DCD Donors Research Articles

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials.

Donor organ shortage still remains a serious obstacle for the access of wait-list patients to kidney transplantation, the best treatment for End-Stage Kidney Disease (ESKD). To expand the number of transplants, the use of lower quality organs from older ECD or DCD donors has become an established routine but at the price of increased incidence of Primary Non-Function, Delay Graft Function and lower-long term graft survival. In the last years, several improvements have been made in the field of renal transplantation from surgical procedure to preservation strategies. To improve renal outcomes, research has focused on development of innovative and dynamic preservation techniques, in order to assess graft function and promote regeneration by pharmacological intervention before transplantation. This review provides an overview of the current knowledge of these new preservation strategies by machine perfusions and pharmacological interventions at different timing possibilities: in the organ donor, ex-vivo during perfusion machine reconditioning or after implementation in the recipient. We will report therapies as anti-oxidant and anti-inflammatory agents, senolytics agents, complement inhibitors, HDL, siRNA and H2S supplementation. Renal delivery of pharmacologic agents during preservation state provides a window of opportunity to treat the organ in an isolated manner and a crucial route of administration. Even if few studies have been reported of transplantation after ex-vivo drugs administration, targeting the biological pathway associated to kidney failure (i.e. oxidative stress, complement system, fibrosis) might be a promising therapeutic strategy to improve the quality of various donor organs and expand organ availability.

Lung Transplantation Using Allografts with Extreme Ischemic Time: A Single-Institution Experience

<h3>Purpose</h3> Six hours has historically been regarded as the limit of acceptable ischemic time (IT) for lung allografts. However, smarter sharing of donor lungs often necessitates use of allografts with IT >6 hours. We characterized the association between IT ≥8 hours and outcomes after lung transplantation (LTx) using a contemporary cohort from a high-volume institution. We hypothesized that longer ITs do not predict greater mortality or graft failure. <h3>Methods</h3> Patients who underwent primary isolated bilateral orthotopic LTx between 1/2016-5/2020 were included. Patients bridged to LTx with ECMO or mechanical ventilation, and ex-vivo perfusion cases were excluded. Recipients were stratified by allograft IT <8h vs ≥8h. Survival to a composite outcome of death or graft failure and perioperative outcomes were compared between IT strata. Unadjusted survival was estimated using the Kaplan-Meier method; adjusted survival was modeled using multivariable Cox regression. <h3>Results</h3> Of 358 patients, 95 (26.5%) received IT ≥8h lungs. IT ≥8h recipients were more likely to be male (69.5% vs 54.4%, p=0.01) and have DCD donors (20.0% vs 5.3%, p<0.01) than IT <8h recipients. On unadjusted analysis, IT ≥8h and <8h recipients had similar survival (<b>Figure</b>) and similar rates of PGD3 at 72 hours (7.4% vs 6.8%, p=0.9), ECMO post-transplant (16.8% vs 10.6%, p=0.1), acute rejection within 30 days (15.8% vs 16.3%, p=0.9), reintubation during the transplant hospitalization (26.3% vs 20.9%, p=0.3), and similar lengths of stay (median 25 vs 21 days, p=0.2). After adjustment, IT ≥8h and <8h recipients had comparable risks of mortality or graft failure (HR 0.83, 95% CI 0.46-1.51). <h3>Conclusion</h3> In a modern cohort, use of lung allografts with IT ≥8h was associated with similar perioperative outcomes and post-transplant survival. Further investigation is required to better understand how broader use impacts post-LTx outcomes and the implications for smarter sharing under an evolving national allocation policy.

Contemporary Indications for Heart-Lung Transplantation

<h3>Purpose</h3> Currently, there are patients who meet criteria for lung transplant who are denied listing because of underlying heart disease. Likewise, there are patients who meet criteria for heart transplant but are denied listing because of lung disease. In addition, end-stage pulmonary hypertension has become more commonly treated with bilateral lung transplantation. From 2006 to 2018, no adult heart-lung transplantation (HLT) was performed in New York State. Given this unmet need our center has renewed interest in HLT. <h3>Methods</h3> All patients who underwent HLT from 06/2019 to 09/2020 were reviewed. Patients were listed per standard UNOS guidelines. The primary outcome was hospital and 1year survival. <h3>Results</h3> 10 patients (50% male; mean age 54±8 years) underwent HLT during this period. All patients had been deemed not appropriate candidates for isolated heart or lung transplant at more than one transplant center. The indication for HLT was interstitial lung disease (ILD) with ischemic cardiomyopathy (n=4), nonischemic cardiomyopathy with PAH (n=2), PAH with RV failure (n=2), and ILD with RV failure (n=2). Median lung allocation score and heart waitlist status were 71 (IQR: 41-85) and 2 (IQR: 1-3) respectively. Three patients had re-operative sternotomies. Two patients bridged to transplant with VA-ECMO, two with VV-ECMO and three patients required IABP. One patient received a DCD donor heart-lung block utilizing normothermic regional perfusion, and two patients received Hep C+ donor organs. One patient was left on central VA-ECMO postoperatively for early lung PGD. No lung PGD grade 3 at 72 hours or significant heart PGD at any time point were observed. At a median follow up of 287 (IQR: 108-401 days), all patients are alive at home. <h3>Conclusion</h3> Our initial center experience demonstrates that appropriately selected patients with end stage heart and lung disease who would otherwise die without transplantation can be offered HLT with excellent short-term outcomes.

Is donation after circulatory determination of death feasible for pediatric patients in italy?

To determine the potential effect of a donation after cardiac death active program on the number of organ donors in a Italian Pediatric Intensive Care Unit (PICU). We conducted a retrospective study of all deaths in PICU of an academic Children Hospital between 2012 and 2020, tracing the organ donation activity. Patients were categorized as brain deaths, deaths despite maximal resuscitation, and deaths after withdrawal or limitation of life support. Patient demographics, premortem physiology, end-of-life circumstances, and functional warm ischemia time were recorded. Eligible donors after cardiac death were identified by the absence of medical contraindication and functional warm ischemia time <60 minutes. Of 124 deaths that occurred during the study period, 34 met criteria for brain death, 23 were potential donors, and 13 became actual donors. Of the remaining 90 patients that met criteria for cardiac death, 66 died despite maximal resuscitation, 24 died after withdrawal or limitation of care and between them 13 were identified as theoretically eligible DCD donors. Of these, 5 patients had a functional warm ischemia time of <1 hour and were potential candidates for DCD of 10 kidneys and 2 lungs. Even if few children could have been eligible for DCD in the study period, an active program could have been able to increase the number of potential organ donors by 20% in the last eight years at our institution. DCD deserves to be explored in Italy as a new option for children.

Research Highlights.

Research Highlights.

Survival benefit of accepting kidneys from older donation after cardiac death donors.

Kidneys from older (age ≥50 years) donation after cardiac death (DCD50) donors are less likely to be transplanted due to inferior posttransplant outcomes. However, candidates who decline a DCD50 offer must wait for an uncertain future offer. To characterize the survival benefit of accepting DCD50 kidneys, we used 2010-2018 Scientific Registry for Transplant Recipients (SRTR) data to identify 92081 adult kidney transplantation candidates who were offered a DCD50 kidney that was eventually accepted for transplantation. DCD50 kidneys offered to candidates increased from 590 in 2010 to 1441 in 2018. However, 34.6% of DCD50 kidneys were discarded. Candidates who accepted DCD50 offers had 49% decreased mortality risk (adjusted hazard ratio [aHR] 0.46 0.510.55 , cumulative mortality at 6-year 23.3% vs 34.0%, P<.001) compared with those who declined the same offer (decliners). Six years after their initial DCD50 offer decline, 43.0% of decliners received a deceased donor kidney transplant (DDKT), 6.3% received living donor kidney transplant (LDKT), 22.6% died, 22.0% were removed for other reasons, and 6.0% were still on the waitlist. Comparable survival benefit was observed even with DCD donors age ≥60 (aHR: 0.42 0.520.65 , P<.001). Accepting DCD50 kidneys was associated with a substantial survival benefit; providers and patients should consider these benefits when evaluating offers.

PREDICTING TIME TO DEATH AFTER WITHDRAWAL IN CONTROLLED DONATION AFTER CIRCULATORY DEATH (DCD) DONORS: A COMPARISON OF 100 DCD LUNG TRANSPLANT (LTX) DONORS VERSUS 59 POTENTIAL DCD DONORS THAT DID NOT PROGRESS

Introduction: Since 2006, controlled DCD donors have been routinely utilized for LTx by our institution, now contributing an additional 25-30 % LTx annually. Donation of lungs from a potential DCD donor can only occur if the patient dies ≤90 minutes post withdrawal of cardio-respiratory support (WCRS). However, 20-25% of potential DCD donors still do not progress to asystole in 90 minutes, leading to disappointment for the patient’s grieving family as well as having major resourcing implications for the donation and transplant teams. Prediction of which patients will die within the 90 minutes limit remains problematic. Previous studies have evaluated ICU variables and clinical WCRS practices to try and predict time to death with limited success. In this study, we compared a cohort of LTx DCD donors with a cohort of potential DCD donors who did not progress, looking for factors that may better predict time to death. Methods: This retrospective study reviewed donor records of all potential DCD donors that were referred to our institution from our local state donor agency, between 2014 and 2018. We included data from all potential DCD donors that been formally accepted as suitable for LTx and where our LTx surgical retrieval team actually attended the donor hospital. Variables evaluated included donor demographics and medical history, hospital location, cause of injury leading to WCRS, ICU hemodynamic and ventilation data, Apache II Score, time, location and method of WCRS and time to death. Analysis of comparison between the 2 cohorts was done using Wilcoxon rank-sum tests and chi-square tests. Results: Between 2014-2018, there were 334 DCD donor referrals to our program, resulting in 159 (48%) potential DCD donors attended for potential LTx retrieval. 100/159 (63%) progressed to DCD LTx, but 59 donors (37%) did not progress in required 90 minutes. Potential DCD donors that did not progress were less likely to be on vasopressin compared to DCD LTx donors (p<0.02), they were more likely to be in CPAP ventilator mode (p<0.01) and in ICU and ventilated longer (P<0.001) before WCRS. There were no differences in donor demographics, P/F ratio, cause of injury leading to WCRS, hospital type/location, donor hemodynamics, abnormal CXR or smoking history (Table 1). Of the 59 who did not die within 90 minutes of WCRS, 26 patients (44%) died within the subsequent 6 hours (Figure 1).Conclusions: Progression to asystole within 90 minutes and subsequent lung donation for DCD LTx is more likely where the potential lung donor has a requirement for mandatory-mode mechanical ventilatory support and vasopressin, suggesting they have a significant brainstem neurological injury. Additionally, development of a protocol that allows potential retrieval of donor lungs in the subsequent 6hrs after WCRS would significantly increase the yield of lungs from this pool of otherwise acceptable donors.

A SINGLE-CENTRE, FIVE-YEAR EXPERIENCE WITH DCD HEART TRANSPLANTATION

Introduction: In 2014 the world first DCD heart transplant with distant procurement (DPP) was performed in Sydney, Australia. Programs are now established in the UK and Europe, as well as a recently commenced multi-centre trial in the USA, with >150 performed worldwide. In established centres, DCD donors account for >20% of heart transplants with excellent early- and mid-term outcomes. Despite these encouraging results, there is still much to be learnt about DCD heart transplantation, and with increasing numbers of hospitals wishing to start DCD heart programs this paper will describe the protocols, lessons learnt and current outcomes from our experience. Materials and Methods: Forty-one DCD heart transplants were performed at our institution between July 2014 and February 2020, utilising a DPP and ex-situ perfusion protocol. Male or female DCD donors under the age of 55 years with no known history of cardiac disease were accepted for retrieval. Recipient selection was based on blood group and cross-matching outcomes, heart mass, and clinical urgency. The donor hearts were perfused on the TransMedics OCS device as outlined in Table 1.For analysis, donor details were collected using electronic donor records (Donate Life, Australia) with recipient data collected from clinical notes and electronic databases at our institution. Results: Patients receiving DCD allografts had excellent outcomes with 97.6 and 95.1% 1- and 5-year survival, respectively.In spite of the similar donor and recipient profiles and a similar rate of utilization of allografts reperfused on the OCS device (74% and 72%, early and late cohort, respectively), the rate of delayed graft function requiring ECMO support has dropped dramatically, from 35% to 14%.Interestingly, prolongation of the functional warm ischemic time was not associated with an increased rate of ECMO, however prolongation of the asystolic warm ischemic time was. A longer agonal period from withdrawal to circulatory arrest was in fact associated with a lower rate of ECMO.Discussion: Over our DCD program experience we have made several changes likely to have contributed to the reduced perioperative ECMO requirement. Primarily, we have adopted a more ‘protective’ approach to the management of the heart on the OCS device, targeting in particular lower coronary flows, with a view to reducing endothelial dysfunction and myocardial oedema. In addition, a design change to the OCS module now allows for a controlled cooling of the heart to 16°C prior to delivery of cardioplegia, proving superior protection to the heart during implantation. Conclusion: DCD heart transplantation clearly provides an additional source of donor allografts with excellent recipient outcomes. Our experiences have reinforced the benefit of a ‘protective’ perfusion strategy on the OCS device, and also raise questions about the true tolerable warm ischemic time, which requires further investigation. Curran Foundation.

Impact of warm ischemia time on outcomes for kidneys donated after cardiac death Post-KAS.

Prolonged warm (WIT) and cold (CIT) ischemia times are often important considerations in the discard of DCD kidneys, but their impact on post-transplant outcomes in the post-KAS era is unclear. We examined the association of ischemia time on delayed graft function (DGF) and death-censored graft failure for DCD kidneys. The 2018 SRTR SAF was utilized to identify post-KAS DCD kidney transplants occurring from 2015 to 2018. Relative risk and Cox regression were used to calculate risk of delayed graft function and hazard of death-censored graft failure, respectively. We identified 4,680 kidneys from DCD donors transplanted from 2015 to 2018 with recorded WIT and CIT times. Median WIT was 21.0minutes (IQR 14.0-28.0), and CIT was 18.5hours (IQR 13.9-23.5). The overall incidence of DGF was 42.7%. In a univariable relative risk regression model, extended CIT (24-30hours:RR 1.37, 95% CI 1.15-1.77; >30hours:RR 1.47, 95% CI 1.22-1.77) and WIT (20-40minutes:RR 1.10, 95% CI 1.03-1.17) were associated with increased risk of DGF. When included in a multivariable model, neither prolonged CIT nor WIT were significantly associated with death-censored graft failure. Prolonged WIT and CIT are associated with increased DGF but not death-censored graft failure in recipients of DCD kidney transplants in the post-KAS era. Extended ischemia alone should not be used as a basis for discard or non-utilization of these organs.

“Does Perioperative Patient Perfusion Obviate the Need for Kidney Machine Perfusion?” A Retrospective Analysis of Patients Receiving a Kidney From “Donation After Circulatory Death” Donors

BackgroundDelayed graft function (DGF) remains a clinically relevant problem in the post-transplant period, especially in patients with a renal graft from a “donation after cardiac death” (DCD) donor. Controversy exists around the optimal perioperative fluid therapy in such patients. These patients may benefit from a perioperative saline loading fluid protocol, which may reduce the risk of DGF. MethodsWe compared 2 cohorts of patients who underwent a renal transplantation with a graft from a DCD donor. From January 2003 until December 2012, patients (N = 46) were hemodynamically managed at the discretion of the care-giving physician, without a preoperative fluid administration protocol (first study period). From January 2015 until March 2019 (N = 26), patients received saline loading before, during, and after kidney transplantation according to a well-defined saline loading fluid protocol (second study period). The relationship between the use of this perioperative fluid protocol and DGF was analyzed using univariable and multivariable logistic regression models. ResultsDGF occurred in 11 of 46 (24%) patients in the first study period and in 1 of 26 (4%) in the second study period (P < .05). In a multivariable model, correcting for cold ischemia time and Kidney Donor Risk Index, the use of a saline loading fluid protocol in the perioperative phase was nearly significantly associated with a decrease in DGF (P = .07). ConclusionIn our DCD transplant population, DGF rates were low. Our data further strongly suggest that implementation of a perioperative saline loading fluid protocol was independently associated with a lower risk of DGF.

Donation after Circulatory Death: Potential Mechanisms of Injury and Preventative Strategies.

Donation after circulatory death (DCD) donors represent a potential means to help address the disparity between the number of patients awaiting liver transplantation (LT) and the availability of donor livers. While initial enthusiasm for DCD LT was high in the early 2000s, early reports of high rates of biliary complications and inferior graft survival resulted in reluctance among many transplant centers to use DCD liver grafts. As with all innovations in transplant practice, there is undoubtedly a learning curve associated with the optimal utilization of liver grafts from DCD donors. More contemporary data has demonstrated that results with DCD LT are improving and the number of DCD LT performed annually has been steadily increasing. In this concise review, potential mechanisms of injury for DCD livers are discussed along with strategies that have been employed in clinical practice to improve DCD LT outcomes.

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

BackgroundDonation after circulatory death (DCD) liver grafts have a poor prognosis after transplantation. We investigated whether the outcome of DCD donor organs can be improved by heme oxygenase 1 (HO-1)-modified bone marrow-derived mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP), and explored its underlying mechanisms.MethodsBMMSCs were isolated, cultured, and transduced with the HO-1 gene. An NMP system was established. DCD rat livers were obtained, preserved by different methods, and the recipients were divided into 5 groups: sham operation, static cold storage (SCS), NMP, BMMSCs combined with NMP, and HO-1/BMMSCs combined with NMP (HBP) groups. Rats were sacrificed at 1, 7, and 14 days after surgery; their blood and liver tissue samples were collected; and liver enzyme and cytokine levels, liver histology, high-mobility group box 1 (HMGB1) levels in monocytes and liver tissues, and expression of Toll-like receptor 4 (TLR4) pathway-related molecules were evaluated.ResultsAfter liver transplantation, the SCS group showed significantly increased transaminase levels, liver tissue damage, and shorter survival time. The HBP group showed lower transaminase levels, intact liver morphology, prolonged survival time, and decreased serum and liver proinflammatory cytokine levels. In the NMP and SCS groups, HMGB1 expression in the serum, monocytes, and liver tissues and TLR4 pathway-related molecule expression were significantly decreased.ConclusionsHO-1/BMMSCs combined with NMP exerted protective effects on DCD donor liver and significantly improved recipient prognosis. The effect of HO-1/BMMSCs was greater than that of BMMSCs and was mediated via HMGB1 expression and TLR4 pathway inhibition.

Estimating the potential pool of uncontrolled DCD donors in the United States.

Organs from uncontrolled DCD donors (uDCDs) have expanded donation in Europe since the 1980s, but are seldom used in the United States. Cited barriers include lack of knowledge about the potential donor pool, lack of robust outcomes data, lack of standard donor eligibility criteria and preservation methods, and logistical and ethical challenges. To determine whether it would be appropriate to invest in addressing these barriers and building this practice, we sought to enumerate the potential pool of uDCD donors. Using data from the Nationwide Emergency Department Sample, the largest all-payer emergency department (ED) database, between 2013 and 2016, we identified patients who had refractory cardiac arrest in the ED. We excluded patients with contraindications to both deceased donation (including infection, malignancy, cardiopulmonary disease) and uDCD (including hemorrhage, major polytrauma, burns, and poisoning). We identified 9828 (range: 9454-10202) potential uDCDs/y; average age was 32 years, and all were free of major comorbidity. Of these, 91.1% had traumatic deaths, with major causes including nonhead blunt injuries (43.2%) and head injuries (40.1%). In the current era, uDCD donors represent a significant potential source of unused organs. Efforts to address barriers to uDCD in the United States should be encouraged.

Variability in deceased donor care in Canada: a report of the Canada-DONATE cohort study.

Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices. This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces. Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34-35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces. These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials. www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.

Kidney transplant outcomes from donation after circulatory death donors of advanced age.

Continued comparison of kidney transplant outcomes between older DCD and donation after brain death (DBD) donors is needed to safely expand the deceased donor pool. We performed a retrospective cohort study using the UNOS/OPTN transplant registry from donors >50years old between 1994 and 2016. Donor age was stratified into 4 groups: 50-54, 55-59, 60-64, and >65years old. Rates of delayed graft function (DGF) and primary non-function (PNF) were compared. Multivariable Cox regression models were constructed to identify factors associated with time to graft failure. The DCD donors within each age group had fewer comorbidities than the DBD donors. Graft survival for DCD kidneys was equivalent or superior to DBD kidneys in all donor age groups. DGF rates were significantly greater for DCD kidneys in all age groups. PNF rates across all groups were similar. In multivariable analysis, DCD status was not independently associated with time to all-cause graft failure in the 50-54 donor age group (HR=1.02, 95% CI=0.93-1.13), 55-59 donor age group (HR=1.07, 95% CI=0.96-1.19), or 60-64 donor age group (HR=1.135, 95% CI=0.97-1.32). Kidneys from carefully selected older DCD donors, particularly ages 50-64, are a potential means to safely expand the deceased donor pool.

Impact of Ex Vivo Lung Perfusion on Utilization of Potential Lung Donors in the United States

Ex vivo lung perfusion (EVLP) is a contemporary tool which aims to improve the utilization of marginal donor lungs. Little is known about the impact of EVLP on the utilization of potential donor organs on a national scale in the United States. This study examines whether EVLP is associated with increased lung utilization among potential donors in a contemporary cohort of United States patients. We used the Organ Procurement and Transplantation Network database to identify all adult potential deceased organ donors, including donors after brain death (DBD) and donors after circulatory determination of death (DCD) in the modern era of EVLP (2015-2018). Our main covariate of interest was use of EVLP, defined by perfusion of either or both lungs prior to transplantation. The primary study endpoint was lung utilization, defined as successful single or double lung transplantation of a potential organ donor. Our analysis was performed using a multivariable logistic regression model adjusted for donor demographics, clinical characteristics, and risk factors. We evaluated the association between EVLP and lung utilization separately among the DCD and DBD potential donor populations. We identified 11,857 potential donors of whom 1,608 (14%) were DCDs. EVLP use increased from 2% to 4% annually during the study period. Among DBD potential donors, EVLP was used in 2% (n=22). Lung utilization was 62% (n=6188) in grafts recovered without EVLP and 49% (n=108) with EVLP. Recovery with EVLP was associated with significantly lower lung utilization (adjusted OR 0.6, 95% CI 0.4-0.8) among DBD potential donors. Among DCD potential donors, EVLP was used in 6% (n=100). Lung utilization was 15% (n=234) without EVLP and 49% (n=49) with EVLP. Recovery with EVLP was associated with significantly improved lung utilization among DCD potential donors (adjusted OR 2.8, 95% CI 1.7-4.6). EVLP is associated with significantly higher lung utilization among potential DCD donors in the United States. In DBD donors, use of EVLP was likely a surrogate for unmeasured high-risk features and appeared to represent attempted salvage of organs that would otherwise have been discarded. EVLP can be a valuable tool to improve lung utilization among DCD donors and if employed more widely, may increase the pool of organs available for transplantation.

Expanding Donor Age Criteria: The UK Experience

Transplant programmes are increasingly considering extended criteria donors, including previous smokers and older-age donors. In January 2018, the UK lung donor offering criteria was increased to 74 years (74 years and 364 days) for both DBD and DCD lung donors, where the donor was a life-time non-smoker or had not smoked within the last 10 years. Prior to this, the upper age limit was 64 years for DCD donors and 69 years for DBD donors. This study aims to assess the impact of the UK extended lung donor age criteria on lung utilisation and transplant. Data were obtained from the UK Transplant Registry on all lung offers from DBD donors over 69 years and DCD donors over 64 years ('older donors'), between January 2018 and September 2019. Utilisation was defined as at least one lung accepted and transplanted. One-hundred and seventy-eight donors meeting the criteria for analysis were identified. Of these, 110 proceeded to donation of at least one solid organ. Lungs were offered from 52 potential DBD donors aged 70-74 years and 126 potential DCD donors aged 65-74 years. Six (11.5%) of the 52 DBD lungs were transplanted and 2 (1.6%) of the 126 DCD lungs were transplanted. Recipient age ranged from 50-66 years. One recipient was listed as urgent at the time of transplant. One-hundred and seventy older donor lung offers were declined. The most common primary reasons for decline recorded were 'past history' (29%), 'poor function' (20%), and 'age' (19%). The cardiothoracic retrieval team attended 28 of the total 178 older donor offers. Although the utilisation rate from older lung donors is low, expanding the donor age criteria in the UK has resulted in an additional 8 transplants, a 1.2% increase. This appears to have benefited the older, non-urgent recipient. Despite the published increases to the donor offering age criteria, 'age' continues to be documented as a reason for organ decline. Further work is required to understand and improve utilisation rates throughout UK lung transplant practice, including the use of older donors. We will continue to review the impact of expanding lung donor age criteria on UK practice, including analysis of recipient outcomes from older age donors.

Donation after Euthanasia (DCD-V) Results in Excellent Long-Term Outcome after Lung Transplantation, Equal to Donation after Brain Death (DBD) and Circulatory Death (DCD-III)

In countries with a legal framework for physician-assisted death, organ donation after euthanasia (DCD-V) can increase the donor pool. DCD-V grafts are characterized by absence of lung injury related to brain-death, intubation and a long agonal phase. We review our experience with LTx after DCD-V and compare outcome with DBD and DCD-III experience in the same era. Between 01/2007-09/2019, 797 LTx were performed, of which 158 from DCD donors, including 20 DCD-V {8M/12F; mean age (range): 50 (28-66y)} due to neuromuscular (8) / mental (9) disorder or untreatable pain (3). After the request for euthanasia was granted in accordance with legislation, an explicit wish for organ donation was expressed by the patient and approved by the Institutional Review Board. Euthanasia was carried out in-hospital (local: 4; remote: 16) adjacent to the operating room in absence of the retrieval team. Twenty patients {7M/13F; age: 53y (27-64)} underwent bilateral LTx for emphysema (n=10), pulmonary fibrosis (n=5), cystic fibrosis (n=3, liver transplant in 1) and bronchiolitis obliterans (n=2). Waiting time was 326d (34-662). Agonal phase was short: 3min (0-14). Warm ischemia time between circulatory arrest and flush was 12min (7-21). Intensive care unit and hospital stay were 6d (2-10) and 28d (16-44). Three patients died due to cardiac problem (3mo), haematological disorder (3mo) or aspergillosis (10y). Follow-up was 4y (2mo-10.5y), CLAD occurred in 4. Five-year patient survival for DCD-V was 89%, equaling the DBD {80% (p=0.68)} and DCD-III cohort {81% (p=0.78)}. CLAD-free survival was 66.7%, equal to DBD {68.2% (p=0.68)} and DCD-III {69.9% (p=0.91)}. Our series represents the largest LTx experience from DCD-V and demonstrates for the first time that long-term outcome is comparable with DBD and DCD-III. DCD-V can further expand the donor pool in nations with a legal framework for physician-assisted death.

A Successful Strategy to Maximize Pulmonary Fibrosis (PF) Patient Access, Waiting List (WL) and Post-Lung Transplant (LTx) Survival

Access to LTx and rates of WL and post-Tx mortality for patients with PF are problematic. We have evolved a strategy to maximize Tx volume and improve survival for PF patients needing LTx. From 2012-2018, PF patients were priority assessed, listed and transplanted from a donor pool that included extended and DCD donors. Ex-vivo perfusion was not used. Patients were categorized as experiencing one of two competing events: LTx or WL death. Multivariable competing risk regression were performed for independent predictors of 1-yr post-listing mortality, and failure to reach LTx. From 187 patients listed, 82% (153/187) underwent LTx (median time to Tx, 2.0 mths), while 16% (29/187) died on WL (median time to death, 1.4 mths) Fig. A. Access to LTx for PF was 6.4 per million population (vs. USA = 2.9 p.m.p). Donors were 62% (88/153) extended criteria, including 24% (37/153) DCD. Single LTx was performed in 24% (36/153) of patients. PF comprised 29% (187/644) of all listed and 28% (153/547) of all transplanted patients during the study period. Multivariable predictors of 1-yr mortality from listing were: not receiving a LTx (HR 26, 95% CI 12 - 58, P < 0.0001), inpatient when listed (HR 3.2, 1.5 - 6.9, P = 0.002) and lower PaO2/FiO2 when listed (per 50mmHg less, HR 1.30, 1.04 - 1.63, P = 0.02). Multivariable predictors of failure to reach LTx were: height (per 1cm less, HR 1.11, 1.06-1.16, P<0.0001), blood type O (HR 4.3, 1.9 - 9.3, P < 0.0001) and inpatient when listed (HR 3.9, 1.8-8.5, P = 0.001). Survival after LTx is shown in Fig. B. Single or DCD LTx recipients had similar survival vs. double or DBD recipients (P = 0.6; 0.7). Follow up was 100% complete (mean: 2.5 ± 1.8 yrs). Pulmonary fibrosis continues to be presented late and requires a rapid transit to LTx. Use of extended and DCD donor organs facilitate a lower mortality risk than continued waitlist time and enable greater LTx access. Despite challenges, the majority of PF patients can reach LTx with excellent 5-yr survival.

Ex Vivo Lung Perfusion on Donor Lungs in the United States: National Trends and Post-Transplant Outcomes

The OPTN added fields to the deceased donor registration (DDR) form on 3/31/2015 and to the transplant recipient registration (TRR) form on 2/28/2018 to capture the utilization of ex vivo lung perfusion (EVLP) on donor lungs prior to transplantation (Tx) in the US. The aim is to examine the data fields currently being collected, summarize the use of EVLP over time, and to compare early transplant outcomes between EVLP lungs and lungs where EVLP was not considered. All adult deceased donors with at least one lung recovered for Tx from 4/1/15- 6/30/19 were analyzed. The prevalence of EVLP was examined over time and by recovering OPO. Post-transplant 1-year recipient survival (Tx between 4/1/15-6/30/18) was compared between donors of lungs with EVLP vs. no EVLP. For adult deceased donors (N=10,167), 19,295 lungs were recovered for the purpose of Tx. EVLP was intended in of 785 lungs and 485 (61.8%) of EVLP donor lungs were Tx. Since data collection began the use of perfusion has increased from 1.7% (N=16) of lungs to 7.4% (N=97) in the most recent quarter (Figure 1). Approximately 65% of the lungs perfused were from non-DCD donors and 35% from DCD donors. 51 of the 58 OPOs have recovered at least one lung that has been perfused. Over time the discard rate for perfused lungs has decreased from approximately 50% in the earliest quarter to approximately 25% in the most recent quarter. 1-yr patient survival between groups (EVLP, n=136; non-EVLP, n=7,169) was not significantly different (p= 0.06). The number of donor lungs perfused prior to Tx in the US has grown over the past 4 years to approximately 7% of all recovered donor lungs. Geographically, the use of EVLP varied greatly across OPOs. Early recipient outcomes did not differ statistically between EVLP intended donor lungs compared to conventional donation.