Beyond Death: Exploring Cultural Perceptions in Cadaveric Organ Donation.

Advancements in medicine introduced a relatively invented death into our lives: Brain Death. It intermingles with our perceptions of classical death due to knowing the heart is beating, the color of the skin is pink, and the body's temperature is warm. Hence, accepting brain death as death might get complicated in terms of relatives of the brain-dead person. The interviews revealed that the reluctance to cadaveric organ donations is highly connected to the cultural perception of death. Furthermore, folklore interferes with altruistic cadaveric donations, particularly folk beliefs, rituals, social norms, and oral traditions.

Role of Dietary Nutritional Treatment on Hepatic and Intestinal Damage in Transplantation with Steatotic and Non-Steatotic Liver Grafts from Brain Dead Donors.

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.

Hypothalamic function in patients diagnosed as brain dead and its practical consequences.

Some patients who have been diagnosed as "dead by neurologic criteria" continue to exhibit certain brain functions, most commonly, neuroendocrine functions. In this chapter, we review the pathophysiology of brain death that can lead either to neuroendocrine failure or to preserved neuroendocrine functioning. We review the evidence on continued hypothalamic functioning in patients who have been declared "brain dead," examine potential mechanisms that would explain these findings, and discuss how these findings create additional confounds for brain death testing. We conclude by reviewing the evidence for the management of hypothalamic-pituitary failure in the setting of brain death and organ transplantation.

A Holistic Assessment of Organ Transplantation Activities, Scientific Productivity on Brain Death in Islamic Countries, and Comparison of the Outcomes with the United Nations Development Statistics.

About one-fourth of the world population belongs to the religion of Islam, and a significant number of people in the Muslim society, including health professionals, are dedicated themselves to the holy book Qur'an but unclear about the religious teachings on organ donation and transplantation. These people are dependent on religious rulings declared by ecclesiastical authorities (scholars and imams). In this study, we aimed to question the attitude of Islamic nations on organ donation and transplantation. Secondly, we endeavored to investigate how the Islamic perspective on these issues influences scientific productivity about the subject of brain death, which is undeviatingly related to organ transplantation. The term "brain death" was searched in Thomson Reuters, Web of Science search engine, only including Muslim countries. All of the data obtained were subjected to bibliometric analysis. We also compared the transplantation statistics of Global Observatory on Donation and Transplantation Organization with the development statistics of the United Nations (UN). The two leading Muslim countries in terms of scientific productivity about brain death are Turkey and Iran. Transplantation proceedings is the leading scientific journal on this subject. These two countries have outperformed other Islamic countries in terms of organ donation and transplantation statistics. We also revealed that the human development index and education index of the UN have a positive correlation with the number of deceased transplantation, which is directly related to the number of brain-death-diagnosed cases (r 0.696, p < 0.05 and r 0.771, p < 0.05, respectively). Additionally, we found a positive correlation between expenditure on research and development data of the UN with the number of total transplantations performed and the number of scientific articles on brain death (r 0.889, p 0.01 and r 0.634, p < 0.05, respectively). There is not a consensus about brain death and organ transplantation in Islamic nations, and the majority of these countries have various hindrances about organ donation and transplantation. The legal authorities, health professionals, religious rulers, and media should spend every effort to educate the people on organ donation and transplantation. And, policymakers of Islamic nations should allocate extra funds for education and scientific activities to break down negative views on organ donation and transplantation.

[Intensive care to facilitate organ donation. ONT-SEMICYUC recommendations]. / Cuidados intensivos orientados a la donación de órganos. Recomendaciones ONT-SEMICYUC.

Intensive care to facilitate organ donation (ICOD) is defined as the initiation or continuation of life-sustaining measures, such as mechanical ventilation, in patients with a devastating brain injury with high probability of evolving to brain death and in whom curative treatment has been completely dismissed and considered futile. ICOD incorporates the option to organ donation allowing a holistic approach to end-of-life care, consistent with the patients wills and values. Should the patient not evolve to brain death, life-supportive treatment must be withdrawal and controlled asystolia donation could be evaluated. ICOD is a legitimate practice, within the ethical and legal regulations that contributes increasing the accessibility of patients to transplantation, promoting health by increasing deceased donation by 24%, and with a mean of 2.3 organs transplanted per donor, and collaborating with the sustainability of health-care system. This ONT-SEMICYUC recommendations provide a guide to facilitate an ICOD harmonized practice in spanish ICUs.

Nurses' Challenges in Caring for an Organ Donor Brain Dead Patient and their solution strategies: A Systematic Review.

BACKGROUND: Caring for brain dead patient is one of the most troublous duties of an Intensive Care Unit (ICU) nurse. This study aimed to determine nursing challenges based on recent literature and identify the strategies to overcome these challenges. MATERIALS AND METHODS: In this systematic review, the standard systematic review guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used with articles published in PubMed, Science Direct, Scientific Information Database (SID), and Google Scholar databases during 2000-2018 on the keywords "brain dead OR brain death" and "nurses OR nursing." After the primary search, 212 articles were found. Eventually, 21 articles were selected for the final evaluation. RESULTS: According to the results, the challenges included the concept and diagnosis of brain death, religious, and cultural beliefs opposing organ donation, lack of knowledge about the care process, interactions with the families. The proposed strategies were providing medical and nursing interventions to maintain a brain dead patient for organ donation, providing working conditions that maintain nurses' health, and increase the quality of care. CONCLUSIONS: Nurses play an important role in the care process of brain dead patients; therefore, recognizing their challenges can be thefirst step in increasing holistic care and maintaining organ vitality for transplantation. It is suggested that nursing authorities commence special educational programs with the aim to increase the knowledge of nurses about the care process of brain dead patients.

Clock Genes Disruption in the Intensive Care Unit.

BACKGROUND: Intensive care unit (ICU) environment disrupts the circadian rhythms due to environmental and other nonphotic synchronizers. The main purpose of this article is to establish whether critically patients have desynchronization at the molecular level after 1 week of stay in the ICU. METHODS: The rhythm of Clock, Bmal1, Cry1, and Per2 genes in neuro-ICU patients (n = 11) on the first day after admission in the unit (1 day) and 1 week later (1 week) was studied, 4 time points throughout the day, at 6, 12, 18, and 24 hours. Human whole blood samples were obtained from neuro-ICU patients. The total RNA was isolated and each sample was reverse transcribed to complementary DNA and quantitative polymerase chain reaction (PCRq) was performed. The possible rhythm was studied using Fourier Series. RESULTS: After 1 week, the clock gene rhythmicity completely disappeared. Messenger RNA (mRNA) expression for the 4 clock genes was shown rhythmicity at the first day after admission in the ICU. Circadian rhythmicity for none of them was observed but rather, ultradian rhythmicity was found. The expression of Clock, Bmal1, and Per2 mRNA after 1 week was similar in the 4-time point studies without significant fluctuation among the 4 time points analyzed. DISCUSSION: Rhythmic mRNA expression is present at the first day after admission in the ICU. However, ICU stay during 1 week affects the molecular machinery of the biological clock generating chronodisruption. Circadian disruption is associated with the risk of several pathologies, thus, it seems to be clear that ICU stay in constant conditions could adversely affect patient evolution and probably, circadian resynchronization restoring clock gene expression could lead to a better clinical evolution of the patient. CONCLUSIONS: Clock genes disruption is observed in neuro-ICU patients. Light therapy as well as melatonin treatment could reduce the impact of ICU stay period in biological clock, thereby improving patients' recovery.

Global Scientific Outputs of Brain Death Publications and Evaluation According to the Religions of Countries.

In 1950s, the concept of brain death, which began to be discussed primarily in terms of medicine and then in terms of religion, law, and ethics, became a central topic in all world countries as it was an early diagnosis of death. Despite the fact that brain death (BD) diagnosis is of importance for benefitting from organ and tissue transplantation of patients in the world, the literature still involves no bibliometric studies that made a holistic evaluation of the publications about this issue. The present study aims to investigate the top-cited articles about BD published between 1980 and 2018, identify the citation collaboration of the journals, demonstrate the collaboration between the countries, define the relationship between organ transplantation and BD, and reveal the latest developments and trend topics about this issue. In addition, this study aims to investigate the relationship between religions of countries and brain death publication productivity. Documents for bibliometric analysis were downloaded from Web of Science. The literature search was performed using the keywords "brain death/dead" during 1980-2018. The correlations between gross domestic product (GDP), Human Development Index (HDI) and publication productivity of the countries on BD were investigated with Spearman's correlation coefficient. There was a high-level, statistically significant correlation between the number of publications and GDP, and HDI and the number of publications about BD (r = 0.761, p < 0.001; r = 0.703, p < 0.001). The USA was the top country in terms of publication productivity, which was followed by developed countries such as Germany, Japan, France, and Spain. However, the contribution of the undeveloped or developing countries such as China, Brazil, Turkey, Iran, and South Africa was found to be considerably important. While many people in the world die with undamaged organs, many other people die needing those organs. Therefore, it is considered that the collaborations and thus multidisciplinary studies about BD should be increased in the world countries, and the countries should be involved in bigger collaborations instead of little clusters. Especially, Muslim countries should be encouraged to do research and publish studies about the issues of brain death and organ transplantation.

No Detectable Electroencephalographic Activity After Clinical Declaration of Death Among Tibetan Buddhist Meditators in Apparent Tukdam, a Putative Postmortem Meditation State.

Recent EEG studies on the early postmortem interval that suggest the persistence of electrophysiological coherence and connectivity in the brain of animals and humans reinforce the need for further investigation of the relationship between the brain's activity and the dying process. Neuroscience is now in a position to empirically evaluate the extended process of dying and, more specifically, to investigate the possibility of brain activity following the cessation of cardiac and respiratory function. Under the direction of the Center for Healthy Minds at the University of Wisconsin-Madison, research was conducted in India on a postmortem meditative state cultivated by some Tibetan Buddhist practitioners in which decomposition is putatively delayed. For all healthy baseline (HB) and postmortem (PM) subjects presented here, we collected resting state electroencephalographic data, mismatch negativity (MMN), and auditory brainstem response (ABR). In this study, we present HB data to demonstrate the feasibility of a sparse electrode EEG configuration to capture well-defined ERP waveforms from living subjects under very challenging field conditions. While living subjects displayed well-defined MMN and ABR responses, no recognizable EEG waveforms were discernable in any of the tukdam cases.

Go in Peace: Brain Death, Reasonable Accommodation and Jewish Mourning Rituals.

Religious objections to brain death are common among Orthodox Jews. These objections often lead to conflicts between families of patients who are diagnosed with brain death, and physicians and hospitals. Israel, New York and New Jersey (among other jurisdictions) include accommodation clauses in their regulations or laws regarding the determination of death by brain-death criteria. The purpose of these clauses is to allow families an opportunity to oppose or even veto (in the case of Israel and New Jersey) determinations of brain death. In New York, the extent and duration of this accommodation period are generally left to the discretion of individual institutions. Jewish tradition has embraced cultural and psychological mechanisms to help families cope with death and loss through a structured process that includes quick separation from the physical body of the dead and a gradual transition through phases of mourning (Aninut,Kriah, timely burial, Shiva, Shloshim, first year of mourning). This process is meant to help achieve closure, acceptance, support for the bereaved, commemoration, faith in the afterlife and affirmation of life for the survivors. We argue that the open-ended period of contention of brain death under the reasonable accommodation laws may undermine the deep psychological wisdom that informs the Jewish tradition. By promoting dispute and conflict, the process of inevitable separation and acceptance is delayed and the comforting rituals of mourning are deferred at the expense of the bereft family. Solutions to this problem may include separating discussions of organ donation from those concerning the diagnosis of brain death per se, allowing a period of no escalation of life-sustaining interventions rather than unilateral withdrawal of mechanical ventilation, engagement of rabbinical leaders in individual cases and policy formulations that prioritize emotional support for families.

A Survey of Multidenominational Rabbis on Death by Neurologic Criteria.

OBJECTIVE: (1) Determine the pervasiveness of the belief that brain death/death by neurologic criteria (BD/DNC) is not death among rabbis. (2) Examine rabbinic beliefs about management after BD/DNC. METHODS: An electronic anonymous survey about BD/DNC determination and management after BD/DNC was created and distributed to members of the Central Conference of American Rabbis (the Reform Rabbinic leadership organization), the Rabbinic Council of America (an Orthodox organization), the Rabbinic Assembly (a Conservative organization), and the Reconstructionist Rabbinic Association. RESULTS: Ninety-nine rabbis (40 Reform, 32 Orthodox, 22 Conservative, and 5 Reconstructionist) completed the survey. Awareness of the requirements for BD/DNC was poor (median of 33% of the requirements correctly identified [interquartile range of 22-66%]), but 81% of rabbis knew that absence of heartbeat is not required for BD/DNC. Although only 5% of all rabbis believed a person who is brain dead could recover, 22% did not believe BD/DNC is death, and 18% believed mechanical ventilation should be continued after BD/DNC. There was a significant relationship between denomination and belief that: (1) a person who is brain dead can recover (p = 0.04); (2) a person who is brain dead is dead (p < 0.001); (3) mechanical ventilation should be continued after BD/DNC (p < 0.001); (4) hydration should be continued after BD/DNC (p = 0.002); (5) nutrition should be continued after BD/DNC (p < 0.001); (6) medications to support blood pressure should be continued after BD/DNC (p < 0.001); and (7) cardiopulmonary resuscitation should be performed when a brain dead person's heart stops (p = 0.006). CONCLUSIONS: Rabbinic knowledge about the intricacies of BD determination is poor. Rabbinic perspectives on management after BD/DNC vary. These empirical data on rabbinic perspectives about BD/DNC may be helpful when considering accommodation of religious objections to BD/DNC.

Towards a holistic definition of death: the biological, philosophical and social deficiencies of brain stem death criteria.

With no statutory definition of death, the accepted medical definition relies on brain stem death criteria as a definitive measure of diagnosing death. However, the use of brain stem death criteria in this way is precarious and causes widespread confusion amongst both medical and lay communities. Through critical analysis, this paper considers the insufficiencies of brain stem death. It concludes that brain stem death cannot be successfully equated with either biological death or the loss of integrated bodily function. The overemphasis of the brain-stem and its consequences leaves  the criteria open to significant philosophical critique. Further, in some circumstances, the use of brain stem death criteria causes substantial emotional conflict for families and relatives. Accordingly, a more holistic and comprehensive definition of death is required.

The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors.

In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)-protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts.

Determination of death: Metaphysical and biomedical discourse.

The prominence of biomedical criteria relying on brain death reduces the impact of metaphysical, anthropological, psychosocial, cultural, religious, and legal aspects disclosing the real value and essence of human life. The aim of this literature review is to discuss metaphysical and biomedical approaches toward death and their complimentary relationship in the determination of death. A critical appraisal of theoretical and scientific evidence and legal documents supported analytical discourse. In the metaphysical discourse of death, two main questions about what human death is and how to determine the fact of death clearly separate the ontological and epistemological aspects of death. During the 20th century, various understandings of human death distinguished two different approaches toward the human: the human is a subject of activities or a subject of the human being. Extinction of the difference between the entities and the being, emphasized as rational-logical instrumentation, is not sufficient to understand death thoroughly. Biological criteria of death are associated with biological features and irreversible loss of certain cognitive capabilities. Debating on the question "Does a brain death mean death of a human being?" two approaches are considering: the body-centrist and the mind-centrist. By bridging those two alternatives human death appears not only as biomedical, but also as metaphysical phenomenon. It was summarized that a predominance of clinical criteria for determination of death in practice leads to medicalization of death and limits the holistic perspective toward individual's death. Therefore, the balance of metaphysical and biomedical approaches toward death and its determination would decrease the medicalization of the concept of death.

Are Brain Dead Individuals Dead? Grounds for Reasonable Doubt.

According to the biological definition of death, a human body that has not lost the capacity to holistically organize itself is the body of a living human individual. Reasonable doubt against the conclusion that it has lost the capacity exists when the body appears to express it and no evidence to the contrary is sufficient to rule out reasonable doubt against the conclusion that the apparent expression is a true expression (i.e., when the conclusion that what appears to be holistic organization is in fact holistic organization remains a reasonable explanatory hypothesis in light of the best evidence to the contrary). This essay argues that the evidence and arguments against the conclusion that the signs of complex bodily integration exhibited in ventilated brain dead bodies are true expressions of somatic integration are unpersuasive; that is, they are not adequate to exclude reasonable doubt against the conclusion that BD bodies are dead. Since we should not treat as corpses what for all we know might be living human beings, it follows that we have an obligation to treat BD individuals as if they were living human beings.

Hypothalamic-Pituitary Function in Brain Death: A Review.

The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord.

Vagal stimulation in brain dead donor rats decreases chronic allograft nephropathy in recipients.

BACKGROUND: Although it has been shown that a vagus nerve stimulation of brain dead (BD) donors leads to an improvement of renal function in recipients in an acute allograft rejection model, its influence on chronic allograft nephropathy is still unknown. In the present study, we assessed the influence of donor vagus nerve stimulation on survival, renal function and histology in a chronic allograft model. METHODS: Brain death was induced in Fisher rats, and electro-stimulation of the vagus nerve was applied in one group (BD + vagus) during the whole course of BD (6 h). Unstimulated BD Fisher donor rats served as controls. Allogeneic Lewis rats were used as recipients and no immunosuppressive medication was administered. Blood and urine samples were collected every second week. Banff classification was assessed from harvested allografts. RESULTS: Vagal stimulation of BD donors resulted in an improved survival of recipients. Long-term renal function was significantly better in these recipients as reflected by improved creatinine clearance. Banff classification revealed significantly reduced vasculopathy and less tubulopathy in the BD + vagus group. CONCLUSIONS: In conclusion, our data demonstrate a long-lasting beneficial effect of vagus nerve stimulation in BD donors on the renal transplantation outcome. Hence, activation of the cholinergic anti-inflammatory pathway in BD donors may represent a novel therapeutic modality to reduce chronic allograft nephropathy without any side effects for the recipient.

Does our society have the proper understanding of death?

Recent developments in medicine in our society have drawn attention to various phenomena related to death, such as brain death, cardiac death, vegetative death, euthanasia, death with dignity, near-death experiences, hospice, and suicide. The definition and conception of death is significant because its reductionist determination may bring about a denial or taboo of death and a certain limitation on the modes of life and death. As religious traditions like Christianity and Buddhism and life and death studies show, human death cannot and should not be explained by physical and biological criterion of death like brain death or cardiac death alone. In a society with such a reductionist definition of death there can be no space for a mature culture of death and only a colossal number of miserable deaths like suicide. Therefore, as Kubler Ross argues, death should be defined in terms of considering the continued existence of certain realities as to psyche, spirit, and the meaning of life beyond physical and biological aspects. The medical and legal approach to death is greatly incomplete and restricted in taking into account the physical and biological aspect of death. Thus, it is necessary to precisely and deeply reconsider the definition and understanding of death from a broader and more comprehensive perspective rather than concentrating solely on the physical and biological criterion of death such as brain death or cardiac death.

Morte encefálica: diagnóstico possível sem utilização de exames complementares / Brain death: possible diagnosis without complementary exams

Objetivo: A necessidade da utilização de testes confirmatórios para o diagnóstico de morte encefálica vem sendo questionada nos últimos tempos. Acredita-se que o exame clínico completo, realizado de acordo com o protocolo do Conselho Federal de Medicina, seja suficiente para constatar a ausência irreversível de função no tronco encefálico. Assim, este estudo teve como objetivo averiguar a real necessidade da utilização de exames complementares no diagnóstico de morte encefálica. Método: Foi realizado estudo prospectivo analisando os prontuários de pacientes que receberam diagnóstico de morte encefálica desde a abertura do protocolo até a realização dos exames clínicos completos e exame complementar (Doppler transcraniano). Resultados: Não foi registrado nenhum caso de recuperação da função cortical e/ou do tronco cerebral após o diagnóstico de morte encefálica utilizando os critérios clínicos. A dificuldade para a realização do Doppler transcraniano e as falhas inerentes ao exame contribuíram para tornar mais lento o diagnóstico. Conclusão: É possível diagnosticar morte encefálica apenas utilizando exame clínico completo, sem a necessidade de exames complementares.

Objective: The need to use confirmatory tests for brain death diagnosis has been questioned lately. It is believed that a full clinical examination, performed according to the protocol of brain death diagnosis of the Brazilian National Council of Medicine, is sufficient to certify the irreversible loss of brain-stem function. Therefore, this study aimed to verify the real need to use complementary exams for brain death diagnosis. Method: We carried out a prospective study analyzing the files of patients with brain death diagnoses since the beginning of the protocol and that underwent a full clinical examination and transcranial Doppler as a complementary exam. Results: No cases of cortical and/or brain-stem function recovery after brain death diagnosis using clinical criteria were registered. Difficulty to perform transcranial Doppler and failures inherent to the exam contributed to late diagnosis. Conclusion: It is possible to diagnose brain death only using a full clinical examination, with no need to perform complementary exams.