Organ Donors: Heartbeating and Non-heartbeating

The limits of organ donation from heart-beating (HB) donors reached a plateau illustrated by the number of postmortem kidneys for transplantation. Programs such as the European Donor Hospital Education Program (EDHEP) and Donor Action have helped to stop a further decrease in the number instead of an expected increase. For kidneys, heart, liver, and lungs one must also explore the use of marginal donors as a possible additional source. Examples are donors with a horseshoe kidney, those at both ends of the age spectrum, and those with medical contraindication such as diabetes. We have enlarged our kidney donor pool considerably with non-heart-beating(NHB) donors. Because we preserve these kidneys in a preservation machine, we are able to perform viability testing. With glutathione S-transferase (GST) as a measure of tubular damage, we now decide whether to transplant based on GST values. For other organs, NHB donation does not seem to be an option other than for the liver when the warm ischemia time is short.     

Donation after cardiac death has a minimal impact on thoracic organ recovery

BACKGROUND: Our organ procurement organization recently developed an aggressive donation after cardiac death program. Thoracic organs are rarely recovered from non-heart-beating donors. Therefore, there is concern that donation after cardiac death may affect the recovery of thoracic organs from donors not allowed to progress to brain death. OBJECTIVE: To evaluate the potential impact of donation after cardiac death on the recovery of thoracic organs. METHODS: On the assumption that prolongation of care on all cases would result in a diagnosis of brain death. By retrospective chart review, all donations after cardiac death were evaluated for thoracic organ potential using the same standards that were used to evaluate brain-dead donors. RESULTS: During the study period there were 34 of 44 (77%) non-heart-beating donors qualified to donate abdominal organs only. Ten of 44 non-heart-beating donors (24%) qualified to potentially donate thoracic organs; the families of 4 of 10 of these donors insisted on the immediate withdrawal of life support, leaving only 6 donors with thoracic organ potential. All 6 of these donors qualified as potential heart donors and 3 as potential lung donors. CONCLUSIONS: A total of 97 organs were recovered and successfully transplanted from 44 non-heart-beating donors. If all the donors who qualified to donate thoracic organs progressed to brain death and if their thoracic organs were transplantable, then 6 additional hearts and 3 pairs of lungs may have been recovered. These data demonstrate that an aggressive donation after cardiac death program contributes significantly to the organ donor pool, with a minimal impact on potential thoracic organ recovery.     

Non–heart-beating donors (then) and donation after cardiac death (now)

In the 1960s and 1970s, before the acceptance of brain death, donated organs were obtained from non–heart-beating donors. Today, this type of donor is referred to as a donor after cardiac death (DCD). After the acceptance of brain death criteria, most of the organs for transplantation were obtained from heart-beating donors. However, because of the shortage of brain-dead heart-beating donors in the 1980s, Maastricht surgeons started using organs obtained from DCD. Subsequently, they defined 4 different categories of non–heart-beating donors. In the United States, DCD donation has only recently gained widespread use. In this article, we present a historical overview of DCD donation; examine current practices for organ preservation and outcomes for kidney, kidney-pancreas, liver, and lung transplantation performed using organs obtained from DCD donors; and reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing database.     

Multiorgan donation in the Netherlands: limited by consent and policy

The percentage of multiorgan donors (MOD) versus single organ donors of kidneys only (SOD-K) has remained markedly low in the Netherlands compared to the other countries in the Eurotransplant region. This suggests a possible loss of donor organs. We investigated the causes of this persisting low percentage of MOD by studying the reasons for kidney donation only. All kidney donors in the Eurotransplant region in 1992 were studied retrospectively. In order to be able to make a comparison between all countries investigated, non-heart-beating donors and donors older than 55 years were excluded. Medical reasons were the most frequent cause for kidney donation only in the Netherlands, but this was not significantly different from the other countries in the Eurotransplant region. Multiorgan donation in the Netherlands was restricted by upper age limits for heart and liver transplantation and by the consent system.     

The UK National Potential Donor Audit

As part of a series of measures designed to improve organ donation rates in the United Kingdom, a potential donor audit has been established by UK Transplant. The audit will identify the number of patients who could be solid organ donors and will establish the obstacles to donation. Results from the first full year of the audit indicate that the overall relative refusal rate for heart-beating solid organ donation is 41.5%. The age and gender of the potential heart-beating donor has little impact on the relative refusal rate, but relatives of ethnic minority groups are more than twice as likely to deny consent than those of white potential heart-beating donors.     

Transplantation of organs: natural limitations,possible solutions--a UK perspective

While the outcome following organ transplantation in the United Kingdom has never been better, the waiting list has never been longer and the organ shortage is now the most pressing issue. UK Transplant has invested in four initiatives to promote donor and transplant numbers: coordinating the coordinators, establishing donor liaison posts, improving living donor coordination, and encouraging non-heart-beating donation. The Potential Donor Audit to be introduced as soon as possible will clarify the likely maximum number of heart-beating donors. A major review of the legal framework covering donation and transplantation in England and Wales is currently underway. It is hoped that in due course the benefits of these initiatives will be translated into a rise in both donor and transplant numbers.     

Pre-arrest heparinization and ventilation during warm ischemia preserves lung function in non-heart-beating donors

BACKGROUND/PURPOSE: To solve the problem of donor scarcity, many attempts have been made including improved community education, relaxed organ acceptance criteria, increased reliance on single lung transplantation, and the use of partial organ donation. Unfortunately, these efforts have produced only modest increases in lung allograft availability; therefore, the so-called non-heart-beating organ donation must be considered. The aim of this study is to assess the viability of the non-heart-beating donor (NHBD) lung transplant rat model and determine the best strategy to manage the donor before and after cardiac arrest. METHODS: Fifty-five inbred Fischer rats were used as donors and recipients in an isogenic model of left lung transplantation. The rats were divided into 6 groups (n = 5): group I, normal controls without transplant; group II, heart-beating donor controls (HBD); group III, NHBD, no heparin, no ventilation during warm ischemia; group IV, NHBD, heparin, no ventilation; group V, NHBD, no heparin, ventilation; group VI, NHBD, heparin, ventilation. All lungs were stored at 4 degrees C for 4 hours. Animals were killed 24 hours after implantation. Gas exchange, pulmonary artery pressure, compliance, chest x-ray score, and histological score were assessed. RESULTS: Heparinized and ventilated animals during warm ischemia (group VI) had similar performance than those transplanted without warm ischemia time in a scenario of heart-beating donor (group II). Groups III, IV, and V transplanted lungs showed severe damage. CONCLUSIONS: The authors conclude that the rat lung transplantation model is useful to study the phenomena that occur in a setting of transplantation using NHBD and that heparinization and ventilation before cardiac arrest is the best strategy to manage non-heart-beating donors in this model.     

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.     

Evaluation of the Donor After Brain Death and Technique for Organ Procurement

ContextRenal transplantation is the best treatment modality for replacement of lost renal function in patients with end-stage renal disease. Nevertheless, the gap between the number of kidneys available for donation and the number of patients waiting for an organ is increasing due to an increase in the number of patients with renal failure and, simultaneously, a shortage of kidneys for transplant.ObjectiveTo review the policies available for kidney donation.Evidence acquisitionA review of literature was performed to describe the available policies. Rates of donation were compared according to the different policies for several Western countries.Evidence synthesisThe classical donor type is the deceased heart-beating donor after brain death; however, shortage of organs forced the expansion of the criteria for donation. The concepts of expanded criteria donation and donation after circulatory death have been adopted more recently. Scores based on donor characteristics and histology criteria from kidney biopsies are also used to refine the quality of organs used for transplantation. Live donation is still marginal in many countries.ConclusionsThere is an urgent need to increase public awareness of kidney transplantation, to improve strategies to identify new potential donors, and to master the techniques of retrieving and preserving organs. Increasing live donation is also essential to overcome organ shortage.Patient summaryThere is an urgent need to increase public awareness of kidney transplantation, to improve strategies to identify new potential donors, and to master the techniques of retrieving and preserving organs. Increasing live donation is also essential to overcome organ shortage.     

Renal transplantation using non-heart-beating donors: a potential solution to the organ donor shortage in Canada.

INTRODUCTION: There is a chronic shortage of cadaveric organ donors for renal transplantation, which might be solved by the use of non-heart-beating donors (patients who suffer cardiac arrest and whose kidneys are harvested subsequently when irreversible heart and respiratory function occur). We carried out a chart review to determine whether the renal transplantation rate would improve if a non-heart-beating donor program was introduced at a Canadian centre. METHODS: We reviewed the charts of all 1547 patients who died in the emergency department or intensive care unit of the Ottawa Hospital, a tertiary care centre serving 1.2 million people in eastern Ontario, between January 1999 and May 2001. The number of potential non-heart-beating donors was determined by the use of predefined criteria. The number of additional kidneys that could be obtained with a non-heart-beating donor program was estimated and compared to the actual number of kidneys procured from conventional brain-dead donors during the same period. The potential increase in the renal transplantation rate was calculated. RESULTS: There were 83 potential non-heart-beating donors during the 29-month study period. The mean (and standard deviation) age of the donors was 40.6 (13.1) years, and 20% were female. The mean serum creatinine value was 75 (29) micromol/L; 44.6% of donors died secondary to trauma. We estimated that the use of non-heart-beating donors would have provided 14 to 41 additional donors during the study period (12-34 kidneys/yr). The cadaveric renal transplantation rate would have increased between 30% and 87%. CONCLUSION: The cadaveric renal transplantation rate could improve significantly if non-heart-beating donors were used in Canadian hospitals.     

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.     

Improving kidney and live donation rates in Asia: living donation

Organ transplantation started with organs donated by living subjects. Increasing demands brought cadaveric organ donation. The brain-death law, mandatory for this procedure, is prevalent in all countries involved in organ transplantation except Pakistan. Spain is the leading country in cadaveric organ donation (32.5 pmp). Despite the sources of living and cadaveric organs, both heart-beating and non-heart-beating, the gap between the demand and supply has widened. An example is the United States, where the numbers of patients on the waiting list for kidney transplantation have risen from 30,000 in 1988 to more than 116,000 in 2001. This has caused a resurgence in living donors all over the world. These can be related, unrelated, spousal, marginal, or ABO-incompatible donors. Family apprehensions, medical care costs, and nonexistent social security can be barriers to this form of organ donation. Unrelated organ donation can open the doors to commercialism. To make this process more successful, transplantation should be made reachable by all sectors of the population. This is possible when transplantation is taken to the public sector institutions and financed jointly by the government and community. To increase living organ donation especially in Asian countries, which face barriers of low literacy rates, ignorance, and cultural and religious beliefs, more efforts are needed. Public awareness and education play an important role. Appreciation and supporting the donors is necessary and justified. It is a noble act and should be recognized by offering job security, health insurance, and free education for the donor's children.     

Non-heartbeating donation of kidneys for transplantation

There is a persistent shortage of kidneys available for transplantation. In the early 1980s, therefore, we published the concept of non-heartbeating (NHB) donation; that is, procurement of kidneys from donors whose death has been accompanied by irreversible circulatory arrest. NHB donors are generally categorized using four definitions; category III (awaiting cardiac arrest) and category IV (cardiac arrest while braindead)--or 'controlled'--donors are the most suitable for initiating NHB donation programs. Delayed graft function is associated with use of kidneys from such donors, but has no effect on graft survival in the short or long term. Use of kidneys from category I (dead upon arrival at hospital) and category II (unsuccessfully resuscitated), or 'uncontrolled', donors is likewise associated with delayed graft function, but also with an increased risk of primary nonfunction. Viability testing of donated organs from these sources is a prerequisite for transplantation. Machine preservation parameters and enzyme release measurements help to distinguish viable from nonviable kidneys. The proportion of NHB donor kidneys in the total pool of postmortem kidneys differs considerably between countries. In The Netherlands, the proportion is nearly 50%. This figure is markedly higher than that in the US and Canada, where national programs have now been initiated to increase rates of NHB donation. In the future, warm preservation techniques might facilitate better viability testing, thereby increasing NHB donation from category I and II donors and further reducing the shortage of kidneys available for transplantation.     

Kidney transplantation with grafts from non-heart-beating donors

We analyzed the function and outcome of 16 kidney transplants performed in our hospital from non-heart-beating donors who were harvested at other hospitals. The cold ischemia times were longer and the delayed graft function rates higher. However, graft function was no different from that of kidneys from heart-beating donors. This experience has encouraged us to use this type of donor to reduce the transplant waiting list.     

Lung transplantation with uncontrolled non-heart-beating donor. Review

The discrepancy between organ availability and the increasing amount of patients on the waiting list has prompted the development of medical strategies to increase the usable organs, including the search for alternative sources of donation, organ optimization and extension of the criteria for donation. The recovery of lungs from non-heart-beating donors (NHBD) is a concept in which death is declared based on cardiopulmonary criteria rather than the currently used definition of "brain death." Obtaining NHBD lungs is currently practiced in many centers. In this review we discuss the current state of lung transplantation from uncontrolled NHBD.     

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.     

Present Data on Organ Donation and Transplantation in Poland

At present, organ transplantation activity in Poland is located in the middle among European Union countries. There are appropriate law regulations, well-organized legal structures, well-educated transplant teams, good transplantation results, and case registries. There are 24 organ transplant teams in 20 centers, including 46 programs. Since 1966, over 18,000 organs have been transplanted 14,300 kidneys; 1800 livers; 1700 hearts; 250 kidney/pancreases and 30 lungs. Every year almost 1500 organs are procured from about 500 cadaveric heart-beating donors (9–14 per million people [pmp]) with 50 from living donors: 800 to 1000 kidneys (21–28 pmp); over 200 livers (5–6 pmp); and 60 to 100 hearts (1.6–2.7 pmp). National transplant registries are maintained in Poltransplant including a central registry of refusals (the policy of presumed consent with registered objection on donation after death is implemented), waiting lists, a cadaveric and living donor registry, and a transplant registry. There are still some actions that should be undertaken to strengthen the transplantation system in Poland, to increase organ availability, to enhance the efficiency and accessibility of transplantation systems, and to improve quality and safety: namely, increasing deceased donations to their full potential, appointing transplant coordinators in every hospital where there is the potential for organ donation, promoting quality improvement programs, and promoting living donation.     

Enhanced development of caspase-independent cortical cell death during cold storage in kidneys of non-heart-beating donors

BACKGROUND: Understanding the mechanisms of injury associated with cardiac arrest is essential for defining strategies aimed at improving preservation and function of kidneys harvested in non-heart-beating (NHB) donors. METHODS: We standardized a model of NHB donors in rats and studied the kinetics and types (apoptosis vs. necrosis) of renal cell death developing during cold storage. Using quantitative polymerase chain reaction, immunoblotting, and caspase inhibition, we also studied the molecular pathways regulating renal cell death in this model. RESULTS: The kinetics and extent of cell death developing in cortical tubules during cold storage were found to be increased in non-heart-beating (NHB) kidneys. Apoptosis of cortical tubules predominated in NHB kidneys exposed to 10 hr of cold storage, whereas necrosis increased after longer periods of cold ischemia. Shortly after cardiac arrest, a rapid up-regulation of Bax and Hsp 70 was found at the protein level in NHB kidneys. After 24 hr of cold storage, induction of Bax was maintained, whereas protein levels of Hsp70 returned to levels comparable to heart-beating (HB) controls. Also, mRNA levels of Bax were found to increase during cold storage in NHB kidneys. Cortical cell death was found to be largely caspase-independent but responsive to hydroxyl-radical scavenging with dimethyl sulfoxide (DMSO). CONCLUSIONS: Cardiac arrest promotes activation of death-inducing molecules such as Bax and is associated with increased development of caspase-independent renal cell death during cold storage. Developing strategies, such as free radical scavenging, aimed at inhibiting cell death during cold storage, could prove useful for improving preservation of NHB kidneys.     

Variation in organ donation in northeastern England 1986 to 2003

Renal transplantation is established as the best form of renal replacement therapy, but demand for kidneys exceeds supply from cadaveric donations. It is therefore important to make the best use of the pool of potential cadaveric organ donors. Donation rates are to a large extent dependent on public opinions, which may be influenced by external events. In northeast England from 1986 to 2003, there was a potential pool of 1170 brain stem-dead donors, of whom 190 (16%) could not be retrieved due to relatives' objections. From 1998 to 2003 we were referred 90 potential non-heart-beating donors, of whom relatives refused donation in 10 (11%). A major reason for not retrieving organs from a potential donor has been lack of consent from the relatives. Refusals appear to vary year by year and are consistently lower for non-heart-beating donors. This therefore raises the possibility that negative or positive media publicity plays a role in this variation.     

Development of a successful non-heart-beating organ donation program

To help alleviate the organ shortage, transplant centers are using organs from expanded-criteria donors, who were considered unsuitable just a few years ago, such as non-heart-beating donors. In 1998, we made a concerted effort to increase the number of non-heart-beating donors recovered by our organ procurement organization. In this paper, we discuss the steps in establishing this program, including transplant center support, estimating the number of potential non-heart-beating donors, organ procurement support, protocol development, hospital development, education, putting the protocol into practice, follow-up, and effect of the program on organ procurement. With the establishment of this program, the number of non-heart-beating donors increased from 2% to 5% per year to over 10% for the past 2 years. From these donors, 61 of 82 recovered kidneys were transplanted into 58 patients, and 18 of 20 recovered livers were transplanted. A non-heart-beating donor program can significantly add to the number of organ transplants and successful transplantations.