Literature Review| Volume 40, ISSUE 5, P303-305, September 2021

Articles That May Change Your Practice: Extracorporeal Membrane Oxygenation and Coronavirus Disease 2019

      Coronavirus disease 2019 (COVID-19) results from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A severe respiratory distress syndrome requiring tracheal intubation develops in approximately 15% to 20% of hospitalized patients with COVID-19, and the mortality rate in these patients can exceed 70%. The extensive use of extracorporeal membrane oxygenation (ECMO) in COVID-19–associated acute respiratory distress syndrome (ARDS) during the pandemic's first wave indicated unfavorable outcomes, raising questions about its usefulness. However, previous reports on the use of ECMO in influenza and other typical causes of ARDS were more promising. Given the theoretical advantages that ECMO may offer patients with COVID-19, ECMO support for these patients is now increasingly widespread.
      Caring for patients with COVID-19 requiring ECMO at high-volume ECMO centers has been associated with improved outcomes, prompting an increase in transports to these centers. For patients who are candidates for ECMO but cannot undergo transport to high-volume ECMO centers due to instability, specialized retrieval teams can offer the initiation of ECMO therapy at peripheral hospitals with subsequent patient transfer for ongoing care. The transportation of patients with COVID-19 receiving ECMO therapy presents a multitude of technical and workflow safety concerns, and the data available regarding the feasibility of ECMO retrieval of patients with COVID-19 are now becoming available. The following is a synopsis of these recently published summaries regarding COVID-19 patients receiving ECMO.
      Nguyen NT, Sullivan B, Sagebin F, Hohmann SF, Amin A, Nahmias J. Analysis of COVID-19 patients with acute respiratory distress syndrome managed with extracorporeal membrane oxygenation at US academic centers.10.1097/SLA.00000000000048 Annals of Surgery: April 9, 2021 - Volume Publish Ahead of Print - Issue - doi: 10.1097/SLA.0000000000004870
      The mortality associated with COVID-19 for patients with respiratory failure or ARDS requiring mechanical ventilation typically exceeds 50%. ECMO is an option in a subset of patients with severe ARDS refractory to conventional therapy, including prone positioning, corticosteroids, and paralysis. There is a paucity of data for ECMO therapy in COVID-19 patients with severe ARDS, and these small case series typically have a mortality in excess of 90%.
      The authors of this study performed a retrospective analysis of data available from more than 650 hospitals in the United States to determine the impact of ECMO on patients with ARDS or acute respiratory failure due to COVID-19 between April and September 2020. The primary outcome was in-hospital mortality, with secondary outcomes including the length of hospital stay, the length of intensive care unit (ICU) stay, and hospitalization costs. The comparison group was composed of patients aged 18 to 64 years with COVID-19 and ARDS who did not receive ECMO therapy.
      A total of 1,182 COVID-19 patients with ARDS underwent ECMO therapy at 155 hospitals. The all-cause mortality was 45.9%, with mean length of hospital and ICU stays of 36.8 and 29.1 days, respectively. The mean cost of hospitalization was $137,376. Mortality was highest (73.7%) in those 65 years of age or older and lowest (25.2%) in those age 30 years or younger. The comparison to those aged 18 to 64 years managed with or without ECMO (1,113 in each group) revealed that mortality was higher for those managed with ECMO compared with those not receiving ECMO (44.6% versus 37.9%, P < 0.01). The mean hospital length of stay and the mean cost were also higher in those receiving ECMO (37.1 versus 23.1 days and $138,403 versus $48,419, both P < 0.01).
      The authors point out that the ECMO and non-ECMO groups were not similar because the ECMO group was composed of much sicker patients who had failed conventional therapies. The data set available to the authors did not permit matching of the ECMO and non-ECMO groups. However, the authors conclude that ECMO as a salvage therapy provided to patients who fail conventional therapy is not futile, with survival of more than half the cohort undergoing ECMO.
      Barbaro 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;396:1071-78.
      The World Health Organization recommends that expert centers with sufficient ECMO volume to maintain proficiency consider ECMO support in COVID-19–related ARDS with refractory hypoxemia if lung-protective mechanical ventilation is insufficient to support the patient. The Extracorporeal Life Support Organization (ELSO) is an international organization that maintains a registry of more than 125,000 ECMO cases among its members, and the registry includes detailed information about COVID-19 patients who receive ECMO therapy.
      A total of 1,035 patients diagnosed with COVID-19 aged 16 years or older who had ECMO support initiated at an ELSO site between January 16, 2020, and May 1, 2020, were included in this study. The primary outcome was in-hospital death, with an analysis of patients and hospital factors performed to determine if these were associated with the primary outcome. Most patients (70%) received care at another hospital before being transferred to an ELSO center, and nearly half of these (47%) had ECMO initiated at the outside hospital and were transported while receiving ECMO support.
      The authors determined that the use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio = 1.89; 95% confidence interval, 1.20-2.97). However, the in-hospital mortality 90 days after the initiation of ECMO was only 37.4%, with independent risk factors for mortality being age, immunocompromised state, chronic respiratory disease, pre-ECMO cardiac arrest, degree of hypoxemia, the presence of acute kidney injury, and the use of ECMO for temporary circulatory support.
      This study is not a randomized controlled trial and cannot draw any definitive conclusions regarding whether ECMO should be used in patients with COVID-19 and severe respiratory failure. However, the data from 213 hospitals in 36 countries provide a generalizable estimate of the potential benefit of ECMO in patients with refractory COVID-19–related respiratory failure when performed in an experienced center, with mortality notably lower than previously published figures. The study also demonstrates the need for sufficient capabilities for interhospital transport of ECMO patients to centers with expertise in ECMO.
      Puslecki M, Baumgart K, Ligowski M, et al. Patient safety during ECMO transportation: single center experience and literature review. Emerg Med Int. 2021; 2021:6633208.
      The ELSO recommends that ECMO therapy be performed in expert centers to ensure optimal patient outcomes. Such centralization requires highly specialized patient transport between referring hospitals and the ECMO centers. The authors of this study performed a systematic review to assess the safety of patients transported while receiving ECMO therapy. The systematic review searched Medline, Embase, Cochrane, and Google Scholar databases to find articles reporting primary or secondary ECMO transportation. A primary transport is defined if the transport team performs the cannulation of the patient and initiates ECMO therapy at the referring hospital and then supervises transfer to the ECMO center. A secondary transport is defined when the patient is already receiving ECMO, with the transport team only performing the transfer. Studies were included if they described medical or technical complications during interhospital transfers of patients with ECMO and were published in 2019 or earlier.
      The systematic review identified 68 articles, 22 of which were included in the review. A total of 2,647 transfers were reported, mainly primary (90%) and as ground transportations (91.6%). The rate of adverse events ranged from 1% through 20%, but notably only major complications were mentioned. There were only 4 deaths during transport (mortality = 0.15%).
      Adverse events were typically categorized as equipment failure, improper preparation (training deficiencies and insufficiencies and inadequate equipment), insufficient documentation, and suboptimal communication. Despite the occurrence in up to 20% of transfers in which adverse events were considered life-threatening within seconds or minutes, there was no significant negative patient impact due to a professional, well-trained, and well-equipped transport team.
      The authors also made comparisons between groups of patients supported with ECMO and then transported versus those treated with ECMO in patient without any transfers between hospitals. The reports showed no statistically significant differences in terms of survival when comparing those who received ECMO and were then transported to the ECMO center versus those at the ECMO center who were then placed on ECMO. Finally, the authors also found that patients cannulated by the mobile teams experienced better outcomes than those cannulated by staff at the referring hospital. The authors concluded that ECMO transportation of critically ill patients can be performed safely by a dedicated, well-trained ECMO transport team.
      Lebreton G, Schmidt M, Ponnaiah M, Folliguet T, Para M, Guihaire J, for the Paris ECMO-COVID-19 Investigators. Extracorporeal membrane oxygenation network organisation and clinical outcomes during the COVID-19 pandemic in Greater Paris, France: a multicentre cohort study. Lancet Respir Med. 2021. doi: 10.1016/S2213-2600(21)00096-5
      The COVID-19 pandemic has resulted in an exponential demand for ECMO. Given the need for centralized care of ECMO patients, a regional hub-and-spoke model is often developed to provide regional ECMO services.
      The authors of this multicenter cohort study included all adults with COVID-19 and severe ARDS requiring ECMO who were admitted to any ICU in Paris, France, between March 9 and June 3, 2020. Seventeen of the ICUs were ECMO capable, with 6 ECMO retrieval teams able to cannulate and transport patients from non-ECMO ICUs to the ECMO centers. All consecutive patients with severe acute respiratory syndrome coronavirus 2 infection who received ECMO for severe ARDS were included in this study. Outcomes included survival status at 90 days after ECMO initiation, complications, and causes of death. A multivariable analysis identified pre-ECMO variables independently associated with 90-day survival after ECMO.
      The study included 302 patients, 165 of whom were cannulated and transferred by an ECMO retrieval team. One hundred thirty-eight patients (46%) were alive 90 days after the initiation of ECMO. Improved 90-day survival was noted in patients with a shorter time between intubation and ECMO (odds ratio [OR] = 0.91 per day decrease), younger age (OR = 2.89 for ≤48 years and 2.01 for 49-56 years versus ≥57 years), and treatment in centers managing at least 30 ECMO cases annually (OR = 2.98). Complications during ECMO included 43% with a major bleeding event, 43% received renal replacement therapy, and 18% with a pulmonary embolism. A total of 138 (46%) patients were alive 90 days after the initiation of ECMO.
      The majority of patients in this study were placed on ECMO by the ECMO retrieval teams and then transferred to an ICU at an ECMO center, with no significant difference in the survival rate compared with the initiation of ECMO on-site at the ECMO center.
      The authors concluded that centralized pooling of resources on a regional level with early transfer to high-volume ECMO centers by retrieval teams capable of initiating ECMO is an optimal strategy for COVID-19 patients requiring ECMO.
      Condella A, Richards JB, Frakes MA, Grant CJ, Cohen JE, Wilcox SR. ECMO transport without physicians or additional clinicians. Prehosp Disaster Med. 2021;36:51-7.
      Safely transporting a patient receiving ECMO therapy requires a skilled, well-trained transport team. The current guidelines indicate that all patients transported on ECMO be accompanied by a physician. As ECMO becomes increasingly common, particularly in the setting of the COVID-19 pandemic, the requirement that a physician be present during transport may limit the ability for such transfers to take place.
      The authors of this retrospective study compared a regional critical care transport organization's experience transporting ECMO patients with and without an accompanying physician. The most common team configuration was a critical care transport nurse, a critical care paramedic, and an ECMO specialist (eg, a perfusionist, specially trained nurse, or respiratory therapist). Over the 7-year study period (2011–2018), 93 patients on ECMO were transported from 21 hospitals to 4 ECMO centers in New England. Of these, 9 were accompanied by a sending physician, 9 by the receiving physician, 1 by a sending physician assistant, and 1 by a sending nurse practitioner. The vast majority (88, 94.6%) were cannulated by the sending physicians, with the remainder by the receiving physician at the sending hospital.
      A total of 21 major adverse events occurred in 20 transports (21.5% of all transports). The most common was loss of ECMO flow (n = 7) and major oxygen desaturation (n = 7). Major adverse events were similarly distributed between accompanied and unaccompanied transports, except for ventricular arrhythmias, which occurred more commonly in unaccompanied transports (7.1% versus 0%, P = 0.02). Multivariate analysis did not demonstrate any parameter being predictive of major adverse events. The major adverse event rate in this retrospective cohort was 21.5%, which is comparable with the range of 1.5% to 32% noted in other published studies.
      The authors concluded there was no association between the rate of major adverse events in transport and the accompaniment of an additional clinician. The authors point out that although a physician is needed to cannulate the patient and initiate ECMO, many sending hospitals are now capable of this task. This removes the need for a physician to be a team member for the sole purpose of cannulation, without compromising patient safety in transport.
      The recently published evidence demonstrates that ECMO is a viable treatment option for select COVID-19 patients with ARDS or acute hypoxemic respiratory failure that is refractory to conventional therapies. Using conventional therapy, this patient cohort has an exceedingly high mortality rate. ECMO may decrease this rate to approximately 40%. The concept of a hub-and-spoke model of ECMO delivery is advocated to concentrate scarce critical care and ECMO resources in centers of excellence, thereby optimizing patient outcome with these scarce resources. One of the keys to success in implementing ECMO using this delivery model is the ability to transport patients to centers of excellence. There is growing evidence that patients can be safely transported to these centers after the initiation of ECMO, as long as the retrieval or transport teams are sufficiently trained and skilled at managing these inherently unstable patients. There is also growing evidence that suggests those receiving ECMO therapy who undergo transport with specialized transport teams have similar outcomes to those receiving ECMO but are not transported. Again, the key factor here in mitigating risk in transport is the transport team itself. Finally, as the initiation of ECMO therapy becomes increasingly common in non-ECMO centers, the composition of the transport team itself may require careful assessment to ensure the team meets the needs of those they serve.


      Russell D. MacDonald, MD, MPH, FCFP, FRCPC, is the medical director at Ornge Transport Medicine; medical director at Toronto Paramedic Services; a professor in the Faculty of Medicine at the University of Toronto; and an attending staff member at Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada. He can be reached at [email protected]