ECMO for ARDS: A Historical Perspective
Long-term applications of ECMO support are an evolution of heart-lung machine use in cardiac surgery. The first successful use of prolonged ECMO in an adult ARDS patient was reported by Hill et al. in 1972 [27]. After only 2 years from first successful cases, the National Institute of Health commissioned a multicentre randomized clinical trial on prolonged ECMO for adults with ARDS [28]. At the time, the main indication for ECMO in ARDS patients was to correct the hypoxaemia while buying time for the lungs to heal [29]. As such, high ECMO blood flow rates were necessary to improve oxygenation, and the veno-arterial configuration was the standard. Following the negative results of the study, which failed to show any survival benefit from ECMO, only few investigators continued studying and improving the technique. Contrary to adult applications, applications in newborn showed encouraging results [30-35]. This contributed to maintain some interest on ECMO.
A landmark contribution to the evolution of adult ECMO came from the pioneering work done in the laboratory of T. Kolobow at the NIH. In a series of study, Kolobow and Gattinoni showed that [36-40] (1) nearly all the metabolic CO2 production could be removed through an artificial lung using much lower extracorporeal blood flows than those required to oxygenate the blood and (2) removal of CO2 through the membrane lung allows to reduce, virtually to zero, ventilation of the native lung. Based on these observations, they developed the concept of extracorporeal CO2 removal (ECCO2R) and proposed the use of a VV bypass configuration instead of the classical VA mode and the use of low-frequency ventilation to allow lung rest [40]. Unfortunately, a single-centre, randomized controlled trial conducted by Morris et al. in 40 ARDS patients failed to show a benefit from this technique [41]. Nevertheless, few centres around the world continued to apply ECMO in adult patients, contributing to improve the ECMO technique for long-term applications [42-45].
Following the concept of lung rest developed by Kolobow et al., several animal and human studies have demonstrated that, though necessary to preserve life, mechanical ventilation (MV) can exacerbate lung damage eventually contributing to mortality [46-54]. This has led to the concept of ventilator-induced lung injury (VILI) [54] and of “protective ventilatory strategy”, mainly consisting of low Vt (6-8 mL/Kg PBW) and limitation of plateau airway pressures (Pplat <28-30 cmH2O). ECMO is a unique technique to master protective ventilation and lung rest since, as Kolobow foresaw, it allows to minimize the need for mechanical ventilation allowing for using extremely low tidal volumes and to apply safe plateau pressures even in the most severe patients. Finally, in 2009, Peek et al. published the results of the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial [55]. The study enrolled 180 adult patients
(18-65 years) with severe but potentially reversible acute respiratory failure, defined as a Murray score >3 or uncompensated hypercapnia with a pH < 7.20. Patients randomized to receive ECMO were transferred to the Leicester ECMO centre, while controls remained in designated treatment centres. The trial showed a survival advantage (47% vs 63% at 6 months) associated with the use of ECMO in adults. Unfortunately, the enthusiasm for the positive results has been mitigated by important limitations of the study. First, not all patients allocated to the ECMO group received ECMO, because they died before or during transportation (five patients) or they improved with conventional treatment after transportation to the ECMO centre (17 patients). Second, as there was no standardized protocol for mechanical ventilation in the control group, significantly fewer patients in the control group received a protective ventilatory strategy. However, despite these limitations, the results of the study have led to an increase in interest in ECMO worldwide. Incidentally, publication of the study almost coincided with the outbreak of H1N1 influenza in 2009. Following the successful use of ECMO in patients with H1N1-induced severe ARDS reported from the Australian and New Zealand experience [50], several countries recurred to the use of ECMO, even organizing national network able to centralize the most severe patients. The published case series from these experiences report survival rates ranging from 68 to 83% [56-63].
Since 2009, the use of respiratory ECMO in adults has continued to grow. The relative simplification of the technique together with the acquisition of experience has push more and more centres to institute specialized ECMO teams able to employ different ECMO techniques for different indications.
