Extracorporeal membrane oxygenation & lung transplant outcomes: COVID-19 pandemic

Introduction

The development of acute respiratory distress syndrome can be attributed to multiple causes, one of which was noted to be coronavirus disease 2019 (COVID-19). The syndrome leads to changes in the lungs, causing respiratory failure, which leads patients to become ventilator dependent. Interventions such as extracorporeal membrane oxygenation (ECMO) has improved outcomes in adult respiratory distress syndrome (ARDS) patients. However, it is not a permanent solution (1). Lung transplantation is indicated for patients with chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, emphysema secondary to alpha 1 antitrypsin deficiency, pulmonary arterial hypertension, bronchiectasis, pulmonary fibrosis, and sarcoidosis. During the COVID-19 pandemic, more patients with ARDS and fibrosis due to COVID-19 also underwent lung transplantation (2). However, long-term management with a lung transplant after a more prolonged ECMO course in a COVID-19 patient is a recent phenomenon that needs further studies to dictate patient selection criteria and long-term outcomes. In this editorial commentary, we comment on the article published by Hunt et al. in the recent issue of J Thorac Cardiovasc Surg (2). We evaluated their paper detailing ECMO as a bridging mechanism in patients who eventually underwent a lung transplant. The occurrence of lung transplants in cases of ARDS is rare but has recently increased during the COVID-19 pandemic where young patients who have developed ARDS and post-COVID-19 fibrosis have required ECMO and lung transplantation (2).

ECMO bridging in pre-transplant patients

The imbalance between the supply and demand of donor lungs led to innovations in managing chronic respiratory failure patients. Lung transplantation in patients on ECMO is becoming increasingly common as surgeons are more at ease operating on patients on ECMO (3). Before 2020, lung transplantation was uncommon in patients with the diagnosis of ARDS that were pretreated with ECMO. Due to an increase in ECMO-dependent patients with COVID-19 who have ARDS or post-COVID fibrosis, the lung transplantation option was considered. Continued ECMO care or withdrawal of care entirely were also options that the patients and families had to consider. Circumstances were challenged by the COVID-19 pandemic, which contributed to the increasing number of lung transplants in younger, otherwise healthy patients with ARDS on ECMO. The enormity of the COVID-19 pandemic, along with the difficulty in weaning these patients off of ECMO, led to lung transplantations being considered as options.

Bain et al. highlighted the increased understanding of ARDS due to COVID-19 infection (4). They compared the increased ventilator dependence in COVID-19 patients with ARDS to non-COVID-19 ARDS patients and certain differences in syndromes from socioeconomic factors to respiratory physiology parameters, which require further studies.

Multiple studies reported the use of ECMO to bridge pre-transplant patients, with studies published by Langer et al. in Germany, Tipograf et al. at Columbia University Medical Center, and Benazzo et al. in Vienna being the most recent (5-7). They noted that bridging patients with ECMO while awaiting the lung transplant improved the time from survival to discharge compared to those patients who did not have the support of ECMO prior to transplantation. These studies emphasized the significance of choosing the right patient, as bridged patients may anticipate long-term survival outcomes comparable to those of non-bridged patients if they have a good chance of surviving the first ninety days (8). Furthermore, appropriate inclusion and exclusion criteria are necessary to ensure the patient’s benefit from the therapy. The inclusion and exclusion criteria are not standardized; however, multiple hospitals developed them. The Mayo Clinic in Florida is one such hospital that developed a multidisciplinary team approach to lung transplantation in COVID-19 patients on ECMO (9).

Florissi et al. reported on lung transplantation cases from 2009 to 2022. They noted a high 90-day survival of 94% of COVID-19 lung transplant patients. However, similar limitations with emphasis on formal diagnosis not being available well into 2020 were noted, leading to the possible inclusion of COVID-19 fibrosis patients (10).

In the recent J Thorac Cardiovasc Surg issue, Hunt et al. (2) compared the outcome of bridging pre-transplant patients with COVID-related acute respiratory distress syndrome (CARDS) and non-COVID-related acute respiratory distress syndrome (NCARDS). The retrospective analysis identified patients who required ECMO preoperatively with corresponding diagnoses. The primary outcome was 1-year survival, with the secondary outcomes including the effect of type and duration of ECMO on survival. The analysis identified 236 patients with ARDS requiring lung transplants; 77% were noted to have CARDS, while 23% were diagnosed with NCARDS. Both cohorts showed no difference in survival at 1 month, 3 months, 6 months, and 1 year (85.8% vs. 81.1%, P=0.2), and duration of ECMO support was not a predictor of survival (P=0.2).

Discussion

The mortality rate of CARDS compared to NCARDS has been studied since the terms were coined to determine the impact of prolonged ECMO use to bridge these patients. Bermudez et al. estimated the incidence of in-hospital mortality at 90 days after ECMO initiation in CARDS patients to be 37.4%, comparable to NCARDS (11). Data from the Extracorporeal Life Support Organization (ELSO) Registry have been utilized to ascertain outcomes of patients with CARDS and NCARDS. These data further confirm that 90-day mortality is similar to NCARDS (12,13). Bain et al. compared the 60-day mortality of CARDS with NCARDS and noted no significant difference in line with the findings by Hunt et al. (2,4).

Bain et al. compared CARDS and NCARDS patients concerning characteristics, noting that the median age was 63 in CARDS patients, of whom 48.1% were female and 66.7% were white. This correlates with the findings of Hunt et al., showing CARDS patients to be older and more likely to be female. Barbaro et al. found that the median age of CARDS patients was 50. However, their study was predominantly male, with only 26% female. They noted the predominant ethnicity as white (32%), followed by Hispanic (24%). The younger age in patients, with males being predominant, differs from the study published by Hunt et al. It involves the registry of all ECMO patients, giving us a better understanding. However, the study by Barbaro et al. was published in 2020 with initial comparisons between CARDS and NCARDS patients (12). Our understanding of the disease and possible treatment modalities has evolved since the initial year of the COVID-19 pandemic.

Limitations of the study by Hunt et al. (2) were that the study period for NCARDS transplant recipients was significantly longer than CARDS, and the retrospective registry data could increase the risk of bias with confounding factors.

Furthermore, late complications were not noted. ECMO support data was only available for 168 out of the 236 patients, and there needed to be more information about the ARDS diagnosis made at listing and the causes of NCARDS. Classification of CARDs vs. COVID-related fibrosis during the initial phase of the COVID-19 pandemic needs to be understood. The ARDS vs. the post-COVID-19 fibrosis reversibility may differ, and that must also be considered. Lastly, the study needs to account for differences between centers’ applicant selection and management. As such, one should proceed with caution when interpreting this data. The best approach would be a strong clinical trial design with precise diagnoses and ECMO data.

Conclusions

Lung transplantation can be done safely in patients with ARDS-associated lung failure who require ECMO support pretransplant. The use of ECMO remains a valuable support for patients with severe lung injury necessitating transplant. The study puts forth the critical question of the selection criteria determining bridging with ECMO for pre-transplant patients to augment the life expectancy of patients with ARDS. Studies like this can help us design inclusion and exclusion criteria. They can help us prepare for the next pandemic to attain the best results for our patients while balancing the demand and supply issues.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Current Challenges in Thoracic Surgery. The article has undergone external peer review.

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-24-7/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-24-7/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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