A Multicenter Study on Long‐Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death

The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one‐to‐one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long‐term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool.     

Impact of a National Controlled Donation After Circulatory Death (DCD) Program on Organ Donation in the United Kingdom: A 10‐Year Study

Organ transplantation is the most successful treatment for some forms of organ failure, yet a lack of organs means many die on the waiting list. In the United Kingdom, the Organ Donation Taskforce was set up to identify barriers to organ donation and in 2008 released its first report (Organ Donation Taskforce Report; ODTR). This study assesses the success since the ODTR and examines the impact of the United Kingdom's controlled donation after circulatory death (DCD) program and the controversies surrounding it. There were 12 864 intended donation after brain death (DBD) or DCD donors from April 2004 to March 2014. When the 5 years preceding the ODTR was compared to the 5 years following, intended DCD donors increased 292% (1187 to 4652), and intended DBD donors increased 11% (3327 to 3698). Organs retrieved per intended DBD donor remained static (3.30 to 3.26), whereas there was a decrease in DCD (1.54 to 0.99) due to a large rise in donors who did not proceed to donation (325 to 2464). The majority of DCD donors who proceeded did so within 30 min from time of withdrawal. Our study suggests further work on converting eligible referrals to organ donation and exploring methods of converting DCD to DBD donors.     

Improving the Outcomes of Organs Obtained From Controlled Donation After Circulatory Death Donors Using Abdominal Normothermic Regional Perfusion

The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD (cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients’ outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty‐seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty‐seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1‐year death‐censored kidney survival was 91%, and delayed graft function rate was 27%. The 1‐year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved.     

Donation After Circulatory Determination of Death Lung Transplantation for Pulmonary Arterial Hypertension: Passing the Toughest Test

Lung transplantation (LTx) is a therapeutic option for severe pulmonary arterial hypertension (PAH) patients failing optimal medical therapy. The use of donation after circulatory determination of death (DCDD) donor lungs for PAH LTx has rarely been reported, primarily reflecting concerns that DCDD lungs represent extended criteria donors, at risk of morbidity and mortality. A retrospective study of all Alfred Hospital DCDD and DNDD (donation after neurologic determination of death) PAH LTx was undertaken. Protocolized fluid/inotrope/ventilator and extracorporeal membrane oxygenation (ECMO) strategies were utilized. Since our first DCDD LTx in 2006, 512 LTx have been performed. Of 31 PAH recipients, 11 received DCDD lungs (11% of DCDD LTx) and 20 received DNDD lungs (5% of DNDD LTx) (p = 0.04). Only one PAH patient died on the LTx waiting list. Peri‐LTx ECMO was utilized in 3/11 (27%) DCDD and 6/20 (30%) DNDD PAH LTx (p = 0.68). Primary graft dysfunction, intensive care, and overall stay were the same in both groups. Survival at 1 and 8 years was 100% and 80% for DCDD versus 100% and 70% for DNDD LTx (p = 0.88), respectively. In conclusion, excellent results can be achieved for PAH LTx. DCDD donor lungs are not extended lungs per se having passed the toughest test.     

In Situ Normothermic Regional Perfusion for Controlled Donation After Circulatory Death—The United Kingdom Experience

Organs recovered from donors after circulatory death (DCD) suffer warm ischemia before cold storage which may prejudice graft survival and result in a greater risk of complications after transplant. A period of normothermic regional perfusion (NRP) in the donor may reverse these effects and improve organ function. Twenty‐one NRP retrievals from Maastricht category III DCD donors were performed at three UK centers. NRP was established postasystole via aortic and caval cannulation and maintained for 2 h. Blood gases and biochemistry were monitored to assess organ function. Sixty‐three organs were recovered. Forty‐nine patients were transplanted. The median time from asystole to NRP was 16 min (range 10–23 min). Thirty‐two patients received a kidney transplant. The median cold ischemia time was 12 h 30 min (range 5 h 25 min–18 h 22 min). The median creatinine at 3 and 12 months was 107 µmol/L (range 72–222) and 121 µmol/L (range 63–157), respectively. Thirteen (40%) recipients had delayed graft function and four lost the grafts. Eleven patients received a liver transplant. The first week median peak ALT was 389 IU/L (range 58–3043). One patient had primary nonfunction. Two combined pancreas–kidney transplants, one islet transplant and three double lung transplants were performed with primary function. NRP in DCD donation facilitates organ recovery and may improve short‐term outcomes.     

Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002–2003 and 2011–2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney‐only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p < 0.0001), listed patients at our center waited less time for transplantation (645 vs. 1045 days; p < 0.0001), and our center had higher transplantation rates and lower numbers of waiting list deaths. This was most apparent for older patients (aged >65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death‐censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients.     

A Comparison of Request Process and Outcomes in Donation After Cardiac Death and Donation After Brain Death: Results From a National Study

Available literature points to healthcare providers’ discomfort with donation after cardiac death (DCD) and their perception of public reluctance toward the procedure. Using a national sample, we report on the communication content of actual DCD and donation after brain death (DBD) approaches by organ procurement organization (OPO) requesters and compare family decision makers’ (FDMs’) experiences of both modalities. We recruited 1601 FDMs using a validated protocol; 347 (21.7%) were of potential DCD donors. Semistructured telephone interviews yielded FDMs’ sociodemographic data, donation attitudes, assessment of approach, final outcomes, and substantiating reasons. Initial analysis consisted of bivariate analyses. Multilevel mixture models compared groups representing authorization outcome and DCD/DBD status. No significant differences in family authorization were found between DCD and DBD cases. Statistically significant associations were found between sociodemographic characteristics and authorization, with white FDMs more likely to authorize DCD or DBD than black FDMs. FDMs of both modalities had similar evaluations of requester skills, topics discussed, satisfaction, and refusal reasons. The findings suggest that the DCD/DBD distinction may not be notable to families. We recommend the use of similar approach strategies and communication skills and the development of education campaigns about the public's acceptance of DCD.     

The Use of Donation After Cardiac Death Allografts Does Not Increase Recurrence of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) recurrence in patients undergoing liver transplantation (LT) with donation after brain death (DBD) and donation after cardiac death (DCD) allografts has not previously been investigated. Rates and patterns of HCC recurrences were investigated in patients undergoing DBD (N = 1633) and DCD (N = 243) LT between 2003 and 2012. LT for HCC was identified in 397 patients (340 DBD and 57 DCD). No difference in tumor number (p = 0.26), tumor volume (p = 0.34) and serum alphafetoprotein (AFP) (p = 0.47) was seen between the groups. HCC recurrence was identified in 41 (12.1%) patients in the DBD group and 7 (12.3%) patients in the DCD group. There was no difference in recurrence‐free survival (p = 0.29) or cumulative incidence of HCC recurrence (p = 0.91) between the groups. Liver allograft was the first site of recurrence in 22 (65%) patients in the DBD group and two (37%) patients in the DCD group (p = 0.39). LT for HCC with DBD and DCD allografts demonstrate no difference in the rate of HCC recurrence. Previously published differences in survival demonstrated between recipients with HCC receiving DBD and DCD allografts despite statistical adjustment can likely be explained by practice patterns not captured by variables contained in the SRTR database.     

Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy

Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1‐ and 3‐year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re‐transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic‐type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT.     

Organ Donation After Euthanasia: A Dutch Practical Manual

Many physicians and patients do not realize that it is legally and medically possible to donate organs after euthanasia. The combination of euthanasia and organ donation is not a common practice, often limited by the patient's underlying pathology, but nevertheless has been performed >40 times in Belgium and the Netherlands since 2005. In anticipation of patients' requests for organ donation after euthanasia and contributing to awareness of the possibility of this combination among general practitioners and medical specialists, the Maastricht University Medical Center and the Erasmus University Medical Center Rotterdam have developed a multidisciplinary practical manual in which the organizational steps regarding this combined procedure are described and explained. This practical manual lists the various criteria to fulfill and the rules and regulations the different stakeholders involved need to comply with to meet all due diligence requirements. Although an ethicist was involved in writing this paper, this report is not specifically meant to comprehensively address the ethical issues surrounding the topic. This paper is focused on the operational aspects of the protocol.     

Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation

Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30‐kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24‐h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short‐term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.     

Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death

The resuscitation of hearts donated after circulatory death (DCD) is gaining widespread interest; however, the method of initial reperfusion (IR) that optimizes functional recovery has not been elucidated. We sought to determine the impact of IR temperature on the recovery of myocardial function during ex vivo heart perfusion (EVHP). Eighteen pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15‐min standoff period was observed and then hearts were reperfused for 3 min at three different temperatures (5°C; N = 6, 25°C; N = 5, and 35°C; N = 7) with a normokalemic adenosine–lidocaine crystalloid cardioplegia. Hearts then underwent normothermic EVHP for 6 h during which time myocardial function was assessed in a working mode. We found that IR coronary blood flow differed among treatment groups (5°C = 483 ± 53, 25°C = 722 ± 60, 35°C = 906 ± 36 mL/min, p < 0.01). During subsequent EVHP, less myocardial injury (troponin I: 5°C = 91 ± 6, 25°C = 64 ± 16, 35°C = 57 ± 7 pg/mL/g, p = 0.04) and greater preservation of endothelial cell integrity (electron microscopy injury score: 5°C = 3.2 ± 0.5, 25°C = 1.8 ± 0.2, 35°C = 1.7 ± 0.3, p = 0.01) were evident in hearts initially reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of myocardial function (cardiac index: 5°C = 3.9 ± 0.8, 25°C = 6.2 ± 0.4, 35°C = 6.5 ± 0.6 mL/minute/g, p = 0.03) during EVHP. We conclude that the avoidance of profound hypothermia during IR minimizes injury and improves the functional recovery of DCD hearts.     

Ethical and logistical concerns for establishing NRP‐cDCD heart transplantation in the United States

Controlled heart donation after circulatory determination of death (cDCD) is well established internationally with good outcomes and could be adopted in the United States to increase heart supply if ethical and logistical challenges are comprehensively addressed. The most effective and resource‐efficient method for mitigating warm ischemia after circulatory arrest is normothermic regional perfusion (NRP) in situ. This strategy requires restarting circulation after declaration of death according to circulatory criteria, which appears to challenge the legal circulatory death definition requiring irreversible cessation. Permanent cessation for life‐saving efforts must be achieved to assuage this concern and ligating principal vessels maintains no blood flow to the brain, which ensures natural progression to cessation of brain function. This practice—standard in some countries—raises unique concerns about prioritizing life‐saving efforts, informed authorization from decision‐makers, and the clinician's role in the patient's death. To preserve public trust, medical integrity, and respect for the donor, the donation conversation must not take place until after an un‐coerced decision to withdraw life‐sustaining treatment made in accordance with the patient's treatment goals. The decision‐maker(s) must understand cDCD procedure well enough to provide genuine authorization and the preservation/procurement teams must be kept separate from the clinical care team.