- Resource Type:
165. Extending Cold Static Preservation at 10°C to Avoid Overnight Lung Transplantation: A Prospective Multi-Center Proof-of-Concept Clinical Trial
May 16, 2022
Joel Cooper , Invited Discussant , Hospital of The University of Pennsylvania
Marcelo Cypel , Abstract Presenter , Toronto General Hospital
102nd Annual Meeting, Boston, MA, USA
Hynes Convention Center, Ballroom ABC
Objective: In preclinical studies, we have demonstrated that cold static preservation (CSP) at 10°C is an effective and reliable strategy for prolonged (>24h) preservation of pulmonary grafts, with underlying protective mechanisms related to the maintenance of mitochondrial health (Science Trans Med, 2021). Here, we report on a prospective multi-center clinical trial designed to investigate the feasibility of intentionally prolonging CSP at 10°C to avoid overnight (10pm - 6am) lung transplants.
Methods: To date, 40 consented patients have been enrolled in this prospective, non-randomized, single armed, multi-center study (n=63 target, NCT04616365). Donors with cross clamp times between 6pm and 4am were allowed to be enrolled in the study with the earliest allowed transplant starting time of 6am. Donor exclusion criteria included the need for ex vivo lung perfusion, while recipient exclusion criteria included re-transplantation and multi-organ transplantation. Lungs meeting study criteria were retrieved and transported in the usual fashion using a cooler with ice. Immediately upon arrival to the transplant hospital, lungs were transferred to a 10°C temperature-controlled refrigerator until implantation. The primary outcome of this study was incidence of ISHLT Primary Graft Dysfunction (PGD) Grade 3 at 72h, with secondary endpoints including: recipient time on the ventilator, ICU Length of Stay (LOS), hospital LOS, 30-day survival and lung function at 1-year. Outcomes were compared to a contemporaneous cohort of recipients at each center selected using propensity score matching for medical diagnosis, BMI, recipient status, and donor type at a 1:2 ratio.
Results: Currently, 37 patients have achieved at least 30 day follow up and were included in the analysis. The median recipient age was 65 years (55 - 74 years). Most patients (97%) received bilateral lung transplantation. Donor and recipient characteristics, and recipient outcomes are shown in Table 1. Mean CSP was significantly longer in the study group vs. matched controls for both the first (11h ± 2.6h vs. 6.1h ± 1.9h; p<0.001) and second implanted lung (13h ± 2.8h vs. 8.1h ± 2.1h, p<0.001). PGD 3 at 72h was 3% in the study group vs. 11% in matched controls (p=0.27). No differences were seen in the need for post-op ECMO (5 vs. 9%; p=0.72), patients extubated by 72h (76 vs. 70%; p=0.66), median ICU LOS (5 vs 5 days; p=0.53), and median hospital LOS (24 vs. 23 days; p=0.33). In a median follow up of 248 days, 2 study patients have died at days 136 and 370 from sepsis and lymphoma, respectively.
Conclusions: Intentional prolongation of donor lung CSP using 10°C storage appears to be clinically safe and feasible, with promising results. Avoidance of overnight transplants using this simple approach has the potential to improve transplantation logistics and performance, potentially significantly altering practice in clinical lung transplantation.
Marcelo Cypel (1), Aadil Ali (1), Stefan Schwarz (2), Tiago Machuca (3), Jonathan Yeung (1), Laura Donahoe (1), Kazuhiro Yasufuku (1), Andrew Pierre (1), Marc de Perrot (1), Thomas Waddell (1), Konrad Hoetzenecker (2), Shaf Keshavjee (1), (1) Division of Thoracic Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, (2) Department of Thoracic Surgery, Medical University of Vienna, Vienna, Vienna, (3) Division of Thoracic Surgery, University of Florida, Gainesville, FL
Joel D. Cooper is Professor of Surgery Emeritus in the Division of Thoracic Surgery at the University of Pennsylvania Health System. He received his undergraduate degree from Harvard College, summa cum laude, Phi Beta Kappa, and his medical degree from Harvard Medical School, cum laude. After completing an internship and residency in surgery at Massachusetts General Hospital, he served as Senior Registrar in Thoracic Surgery, Southwest Regional Hospital Board, Frenchay Hospital, Bristol, England and completed a fellowship in the Department of Medicine, Hammersmith Hospital, London, England. Returning to Massachusetts General Hospital, he served as Chief Resident in Surgery and was a Clinical and Research Fellow in Thoracic Surgery, Massachusetts General Hospital.
Dr. Cooper’s special interests include general thoracic, esophageal and tracheal surgery, adult lung transplantation, lung volume reduction surgery, lung cancer and swallowing disorders. He is widely recognized for his contributions in the field of tracheal surgery, esophageal surgery, pulmonary physiology, lung transplantation and surgery for emphysema. Dr. Cooper is past president of the American Association for Thoracic Surgery, a member of the Institute of Medicine of the National Academy of Sciences, and the recipient of numerous honorary degrees. He has received the Jacobson Innovation Award from the American College of Surgeons and the Earl Bakken Scientific Achievement Award from the Society of Thoracic Surgeons.
Over the past 49 years Dr. Cooper has served as the Chief of Thoracic Surgery at The University of Toronto, Washington University in St. Louis, and The University of Pennsylvania Health System.
Dr. Cooper currently serves as an active member of numerous professional societies and has served on the editorial boards of many scientific journals. He also is the author or coauthor of more than 400 original publications.
Marcelo Cypel MD, MSc, FACS, FRCSC
Surgical Director Ajmera Transplant Centre at UHN
Surgical Director UHN ECLS Program
Canada Research Chair in Lung Transplantation
Professor of Surgery, Division of Thoracic Surgery
University of Toronto, University Health Network
Senior-Scientist, Toronto General Research Institute