ECMO for severe ARDS associated with COVID-19: now we know we can, but should we?
Authors: Kiran Shekar, Arthur S Slutsky, Daniel Brodie
Journal: The Lancet Respiratory Medicine (2020)

The initial months of the COVID-19 pandemic were dominated by studies reporting poor and varied outcomes in patients who developed severe acute respiratory distress syndrome (ARDS) associated with the disease. Variable mortality could have been related to heterogeneity in patient populations and pre-pandemic intensive care infrastructure, resource constraints imposed during the pandemic, and variability in duration of follow-up. As the pandemic has evolved, lower mortality attributable to the disease has been reported. For instance, in a cohort of 742 patients with COVID-19-associated ARDS from Spain, mortality for severe ARDS was 39%,1Ferrando C Suarez-Sipmann F Mellado-Artigas R et al.Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS.Intensive Care Med. 2020; (https://doi: 10.1007/s00134-020-06192-2 published online July 29.)Crossref PubMed Scopus (273) Google Scholar similar to findings of a large epidemiological study of patients with severe ARDS who did not have COVID-19.2Bellani G Laffey JG Pham T et al.Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries.JAMA. 2016; 315: 788-800Crossref PubMed Scopus (3329) Google Scholar Early reports also suggested that patients with severe ARDS associated with COVID-19 should not receive venovenous extracorporeal membrane oxygenation (ECMO) because mortality ranged from 84–100% in patients treated with ECMO. In The Lancet Respiratory Medicine, Matthieu Schmidt and colleagues3Schmidt M Hajage D Lebreton G et al.Extracorporeal membrane oxygenation Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study.Lancet Respir Med. 2020; (published online Aug 13.)https://doi.org/10.1016/S2213-2600(20)30328-3Summary Full Text Full Text PDF Scopus (318) Google Scholar present a cohort study of 83 patients (median age 49 [IQR 41–56] years; 61 [73%] men) who received ECMO for severe ARDS associated with COVID-19 in the Paris–Sorbonne University Hospital Network intensive care units (ICUs). Their results showed an estimated 31% (95% CI 22–42) probability of death at 60 days, which is similar to that seen in studies of ECMO for severe ARDS outside the pandemic.4Combes A Hajage D Capellier G et al.Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.N Engl J Med. 2018; 378: 1965-1975Crossref PubMed Scopus (1427) Google Scholar However, 24% of patients were still in the ICU on day 60. Notably, patients received outstanding pre-ECMO management with high adherence to evidence-based ARDS practices, including prone-positioning in 78 (94%) patients. During ECMO, lung-protective ventilation was achieved with median tidal volumes of 2·5 (IQR 1·8–4·2) mL/kg of predicted bodyweight, the median driving pressure decreased from 18 (IQR 16–21) cm H2O pre-ECMO to 12 (12–14) cm H2O on ECMO day 1, and there was an approximate 75% decrease in mechanical power (24·7 [IQR 22·0–27·3] J/min pre-ECMO to 6·1 [4·1–11·0] J/min on ECMO day 1). The outcome data appear impressive given that the patients represent a very severe subset of ARDS (median PaO2/FiO2 60 [IQR 54–68] mm Hg), while receiving a median applied positive end-expiratory pressure of 14 (IQR 12–14) cmH2O, and were similar to or sicker than ECMO-treated patients with ARDS not associated with COVID-19 reported in the EOLIA trial in 2018.4Combes A Hajage D Capellier G et al.Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.N Engl J Med. 2018; 378: 1965-1975Crossref PubMed Scopus (1427) Google Scholar However, it is difficult to draw valid conclusions from comparisons with historical data, especially given that these patients were substantially younger than previously reported patients with severe ARDS associated with COVID-19, and increased age is a well supported risk factor for mortality. Furthermore, although the data are encouraging, the results might not be generalisable, as they come primarily from one highly experienced ECMO centre, and there is a known relationship between hospital-level volume of ECMO cases and patient outcomes when using ECMO.5Barbaro RP Odetola FO Kidwell KM et al.Association of hospital-level volume of extracorporeal membrane oxygenation cases and mortality. Analysis of the extracorporeal life support organization registry.Am J Respir Crit Care Med. 2015; 191: 894-901Crossref PubMed Scopus (492) Google Scholar The authors suggest that ECMO should be considered for patients with COVID-19 with profound respiratory failure despite optimised conventional care. Although this conclusion is reasonable, much remains unknown about the role of ECMO in ARDS associated with COVID-19, including the patients who would benefit the most (or those that would be harmed), long-term outcomes, and the cost-to-benefit ratio. It is possible that going forward, fewer patients with COVID-19 will develop profound respiratory failure, given the findings from the RECOVERY trial6Horby P Lim WS Emberson JR et al.Dexamethasone in hospitalized patients with Covid-19—preliminary report.N Engl J Med. 2020; (https://doi.org.10.1056/NEJMoa2021436 published online July 17.)Google Scholar showing reduced mortality in patients with COVID-19 who were ventilated and given dexamethasone. Notably, only 12 (14%) patients in the study of Schmidt and colleagues received corticosteroids before ECMO day 8. There was a high incidence of pulmonary embolism during ECMO (16 [19%] patients) despite the authors selecting higher anticoagulation targets than would typically be used for patients with ARDS that is not associated with COVID-19. This finding highlights the importance of the coagulation system in patients with COVID-19 in general, and specifically highlights the need to investigate anticoagulation targets during ECMO in these patients. There are substantially more extracorporeal life support organisation (ELSO) registered ECMO centres today than existed during the 2009 influenza A (H1N1) pandemic (430 centres vs 164 centres), and this number will probably increase. How do we ensure that quality of care is adequate on a large scale, especially during the stress of pandemics? One approach is to adopt the ELSO guidance for responsible ECMO use.7Shekar K Badulak J Peek G et al.Extracorporeal life support organization coronavirus disease 2019 interim guidelines: a consensus document from an international group of interdisciplinary extracorporeal membrane oxygenation providers.ASAIO J. 2020; 66: 707-721Crossref PubMed Scopus (257) Google Scholar, 8Ramanathan K Antognini D Combes A et al.Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases.Lancet Respir Med. 2020; 8: 518-526Summary Full Text Full Text PDF PubMed Scopus (389) Google Scholar Another is to concentrate ECMO activity in dedicated high-volume centres enabled by mobile ECMO teams, a model followed by the Paris–Sorbonne University Hospital Network, which delivered comprehensive pre-ECMO management and judicious patient selection. With the presented data in hand, is there a need for randomised trials of ECMO specific to ARDS associated with COVID-19? From a strictly academic perspective, it could be argued that they are needed. However, large randomised trials would be difficult to do during the pandemic, and although there is controversy,9Fan E Beitler JR Brochard L et al.COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted?.Lancet Respir Med. 2020; 8: 816-821Summary Full Text Full Text PDF PubMed Scopus (333) Google Scholar it might be that ARDS associated with COVID-19 is similar to ARDS not associated with COVID-19 from a mechanics and gas exchange perspective1Ferrando C Suarez-Sipmann F Mellado-Artigas R et al.Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS.Intensive Care Med. 2020; (https://doi: 10.1007/s00134-020-06192-2 published online July 29.)Crossref PubMed Scopus (273) Google Scholar, 9Fan E Beitler JR Brochard L et al.COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted?.Lancet Respir Med. 2020; 8: 816-821Summary Full Text Full Text PDF PubMed Scopus (333) Google Scholar (although perhaps not from a coagulation perspective). In the meantime, the more important question concerns the degree to which ECMO should be used in ARDS associated with COVID-19 given the resources required. In the study by Schmidt and colleagues, the median length of ECMO support (20 days) and ICU length of stay (36 days) was very high (compared with a median of 11 days of ECMO support and 23 days in ICU in the EOLIA trial4Combes A Hajage D Capellier G et al.Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.N Engl J Med. 2018; 378: 1965-1975Crossref PubMed Scopus (1427) Google Scholar). The scale and quality of ECMO care, if replicated in other jurisdictions, might potentially save lives; however, clearly at a cost in terms of resources and potential complications.10MacLaren G Fisher D Brodie D Preparing for the most critically ill patients with COVID-19: the potential role of extracorporeal membrane oxygenation.JAMA. 2020; 3231245Crossref PubMed Scopus (307) Google Scholar Any decisions on whether and when to use ECMO for very severe COVID-19 would have to be made locally with a clear recognition of the extensive resources required (mainly human resources), the expected caseload, and the potential implications for other patients. KS acknowledges research support from Metro North Hospital and Health Service. KS is the chair of the ELSO COVID-19 guidelines working group. ASS is on the medical advisory board for Baxter and Xenios. DB receives research support from ALung Technologies, and was previously on their medical advisory board. He has been on the medical advisory boards for Baxter, BREETHE, Xenios, and Hemovent. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort studyThe estimated 60-day survival of ECMO-rescued patients with COVID-19 was similar to that of studies published in the past 2 years on ECMO for severe ARDS. If another COVID-19 outbreak occurs, ECMO should be considered for patients developing refractory respiratory failure despite optimised care. Full-Text PDF