ECMO support for COVID-19: a balancing act – Authors' reply

Abstract

We thank Yang Zhang and colleagues for their thoughtful letter in response to our study of extracorporeal membrane oxygenation (ECMO) support for COVID-19 from the Extracorporeal Life Support Organization (ELSO) Registry.1Barbaro RP MacLaren G Boonstra PS et al.Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization Registry.Lancet. 2020; 396: 1071-1078Summary Full Text Full Text PDF PubMed Scopus (438) Google Scholar They raise difficult questions concerning bleeding, thrombosis, and the use of anticoagulation in patients with COVID-19 receiving ECMO support. Before the COVID-19 pandemic, considerable international practice variation and uncertainty existed regarding the optimal anticoagulation strategy during ECMO.2Protti A Iapichino GE Di Nardo M Panigada M Gattinoni L Anticoagulation management and antithrombin supplementation practice during veno-venous extracorporeal membrane oxygenation: a worldwide survey.Anesthesiology. 2020; 132: 562-570Crossref PubMed Scopus (35) Google Scholar In part, consensus is lacking because the key outcomes of bleeding and clotting are multifactorial in origin and might also be disease-specific. Consequently, determining the role of ECMO and anticoagulation in bleeding and clotting events is difficult outside of randomised clinical trials. For example, in the ECMO to Rescue Lung Injury in Severe ARDS Trial,3Combes 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 (1074) Google Scholar bleeding that led to transfusion was more common in patients receiving ECMO support, but massive bleeding and haemorrhagic stroke occurred at comparable rates between the treatment and control groups. COVID-19 has compounded this uncertainty. Compared with patients in the ELSO Registry who received ECMO support in 2019, we found no evidence of increased rates of mechanical failure or patient-related bleeding complications in patients with COVID-19.1Barbaro RP MacLaren G Boonstra PS et al.Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization Registry.Lancet. 2020; 396: 1071-1078Summary Full Text Full Text PDF PubMed Scopus (438) Google Scholar However, in another report,4Schmidt M Hajage D Lebreton G et al.Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study.Lancet Respir Med. 2020; 8: 1121-1131Summary Full Text Full Text PDF PubMed Scopus (241) Google Scholar 19% of patients with COVID-19 receiving ECMO support had pulmonary embolism during ECMO; in response, the investigators increased the anti-Xa target. It is unknown to what extent higher doses of anticoagulation reduce thrombotic complications in patients with COVID-19 receiving ECMO support and whether these higher doses of anticoagulation increase the risk of major haemorrhagic events. We acknowledge that the pathophysiology of COVID-19 might put patients at greater risk of haematological complications. However, the observational nature of our study and the absence of comparison groups prevent us from addressing whether ECMO in general, or whether specific anticoagulation strategies, were differentially associated with bleeding or thrombotic complications. To address the relationship between anticoagulation, bleeding, and thrombosis in patients receiving ECMO support, investigators need to identify core data elements that rigorously characterise anticoagulation practice, address plausible confounders, and measure validated indices of bleeding, thrombosis, and related outcomes. Without this foundational work, observational studies of anticoagulation, bleeding, and thrombosis during ECMO might yield misleading results. Once completed, ECMO databases such as the ELSO Registry should incorporate that work. Both mechanistic and randomised clinical trials will be required to discern the relationship between ECMO anticoagulation strategies and haematologic outcomes. RPB reports grants from the National Institutes of Health (R01 HL153519-ASCEND; K12 HL138039-TACTICAL; R01 HD01543-Pediatric Implantable Artificial Lung) outside this Correspondence; and is a member of the ELSO Steering Committee as the ELSO Registry Chair. DB reports grants from ALung Technologies; personal fees from Baxter, Xenios, and Abiomed; and serves on the advisory medical board (unpaid) of Hemovent. DB and GM serve on the ELSO Board of Directors (unpaid). ECMO support for COVID-19: a balancing actWe read with great interest the analysis of data from the Extracorporeal Life Support Organization (ELSO)1 Registry. It provides valuable data that support the use of extracorporeal membrane oxygenation (ECMO) for patients with COVID-19. However, it is widely acknowledged that many critically ill patients with COVID-19 present with coagulation abnormalities that include thrombotic microangiopathy and venous and arterial thromboembolic complications.2,3 Hence, anticoagulants have been used in these critically ill patients both therapeutically and prophylactically. Full-Text PDF Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registryIn patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. Full-Text PDF