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Background: Use of lungs donated after circulatory death (DCD) has expanded, but changes in donor/recipient characteristics and comparison to brain dead donors (DBD) has not been studied. We examined the evolution of the use of DCD lungs for transplantation and compare outcomes to DBD lungs. Methods: The SRTR database was used to construct three 5-year intervals. Perioperative variables and survival were compared by era and for DCD vs. DBD. Geographic variation was estimated using recipient permanent address. Results: 728 DCD and 27,205 DBD lung transplants were identified. DCD volume increased from Era 1 (n = 73) to Era 3 (n = 528), representing 1.1% and 4.2% of lung transplants. Proportionally more DCD recipients were in ICU or on ECMO pre-transplant, and had shorter waitlist times. DCD donors were older, had lower PaO2/FiO2 ratios compared to DBD, more likely to be bilateral, had longer ischemic time, length of stay, post-op dialysis, and increased use of lung perfusion. There was no difference in overall survival. Geographically, use was heterogeneous. Conclusion: DCD utilization is low but increasing. Despite increasing ischemic time and transplantation into sicker patients, survival is similar, which supports further DCD use in lung transplantation. DCD lung transplantation presents an opportunity to continue to expand the donor pool. [ABSTRACT FROM AUTHOR]

Summary: Donation after circulatory death (DCD) is a potential source of reducing organ demand. In Italy, DCD requires a 20‐min no‐touch period that prolongs warm ischemia and increases delayed graft function (DGF) risk and graft loss. We report here our preliminary experience of sequential use of normothermic regional perfusion (NRP), as standard procedure, and hypothermic oxygenated perfusion (HOPE), as an experimental technique of organ preservation, in 10 kidney transplants (KT) from five DCD Maastricht III with extensive functional warm ischemia time (fWIT) up to 325 min. During NRP, renal function tests were evaluated to accept organs which were retrieved according to standard fashion with biopsy. While waiting for pathology and cross‐match results, organs were preserved with HOPE through pressure‐ and temperature‐controlled arterial pulsatile flow. All grafts with Karpinski score ≤4 were used for conventional single KT with mean cold ischemia time of 584 ± 167 min and mean fWIT of 151 ± 132 min. At the end of HOPE, lactate levels increased significantly in all cases with DGF (P = 0.0095), which were 3/10 (30%). No primary nonfunctions were recorded, and all patients had sCr < 1.5 mg/dl at 6‐month post‐KT. NRP and HOPE for DCD may overcome fWIT limits safely, and lactate during HOPE predicts DGF. [ABSTRACT FROM AUTHOR]

Survival of expanded criteria donor ( ECD) kidneys and their recipients has not been thoroughly evaluated in Europe. Therefore, we compared the outcome of ECD and non- ECD kidney transplantations in a Dutch cohort, stratifying by age and diabetes. In all first Dutch kidney transplants in recipients ≥18 years between 1995 and 2005, both relative risks (hazard ratios, HR) and adjusted absolute risk differences ( RD) for ECD kidney transplantation were analysed. In 3062 transplantations [recipient age 49.0 (12.8) years; 20% ECD], ECD kidney transplantation was associated with graft failure including death [ HR 1.62 (1.44-1.82)]. The adjusted HR was lower in recipients ≥60 years of age [1.32 (1.07-1.63)] than in recipients 40-59 years [1.71 (1.44-2.02) P = 0.12 for comparison with ≥60 years] and recipients 18-39 years [1.92 (1.42-2.62) P = 0.03 for comparison with ≥60 years]. RDs showed a similar pattern. In diabetics, the risks for graft failure and death were higher than in the nondiabetics. ECD kidney grafts have a poorer prognosis than non- ECD grafts, especially in younger recipients (<60 years), and diabetic recipients. Further studies and ethical discussions should reveal whether ECD kidneys should preferentially be allocated to specific subgroups, such as elderly and nondiabetic individuals. [ABSTRACT FROM AUTHOR]

Kidney grafts are often preserved initially in static cold storage ( CS) and subsequently on hypothermic machine perfusion ( MP). However, the impact of CS/ MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/ MP time in a single-center retrospective cohort of 59 donation after circulatory death ( DCD) and 177 matched donation after brain death ( DBD) kidney-alone transplant recipients. With mean overall CS/ MP times of 6.0 h/30.0 h, overall incidence of delayed graft function ( DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P < 0.0001). In logistic regression, DCD recipient ( P < 0.0001), longer CS time ( P = 0.0002), male recipient ( P = 0.02), and longer MP time ( P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type ( DBD vs. DCD), CS time (<6 vs. ≥6 h), and MP time (<36 vs. ≥36 h) on DGF incidence, one clearly sees an unfavorable effect of MP time ≥36 h ( P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h ( P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post-transplant. Long CS/ MP time detrimentally affects early DCD/ DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation. [ABSTRACT FROM AUTHOR]

The shortage of organs remains one of the biggest challenges in transplantation. To address this, we are increasingly turning to donation after circulatory death ( DCD) donors and now in some countries to uncontrolled DCD donors. We consolidate the knowledge on uncontrolled DCD in Europe and provide recommendations and guidance for the development and optimization of effective uncontrolled DCD programmes. [ABSTRACT FROM AUTHOR]

In an era where there is a shortage of lungs for transplantation is increased utilization of lungs from donation after circulatory death ( DCD) donors. We review the reports of 11 controlled and 1 uncontrolled DCD programs focusing on donor criteria, procedural criteria, graft assessment, and preservation techniques including the use of ex vivo lung perfusion. We have formulated conclusions and recommendations for each of these areas, which were presented at the 6th International Conference on Organ Donation. A table of recommendations, the grade of recommendations, and references are provided. [ABSTRACT FROM AUTHOR]

Donation after circulatory death ( DCD) donors are increasingly being used as a source of pancreas allografts for vascularized organ and islet transplantation. We provide practice guidelines aiming to increase DCD pancreas utilization. We review risk assessment and donor selection criteria. We report suggested factors in donor and recipient clinical management and provide an overview of the activities and outcomes of vascularized pancreas and islet transplantation. [ABSTRACT FROM AUTHOR]

Donation after circulatory death ( DCD) donors provides an invaluable source for kidneys for transplantation. Over the last decade, we have observed a substantial increase in the number of DCD kidneys, particularly within Europe. We provide an overview of risk factors associated with DCD kidney function and survival and formulate recommendations from the sixth international conference on organ donation in Paris, for best-practice guidelines. A systematic review of the literature was performed using Ovid Medline, Embase and Cochrane databases. Topics are discussed, including donor selection, organ procurement, organ preservation, recipient selection and transplant management. [ABSTRACT FROM AUTHOR]

Donation after circulatory death ( DCD) donors are becoming an increasingly important population of organ donors in Europe and worldwide. We report the state of the art regarding controlled DCD donation describing the organizational and technical aspects of establishing a controlled DCD programme and provide recommendations regarding the introduction and development of this type of programme. [ABSTRACT FROM AUTHOR]

This report deals with organ retrieval procedures in both controlled and uncontrolled DCD, looking at the ethical, legal, and psychosocial aspects during the different phases of the process. A recently published report by the UK Donation Ethics Committee ( UKDEC) has served as an important reference document to outline the steps in the controlled DCD patient-donor pathway (Academy of Medical Royal Colleges. UK Donation Ethics Committee. An ethical framework for controlled donation after circulatory death. December 2011). For uncontrolled DCD, the UKDEC pathway description was adapted. At the 6th International Conference in Organ Donation held in Paris in 2013, an established expert European Working Group reviewed the UKDEC reports, which were then considered along with the available published literature. Along this pathway, the crucial ethical, legal, and psychosocial aspects have been flagged, and relevant recommendations have been formulated based on a consensus of the working group. [ABSTRACT FROM AUTHOR]

Donation after cardiac death ( DCD) liver transplantation is increasingly common but concerns exist over the development of biliary complications and ischemic cholangiopathy ( IC). This study aimed to compare outcomes between DCD and donation after brain death ( DBD) liver grafts. Studies reporting on post-transplantation outcomes after Maastricht category III DCD liver transplantation were screened for inclusion. Odds ratios ( OR) with 95% confidence intervals were produced using random-effects models for the incidence of biliary complications, IC, graft and recipient survival. Meta-regression was undertaken to identify between-study predictors of effect size for biliary complications and IC. PROSPERO Record: CRD42012002113. Twenty-five studies with 62 184 liver transplant recipients ( DCD = 2478 and DBD = 59 706) were included. In comparison with DBD, there was a significant increase in biliary complications [ OR = 2.4 (1.9, 3.1); P < 0.00001] and IC [ OR = 10.5 (5.7, 19.5); P < 0.00001] following DCD liver transplantation. In comparison with DBD, at 1 year [ OR = 0.7 (0.5, 0.8); P = 0.0002] and 3 years [ OR = 0.6 (0.5, 0.8); P = 0.001], there was a significant decrease in graft survival following DCD liver transplantation. At 1 year, there was also a nonsignificant decrease [ OR = 0.8 (0.6, 1.0); P = 0.08] and by 3 years a significant decrease [ OR = 0.7 (0.5, 1.0); P = 0.04] found in recipient survival following DCD liver transplantation. Eleven factors were entered into meta-regression models, but none explained the variability in effect size between studies. DCD liver transplantation is associated with an increase in biliary complications, IC, graft loss and mortality. Significant unexplained differences in effect size exist between centers. [ABSTRACT FROM AUTHOR]

Success of clinical pancreatic islet transplantation depends on the mass of viable islets transplanted and the proportion of transplanted islets that survive early ischaemia reperfusion injury. Novel pancreas preservation techniques to improve islet preservation and viability can increase the utilization of donation after cardiac death donor pancreases for islet transplantation. Rat pancreases were retrieved after 30 min of warm ischaemia and preserved by static cold storage, hypothermic machine perfusion or retrograde portal venous oxygen persufflation for 6 h. They underwent collagenase digestion and density gradient separation to isolate islets. The yield, viability, morphology were compared. In vitro function of isolated islets was compared using glucose stimulated insulin secretion test. Portal venous oxygen persufflation improved the islet yield, viability and morphology as compared to static cold storage. The percentage of pancreases with good in vitro function (stimulation index > 1.0) was also higher after oxygen persufflation as compared to static cold storage. Retrograde portal venous oxygen persufflation of donation after cardiac death donor rat pancreases has the potential to improve islet yield. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the functional preservation of the lung graft with anterograde lung perfusion in a model of donation after cardiac death. Thirty minutes after cardiac arrest, in situ anterograde selective pulmonary cold perfusion was started in six swine. The alveolo-capillary membrane was challenged at 3, 6, and 8 h with measurements of the mean pulmonary arterial pressure ( mPAP), the pulmonary vascular resistance (PVR), the PaO2/FiO2 ratio, the transpulmonary oxygen output (tpVO2), and the transpulmonary CO2 clearance (tpCO2). Mitochondrial homeostasis was investigated by measuring maximal oxidative capacity ( Vmax) and the coupling of phosphorylation to oxidation (ACR, acceptor control ratio) in lung biopsies. Inflammation and induction of primary immune response were assessed by measurement of tumor necrosis factor alpha (TNFα), interleukine-6 (IL-6) and receptor for advanced glycation endproducts (RAGE) in bronchoalveolar lavage fluid. Data were compared using repeated measures Anova. Pulmonary hemodynamics ( mPAP: P = 0.69; PVR: P = 0.46), oxygenation (PaO2/FiO2: P = 0.56; tpVO2: P = 0.46), CO2 diffusion (tpCO2: P = 0.24), mitochondrial homeostasis ( Vmax: P = 0.42; ACR: P = 0.8), and RAGE concentrations ( P = 0.24) did not significantly change up to 8 h after cardiac arrest. TNFα and IL-6 were undetectable. Unaffected pulmonary hemodynamics, sustained oxygen and carbon dioxide diffusion, preserved mitochondrial homeostasis, and lack of inflammation suggest a long-lasting functional preservation of the graft with selective anterograde in situ pulmonary perfusion. [ABSTRACT FROM AUTHOR]

Kidneys from uncontrolled donors after cardiac death ( DCD) expand the donor pool, but are associated with more primary nonfunction ( PNF) and delayed graft function ( DGF) compared with more conventional donor kidneys. It remains unclear, which factors influence outcome of uncontrolled donation. Therefore, we studied which donor, graft, and recipient characteristics are associated with PNF in a large cohort study. The association between different characteristics and short-term graft function was analyzed for kidneys procured in the Maastricht region from 1 January 1981 to 1 July 2009. Patients were followed until 7 January 2010. A total of 135 uncontrolled donor kidneys were included in this study. The incidence of PNF and DGF was 22% and 61%, respectively. Increasing donor age is an independent risk factor for graft failure in a univariate analysis ( OR 1.035, 95% CI 1.004-1.068, P = 0.028). Donor age remains strongly associated with PNF in a multivariate analysis ( OR 1.064, 95% CI 1.013-1.118, P = 0.014). However, the predictive value of donor age alone is poor ( AURC 0.640, 95% CI 0.553-0.721). Increasing donor age of uncontrolled DCD donors is a major risk factor for PNF. Other clinically relevant variables were not associated with PNF. Donor age is strongly associated with PNF and remains an important parameter in donor selection. [ABSTRACT FROM AUTHOR]

This study aims to perform a detailed prospective observational multicenter cost-effectiveness study by comparing liver transplantations with Donation after Brain Death ( DBD) and Donation after Cardiac Death ( DCD) grafts. All liver transplantations in the three Dutch liver transplant centers between 2004 and 2009 were included with 1-year follow-up. Primary outcome parameter was cost per life year after transplantation. Secondary outcome parameters were 1-year patient and graft survival, complications, and patient-level costs. From 382 recipients that underwent 423 liver transplantations, 293 were primarily transplanted with DBD and 89 with DCD organs. Baseline characteristics were not different between both groups. The Donor Risk Index was significantly different as were cold and warm ischemic time. Ward stay was significantly longer in DCD transplantations. Patient and graft survival were not significantly different. Patients receiving DCD organs had more and more severe complications. The cost per life year for DBD was € 88 913 compared to € 112 376 for DCD. This difference was statistically significant. DCD livers have more and more severe complications, more reinterventions and consequently higher costs than DBD livers. However, patient and graft survival was not different in this study. Reimbursement should be differentiated to better accommodate DCD transplantations. [ABSTRACT FROM AUTHOR]

Warm ischemia-reperfusion injury related to donation after cardiac death donors is a crucial and inevitable issue. As surfactant function is known to deteriorate during warm ischemia, we hypothesized that surfactant inhalation during warm ischemia would mitigate warm ischemia-reperfusion injury. We used an isolated rat lung perfusion model. The rats were divided into three groups: sham, control, and surfactant. In the control and surfactant groups, cardiac arrest was induced by ventricular fibrillation. Ventilation was restarted 110 min later; subsequently, the lungs were flushed, and heart and lung block was recovered. In the surfactant group, a natural bovine surfactant Surfacten® was inhaled for 3 min at the end of warm ischemia. Then, the lungs were reperfused for 80 min. Surfactant inhalation significantly improved graft functions, effectively increased lung tissue ATP levels, and significantly decreased mRNA levels of IL-6 and IL-6/IL-10 ratio at the end of reperfusion. Histologically, lungs in the surfactant group showed fewer signs of interstitial edema and hemorrhage, and significantly less neutrophilic infiltration than those in the control group. Our results indicated that surfactant inhalation in the last phase of warm ischemia maintained lung tissue energy levels and prevented cytokine production, resulting in the alleviation of warm ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP < 50 mmHg; oxygen saturation <30%; mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Of all the time periods during procurement, only asystole-cross clamp period was significantly different between patients with ITBS versus no ITBS ( P = 0.048) and between the patients who had overall biliary complications versus no biliary complications ( P = 0.047). On multivariate analysis, only asystole-cross clamp period was significant predictor for development of ITBS ( P = 0.015) and development of overall biliary complications ( P = 0.029). Hemodynamic changes in the agonal period did not emerge as risk factors. The results of the study raise the possibility of utilizing asystole-cross-clamp period in place of or in conjunction with donor warm ischemia time in determining viability or quality of liver grafts. [ABSTRACT FROM AUTHOR]

Advanced age donors have inferior outcomes of liver transplantation for Hepatitis C (HCV). Aged donors grafts may be transplanted into young or low model for end stage liver disease (MELD) patients in order to offset the effect of donor age. However, it is not well understood how to utilize liver grafts from advanced aged donors for HCV patients. Using the UNOS database, we retrospectively studied 7508 HCV patients who underwent primary liver transplantation. Risk factors for graft failure and graft survival using advanced aged grafts (donor age ≥ 60 years) were analyzed by Cox hazards models, donor risk index (DRI) and organ patient index (OPI). Recipient's age did not affect on graft survival regardless of donor age. Advanced aged grafts had significant inferior survival compared to younger aged grafts regardless of MELD score ( P < 0.0001). Risk factors of HCV patients receiving advanced aged grafts included donation after cardiac death (DCD, HR: 1.69) and recent hospitalization (HR: 1.43). Advanced aged grafts showed significant difference in graft survival of HCV patients with stratification of DRI and OPI. In conclusion, there was no offsetting effect by use of advanced aged grafts into younger or low MELD patients. Advanced aged grafts, especially DCD, should be judiciously used for HCV patients with low MELD score. [ABSTRACT FROM AUTHOR]

The aim of the present study was to describe the current situation of donation after circulatory death (DCD) in the Council of Europe, through a dedicated survey. Of 27 participating countries, only 10 confirmed any DCD activity, the highest one being described in Belgium, the Netherlands and the United Kingdom (mainly controlled) and France and Spain (mainly uncontrolled). During 2000-2009, as DCD increased, donation after brain death (DBD) decreased about 20% in the three countries with a predominant controlled DCD activity, while DBD had increased in the majority of European countries. The number of organs recovered and transplanted per DCD increased along time, although it remained substantially lower compared with DBD. During 2000-2008, 5004 organs were transplanted from DCD (4261 kidneys, 505 livers, 157 lungs and 81 pancreas). Short-term outcomes of 2343 kidney recipients from controlled versus 649 from uncontrolled DCD were analyzed: primary non function occurred in 5% vs. 6.4% ( P = NS) and delayed graft function in 50.2% vs. 75.7% ( P < 0.001). In spite of this, 1 year graft survival was 85.9% vs. 88.9% ( P = 0.04), respectively. DCD is increasingly accepted in Europe but still limited to a few countries. Controlled DCD might negatively impact DBD activity. The degree of utilization of DCD is lower compared with DBD. Short-term results of DCD are promising with differences between kidney recipients transplanted from controlled versus uncontrolled DCD, an observation to be further analyzed. [ABSTRACT FROM AUTHOR]

The use of lungs from donation after cardiac death (DCD) donors is one of the strategies to increase the donor pool. The aim of this study was to assess the surfactant alterations in DCD donor lungs. Pigs were sacrificed and left untouched for 1 (DCD1), 2 (DCD2) and 3 (DCD3) h. Lungs were then topically cooled with saline for 1, 2 or 3 h to reach a total ischemic time of 4 h. Heart-beating donors (HBD) served as control group. Bronchoalveolar lavage (BAL) samples were assessed for protein levels and surfactant function. Left lungs were prepared for ex-vivo evaluation. Pulmonary vascular resistance (PVR), oxygenation, airway pressure (AWP) and wet-to-dry weight ratio were significantly different between HBD and DCD3 groups ( P < 0.05). BAL protein levels were statistically higher in DCD3 compared with HBD group ( P < 0.05). Surface tension and surface tension measured at minimal bubble diameter (adsorption) were lower in HBD compared with DCD groups ( P < 0.05). Adsorption was also lower in DCD1 compared with DCD2 ( P < 0.05). Adsorption and surface tension were correlated with oxygenation and AWP ( P < 0.05). This study has shown that lung function deteriorates with increasing warm ischemic time intervals. BAL protein, surface tension, adsorption, peak AWP and PVR increase significantly after 2 h of warm ischemia together with a significant reduction of the ratio PaO/FiO. [ABSTRACT FROM AUTHOR]

A clinical score to identify kidneys from donors after cardiac death (DCD) with a high risk of dysfunction following transplantation could be a useful tool to guide the introduction of new algorithms for the preservation of these organs and improve their outcome after transplantation. We investigated whether the deceased donor score (DDS) system could identify DCD kidneys with higher risk of early post-transplant dysfunction. The DDS was validated in a cohort of 168 kidney transplants from donors after brain death (DBD) and then applied to a cohort of 56 kidney transplants from DCD. In the DBD cohort, the DDS grade predicted the incidence of delayed graft function (DGF) and levels of serum creatinine at 3 and 12 months post-transplant. Similarly, in the DCD cohort, the DDS grade correlated with DGF and also predicted the levels of serum creatinine at 3 and 12 months. Interestingly, the DDS identified a subgroup of marginal DCD kidneys in which minimization of cold ischemia time produced better early clinical outcome. These results highlight the impact of early interventions on clinical outcome of marginal DCD kidneys and open the possibility of using the DDS to identify those kidneys that may benefit most from therapeutic interventions before transplantation. [ABSTRACT FROM AUTHOR]

As a result of the ever widening disparity between organ supply and demand, a resurgence of interest has occurred in kidney recovery from donation after cardiac death (DCD) donors. New techniques of in situ extracorporeal support offer the potential to reduce warm ischemic injury and optimize donor management prior to organ recovery. In addition, preliminary outcomes using kidneys from selected deceased donors with rising serum creatinine levels have been promising. However, contraindications to successful organ donation and transplantation may include the presence of abdominal compartment syndrome, generalized bowel infarction, refractory shock with profound metabolic and lactic acidosis, and acute anuric renal failure, particularly in the setting of DCD. We report herein the successful recovery and transplantation of kidneys from an unstable donor with the above constellation of conditions in the setting of extracorporeal support after declaration of death by asystole. [ABSTRACT FROM AUTHOR]

Emergency liver transplantation is a life-saving procedure in selected subset of children with acute liver failure (ALF), when most recipients receive a segmental graft from a living or heart-beating deceased donor. The increased use of full-liver grafts from donors after cardiac death (DCD) has had a beneficial impact on elective liver transplantation in adults. These grafts however are more susceptible to poor initial function, and most centres are reluctant to consider their use as segmental grafts, let alone in the situation of ALF where good initial function is imperative. In this short article, we describe the use and successful outcome in two children aged 6 weeks and 6 years with acute liver failure who received reduced-size DCD liver grafts. [ABSTRACT FROM AUTHOR]