Case Studies
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Interest(s): Advanced Practice Professionals, Donor Management, Emerging Technology, Innovation, Legal and Regulatory, Marginal / Increased Risk Organs, Organ Allocation (Offer and Acceptance), Organ Preservation and Perfusion, Organ Transportation / Logistics, Patient Safety, Waitlist Management
Organ(s): Lung
Patient Group(s): Adult
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Allograft Physiology Assessed After Two-Hours on Ex-vivo Lung Perfusion (EVLP) Associates with Utilization Decision Making
Anil
Trindade
, MD
, Associate Professor of Medicine
, Vanderbilt University Medical Center
The Challenge
Lung transplantation can be a life-saving therapy for patients with advanced lung disease, though limitations in donor lung supply have resulted in a waitlist mortality rate of 18.8%.1 Unfortunately, only 25% of available donor lungs are utilized, further confounding the supply problem.2 Ex-vivo lung perfusion (EVLP) has improved donor lung utilization by enabling closer monitoring of non-standard donor lungs in an inflated, perfused, normothermic state, allowing for the evaluation of gas exchange, vascular permeability, pulmonary vascular resistance, lung weight, and metabolic activity, as well as radiographic and bronchoscopic assessments. This has resulted in increased utilization of extended criteria donors, faster time to transplants for recipients, and fewer waitlist deaths.3 This is particularly important for lungs from donors after circulatory death (DCD), where variable warm ischemic times may negatively impact allograft health.4 Recipients of lungs that underwent EVLP with acellular perfusate at a single transplant center have demonstrated non-inferior short and long-term outcomes.5
Assessment of donor lungs on EVLP traditionally occurs for up to 5 hours. However, due to the resource-intensive nature of EVLP, if information regarding usability of donor lungs can be gleaned at earlier time points, then shorter durations of EVLP may be advantageous.
We sought to determine whether physiologic parameters obtained during earlier time points on EVLP are adequate to inform the decision of whether to utilize donor lungs
The Approach
We performed a dual-center, retrospective analysis of consecutive donor lungs referred for remote, centralized EVLP (rc-EVLP) assessment at Mayo Clinic Jacksonville and Vanderbilt University Medical Center between 12/1/2020 – 3/20/2023. Permission to perform this study was obtained by the Institutional Review Boards at both centers [VUMC #230889 on 7/6/2023 and Mayo Jacksonville #23-007861(Exempt Status) on 10/11/23].
Donor lungs were referred for rc-EVLP by the transplant teams based on previously described criteria.7 In general, lungs were considered for rc-EVLP if they did not meet standard criteria, required additional evaluation time, or would not be used for transplantation without EVLP. Such scenarios included DCD donors, a PaO2/FiO2 ratio < 300 mm Hg, pulmonary edema, expected cold ischemic time exceeding 6 hours, donor age greater than 55 years, donor receipt of more than 10 units of blood products, and abnormal imaging or bronchoscopic findings. EVLP was not indicated if it was unlikely to increase the likelihood of organ utilization; some exclusion criteria used by the participating transplant centers included confirmed pneumonia, persistent purulent secretions, significant lung trauma, and/or lungs from HIV donors. Personnel at transplant centers were responsible for assessing lung quality and determining the need for EVLP.
The Results
A total of 78 donor lungs were referred for rc-EVLP assessment during the study period, of which 45 (58%) were for lung transplant candidates at Mayo Clinic Jacksonville, and the remaining 33 (42%) were for Vanderbilt patients. The indication for rc-EVLP was for further assessment of extended-criteria organs for 62 (79%) of the donors, while the remainder were referred to interrupt the cold ischemic time to facilitate logistics associated with organ transport and/or transplant center workflow. Baseline characteristics of donor lungs referred for rc-EVLP assessment are listed in Table 1.
Overall, 46 (59%) donor lungs were accepted for implantation following rc- EVLP. Lungs were more likely to be utilized if the indication for EVLP was interruption of cold ischemic time versus further assessment of extended-criteria donor lungs [15/16 (94%) vs 31/62 (50%), p<0.01]. Lungs were also more likely to be utilized from brain dead donors rather from donors after circulatory death [40/59 (68%) vs. 6/19 (32%), p<0.01]. Donor age, sex, smoking history, gas exchange prior to procurement, cold ischemic time prior to EVLP (CIT1), and sequence number were not predictive of lung acceptance and utilization.
Donor lungs were assessed on rc-EVLP for a median of 220 minutes (IQR 209 – 240). There were several physiologic parameters obtained on EVLP within the first 2 hours that were associated with acceptance and utilization of donor lungs (Table 1), including perfusate loss at 1-hour, peak airway pressure and static compliance at 2 hours, and oxygen transfer at 1 and 2 hours. There was a non-significant trend towards increased glucose utilization and lactic acid production in lungs declined following 1 or 2 hours of EVLP. Pulmonary arterial pressure and pulmonary vascular resistance did not associate with the decision to utilize the allograft following EVLP.
Insights & Lessons Learned
In a dual center, retrospective cohort of donor lungs conditioned on remote, centralized EVLP, we demonstrate that physiologic parameters obtained as early as 2-hours associate with the decision to utilize donor lungs. This suggests that EVLP duration as short as 2 hours may be sufficient for decision making. EVLP has revolutionized the field of lung transplantation allowing for increased utilization of donor lungs that would previously have been discarded, with acceptable short and long-term outcomes. Moreover, by interrupting cold ischemic time, EVLP can provide increased flexibility
with allograft and recipient logistical planning; this is particularly important given the recent changes with the lung composite allocation score that has resulted in increased travel distances to procure donor lungs. With the expected increase in EVLP demand, identifying strategies to streamline donor lung assessment and reduce costs is important.
This is one of the first studies to demonstrate that short assessments on EVLP may be sufficient for evaluating marginal donor lungs. The multicenter nature of this study and the use of remote centralized EVLP decreases noise and increases generalizability. Limitations of this study include the retrospective nature, which increases the likelihood for bias. Moreover, although this is a dual center study, both centers are located in the southeast; practice patterns and outcomes regarding remote EVLP may differ by region, especially for centers on the west coast. Finally, while there was guidance for referral of donor lungs for EVLP assessment, decision making regarding utilization post-EVLP was subjective and at the discretion of the implanting surgeon at each center. This work suggests that shorter evaluation periods of donor lungs may be sufficient for assessing allograft quality. Future prospective studies to further assess the role of time-limited EVLP trials are warranted.