo group. following the fourth planned interim analysis the trial was ended due to futility. a total of 249 patients were enrolled at study termination. thirty-five control group patients (28%) required emergency cross-over to ecmo. results of eolia demonstrated no significant difference in 60-day mortality between the ecmo group and the control group (35% vs 46%, respectively). the interpretation of this result however is complicated by the cross-over patients. the secondary endpoint, treatment failure, demonstrated a relative risk of 0.62 (p<0.001) in favor of the ecmo group. results of the secondary endpoint should be interpreted cautiously due to the primary end point results. with respect to safety, the ecmo group had significantly higher rates of severe thrombocytopenia and bleeding requiring transfusion, but lower rates of ischemic stroke. the primary limitation to the eolia trial was that it was underpowered. for eolia to have been properly powered to detect significance of an 11% reduction in mortality a total of 624 patients would need to have been enrolled. such a trial would take 9 years based on the eolia recruitment rates and is likely not feasible. the main conclusion the study authors drew from these results is that early ecmo initiation in severe ards patients does not provide a mortality benefit compared to continued standard of care treatment. subsequent editorials by key opinion leaders suggest that the practical implication is that ecmo may improve mortality if used as a rescue therapy for patients failing conventional ards therapies.