key: cord-0901567-nbqyl0ip authors: de Chambrun, Pineton; Brodie, Daniel; Combes, Alain title: Appraising the Real-Life Need for Extracorporeal Membrane Oxygenation during the COVID-19 Pandemic date: 2021-03-30 journal: American journal of respiratory and critical care medicine DOI: 10.1164/rccm.202104-0897ed sha: 403b29f5ccc7e7deeeb2005745d1b435827b32d9 doc_id: 901567 cord_uid: nbqyl0ip nan The coronavirus disease (COVID-19) has become the leading cause of acute respiratory distress syndrome (ARDS) worldwide since January 2020. In a recent meta-analysis of 69 studies including 57,420 adult patients requiring invasive mechanical ventilation for COVID-19, the overall case fatality rate was estimated as 45% (95% confidence interval [CI] , 39-52%) (1) and was higher than in the LUNG-SAFE cohort (40%; 95% CI, 38-42%) (2) . Since the publication of the EOLIA trial (3) and its post hoc Bayesian analysis (4), venovenous extracorporeal membrane oxygenation (ECMO) has increasingly been used for patients with severe ARDS. As the COVID-19 pandemic drastically increased the demand for ECMO, data on the outcomes of this very specific population were eagerly awaited. In the largest series published to date, including 1,035 patients with COVID-19 from the Extracorporeal Life Support Organization registry, originating from 213 hospitals in 36 countries (5), the estimated 90-day probability of mortality was 37% (95% CI, 34-40%). It was 36% (95% CI, 27-48%) in a cohort of 83 ECMO-treated patients at the Paris-Sorbonne University hospitals in France (6) . More recently, the 60-day mortality rate of 190 ECMOtreated patients with COVID-19-related ARDS in 55 centers in the United States was 33% (7) . The authors performed an emulated target trial in this cohort, comparing patients initiated on ECMO in the first 7 days of ICU admission with those who did not receive ECMO, with lower mortality in the ECMO group (hazard ratio, 0.55; 95% CI, 0.41-0.74). These three cohorts reported early results with a significant proportion of patients without a final disposition at the end of follow-up. Moreover, these studies did not capture the overall proportion of mechanically ventilated patients with COVID-19 that required ECMO support at a regional or national level. In this issue of the Journal, Diaz and colleagues (pp. 34-43) report the results of a population-based study focusing on patients with COVID-19-related ARDS treated with ECMO during the first wave of the pandemic in Chile (8) . This is indeed the first cohort study evaluating the need for ECMO in COVID-19-related ARDS at a national level, in a country that has developed a coordinated national ECMO program (9, 10), using data from comprehensive national databases of mechanically ventilated and ECMO-treated patients. During the study period, 13 ECMO centers were commissioned by the Chilean National Advisory Commission to provide ECMO in adult patients with COVID-19. Members of the Commission evaluated and authorized the procedure and the referral to ECMO centers, including mobile ECMO. Patient selection criteria and ECMO management were based on the initial Extracorporeal Life Support Organization COVID-19 guidelines (11) . The authors used the Chilean databases to identify all mechanically ventilated and ECMO-supported patients with COVID-19 between March 3, 2020, and August 31, 2020. The age-adjusted cumulative incidences of ECMO use were 0.42 per 100,000 population, 14.89 per 100,000 COVID-19 cases, and 1.2% per mechanically ventilated patients with COVID-19, respectively, which represents twice the frequency observed in a 3-month period in Australia and New Zealand during the 2009 influenza A (H1N1) pandemic (12) . The authors also provide a detailed description of 85 of the 94 patients who received ECMO with follow-up until March 3, 2021. Patients were cannulated early after intubation, and most of them had received neuromuscular blockers (94%) and prone positioning (92%) before ECMO. The median durations of ECMO, ICU, and hospital length of stay were 16 (interquartile range [IQR], 10-27), 40 (IQR, 21-57), and 50 (IQR, 24-69) days, respectively. Interestingly, late cannulation (.10 days of invasive mechanical ventilation before ECMO) was not associated with a higher mortality, in contrast to previous observations in ECMO for non-COVID-19-related ARDS (13, 14) as well as for ECMO in patients with COVID-19 (6, 15) . At the end of the follow-up period, the mortality rate was 39%, similar to that reported in previous COVID-19 ECMO cohorts (5-7) (see Table 1 ). It should again be noted that all ECMO survivors were discharged home in this Chilean series, whereas other cohorts have reported estimated mortality rates, with the outcome of some patients remaining unknown at the end of follow-up. However, this result should be analyzed in the context of a somewhat milder severity of ARDS at the time of ECMO initiation (lower driving pressure and higher Pa O 2 /FI O 2 ; see Table 1 ). It should also be noted that positive end-expiratory pressure was markedly lower before ECMO in this Chilean cohort than in the other three (Table 1) . Setting positive end-expiratory pressure at a higher degree might have recruited more collapsed lung and improved Pa O 2 /FI O 2 , potentially obviating the need for ECMO, especially considering that the median driving pressure was only 15 cm H 2 O. Although many questions remain, including the most appropriate indications for ECMO in this setting, as well as longer-term outcomes of patients who received ECMO for COVID-19 (for instance, functional, neuropsychological, and long-term mortality), this is nonetheless important population-level data offering numerous insights into the use of ECMO during the pandemic. Furthermore, Diaz and colleagues should be commended for achieving excellent outcomes with ECMO for COVID-19 under such difficult circumstances. It stands to reason that a substantial portion of their success may have derived from the comprehensive coordination of a national system for deploying ECMO across all of Chile: a model for other countries to follow. Author disclosures are available with the text of this article at www.atsjournals.org. The evolution of allergy immunotherapy Passive prophylactic administration with a single dose of anti-Fel d 1 monoclonal antibodies REGN1908-1909 in cat allergen-induced allergic rhinitis: a randomized, double-blind, placebo-controlled trial Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement Does evidence support the use of cat allergen immunotherapy? The major cat allergen, Fel d 1, in diagnosis and therapy Fel d 1-derived peptide antigen desensitization shows a persistent treatment effect 1 year after the start of dosing: a randomized, placebo-controlled study Circassia announces top-line results from cat allergy phase III study Monoclonal antibody-standardized cat extract immunotherapy: risk-benefit effects from a double-blind placebo study IgE and IgG antibodies as regulators of mast cell and basophil functions in food allergy EAACI allergen immunotherapy user's guide Tolerance mechanisms in allergen immunotherapy Combining anti-IgE with oral immunotherapy Case fatality rates for patients with COVID-19 requiring invasive mechanical ventilation: a meta-analysis LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and posterior probability of mortality benefit in a post hoc Bayesian analysis of a randomized clinical trial Extracorporeal Life Support Organization. Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study STOP-COVID Investigators. Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19 National Advisory Commission for Adult ECMO. Extracorporeal membrane oxygenation for COVID-19-associated severe acute respiratory distress syndrome in Chile: a nationwide incidence and cohort study Impact of the novel influenza A (H1N1) during the 2009 autumn-winter season in a large hospital setting in Influenza A pandemics: clinical and organizational aspects: the experience in Chile Extracorporeal life support organization coronavirus disease 2019 interim guidelines: a consensus document from an international group of interdisciplinary extracorporeal membrane oxygenation providers Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure: the Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score Survival after extracorporeal membrane oxygenation in severe COVID-19 ARDS: results from an international multicenter registry The standard metrics of accuracy are impressive (e.g., a c-statistic of 0.901). Accepting nine false alarms for every onetruepositive,HAVENwillidentifymorethan40% ofcardiacarrestsor unplanned ICU admissions within the preceding 48 hours and provide as muchas12-hour noticefor morethan 25% So why should we care? Because, reading the report carefully