Non-heart-beating donors: experience from the Hospital Clinico of Madrid

Non-heart-beating donors (NHBD) have received attention in the last few years as an alternative source to increase the pool of kidney donors. The majority of reports focus on NHBD from controlled donors, i.e. patients who die in hospital. This report focuses on our experience using uncontrolled NHBD, i.e. patients who die outside of hospital and are transported to hospital for organ donation. We evaluated 188 renal transplantations performed in two periods 1989-1992 and 1995-2000. As to the latter period, renal transplantations from NHBD were compared to those from 345 heart-beating donor (HBD). Graft survival at 7 years shows a better tendency in NHBD group, with no statistical significance. When patients over 60 years of age were excluded from the group of patients receiving HBD kidneys, results were the same. At 2 years renal function post-transplantation was better in NHBD organs, as evaluated by serum creatinine and creatinine clearance, while after 2 years it was similar. The incidence of acute renal rejection was lower in NHBD; however, delayed graft function, as expected, was more prevalent in NHBD, although interestingly it did not influence long-term survival. In conclusion NHBD from deaths outside the hospital may be a good source of donor kidneys and also a way to successfully increase the pool for organ transplantation.     

Renal transplantation from non-heart beating donors: a promising alternative to enlarge the donor pool

The aim of this study was to compare the survival and midterm function of kidneys from non-heart beating donors (NHBD) with those of kidneys from heart beating donors (HBD). From 1989 to 1998, 144 kidneys were procured from NHBD at the Hospital Clínico San Carlos in Madrid, of which 95 were transplanted. The kidney grafts were maintained from the moment of the diagnosis of cardiac arrest until the time of procurement by cardiopulmonary bypass. There was no significant difference in renal function and the number of rejection episodes between the NHBD and HBD transplants. The NHBD kidneys showed a 5.73-fold increase in the incidence of delayed graft function (adjusted relative risk 95% confidence interval, 2.82 to 11.62). One- and five-year survival rates for NHBD grafts were 84.6 and 82.7%, respectively, compared with 87.5 and 83.9% for HBD (P = 0.5767). Cox analysis showed that the predictive factors for worse NHBD graft survival were type of NHBD donor and the occurrence of corticoresistant rejection. Ninety of the NHBD organs were procured from subjects suffering irreversible cardiac arrest on the street who were transferred to our center for the sole purpose of donation. Fifty-four of these kidneys were transplanted and all showed primary function. When a strict protocol is adhered to, the outcome of renal transplant from NHBD compares well with that from HBD. It is believed that the high number of organs obtained from subjects undergoing irreversible cardiac arrest on the street might encourage the adoption of new criteria for the management of this type of pathology with the ultimate goal of kidney donation.     

The non-heart-beating donor: Bridging the gap to the future

Renal grafts from NHBDs result in long-term function that does not compromise current clinical standards and therefore make the NHBD a viable way to expand the donor pool. Several programs around the world are beginning to use NHBD livers in clinical transplantation; thus, there is certain to be a surge of reports appearing in the literature in the near future. It appears from available data to date that NHBD livers retrieved in a controlled fashion from category 3 donors may offer a safe source for more organs. Further research and clinical experience with NHBD transplantation for both kidney and liver should help define reproducible and acceptable methods. However, until an alternative source of organs becomes available, the NHBD represents an increasingly important means to alleviate the growing demand for transplant organs.     

Retrieving organs from non-heart-beating organ donors: a review of medical and ethical issues

PURPOSE: The increasing gap between numbers of individuals awaiting organ replacement surgery and the supply of organs available for transplant underpins attempts to increase the number of organs available. One practice, used in other countries, is the recovery of organs from non-heart-beating organ donors (NHBD). The purpose of this review is to discuss ethical issues surrounding the use of organs from these donors. SOURCE: Narrative review from selected Medline references, and other published reports. Principal findings: NHBD protocols have been established in many countries including the United States. Despite numerous publications, and extensive debate in the literature, significant ethical issues remain unresolved in the retrieval of organs from donors that have died from cessation of cardiac activity. The ethical concerns primarily arise in the determination of death, the tension between the time constraints on recovering organs viable for transplantation, and procedures to enhance organ viability. Despite a concerted effort in the United States, less than half of the organ procurement organizations have NHBD protocols. CONCLUSION: Canadian centres can learn from the difficulties encountered in other centres that have developed NHBD protocols. A moratorium on Canadian NHBD protocols should be considered until a National consensus reflecting Canadian values has been undertaken.     

Non-heart-beating donors from the streets: an increasing donor pool source

BACKGROUND: Non-heart-beating donors have become a source for organ donation, especially kidneys. The emergency room and the critical care unit are the two sources for this kind of donor. Three years ago, our hospital began a policy of obtaining organs and tissues successfully from subjects who died in the streets. METHODS: We consider as potential organ donors people who die out-of-hospital, are less than 50 years old, with less than 15 min of asystolia without cardiac massage, with a known etiology of death, and without general contraindications for donating. After death diagnosis, the cadaver is taken to the hospital where an emergency room doctor certifies the death. Afterward, the cadaver is transferred to the operating room where a cardiopulmonary bypass is performed to preserve the organs while the legal aspects of donation go on. RESULTS: Up to now, 111 cadavers have been taken as non-heart-beating donors; 53 of them have been actual donors. The average time before arrival to the hospital was 68+/-2.64 min, and the average interval between cardiac arrest and the beginning of cardiopulmonary bypass was 111.33+/-7.09 min. We have obtained 105 kidneys, 12 livers, 84 corneas, and 31 pancreata for islets isolation as well as 49 long bones. Seventy-two kidneys were transplanted, with a probability of survival of 83% at 36 months. CONCLUSIONS: Our experience indicates that it is possible to obtain organs for transplant from donors who die in the streets and are brought to the hospital under strict selection criteria.     

Why did it take so long to start a non-heart-beating donor program in Belgium?

The first cadaver kidney transplant, performed in June 1963 in Belgium, was from a heart beating donor (HBD). It was the first ever in the world. Since that period, almost all cadaver organs were procured from brain death donors. When the Belgian law on organ donation and transplantation was published on February 1987, with its opting-out principle, no emphasis was placed on procuring organs after cardiac death. Based on the Maastricht experience, in the early nineties, the transplant community interpellated the National Belgian Council of Physicians to facilitate organ procurement in Non-Heart-Beating Donors (NHBD) following the law. But, the transplant community had to wait for the impulse of the first International Congress on NHBD in 1995,where the 4 categories of Maastricht NHBD were defined. It also published 12 Statements and Recommendations which were eventually approved by the European Council. Then all local Ethical Committees received queries for approving local NHBD programs. Almost all centres requested viability testing assessment of the NHBD organ prior to implantation, and proposed the introduction of machine perfusion technology. Finally, all centres joined their efforts and made a collaborative agreement with Organ Recovery Systems for a 24/7 machine perfusion service from a central laboratory. During a three year period (2003-2005), 46 NHBD kidneys were recovered. Among these kidneys, 32 were perfused in the Organ Recovery Systems central laboratory. The Delayed Graft Function (DGF) rate for these perfused kidneys was 25%. Only one graft was lost in this subgroup. Livers, pancreases (for islet preparation) and lungs (for experimental ex-vivo evaluation) were also recovered from these non-heart-beating donors.     

A comparison of the results of renal transplantation from non-heart-beating, conventional cadaveric, and living donors

BACKGROUND: In an attempt to address the shortage of conventional kidney donors, a non-heart-beating donor (NHBD) organ retrieval program has been established. We compared the results of kidney transplants from NHBDs (N = 77) with those from heart-beating cadaveric (HBD; N = 224) and living donors (LD; N = 49), performed in the same eight-year period. METHODS: Patients dying after failed attempts at resuscitation in the accident department or after intracerebral hemorrhage/anoxia were considered as potential NHBDs. After death, in situ kidney perfusion and cooling were achieved using an intra-aortic catheter inserted via a femoral artery cut down. Kidney retrieval and transplant operations were performed using standard techniques. RESULTS: The median (range) warm ischemic time for NHBD kidneys was 25 minutes (5 to 53 min). The initial function rates for NHBD, HBD, and LD transplants were 6.5, 76.3, and 93%, respectively. Primary nonfunction occurred in 5 of 75 evaluable NHBD transplants (7%) compared with only 6 out of 224 (2.7%) HBD and 1 out of 49 (2%) LD transplants (P = NS). Eighty-four percent of NHBD kidney recipients required postoperative dialysis for a median of 19 days. The mean (SD) serum creatinine at 12 months was 179 (73) micromol/L in NHBD kidneys compared with 152 (57) micromol/L for HBD kidneys and 138 (44) micromol/L for LD kidneys. The actuarial five-year graft survival rates for NHBD, HBD, and LD transplants were 79, 75, and 78%, respectively. During the period under study, NHBD organs accounted for 22% of the total renal transplant program. CONCLUSIONS: Despite being associated with poor initial graft function, the long-term allograft survival of NHBD kidneys does not differ significantly from the results of HBD and LD transplants.     

Liver transplantation from non-heart-beating donors: current status and future prospects.

Liver transplantation is the treatment of choice for many patients with acute and chronic liver failure, but its application is limited by a shortage of donor organs. Donor organ shortage is the principal cause of increasing waiting lists, and a number of patients die while awaiting transplantation. Non-heart-beating donor (NHBD) livers are a potential means of expanding the donor pool. This is not a new concept. Prior to the recognition of brainstem death, organs were retrieved from deceased donors only after cardiac arrest. Given the preservation techniques available at that time, this restricted the use of extrarenal organs for transplantation. In conclusion, after establishment of brain death criteria, deceased donor organs were almost exclusively from heart-beating donors (HBDs). To increase organ availability, there is now a resurgence of interest in NHBD liver transplantation. This review explores the basis for this and considers some of the published results.     

A case-control comparison of the results of renal transplantation from heart-beating and non-heart-beating donors.

INTRODUCTION: The decline in heart-beating brainstem dead organ donors has necessitated the search for other organ sources. In the field of renal transplantation one alternative source currently available, but little used, is that of kidneys from non-heart-beating donors (NHBD). Reticence to use NHBD kidneys is in part due to concerns over the effect that warm ischemic may have subsequent graft function. Presented here are the results of the NHBD renal transplants at the Leicester transplant unit, and compared with matched heart-beating donor transplants as a case control analysis. METHODS: In order to analyze any differences in graft performance between the two organ sources, the confounding effect of other variables known to influence the outcome of renal transplantation was minimized by matching NHBD and HBD transplants for the following criteria: donor age and sex, first or re-transplant, anastomosis and cold times, tissue match and PRA sensitisation. Transplant performance was assessed primarily by graft survival, the statistical evaluation of which was by log rank analysis of Kaplan-Meier curves. RESULTS: 72 NHBD and 192 HBD transplants were performed over an eight year period. Of the 192 HBD transplants, 105 matched one or more of the NHBD by the criteria outlined above, and thus constituted the control group for comparison. There was no significant difference in overall graft survival between the two groups. The 5 year survival for the NHBD was 73% compared with 65% for HBD kidneys. When death with a functioning graft is treated as censored data, then these figures become 75% and 81% respectively, again without statistical significance. CONCLUSION: NHBD kidneys are a valuable additional source of organs for transplantation, with long-term survival, comparable to transplants from HBD.     

Long-term renal function in kidneys from non-heart-beating donors: A single-center experience

BACKGROUND: Cadaveric kidneys from brain-stem-dead donors continue to be limited because the number of donors has reached a plateau. Wide recruitment of non-heart-beating donors (NHBD) could significantly increase the donor pool. NHBD renal transplants are underused because of the concern of poor quality graft function from such donors. In response to this perception, we reviewed 46 NHBD renal transplants performed in our center since 1998. METHODS: All NHBD kidneys were machine-perfused using the Newcastle continuous-hypothermic pulsatile preservation system before transplantation. A control heart-beating-donor (HBD) group was taken as the next consecutive HBD renal transplant to the NHBD transplant. The outcome and quality of function of the groups of renal transplants were analyzed for short-term and long-term performance. RESULTS: The renal transplant patients were matched for donor and recipient factors. Survival rates for allografts and patients were similar for 1 to 3 years. There was an increased incidence of delayed graft function in the NHBD renal transplants in the perioperative period. The creatinine clearance was 22.8+/-2.3 mL/minute for NHBD patients and 44.4+/-2.9 mL/minute for HBD patients at the time of discharge from hospital. This difference equalized after 3 months and the creatinine clearance for NHBD was 44.2+/-2.4 mL/minute and for HBD 49.2+/-3.4 mL/minute. CONCLUSIONS: Our results for NHBD renal transplants confirm that such grafts suffer primary warm ischemic injury, shown by the increased incidence of acute tubular necrosis and consequent delayed graft function. This produced poor renal function at the time of hospital discharge. After 3 months, the renal function of NHBD cases improved to the level seen in HBD patients.     

Ethical and legal issues in non-heart-beating organ donation

Procurement of kidneys and livers from non-heart-beating donors (NHBD) raises ethical and legal issues that need to be considered before wider use of these donors is undertaken. Although NHBDs were used in kidney transplantation as early as the 1960s, retrieval of these organs is not universally accepted today. From a medical point of view, these organs were considered "marginal" because the majority showed delayed or impaired function early after implantation. Legal problems relate to determination of death on cardiopulmonary criteria, the issue of valid consent, and the use of preservation measures. Among ethical issues involved are observance of the dead-donor rule, decisions with respect to resuscitation and withdrawal of life-sustaining treatment, respect for the dying patient and the dead body, and proper guidance of the family. In The Netherlands NHB donation was pioneered by the Maastricht Centre as early as 1981. Today, all seven transplant centers procure and transplant these organs, and NHBDs have become an important source of transplantable kidneys and livers. Recent legislation in The Netherlands also supports NHB donation by allowing the use of organ-preserving measures, even in the absence of family consent. As a result, one of every three kidneys transplanted in The Netherlands in 2004 derives from a NHBD. This article explores Dutch NHBD practice, protocols, and results and compares these data internationally.     

Ethical and legal issues in non-heart-beating organ donation

Procurement of kidneys and livers from non-heart-beating donors (NHBDs) raises ethical and legal issues that need to be considered carefully before wider use of these donors. Although NHBDs were used in kidney transplantation as early as the 1960s, retrieval of these organs is by no means universally accepted today. From a medical point of view, these organs have long been considered "marginal" because the majority show delayed or impaired graft function. Legal problems include determination of death by cardiopulmonary criteria, the issue of proper consent, and the use of organ preservation measures. Among ethical issues raised are the observance of the Dead-donor Rule, the decision-making surrounding resuscitation, the withdrawal of life-support, the respect for a dying patient and the dead body, as well as proper information to and guidance for the family. In the Netherlands NHB donation was pioneered in the Maastricht Medical Center in 1980s. Today, all seven transplant centers retrieve and transplant organs from these donors, and NHBDs have become an important source of transplantable kidneys and livers. Recent legislation in the Netherlands also supports the use of NHBDs by making possible the use of organ preservation measures after circulatory arrest, even in the absence of family consent. As a result, one of every three kidneys transplanted in the Netherlands in 2004 was obtained from a NHBD. In this study, Dutch NHBD protocols, practice, and results are analyzed and compared with international practices.     

Prélèvements sur « donneurs décédés après arrêt cardiaque » : l’expérience du Samu de la Seine-Saint-Denis

The use of non-heart-beating donors (NHBD) could help shorten the list of patients who are waiting for a kidney transplant. The aim of this study was to evaluate efficiency of prehospital management of non-heart-beating donors in Seine-Saint-Denis area. We performed a retrospective cohort study of non-heart-beating donor managed by prehospital medical team of Samu 93 from February 2007 to January 2008. There were 28 non-heart-beating donors included consecutively. Twenty-five NHBD (89%) were canuled by Gillot probe within 150 min from patient collapse. Fourteen NHBD were harvested and 17 kidneys were transplanted. Six-month survival rate for NHBD grafts was 94%. In the same time, eight brain dead donors were managed by Samu 93 and were harvested leading to transplant 16 kidneys. Finally, 50% of overall kidney transplant activity in Seine-Saint-Denis was provided by NHBD grafts.     

Liver transplantation from an uncontrolled non-heart-beating donor maintained on extracorporeal membrane oxygenation

Liver transplantation, a definitive treatment for end-stage liver disease, has achieved excellent results. However, potential recipients on the waiting list outnumber donors. To expand the donor pool, marginal grafts from older donors, steatotic livers, and non-heart-beating liver donors (NHBD) have been used for transplantation. Reducing the warm ischemia time of NHBD is the critical factor in organs preservation. Liver transplantation using grafts from NHBD have been reported to display a high incidence of primary graft nonfunction and biliary complications. The authors report a liver graft donor who was maintained on extracorporeal membrane oxygenation (ECMO) after successful cardiopulmonary resuscitation. Core body temperature was 5 degrees C. Procurement of the liver using a rapid flush technique was performed 4 hours after instituting ECMO. Graft function recovered fully after transplantation. In conclusion, ECMO may be used to reduce warm ischemia time in liver grafts obtained from uncontrolled NHBD, thereby increasing graft salvage rates.     

The trouble with kidneys derived from the non heart-beating donor: a single center 10-year experience

BACKGROUND: The demand for renal transplantation has increasingly outstripped the supply of donor organs especially over the past 10 years. Although related and unrelated live donation is being promoted as one option for increasing the donor pool, it is unlikely that this will in itself be able to bridge the gap. Non-heart beating donors (NHBD) can provide an alternative supply of organs, which should substantially increase the donor pool. METHODS: In Newcastle, NHBD kidneys have been used for transplantation for a period of 10 years. In the early period (1988-1993) excellent results were obtained (90.5% success); however, these donors were controlled NHBD, Maastricht category III. In the second phase (1994-1998) increasing numbers of donors were obtained from the Accident and Emergency Department unit. These were failed resuscitation for cardiac arrest (category II). The rates of success in this period were poor (45.5% success) and the program was halted. The third phase of the program used machine perfusion of the kidneys and glutathione S transferase enzyme analysis to assess viability. RESULTS: Using such approaches renal transplants from largely category II donors produced a success rate of 92.3% which was significantly better than the phase II period of the program (P=0.023, Fisher two-tail test). CONCLUSION: Machine perfusion and viability assessment of NHB kidneys in phase III of the program has increased our donor pool as well as improved the graft survival. This is particularly relevant for the use of the category II NHB donor where the incidence of primary nonfunction was high, illustrated by phase II where machine perfusion/viability assessment was not used.     

Anti-vimentin antibody detection in recipients of heart-beating and non-heart beating donor kidneys

Alternative donor sources include non-heart-beating donors (NHBDs). There donors have been exposed to significant ischemia, so that it is common to utilize machine perfusion to either improve the organs or at least assess their viability. Both prolonged warm ischemia and machine perfusion can potentially damage the vascular endothelium, thereby exposing vimentin to antigenic recognition. The aim of this study was to determine whether anti-vimentin antibodies could be detected in the blood of renal transplant recipients at specific time points after transplant and whether they could be related to the donor source. Fifty-one recipients of NHBD kidneys were compared to 52 recipients of heart-beating donor (HBD) kidneys. All recipients had similar anti-vimentin levels pretransplant. However, at 1 month those kidneys from Maastricht category II NHB donors showed significantly higher levels. At 6 months both Maastricht category II and category III NHB donor recipients displayed significantly higher levels than recipients of HBD kidneys.     

Kidney transplantation from non–heart-beating donors: a Spanish view

All over the world, the waiting list and waiting time for transplant will inevitably become longer as the demand for kidneys continues to exceed the supply. Although there is a need to extend the use of brain-dead donors with heartbeats, there is still room for additional sources of organs, and this has prompted the use of the non–heart-beating donor (NHBD). The viability of the kidney from the NHBD, which is invariably subjected to a period of warm ischemia, is the most crucial factor for transplant outcome. However, in our experience, by applying a strict warm ischemia protocol and carefully managing the donor, the percentage of non-functioning grafts is low. The results presented in terms of graft survival and mid-term renal function with NHBD are encouraging and comparable to those related to the use of kidneys from young heart-beating donors. Based on these data, NHBDs should not be considered suboptimal, since other marginal donors such as elderly donors, for instance, have resulted in worse outcomes. In our experience, the NHBD kidney is an extremely useful contribution to the donor pool, and its use has allowed us to increase the total number of kidney transplants performed and, as consequence, to decrease the waiting list.     

Non-heart-beating donation: ten evidence-based ethical recommendations

The renewed interest in non-heart-beating donation (NHBD) in the past decade has resulted in renewed examination of the concept and meaning of death; of the nature of consent; of the propriety of interventions for the benefit of the recipient and not the donor; of potential conflicts of interest; and of defining futility. There is recognition of the need to maintain public trust. Recent experience indicates that NHBD could make a significant contribution to total renal transplant numbers. While there is graft dysfunction in the short term, the long-term results are comparable to those of transplants from heart-beating kidney donors, and in one series, even to living donors. The University of Zurich's experience indicates that waiting 10 minutes after asystole and not using in situ cooling do not adversely affect long-term outcomes. NHBD under ideal conditions could be extended to other organs such as the liver and pancreas. Ethical concerns are not insurmountable and can be minimized if cooling procedures and the use of drugs, such as heparin and phentolamine, is minimized, and if a period of 10 minutes is allowed to elapse after asystole before death is declared. We make a series of evidence-based recommendations for protocol development.     

Controlled donation after cardiac death: a European perspective

Terminally ill patients who do not meet brain death criteria and die of cardiac arrest after withdrawal of life support may be considered as potential organ donors: such donors are referred to as controlled donors after cardiac death (DCD). Controlled DCD donors are increasingly being used in Northern Europe and the United States in an effort to expand the donor pool. Ethical concerns regarding the diagnosis of death based on cardiopulmonary rather than neurological criteria have largely been resolved over the past decade. Follow-up studies of recipients by several transplant centers have shown that functioning controlled DCD kidneys are equivalent to kidneys from conventional brain-dead donors with respect to long-term prognosis. Concerns about long-term repercussions for the higher incidence of delayed graft function with DCD kidneys are not supported by the current evidence. The donor pool may be further expanded by transplanting selected kidneys from older DCD, in particular for the increasing population of older kidney transplant candidates. Successful transplantation of these delicate organs is possible when donors and recipients are carefully managed by well-trained, motivated, and effectively collaborating transplant personnel.     

Non-heart-beating Donors: Renewed Source of Organs for Renal Transplantation during the Twenty-first Century

Abstract The growing demand of organs for renal transplantation makes it necessary to explore alternative routes for kidney donation. Non-heart-beating donors (NHBDs) are a valuable source of cadaveric organs and have been the subject of renewed interest in recent years. In addition to difficulties with legal and ethical acceptability, there are concerns regarding medical safety. The current NHBD program at St. George’s Hospital in London was started in March 1995. A total of 41 kidneys from category I to III donors (according to the Maastricht classification) were retrieved from the Accident and Emergency Department and several intensive care units and were subsequently transplanted. Cold in situ perfusion was commenced via femoral access or rapid aortic cannulation in most donors. Of these transplanted kidneys, 35 started functioning within 4 weeks. The permanent nonfunction (PNF) rate was 14.6% (6/41) and the estimated 1-year graft survival 82.9% (34/41). The delayed graft function (DGF) rate (defined as recipients requiring posttransplant dialysis for 3 days or longer) was 80.0% (28/35). The median serum creatinine concentration in patients with a functioning graft at 1 year was 165 μmol/L. NHBD kidneys have contributed about 15% to the regional transplant activity over the last 6 years, even though not all potential NHBDs were used. It was possible to lower the PNF rate with strict donor selection criteria and more recently with pulsatile machine perfusion. NHBDs represent a valuable source for kidneys and can extend the donor pool. More experience is currently needed to continue to lower PNF rates reliably before promoting more widespread use of NHBDs for renal transplantation.