Brain death in Britain as reflected in renal donors.

The diagnostic mix of 1228 brain-dead renal donors in Britain was similar to that of 479 cases of brain death recently reported from three neurosurgical units. About half the donors came from non-teaching hospitals without a neurosurgical unit, many of them small and distant from the centre. The different circumstances that preceded brain deaths were examined--namely, diagnosis and whether the fatal ictus of brain damage occurred when the patient was already in hospital--to explain why donors spend varying times on the ventilator. Head injuries accounted for half the donors, and intracranial haemorrhage for almost a third. While many potential donors are not made available, the size of the pool has been overestimated, particularly in regard to head injury. Reduction in organ donation since "Panorama" has been very uneven, with some places increasing their yield; this suggests reluctance of doctors to initiate donation rather than relatives withholding permission.     

Brain-stem auditory evoked potentials and brain death

BAEP records were obtained from 30 brain-dead patients. Three BAEP patterns were observed: (1) no identifiable waves (73.34%), (2) an isolated bilateral wave I (16.66%) and (3) an isolated unilateral wave I (10%). When wave I was present, it was always significantly delayed. Significant augmentation of wave I amplitude was present bilaterally in one case and unilaterally in another. On the other hand, in serial records from 3 cases wave I latency tended to increase progressively until this component disappeared. During the same period. wave I amplitude fluctuations were observed. A significant negative correlation was found for wave I latency with heart rate and body temperature in 1 case. Two facts might explain the progressive delay and disappearance of wave I in brain-dead patients: a progressive hypoxic-ischaemic dysfunction of the cochlea and the eight nnerve plus hypothermia, often present in brain-dead patients. Then the incidence of wave I preservation reported by different authors in single BAEP records from brain-dead patients might depend on the moment at which the evoked potential study was done in relation to the onset of the clinical state. It is suggested that, although BAEPs provide an objective electrophysiological assessment of brain-stem function, essential for BD diagnosis, this technique could be of no value for this purpose when used in isolation.     

Brain death and marginal grafts in liver transplantation

It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in liver transplantation. In addition, one of the mechanisms to avoid the shortage of liver grafts for transplant is the use of marginal livers, which may show higher risk of primary non-function or initial poor function. To our knowledge, very few reviews have focused in the field of liver transplantation using brain-dead donors; moreover, reviews that focused on both brain death and marginal grafts in liver transplantation, both being key risk factors in clinical practice, have not been published elsewhere. The present review aims to describe the recent findings and the state-of-the-art knowledge regarding the pathophysiological changes occurring during brain death, their effects on marginal liver grafts and summarize the more controversial topics of this pathology. We also review the therapeutic strategies designed to date to reduce the detrimental effects of brain death in both marginal and optimal livers, attempting to explain why such strategies have not solved the clinical problem of liver transplantation.     

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

The Qatari law, as in many other countries, uses brain death as the main criteria for organ donation and cessation of medical support. By contrast, most of the public in Qatar do not agree with the limitation or withdrawal of medical care until the time of cardiac death. The current study aims to examine the duration of somatic survival after brain death, organ donation rate in brain-dead patients as well as review the underlying etiologies and level of support provided in the state of Qatar. This is a retrospective study of all patients diagnosed with brain death over a 10-year period conducted at the largest tertiary center in Qatar (Hamad General Hospital). Among the 53 patients who were diagnosed with brain death during the study period, the median and mean somatic survivals of brain-dead patients in the current study were 3 and 4.5 days respectively. The most common etiology was intracranial hemorrhage (45.3%) followed by ischemic stroke (17%). Ischemic stroke patients had a median survival of 11 days. Organ donation was accepted by only two families (6.6%) of the 30 brain dead patients deemed suitable for organ donation. The average somatic survival of brain-dead patients is less than one week irrespective of supportive measures provided. Organ donation rate was extremely low among brain-dead patients in Qatar. Improved public education may lead to significant improvement in resource utilization as well as organ transplant donors and should be a major target area of future health care policies.     

Brain death and the anencephalic newborn

We will set the stage for our analysis by reviewing selected medical aspects of anencephaly, outlining the history of the use of anencephalics as organ sources, and summarising the results of an important study recently completed at Loma Linda University. We will then employ some of the arguments and justifications underlying the Uniform Determination of Death Act (UDDA) to claim that anencephaly is morally equivalent to brain death, i.e., the reasons for considering brain-dead patients to be dead also apply to anencephalics. Finally, we will critique our proposal and discuss its implications.     

Organ transplantation in Nepal: Ethical,legal, and practical issues

In Nepal, live donor organ transplantation is only 14 years old with the first successful kidney transplant made in 2008 and a successful liver and bone marrow transplant made in 2016. However, transplantation of cadaveric cornea dates back to 1998. There are still no cases of animal-to-human organ transplantation in Nepal. There are stringent laws to regulate human body organ transplantation in Nepal which are amended from time to time. However, there is a racket of human traffickers who lure rural people from this low-income country into the illegal organ trade. Furthermore, there is a substantial lack of awareness of organ donation among the general public. This article focuses on the stipulations of ethical, legal, and practical issues of obtaining organs procured from living and brain-dead donors that support the process of transplantation in Nepal. In addition, the article also explores the legal and practical issues of organ trafficking and organ donation awareness in Nepal on the basis of factual data and findings from other studies.     

On the acceptability of xenografts

Transplantation represents a major advance in modern medicine with a major impact on the interactions between individuals and society. The numbers of patients undergoing organ transplantation increased steadily over the years and around 250,000 individuals are living nowadays in Europe with a transplanted organ. On the other hand, the numbers of cadaveric (brain-dead) donors used for organ transplantation remains stable, at around 5,000 each year, and the numbers of transplantation from living donors only slowly increase in Europe. Therefore, a gap is growing between the numbers of patients in need of a transplant and the numbers of organs available for transplantation. About 45,000 patients are currently on renal transplant waiting lists in Europe and, depending on the countries considered, 15 to 30 % of candidates for liver or heart transplantation die before a life-saving transplant becomes available to them. There is therefore an urgent need to implement innovative research and to take full advantage of recent biotechnological advances to explore new avenues in xenotransplantation, and to simultaneously address the ethical, societal and public health issues related to organ replacement. Much progresses have been accomplished in the understanding of xenograft rejection processes that include hyperacute, acute vascular and cellular rejection mechanisms. Strategies to promote xenograft survival that are currently under evaluation include genetic engineering of donor pigs, adapted immunosuppressive treatments and tolerance induction. Also, the psychological acceptance has been evaluated.     

Changes in the nitric oxide level in the rat liver as a response to brain injury

Liver disturbances stimulate inflammatory reaction in the brain but little is known if injury to the brain can significantly influence liver metabolism. This problem is crucial in modern transplantology, as the condition of the donor brain seems to strongly affect the quality (viability) of the graft, which is often obtained from brain-dead donors, usually after traumatic brain injury. Because nitric oxide is one of the significant molecules in brain and liver biology, we examined if brain injury can affect NO level in the liver. Liver samples of Wistar rats were collected and studied with EPR NO-metry to detect NO level changes at different time points after brain injury. Shortly after the trauma, NO level in the liver was similar to the control. However, later there was a significant increase in the NO content in the livers starting from the 2nd day after brain injury and lasting up to the 7th day. It seems that the response to a mechanical brain injury is of the systemic, rather than local character. Therefore brain metabolism disturbances can influence liver metabolism at least by stimulating the organ to produce NO.     

ARGUMENTS AGAINST PROMOTING ORGAN TRANSPLANTS FROM BRAIN‐DEAD DONORS,AND VIEWS OF CONTEMPORARY JAPANESE ON LIFE AND DEATH

As of 2009, the number of donors in Japan is the lowest among developed countries. On July 13, 2009, Japan's Organ Transplant Law was revised for the first time in 12 years. The revised and old laws differ greatly on four primary points: the definition of death, age requirements for donors, requirements for brain‐death determination and organ extraction, and the appropriateness of priority transplants for relatives. In the four months of deliberations in the National Diet before the new law was established, various arguments regarding brain death and organ transplantation were offered. An amazing variety of opinions continue to be offered, even after more than 40 years have elapsed since the first heart organ transplant in Japan. Some are of the opinion that with the passage of the revised law, Japan will finally become capable of performing transplants according to global standards. Contrarily, there are assertions that organ transplants from brain‐dead donors are unacceptable because they result in organs being taken from living human beings. Considering the current conditions, we will organize and introduce the arguments for and against organ transplants from brain‐dead donors in contemporary Japan. Subsequently, we will discuss the primary arguments against organ transplants from brain‐dead donors from the perspective of contemporary Japanese views on life and death. After introducing the recent view that brain death should not be regarded as equivalent to the death of a human being, we would like to probe the deeply‐rooted views on life and death upon which it is based.     

Anti-Apoptotic Effects of 3,3’,5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats

Background

Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3’,5-Triiodo-L-thyronine (T₃). T₃ pre-conditioning leads to anti-apoptotic and pro-mitotic effects in liver tissue following ischemia/reperfusion injury. Therefore, we aimed to study the effects of T₃ pre-conditioning in the liver of brain-dead rats.

Methods

Brain death (BD) was induced in mechanically ventilated rats by inflation of a Fogarty catheter in the epidural space. T₃ (0.1 mg/kg) or vehicle was administered intraperitoneally 2 h prior to BD induction. After 4 h of BD, serum and liver tissue were collected. RT-qPCR, routine biochemistry, and immunohistochemistry were performed.

Results

Brain-dead animals treated with T₃ had lower plasma levels of AST and ALT, reduced Bax gene expression, and less hepatic cleaved Caspase-3 activation compared to brain-dead animals treated with vehicle. Interestingly, no differences in the expression of inflammatory genes (IL-6, MCP-1, IL-1β) or the presence of pro-mitotic markers (Cyclin-D and Ki-67) were found in brain-dead animals treated with T₃ compared to vehicle-treated animals.

Conclusion

T₃ pre-conditioning leads to beneficial effects in the liver of brain-dead rats as seen by lower cellular injury and reduced apoptosis, and supports the suggested role of T₃ hormone therapy in the management of brain-dead donors.     

Myoglobin content and citrate synthase activity in different parts of the normal human heart

Myoglobin (Mb) content and citrate synthase (CS) activity were determined in myocardial samples from nine human brain-dead organ donors with normal hearts. Six regions of each heart were analyzed: right and left atria, right ventricle, left ventricular subepicardium, subendocardium, and anterior papillary muscle. The Mb content was similar, whereas the CS activity was higher in the left than in the right heart at both atrial and ventricular levels. Mb content and CS activity were higher in ventricles than in atria. The subendocardial layer and papillary muscle of the left ventricle had a higher Mb content than the subepicardial layer, whereas CS activity was similar in these three locations. The results suggested a closer relationship between CS activity (oxidative potential) and work load than between Mb content and work load. Mb content may, instead, be related to intramuscular oxygen tension (PO2) on the basis of a comparison between our Mb data and those of others on regional variations in myocardial PO2.     

Brain-dead kidney donor: selection,care, and administration.

Over four and a half years a district general hospital provided 34 cadaveric kidneys for transplantation. All brain-dead patients were regarded as potential donors, flow charts being used to maintain circulation and urine formation and facilitate administration. With this system the time lapse between diagnosis of brain death and removal of kidneys ranged from three to six hours and ischaemia was minimised. It is concluded that adoption of the system by other hospitals of comparable size would result in enough good-quality kidneys to satisfy present needs, thus reducing the initial high failure rate and enabling more patients to be accepted for dialysis.     

Brain death and organ donation in a neurosurgical unit: audit of recent practice.

OBJECTIVE--To assess the potential for increasing the yield of donors by comparing the current pattern of brain death and organ donation in a neurosurgical unit with that reported in 1981 and with a recent national audit. DESIGN--Retrospective review of all deaths for 1986, 1987, and 1988 and prospective data for 1989. SETTING--A regional neurosurgical unit serving 2.7 million population. RESULTS--Of 553 deaths, 35% (191) patients died while on a ventilator and 17% (92) after discontinuation of ventilation. Medical contraindications to donation were found in 23% (32) of 141 patients tested for brain death, in 38% (19) of 50 patients who died while being ventilated who were not tested, and in 12% (11) of 92 patients no longer being ventilated. Consent for donation was sought in 88% (96) of 109 medically suitable brain dead patients and granted in 70% (67) of these. Half those with permission for multiorgan donation had only the kidneys removed. CONCLUSIONS--More organs may be lost owing to transplant team logistics than by failure to seek consent from relatives of brain dead patients. The estimated size of the pool of potential donors depends on what types of patients might be considered. Ensuring that all who die while being ventilated are tested for brain death and considering the potential for donation before withdrawing ventilation could yield more donors. Ventilating more patients who are hopelessly brain damaged to secure more donors raises ethical and economic issues.     

Liver transplantation in adults

Liver transplantation allows to treat patients with end-stage cirrhosis as well as some liver malignancies (small size hepatocellular carcinoma) with a life expectancy exceeding 70 and 60 % at 5 years, respectively. Current immunosuppressive agents make it possible to prevent chronic rejection in more than 90 % of the patients and to preserve an excellent quality of life in most cases. The principal limiting factor for liver transplantation is represented by the scarcity of brain-dead donors. Indeed, despite the selection of those candidates who have the best chance of surviving after transplantation, several months are usually necessary for obtaining a graft and the mortality on the waiting list may reach 10 to 15 %. Organ shortage incited to develop alternatives to conventional transplantation, the most important of which are living donor transplantation and split liver transplantation. Living donor transplantation can be applied to about 20 to 30 % of candidates. Thought initially smaller, the partial graft regenerates and its volume is restored within a few weeks. The results of living donor transplantation in terms of survival are comparable to those of cadaveric transplantation. The risk for the donor has to be lower than 1 % which makes that selection must be especially cautious. Donors must be direct relatives or spouses. Split liver transplantation technique, based on the separation of a cadaveric graft into two functional parts transplanted in two distinct recipients, although attractive, is applicable to less than 25 % of the donors. Education for organ donation in the general population still remains a priority.     

The gradual onset brain death model: a relevant model to study organ donation and its consequences on the outcome after transplantation

Organs used for transplantation are usually derived from heart-beating brain dead donors. However, brain death is known to have negative effects on donor organ quality, previously studied using a difficult to control sudden onset experimental model. We have now developed a reproducible gradual onset brain death model in rats without requiring inotropic support. Fisher inbred rats weighing 260-300 g were used. Brain death was induced by a gradual inflation of a subdurally placed balloon catheter. During induction and the period following brain death, the animals were mechanically ventilated and blood pressure was continuously monitored. The blood pressure registration showed a characteristic pattern during brain death induction, in which a decrease in blood pressure, a hypotensive period in which the Cushing response occurred, and a sharp peak were consistent findings. After brain death was induced, blood pressure was maintained at normotensive levels up to 4 h. After the experiments, neuropathological evaluation of the brain located haemorrhagic cerebral parenchyma, and immunocytochemistry of liver tissue revealed a significant influx of polymorph nuclear cells, as was previously observed as well. This improved model allows the study of brain death on donor organ quality without the use of inotropic support.     

The effect of total spinal anesthesia on cardiac function in a large animal model of brain death

Brain death (BD) causes cardiac dysfunction in organ donors, attributable to the catecholamine storm that occurs with raised intracerebral pressure (ICP). However the direct contribution of the spinal sympathetics has not been well described. We examined the effect of total spinal anesthesia (TSA) on cardiac function in a large animal model of BD. Eighteen pigs were allocated to 3 experimental groups: Group?1, the saline-treated control group; Group?2, TSA administered prior to BD; and Group?3, TSA administered 30?min after BD. Inflation of an intracerebral balloon-tipped catheter was used to induce BD. Ventricular function was assessed using a pressure-volume loop catheter and magnetic resonance imaging. Serum catecholamine levels were assessed with high performance liquid chromatography. Inflation of the intracerebral balloon-tipped catheter was associated with a dramatic rise in heart rate and blood pressure, along with increased concentrations of serum epinephrine and norepinephrine. This phenomenon was not observed in Group 2. In Group 1, there was a significant decline in contractility, whereas groups 2 and?3 saw no change. Group 2 had greater contractile reserve than groups 1 and 3. Our data demonstrate the central role of spinal sympathetics in the hemodynamic response to raised ICP. Further work is required to determine the utility of TSA in reversing cardiac dysfunction in BD donors.     

Is there an Asian bioethics?

Japan and China have long resisted the Western trend of organ transplantation from brain-dead patients, based on a 'Confucian' respect for integrity of ancestors' bodies. While their general publics continue to harbor grave doubts about such practices, their medical and political elites are hastening towards the road of organ-harvesting and organ-marketing, largely for economic reasons. This report illustrates the ways that economics is motivating brain-death legislation in Japan and criminal executions in China.     

Brain stem death and organ donation.

Organs for donation are in short supply in the United Kingdom, resulting in allegations that relatives of potential donors are not being asked for consent. Legislation on "required request" has been proposed to overcome this. The incidence, causes, complications, and patterns of organ donation in brain stem dead patients in one referral centre were studied over 12 months. Data were collected on all patients fulfilling criteria for brain stem death or considered suitable for donating organs after circulatory arrest. Forty two patients fulfilled the criteria for brain stem death, and in 10 further patients circulatory arrest occurred before formal testing was finished. The major causes of brain stem death were head injury (28) and intracranial haemorrhage (17). Consent to organ donation was obtained for 24 potential donors, and organs were donated by 23 of them. Twenty nine patients did not donate organs. The commonest reasons for failure to donate were medical unsuitability (13) and the coroner not releasing the body (eight). Consent was not sought in three cases, and the relatives refused consent in the remaining five. This study suggests that required request will not considerably increase the supply of donor organs.     

Diagnosis and management of brain death.

Finland was the first country in which brain death was legally accepted. Since 1975, 37 cases of brain death had been recorded in a university hospital in Finland, and these were reviewed. The cause for brain death was intracranial bleeding in 32 cases, other cerebrovascular disorder in two, and intracranial neoplasm in three. In 21 brain death was diagnosed clinically. In 16 cases confirmatory investigations (electroencephalography, cerebral angiography) were needed. After brain death had been established artificial support was withdrawn in 15 patients and organ transplantation was carried out in 10. In 12 patients, however, diagnosis of brain death did not influence management, though the heart stopped beating on average 25 hours after diagnosis. The Finnish criteria for brain death seem to be reliable and suitable for routine use.     

Brain-stem auditory evoked potential monitoring. Variations of stimulus artifact in brain death

Brain-stem auditory evoked potentials (BAEPs) were recorded in 20 subjects with brain death (mean age, 33.2 ± 15.1 years) and 20 healthy volunteers (mean age, 29.8 ± 6.8 years). Brain death was due to head injury (n = 14), encephalitis (n = 3), brain-stem hemorrhage (n = 1), cerebellar hemorrhage (n = 1) or cerebral infarction (n = 1). The presence, latency and amplitude of the individual BAEP components and variations of the stimulus artifact were evaluated. The mean ( ± S.D.) amplitude of the stimulus artifact was 0.26 ± 0.12 μV in the brain-dead subjects and 0.09 ± 0.05 μv in the control group (P < 0.001, t test). The causes of the phenomenon of increasing stimulus artifacts in the evolution of brain death remain unclear.