Miguel M Leiva-Juárez1, Andreacarola Urso1, Elisabet Arango Tomás1, David J Lederer1, Pablo Sanchez2, Bartley Griffith2, R Duane Davis3, Mani Daneshmand3, Matthew Hartwig3, Edward Cantu4, Michael J Weyant5, Christian Bermudez6, Jonathan D'Cunha6, Tiago Machuca7, Thomas Wozniak8, William Lynch9, Hassan Nemeh9, Michael Mulligan10, Tae Song11, Michael Jessen12, Phillip C Camp13, Christiano Caldeira14, Bryan Whitson15, Daniel Kreisel16, Danny Ramzy17, Frank D'Ovidio18. 1. Section of General Thoracic Surgery, Lung Transplant Program, Columbia University Medical Center, New York, New York. 2. Department of Cardiac Surgery, University of Maryland Medical Center, Baltimore, Maryland. 3. Department of Cardiovascular and Thoracic Surgery, Duke University, Durham, North Carolina. 4. Division of Cardiac Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. 5. Department of Cardiothoracic Surgery, University of Colorado Denver, Denver, Colorado. 6. Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 7. Division of Thoracic and Cardiovascular Surgery, University of Florida, Gainesville, Florida. 8. Department of Cardiothoracic Surgery, Indiana University, Bloomington, Indiana. 9. Department of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan. 10. Department of Thoracic Surgery, University of Washington, Seattle, Washington. 11. Division of Cardiothoracic Surgery, University of Chicago, Chicago, Illinois. 12. Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern, Dallas, Texas. 13. Department of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts. 14. Department of Thoracic Surgery, Largo Medical Center, Largo, Florida. 15. Division of Cardiac Surgery, Ohio State University, Columbus, Ohio. 16. Department of Cardiothoracic Surgery, Barnes Jewish Hospital, Saint Louis, Missouri. 17. Department of Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California. 18. Section of General Thoracic Surgery, Lung Transplant Program, Columbia University Medical Center, New York, New York. Electronic address: fd2133@cumc.columbia.edu.
Abstract
BACKGROUND: Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic-cold preservations affect outcomes. METHODS: A total of 110 patients were retrospectively analyzed. Duration of 3 preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics. RESULTS: Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (<264 vs ≥264 minutes) and post-EVLP (<287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88-20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56-161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36-95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes. CONCLUSIONS: Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP.
BACKGROUND: Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic-cold preservations affect outcomes. METHODS: A total of 110 patients were retrospectively analyzed. Duration of 3 preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics. RESULTS: Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (<264 vs ≥264 minutes) and post-EVLP (<287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88-20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56-161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36-95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes. CONCLUSIONS: Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP.
Authors: John P Reilly; Nuala J Meyer; Michael Gs Shashaty; Brian J Anderson; Caroline Ittner; Thomas G Dunn; Brian Lim; Caitlin Forker; Michael P Bonk; Ethan Kotloff; Rui Feng; Edward Cantu; Nilam S Mangalmurti; Carolyn S Calfee; Michael A Matthay; Carmen Mikacenic; Keith R Walley; James Russell; David C Christiani; Mark M Wurfel; Paul N Lanken; Muredach P Reilly; Jason D Christie Journal: J Clin Invest Date: 2021-01-04 Impact factor: 14.808
Authors: Ashwini Arjuna; Michael T Olson; Rajat Walia; Ross M Bremner; Michael A Smith; Thalachallour Mohanakumar Journal: Expert Rev Respir Med Date: 2020-10-25 Impact factor: 3.772