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Donation after circulatory death (DCD) is emerging as an alternative pathway to donation after brain death (DBD) to expand the cardiac organ donor pool.1 We describe the surgical technique and circuit configuration for in-situ organ reperfusion with thoracoabdominal normothermic regional perfusion (TA-NRP) using portable venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Data de publicació electrònica: 18-06-2021 El incremento en el número de pacientes en lista de espera de trasplante renal ha llevado a intentar aumentar el número de posibles donantes incorporando candidatos que anteriormente no se habrían considerado óptimos, incluyendo entre estos a los donantes de pacientes de asistolia (DA) y aquellos con criterios «expandidos» (DCE). Los receptores de injertos de DA controlada (DAc) sufren más función retrasada del injerto, pero presentan una evolución a largo plazo equiparable a los de donantes de muerte encefálica, lo que ha permitido un aumento en el número de trasplantes de DAc en distintos países en los últimos años. De forma paralela, el uso de DAc con criterios expandidos (DAc/DCE) se ha incrementado en los últimos años en diferentes países, permitiendo acortar la lista de espera del trasplante renal. El uso de estos injertos, aunque se relaciona con una mayor frecuencia de función retrasada del injerto, ofrece supervivencias del injerto a largo plazo similares o solo ligeramente inferiores a las de los donantes de muerte encefálica con criterios expandidos. Distintos estudios han observado que los receptores de injertos DAc/DCE tienen peor función renal que los DAc/estándar y que los donantes de muerte encefálica/DCE. La mortalidad asociada al trasplante de injertos de DAc/DCE se relaciona principalmente con la elevada edad del receptor. Los pacientes que reciben un trasplante renal de DAc/≥ 60 años presentan mejor supervivencia que los que continúan en la lista de espera, aunque este hecho no se ha demostrado en los receptores de DAc/> 65 años. La utilización de este tipo de órganos debe llevar pareja la optimización de los tiempos quirúrgicos y el menor tiempo de isquemia fría posible. The increase in the number of patients on the kidney transplant waiting list has led to an attempt to increase the number of potential donors by incorporating candidates that previously would not have been considered optimal, including donors after cardiac death (DCD) and those with “expanded” criteria (ECD). Recipients of controlled DCD (cDCD) grafts suffer more delayed graft function (DGF), but have a long-term evolution comparable to those of brain-dead donors, which has allowed an increase in the number of cDCD transplants in different countries in recent years. In parallel, the use of cDCD with expanded criteria (cDCD/ECD) has increased in recent years in different countries, allowing the waiting list for kidney transplantation to be shortened. The use of these grafts, although associated with a higher frequency of DGF, offers similar or only slightly lower long-term graft survival than those of brain death donors with expanded criteria. Different studies have observed that cDCD/ECD graft recipients have worse kidney function than cDCD/standard and brain death/ECD. Mortality associated with cDCD/ECD graft transplantation mostly relates to the recipient age. Patients who receive a cDCD/≥60 graft have better survival than those who continue on the waiting list, although this fact has not been demonstrated in recipients of cDCD/>65 years. The use of this type of organ should be accompanied by the optimization of surgical times and the shortest possible cold ischemia.

Expanding Donation after circulatory death (DCD) multi-organ recovery to include the heart presents logistical and technical challenges for all teams participating in the process. Strategies to optimally coordinate the activities of multi-organ DCD recovery teams to facilitate expeditious, coordinated multi-organ protection and safe recovery are discussed.

The specific effect of donation after circulatory death (DCD) liver grafts on fibrinolysis, blood loss, and transfusion requirements after graft reperfusion is not well known. The aim of this study was to determine whether transplantation of controlled DCD livers is associated with an elevated risk of hyperfibrinolysis, increased blood loss, and higher transfusion requirements upon graft reperfusion, compared with livers donated after brain death (DBD).A retrospective single-center analysis of all adult recipients of primary liver transplantation between 2000 and 2019 was performed (total cohort n = 628). Propensity score matching was used to balance baseline characteristics for DCD and DBD liver recipients (propensity score matching cohort n = 218). Intraoperative and postoperative hemostatic variables between DCD and DBD liver recipients were subsequently compared. Additionally, in vitro plasma analyses were performed to compare the intraoperative fibrinolytic state upon reperfusion.No significant differences in median (interquartile range) postreperfusion blood loss (1.2 L [0.5-2.2] versus 1.3 L [0.6-2.2]; P = 0.62), red blood cell transfusion (2 units [0-4] versus 1.1 units [0-3]; P = 0.21), or fresh frozen plasma transfusion requirements (0 unit [0-2.2] versus 0 unit [0-0.9]; P = 0.11) were seen in DCD compared with DBD recipients, respectively. Furthermore, plasma fibrinolytic potential was similar in both groups.Transplantation of controlled DCD liver grafts does not result in higher intraoperative blood loss or more transfusion requirements, compared with DBD liver transplantation. In accordance with this, no evidence for increased hyperfibrinolysis upon reperfusion in DCD compared with DBD liver grafts was found.

Peer reviewed: True, The increasing number of patients on the kidney transplant waiting list underlines the need to expand the donor pool and improve kidney graft utilization. By protecting kidney grafts adequately from the initial ischemic and subsequent reperfusion injury occurring during transplantation, both the number and quality of kidney grafts could be improved. The last few years have seen the emergence of many new technologies to abrogate ischemia-reperfusion (I/R) injury, including dynamic organ preservation through machine perfusion and organ reconditioning therapies. Although machine perfusion is gradually making the transition to clinical practice, reconditioning therapies have not yet progressed from the experimental setting, pointing towards a translational gap. In this review, we discuss the current knowledge on the biological processes implicated in I/R injury and explore the strategies and interventions that are being proposed to either prevent I/R injury, treat its deleterious consequences, or support the reparative response of the kidney. Prospects to improve the clinical translation of these therapies are discussed with a particular focus on the need to address multiple aspects of I/R injury to achieve robust and long-lasting protective effects on the kidney graft.

Lung transplantation with lungs procured from donors after circulatory death (DCD) has been established as an alternative technique to traditional donation after brain death (DBD) with comparable outcomes. Recently, in situ thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a novel technique employed in the procurement of cardiac allografts after circulatory death. TA-NRP, in contrast to ex situ machine perfusion, has the advantage of allowing in situ assessment of donor organs prior to final acceptance. However, there are some concerns that this technique may adversely impact the quality of lung allografts. Here, we present a case of a successful bilateral sequential lung transplantation in a patient with postinflammatory pulmonary fibrosis due to acute respiratory distress syndrome (ARDS), with lungs procured after normothermic in situ lung perfusion. Apart from the lungs, heart, liver, and kidneys were also successfully transplanted from this donor.

BACKGROUND: There is a continued interest in ex situ heart perfusion as an alternative strategy for donor heart preservation. We hypothesize that oxygenated machine perfusion of donor hearts at a temperature that avoids both normothermia and deep hypothermia offers adequate and safe preservation. METHODS: Cardioplegia-arrested porcine donor hearts were randomly assigned to six hours of preservation using cold storage (CS, n = 5) or machine perfusion using an oxygenated acellular perfusate at 21°C (MP, n = 5). Subsequently, all grafts were evaluated using the Langendorff method for 120 min. Metabolic parameters and histology were analyzed. Systolic function was assessed by contractility and elastance. Diastolic function was assessed by lusitropy and stiffness. RESULTS: For both groups, in vivo baseline and post-Langendorff biopsies were comparable, as were lactate difference and myocardial oxygen consumption. Injury markers gradually increased and were comparable. Significant weight gain was seen in MP (p = 0.008). Diastolic function was not impaired in MP, and lusitropy was superior from 30 min up to 90 min of reperfusion. Contractility was superior in MP during the first hour of evaluation. CONCLUSION: We conclude that the initial functional outcome of MP-preserved hearts was transiently superior compared to CS, with no histological injury post-Langendorff. Our machine perfusion strategy could offer feasible and safe storage of hearts prior to transplantation. Future studies are warranted for further optimization. ispartof: ARTIFICIAL ORGANS vol:46 issue:2 pages:246-258 ispartof: location:United States status: published

In 2019 a total of 756 people died in Germany while registered on the waiting list for an organ transplantation. With 10.8 organ donors/million inhabitants in 2019, Germany belongs to the bottom group in the Eurotransplant foundation as well as worldwide. All political attempts to increase the number of organ donations have so far been unsuccessful. Furthermore, the pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a further decline in organ donations. Critical care physicians play an important role in the identification of potential doners and are also the main point of contact for relatives; however, multiple uncertainties exist regarding the process of organ donation not only in discussions in the media and society but also among physicians involved in intensive care medicine. Many assumptions and hypotheses, which have been associated with the low number of donors, lack scientific evidence and are discussed in this article.Im Jahr 2019 starben in Deutschland 756 Menschen, während sie auf der Warteliste für ein Spenderorgan standen. Sowohl im Eurotransplant-Verbund als auch weltweit gehört Deutschland mit 10,8 Organspendern/Mio. Einwohner im Jahr 2019 zur Schlussgruppe. Sämtliche politischen Versuche, die Spenderzahlen zu steigern, scheinen bislang ohne Effekt geblieben zu sein. Darüber hinaus hat die durch das „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV-2) ausgelöste Pandemie zum weiteren Rückgang der Spenderzahlen geführt. Der Intensivmedizinerin kommt im Prozess der Erkennung möglicher Spender sowie als erste Ansprechpartnerin für die Angehörigen eine zentrale Rolle zu. Jedoch existieren nicht nur in den gesellschaftlichen und medialen Diskussionen um das Thema Organspende viele Unklarheiten, sondern auch bei den intensivmedizinisch tätigen Ärzten. Viele Annahmen und Hypothesen, die mit den niedrigen Spenderzahlen in einen Zusammenhang gebracht werden, lassen sich wissenschaftlich jedoch nicht belegen und sollen in diesem Beitrag diskutiert werden.

Supplemental Digital Content is available in the text., Background. Uncontrolled donation after circulatory death (DCD) donors are an extraordinary resource to increase the number of lungs available for transplantation. However, the risk of the warm ischemia resulting from cardiac arrest to irreversibly damage the organs is considerable. Moreover, graft preservation issues and organizational problems often worsen the dangerous effects of warm ischemia. Ex vivo lung perfusion (EVLP) enables us to evaluate and recondition lungs whose functionality is doubtful, as well as to overcome the difficulties related to time and logistics. Methods. We report the case of uncontrolled DCD lungs successfully treated with an exceptionally prolonged EVLP. Because the donor’s blood count and liver biopsy showed signs of possible leukemia, EVLP was protracted up to 17 h while waiting for immunohistochemical analyses to rule out this diagnosis; eventually, the results came back negative, and the lungs were judged suitable for transplantation. Results. The recipient was a 32-y-old male individual with cystic fibrosis, colonized by Pandoraea pnomenusa. Bilateral transplantation required central extracorporeal membrane oxygenation. The patient was extubated after 36 h and was discharged 21 d after the operation. Despite early recolonization by Pandoraea pnomenusa and airway complications requiring pneumatic dilatation, he is alive and has a satisfactory respiratory function 15 mo after transplantation. Conclusions. Uncontrolled DCD represents a challenge due to both logistical issues and the complexity of graft evaluation before procurement. EVLP with cellular perfusate could be a valuable tool to overcome these limits. Nonetheless, caution should be exercised when interpreting the effects of this technique on airway healing.

Introduction. Circulatory-respiratory death declaration is a common duty of physicians, but little is known about the amount of education and physician practice patterns in completing this examination. Methods. We conducted an online survey of physicians evaluating the rate of formal training and specific examination techniques used in the pronouncement of circulatory-respiratory death. Data, including level of practice, training received in formal death declaration, and examination components were collected. Results. Respondents were attending physicians (52.4%), residents (30.2%), fellows (10.7%), and interns (6.7%). The majority of respondents indicated they had received no formal training in death pronouncement, however, most reported self-perceived competence. When comparing examination components used by our cohort, 95 different examination combinations were used for death pronouncement. Conclusions. Formal training in death pronouncement is uncommon and clinical practice varies. Implementation of formal training and standardization of the examination are necessary to improve physician competence and reliability in death declarations.

There are concerns that simultaneous pancreas-kidney (SPK) transplants from donation after circulatory death (DCD) donors have a higher risk of graft failure than those from donation after brain death (DBD) donors. A UK registry analysis of SPK transplants between 2005 and 2018 was performed. Pancreas survivals of those receiving organs from DCD or DBD donors were compared. Multivariable analyses were used to adjust for baseline differences between the two groups and to identify factors associated with pancreas graft loss. A total of 2228 SPK transplants were implanted; 403 (18.1%) were from DCD donors. DCD donors were generally younger, slimmer, less likely to have stroke as a cause of death, with lower terminal creatinines and shorter pancreas cold ischemic times than DBD donors. Median (IQR) follow-up was 4.2 (1.6-8.1) years. On univariable analysis, there were no statistically significant differences in 5-year death-censored pancreas graft survival between the two donor types (79.5% versus 80.4%; p = .86). Multivariable analysis showed no statistically significant differences in 5-year pancreas graft loss between transplants from DCD (n = 343) and DBD (n = 1492) donors (hazard ratio 1.26, 95% CI 0.76-1.23; p = .12). The findings from this study support the increased use of SPK transplants from DCD donors.

Transplantation of any organ into a recipient requires a donor. Lung transplant has a long history of an inadequate number of suitable donors to meet demand, leading to deaths on the waiting list annually since national data was collected, and strict listing criteria. Before the Uniform Determination of Death Act (UDDA), passed in 1980, legally defined brain death in the U.S., all donors for lung transplant came from sudden death victims [uncontrolled Donation after Circulatory Death donors (uDCDs)] in the recipient's hospital emergency department. After passage of the UDDA, uDCDs were abandoned to Donation after Brain Death donors (DBDs)-perhaps prematurely. Compared to livers and kidneys, many DBDs have lungs that are unsuitable for transplant, due to aspiration pneumonia, neurogenic pulmonary edema, trauma, and the effects of brain death on lung function. Another group of donors has become available-patients with a devastating irrecoverable brain injury that do not meet criteria for brain death. If a decision is made by next-of-kin (NOK) to withdraw life support and allow death to occur by asphyxiation, with NOK consent, these individuals can have organs recovered if death occurs relatively quickly after cessation of mechanical ventilation and maintenance of their airway. These are known as controlled Donation after Circulatory Death donors (cDCDs). For a variety of reasons, in the U.S., lungs are recovered from cDCDs at a much lower rate than kidneys and livers. Ex-vivo lung perfusion (EVLP) in the last decade has had a modest impact on increasing the number of lungs for transplant from DBDs, but may have had a larger impact on lungs from cDCDs, and may be indispensable for safe transplantation of lungs from uDCDs. In the next decade, DCDs may have a substantial impact on the number of lung transplants performed in the U.S. and around the world.

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF 7 days, 576 (31·2%) had DGF 7-14 days, and 345 (18·7%) had DGF14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF14 days is a novel early biomarker for significantly worse longer-term outcomes.

Introduction: T-tube placement during liver transplantation (LT) is still debated. We performed a retrospective study to evaluate the usefulness of T-tube after LT in two cohorts differing in post-transplant risk. Methods: A total of 327 LTs performed between 2015 and 2018 were included in the analysis. LTs from donation after circulatory death and living donation, split-liver transplants, and LTs with hepaticojejunostomy were excluded. T-tube was reserved for marginal grafts, high-risk recipients, and bile duct size discrepancy. A balance of risk (BAR) score of ≤9 defined the low-risk cohort (232 patients, 68 with and 164 without T-tube), while a BAR score of &gt, 9 defined the high-risk cohort (95 patients, 43 with and 52 without T-tube). Postoperative complications were estimated with the comprehensive complication index (CCI). Postoperative biliary complications were classified in anastomotic stricture (AS), non-anastomotic stricture (NAS), and biliary leakage (BL). Results: In the low-risk cohort, LTs with and without T-tube had similar rates of NAS (0 vs. 2.9%, p = 0.36), AS (2.9 vs. 2.4%, p = 0.83), and BL (1.4 vs. 2.4%, p = 0.64). Analogous outcomes were found in the high-risk cohort: NAS (0 vs. 0), AS (0 vs. 5.7%, p = 0.11), and BL (0 vs. 1.3%, p = 0.27). There were more postoperative complications among patients with T-tube, in both the low-risk (CCI 29 vs. 21, p &lt, 0.001) and high-risk (CCI 51 vs. 29, p &lt, 0.001) cohort. No differences in primary non-function, hepatic artery thrombosis, and mortality were observed. Conclusions: T-tube placement did not influence postoperative biliary complications. Although the two cohorts were normalized for post-transplant risk, LT recipients with T-tube had a more complicated course.

Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.

Background Several techniques have been developed to reduce the warm ischaemic injury of donation after circulatory death (DCD) organs before procurement. There are scarce data about the in situ preservation techniques for kidney graft outcomes. The aim of this systematic review was to evaluate the best in situ preservation method for kidney graft outcomes from organs obtained from controlled and uncontrolled DCD. Methods A systematic review of the PubMed (MEDLINE), Embase, LILACS and Cochrane databases was conducted. Studies that compare two or more in situ preservation techniques were identified and included. Only studies which provided enough data to calculate odds ratio were eligible for meta-analysis. PROSPERO registration: CRD42020179598. Results The search strategy yielded 7,121 studies. Ultimately, 14 retrospective studies were included. Because of heterogeneity, the included studies provided weak evidence that normothermic regional perfusion (NRP) is the best in situ preservation technique in terms of delayed graft function (DGF) rates. Regarding primary nonfunction (PNF), we carried out a meta-analysis of 10 studies with a pooled OR of 0.83 (95% CI: 0.40-1.71), for the NRP. In regard to DGF, pooled OR for NRP was 0.36 (95% CI: 0.25-0.54). Conclusions NRP in the DCD donor could improve kidney graft function and be considered the in situ preservation technique of choice for abdominal organs.

OBJECTIVES Liver allograft shortage has necessitated greater use of donations after circulatory death. Limited data are available to compare recipients' health care utilization for donation after circulatory death versus brain death. MATERIALS AND METHODS Liver transplant data for our center from November 2016 until May 2019 were obtained (208 donations after brain death and 39 after circulatory death). We excluded patients

Uvod: Proces darovanja organov je ključen za proces presaditve organov kot metode zdravljenja, katerega namen je ponovna vzpostavitev določenih funkcij človeškega telesa s prenosom dela telesa darovalca v telo prejemnika. Transplantacijska medicina se v globalnem merilu spopada s problemom pomanjkanja ustreznih organov za presaditev, zato v zadnjih letih narašča število odvzemov organov darovalcem po tako imenovani cirkulatorni smrti. V primerjavi z odvzemom organov po potrjeni možganski smrti, ki je prevladujoča metoda darovanja organov po svetu, se pri darovanju po cirkulatorni smrti odvzem organov izvede po potrjeni smrti na podlagi kardiopulmonalnih kriterijev, torej po dokončni odsotnosti dihanja in spontanega krvnega obtoka. Vendar pa se pri darovanju po cirkulatorni smrti pojavljajo, poleg strokovnih, tudi številni etični pomisleki, dileme in nesoglasja. Namen: S pregledom strokovne in znanstvene literature nameravamo opredeliti darovanje po cirkulatorni smrti kot strategijo za spopadanje z globalnim izzivom pomanjkanja primernih organov in pridobiti vpogled v etično problematiko darovanja organov, ki se pojavlja pri tej metodi. Cilj diplomskega dela je opredeliti in predstaviti specifične etične probleme in dileme, ki spremljajo darovanje organov po cirkulatorni smrti. Metode dela: Opravili smo pregled domače in tuje strokovne in znanstvene literature s tematiko etičnih vidikov darovanja organov po cirkulatorni smrti, objavljene od leta 2010 dalje. Literaturo za diplomsko delo smo iskali v podatkovnih bazah Cinahl, Medline z iskalnikom Pub Med ter v spletnem portalu DiKul preko oddaljenega dostopa Digitalne knjižnice Univerze v Ljubljani. Literaturo smo iskali v slovenskem in angleškem jeziku v obdobju od februarja 2022 do maja 2022 s pomočjo naslednjih ključnih besed: organ donation, circulatory death, ethics, DCD, transplantation, darovanje organov, cirkulatorna smrt in etika. Rezultati: V skladu s cilji diplomskega dela smo z analizo izbrane literature strukturirali tri poglavitne etične probleme, ki spremljajo darovanje po cirkulatorni smrti: potrditev smrti in kršenje pravila mrtvega darovalca konflikti interesov ter presaditev srca po cirkulatorni smrti in uporaba zunajtelesne membranske oksigenacije po potrjeni smrti. Razprava in zaključek: Darovanje organov po cirkulatorni smrti se v nekaterih protokolih nevarno približa kršenju pravila mrtvega darovalca, ki je temeljni element transplantacijske medicine. Zato je z etičnega vidika potrebno pri uvajanju protokolov darovanja po cirkulatorni smrti v prakso skrbno preučiti in izbrati zgolj tiste postopke in merila, ki najbolj nedvomno potrdijo dokončnost stanja smrti in preprečujejo konflikte interesov. Zaupanje in podpora strokovne in splošne javnosti v sistem transplantacij organov se ob izvajanju etično in strokovno vprašljivih praks lahko hitro poruši. Introduction: The process of organ donation is key to the process of organ transplantation as a method of treatment that aims to restore certain functions of the human body by transferring part of the donor's body into the recipient's body. Transplantation medicine is facing a global shortage of suitable organs for transplantation, and, therefore, there has been an increase in the number of organ donations after so-called circulatory death in recent years. Compared to organ harvesting after the confirmed brain death, which is the predominant method of organ donation worldwide, in the case of donation after circulatory death, organ harvesting is performed after confirmed death based on cardiopulmonary criteria, i.e. after the definitive absence of respiration and spontaneous circulation. However, in addition to professional concerns, donation after circulatory death also raises a number of ethical concerns, dilemmas and disagreements. Purpose: Through a review of the professional and scientific literature, we aim to identify donation after circulatory death as a strategy to address the global challenge of the suitable organs shortage and to gain an insight into the ethical issues of organ donation that arise in this method. The aim of this thesis is to identify and present the specific professional-ethical problems and dilemmas that accompany organ donation after circulatory death. Methods: We conducted a review of the national and international professional and scientific literature on the ethical aspects of organ donation after circulatory death, published since 2010. Literature for the thesis was searched in the Cinahl and Medline databases using the Pub Med search engine and in the DiKul web portal via remote access of the University of Ljubljana Digital Library. We searched the literature in Slovenian and English language between February 2022 and May 2022 using the following keywords: organ donation, circulatory death, ethics, DCD, transplantation, darovanje organov, cirkulatorna smrt and etika. Results: In line with the aims of the thesis, we have structured the analysis of the selected literature around three main ethical issues that accompany donation after circulatory death: confirmation of death and violation of the dead donor rule conflicts of interest heart transplantation after circulatory death and the use of extracorporeal membrane oxygenation after confirmed death. Discussion and conclusion: Organ donation after circulatory death comes dangerously close in some protocols to breaking the dead donor rule, which is a fundamental element of transplantation medicine. Therefore, from an ethical point of view, when introducing protocols of donation after circulatory death into practice, it is necessary to carefully consider and select only those procedures and criteria that most clearly confirm the finality of the state of death and avoid conflicts of interest. The trust and support of the professional and general public in the organ transplantation system can be quickly eroded when ethically and professionally questionable practices are carried out.

The use of livers from donation after circulatory death (DCD) is historically characterized by increased rates of biliary complications and inferior short-term graft survival (GS) compared to donation after brain death (DBD) allografts. This study aimed to evaluate the dynamic prognostic impact of DCD livers to reveal whether they remain an adverse factor even after patients survive a certain period following liver transplant (LT). This study used 74 961 LT patients including 4065 DCD LT in the scientific registry of transplant recipients from 2002-2017. The actual, 1 and 3-year conditional hazard ratio (HR) of 1-year GS in DCD LT were calculated using a conditional version of Cox regression model. The actual 1-, 3-, and 5-year GS of DCD LT recipients were 83.3%, 73.3%, and 66.3%, which were significantly worse than those of DBD (all P

Controlled donation after circulatory death (cDCD) is used for "extended criteria" donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12-1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time18 h, 1.57; 95% CI 1.20-2.03, vs aRR with cold ischemia time ≥18 h, 1.79; 95% CI 1.31-2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.

Shortage of deceased donor organs for transplantation has led to the increased use of organs from donation after circulatory death (DCD) donors. There are currently no reports describing outcomes after multiorgan transplantation with DCD livers. The use of DCD organs for multiorgan transplantation can be enhanced if the detrimental effects of prolonged cold ischemia and subsequent ischemia-reperfusion injury are overcome. We present a case in which the liver and lungs of a DCD donor were preserved using ex situ machine perfusion for combined liver-lung transplantation. The recipient was a 19-year-old male patient requiring bilateral lung transplantation for severe progressive pleural parenchymal fibroelastosis and portal hypertension with portal vein thrombosis. The donor liver was preserved with dual hypothermic oxygenated machine perfusion, whereas the lungs were perfused using ex vivo lung perfusion. With ex vivo lung perfusion, total preservation time of right and left lung reached 17 and 21 h, respectively. Now, 2 y after transplantation, liver function is normal and lung function is improving. To conclude, we suggest that combined transplantation of DCD liver and lungs is feasible when cold ischemia is reduced with ex situ machine perfusion preservation.

BACKGROUND AND AIMS: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on surgeon's experience. We present an objective, non-invasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analysing biomolecular composition.APPROACH AND RESULTS: A novel porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality pre-mortem, during warm ischemia (WI) and post-NRP. 10% of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 min of WI and after two hours of NRP, and analysed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS) and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of haemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualised rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different to pre-ischemic and post-NRP livers as measured using a handheld Raman spectrometer.CONCLUSIONS: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage.

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BACKGROUND: Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited. METHODS: In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications. RESULTS: A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.). ispartof: NEW ENGLAND JOURNAL OF MEDICINE vol:384 issue:15 pages:1391-1401 ispartof: location:United States status: published

Donation after circulatory death (DCD) donors are an increasingly more common source of livers for transplantation in many parts of the world. Events that occur during DCD liver recovery have a significant impact on the success of subsequent transplantation. This working group of the International Liver Transplantation Society evaluated current evidence as well as combined experience and created this guidance on DCD liver procurement. Best practices for the recovery and transplantation of livers arising through DCD after euthanasia and organ procurement with super rapid cold preservation and recovery as well as postmortem normothermic regional perfusion are described, as are the use of adjuncts during DCD liver procurement.

The use of cold preservation solutions to rapidly flush and cool the kidney followed by static cold storage in ice has been the standard kidney preservation technique for the last 50 y. Nonetheless, changing donor demographics that include organs from extended criteria donors and donation after circulatory death donors have led to the adoption of more diverse techniques of preservation. Comparison of hypothermic machine perfusion and static cold storage techniques for deceased donor kidneys has long been debated and is still contested by some. The recent modification of hypothermic machine perfusion techniques with the addition of oxygen or perfusion at subnormothermic or near-normothermic temperatures are promising strategies that are emerging in clinical practice. In addition, the use of normothermic regional perfusion to resuscitate abdominal organs of donation after circulatory death donors in situ before cold flushing is also increasingly being utilized. This review provides a synopsis of the different types of preservation techniques including their mechanistic effects and the outcome of their application in clinical practice for different types of donor kidney.

There is a dearth of effective parameters for selecting potentially transplantable liver grafts from expanded-criteria donors. In this study, we used a nuclear magnetic resonance (NMR) relaxation analyzer-based assay to assess the viability of ex vivo livers obtained via porcine donation after circulatory death (DCD). Ex situ normothermic machine perfusion (NMP) was utilized as a platform for viability test of porcine DCD donor livers. A liver-targeted contrast agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), was injected into the perfusate during NMP, and the dynamic biliary excretion of the Gd-EOB-DTPA was monitored by measuring the longitudinal relaxation time (T1). The longitudinal relaxation rate (R1) of the bile was served as a parameter. The delay of increase in biliary R1 during early stage of NMP indicated the impaired function of liver grafts in both warm and cold ischemia injury, which was correlated with the change of alanine aminotransferase. The preservative superiority in cold ischemia of dual hypothermic oxygenated machine perfusion could also be verified by assessing biliary R1 and other biochemical parameters. This study allows for the dynamic assessment of the viability of porcine DCD donor livers by combined usage of ex situ NMP and NMR relaxation time based assay, which lays a foundation for further clinical application.

Background: Early allograft dysfunction (EAD) is associated with decreased graft and patient survival rates. This study aimed to identify the severity of EAD and develop a predictive model for EAD after donation after circulatory death (DCD) liver transplantation (LT). Furthermore, the influence of operative time on EAD incidence was also evaluated. Methods: In this retrospective, multicentre cohort study, nomograms were established based on a single-centre training cohort (n=321) and validated in a 3-center validation cohort (n=501). Results: The incidence rate of EAD was 46.4% (149/321) in the training cohort and 40.5% (203/501) in the validation cohort. Of the 149 EAD patients in the training cohort, 77 patients with either elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were classified as having EAD type A, and the rest of the EAD patients were classified as having EAD type B. Recipients with EAD type B had lower graft and patient survival rates than recipients with EAD type A (P=0.043 and 0.044, respectively). We further developed a nomogram to predict EAD (graft weight, cold ischemia time, donor age, model for end-stage liver disease (MELD) score) and another nomogram to predict EAD type B (graft weight, cold ischemia time, MELD score). The nomograms for the prediction of EAD and EAD type B had good discrimination [concordance index (C-index) =0.712 (0.666–0.758), 0.707 (0.641–0.773)] and calibration [Hosmer-Lemeshow (HL) P=0.384, P=0.425] in the validation cohort. An increased operative time (>6 h) was associated with increased EAD and EAD type B incidence in the high-risk group (P=0.005, P=0.020, respectively). Conclusions: EAD type B was associated with decreased graft and patient survival rates. The novel nomograms effectively predicted the incidence of EAD and EAD type B in DCD LT patients.

Brain death differs from traditional circulatory death, and understanding how it differs is important. Public awareness of brain death is based largely on inaccurate media representations, common examples of which are described here. The purpose of this article is to motivate lay understanding of brain death by tracing key moments in the history of how we've come to define and recognize brain death as death. This article also considers criticisms of brain death and rebuttals to those criticisms.

Context The request process for donation after circulatory death (DCD) and family concerns about DCD differ in significant ways from the process for, and family concerns about, donation after brain death (DBD). In addition, donation rates for DCDs are typically lower than for DBDs. Although there has been a great deal of research on how the concerns of DBD families impact donation, limited research exists on family concerns and decision-making in the DCD request process. Objective To determine the concerns of families approached for DCD and explore how those might be addressed to increase DCD donation rates. Design, setting, and participants Written request response forms were completed by organ procurement and family services coordinators from 4 organ procurement organizations in 4 different states. They were filled out as soon as possible after speaking with families about DCD. Main outcome measures Responses were marked on a 12-item instrument, and anecdotal observations and detailed comments about family concerns, donor registration status, and decisions made were noted. Results Family concerns that block DCDs differ in many ways from those that block DBDs. These concerns arise from stresses peculiar to the DCD situation and must be addressed for these types of donations to increase. Purpose of the study The purposes of the study are to identify family concerns about donating organs that are specific to DCD and that may differ from DBD and to distinguish how those concerns might be addressed in ways that increase the likelihood of donation.

Worldwide, the majority of heart transplant organs are from donation after brain death. However, the shortage of suitable donors places severe limitations on this route. One option to increase the donor pool is to use organs from donation after circulatory death (DCD). Transplant centers for solid organs have been using DCD organs for years. At this time, 40% of solid organ transplantation in the United Kingdom uses organs from DCD. Use of DCD for solid organ transplants in Canada is also rising. Recently, there has been interest in using DCD organs for heart transplantation. The authors will discuss their experience of 4 heart transplants with organs from DCD donors after normothermic regional perfusion (NRP). The authors' first heart transplant using a DCD organ was in January 2020, and the fourth was in March 2020, just before the coronavirus disease 2019 (COVID-19) pandemic. The authors' protocol using NRP allows adequate evaluation of the donor heart to confidently determine organ acceptance. The co-location of the donor and the recipient in neighboring operating rooms limits ischemic times. Avoidance of an expensive ex vivo organ perfusion machine is an additional benefit for programs that may not have the resources required to purchase and maintain the machine. Some hospitals may not have the resources and space to be able to co-locate both the donor and recipient. Use of cold storage may be an option to transport the procured organ, similar to donation after brain death organs. The authors hope that this technique of NRP in DCD donors can help further increase the donor pool for heart transplantation in the United States.

Kidney transplant restores renal function in eligible patients with end-stage renal failure who require renal replacement therapy. There remains a significant disparity between the demand and supply of suitable kidneys for transplant. In recent years, pediatric donors have formed an important area for expansion of the donor pool. However, neonatal donation (< 28 days) remains an underutilized resource. We describe a case of en bloc kidney transplant from a 5-day-old donor after circulatory death into an adult recipient. One kidney thrombosed almost immediately, leaving a single 4.5-cm, poorly functioning kidney. Eighteen months after transplant, the recipient has shown good function with the estimated glomerular filtration rate continuing to improve. This case demonstrates that a single neonatal kidney can grow and adapt to provide adequate renal function in an adult. This experience suggests that a single kidney from a neonate can sustain renal function in adults, and every effort should be made to maximize their use in transplant.