Effects of polyethylene glycol-20k IV solution on donor management in a canine model of donor brain death.

BACKGROUND: Traditionally, vasopressors and crystalloids have been used to stabilize brain dead donors; however, the use of crystalloid is fraught with complications. This study aimed to investigate the effectiveness of a newly developed impermeant solution, polyethylene glycol-20k IV solution (PEG-20k) for resuscitation and support of brain dead organ donors. METHODS: Brain death was induced in adult beagle dogs and a set volume of PEG-20k or crystalloid solution was given thereafter. The animals were then resuscitated over 16 h with vasopressors and crystalloid as necessary to maintain mean arterial pressure of 80-100 mmHg. The kidneys were procured and cold-stored for 24 h, after which they were analyzed using the isolated perfused kidney model. RESULTS: The study group required significantly less crystalloid volume and vasopressors while having less urine output and requiring less potassium supplementation than the control group. Though the two groups' mean arterial pressure and lactate levels were comparable, the study group's kidneys showed less preservation injury after short-term reperfusion indexed by decreased lactate dehydrogenase release and higher creatinine clearance than the control group. CONCLUSIONS: The use of polyethylene glycol-20k IV solution for resuscitating brain dead donors decreases cell swelling and improves intravascular volume, thereby improving end organ oxygen delivery before procurement and so preventing ischemia-reperfusion injury after transplantation.

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.

Pronounced Dead Twice: What Should an Attending Physician Do in Between?

BACKGROUND Organ donation after cardiac death (DCD) is a well-accepted practice in the medical, philosophical, and legal fields. It is important to determine the amount of time required for the loss of circulation to lead to irreversible brain loss, and ultimately brain death. CASE REPORT We report a rare case of organ donation after cardiac death. During organ procurement, it was noted that the patient's aortic and renal arteries were pumping and pulsing, and her cardiopulmonary activities were back to unexpected levels. The organ procurement surgery was stopped. At the time, the patient was given Fentanyl and Lorazepam. Subsequently, she was pronounced dead again 18 minutes after she was initially pronounced dead. After a complete autopsy, the cause of death was determined to be acute Fentanyl toxicity due to a Fentanyl injection in the hospital. The manner of death was determined to be homicide. CONCLUSIONS What should an attending physician do in the rare case that the organ procurement team notices the patient is still alive? It is our opinion that: first, the organ procurement team should leave the room immediately and withdraw from the case, and second, the attending physician should let nature run its course and refrain from excessive medical intervention.

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.

Jahi McMath: Lessons Learned.

Jahi McMath's story has been an important reference in medicine and ethics as the landscape of the understanding of death by neurologic criteria is shifting, with families actively questioning the once-firm criterion. Palliative care providers have a role in seeking understanding and collaborating with families and clinical teams to navigate the many challenges that arise when a medical team has determined that a child has died, and their parents disagree. In this case-based narrative discussion we consider the complexity of the family experience of brain death.

Laser interstitial thermal therapy for in-field recurrence of brain metastasis after stereotactic radiosurgery: does treatment with LITT prevent a neurologic death?

Brain metastasis (BM) affects up to one-third of adults with cancer and carries a historically bleak prognosis. Despite advances in stereotactic radiosurgery (SRS), rates of in-field recurrence (IFR) after SRS range from 10 to 25%. High rates of neurologic death have been reported after SRS failure, particularly for recurrences deep in the brain and surgically inaccessible. Laser interstitial thermal therapy (LITT) is an emerging option in this setting, but its ability to prevent a neurologic death is unknown. In this study, we investigate the causes of death among patients with BM who undergo LITT for IFR after SRS. We conducted a single institution retrospective case series of patients with BM who underwent LITT for IFR after SRS. Clinical and demographic data were collected via chart review. The primary endpoint was cause of death. Between 2010 and 2018, 70 patients with BM underwent LITT for IFR after SRS. Median follow-up after LITT was 12.0 months. At analysis, 49 patients died; a cause was determined in 44. Death was neurologic in 20 patients and non-neurologic in 24. The 24-month cumulative incidence of neurologic and non-neurologic death was 35.1% and 38.6%, respectively. Etiologies of neurologic death included local recurrence (n = 7), recovery failure (n = 7), distant progression (n = 5), and other (n = 1). Among our patient population, LITT provided the ability to stabilize neurologic disease in up to 2/3 of patients. For IFR after SRS, LITT may represent a reasonable treatment strategy for select patients. Additional work is necessary to determine the extent to which LITT can prevent neurologic death after recurrence of BM.

Comparison of medical and allied health students' attitudes on organ donation: Case study from a private university in Karachi - Short Report.

Organ transplantation is often the only hope for patients with end-stage organ failure. Organ transplant surgeries are increasingly becoming available in Pakistan. From May-July 2017, using convenience sampling and statistical programme R 3.4.1, we assessed and compared the organ donation attitudes among medical and allied health undergraduate students of the Hamdard University in Karachi. Compared to non-medical students, medical students were more likely to be concerned that family members of brain-dead patients would be upset if approached for organ donation, and felt that appropriate time for bringing up organ donation would be after the declaration of brain death has taken place. Medical students also considered prolonging life by using human organ transplants more appropriate, and considered organ donation desirable when a patient has been declared brain dead. As demand of human organs for transplantation far exceeds the supply, there is need to better understand the dynamics underpinning positive attitudes towards organ donation, and to improve educational activities by encouraging debate and acceptance of organ donation for saving lives.

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.

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.

Rethinking Brain Death as a Legal Fiction: Is the Terminology the Problem?

Brain death, or the determination of death by neurological criteria, has been described as a legal fiction. Legal fictions are devices by which the law treats two analogous things (in this case, biological death and brain death) in the same way so that the law developed for one can also cover the other. Some scholars argue that brain death should be understood as a fiction for two reasons: the way brain death is determined does not actually satisfy legal criteria requiring the permanent cessation of all brain function, and brain death is not consistent with the biological conception of death as involving the irreversible cessation of the functioning of an organism as a whole. Critics counter that the idea that brain death is a legal fiction is deceptive and undemocratic. I will argue that diagnosing brain death as a hidden legal fiction is a helpful way to understand its historical development and current status. For the legal-fictions approach to be ethically justifiable, however, the fact that brain death is a legal fiction not aligned with the standard biological conception of death must be acknowledged and made transparent.

Brain Death: A Conclusion in Search of a Justification.

At its inception, "brain death" was proposed not as a coherent concept but as a useful one. The 1968 Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death gave no reason that "irreversible coma" should be death itself, but simply asserted that the time had come for it to be declared so. Subsequent writings by chairman Henry Beecher made clear that, to him at least, death was essentially a social construct, and society could define it however it pleased. The first widely endorsed attempt at a philosophical justification appeared thirteen years later, with a report from the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research and a seminal paper by James Bernat, Charles Culver, and Bernard Gert, which introduced the insightful tripartite scheme of concept, criterion, and tests for death. Their paper proposed that the correct concept of death is the "permanent cessation of functioning of the organism as a whole," which tenuously remains the mainstream concept to this day. In this essay, I focus on this mainstream concept, arguing that equating brain death with death involves several levels of incoherence: between concept and criterion, between criterion and tests, between tests and concept, and between all of these and actual brain death praxis.

A Conceptual Justification for Brain Death.

Among the old and new controversies over brain death, none is more fundamental than whether brain death is equivalent to the biological phenomenon of human death. Here, I defend this equivalency by offering a brief conceptual justification for this view of brain death, a subject that Andrew Huang and I recently analyzed elsewhere in greater detail. My defense of the concept of brain death has evolved since Bernard Gert, Charles Culver, and I first addressed it in 1981, a development that paralleled advances in intensive care unit treatment. The century-old concept of the organism as a whole provides the fundamental justification for the equivalency of brain death and human death. In our technological age, in which increasing numbers of components and systems of an organism can be kept alive, and for longer intervals, the permanent cessation of functioning of the organism as a whole is the phenomenon that best corresponds to its death.

Ischemic Stroke after Use of Cannabis: a Case Report and Review of Literature

Cannabis or marijuana is the most commonly used recreational drug after alcohol in the world, and usage is generally recognized as having few serious adverse effects. However, usage is restricted in South Korea. The report of ischemic stroke associated with cannabis is rare in literature. We present a case of a 47-year-old female patient with no underlying disease presenting with acute ischemic stroke after smoking cannabis in South Korea. The result for synthetic cannabinoid metabolites (delta-9 tetrahydrocannabinol) screening was positive. Absence of other vascular risk factors and drug screening results suggest a causal role of cannabis in this ischemic stroke case. The patient eventually progressed to brain death. The underlying mechanism, clinical manifestation, and imaging findings of cannabis-related stroke will be reviewed.

Ginkgo biloba extract EGb761 attenuates brain death-induced renal injury by inhibiting pro-inflammatory cytokines and the SAPK and JAK-STAT signalings.

This study aimed to investigate the protective effects of EGb761, a Ginkgo Biloba extract, against brain death-induced kidney injury. Sixty male Sprague Dawley rats were randomly divided into six groups: sham, brain-death (BD), BD + EGb b48h (48 hours before BD), BD + EGb 2 h (2 hours after BD), BD + EGb 1 h, and BD + EGb 0.5 h. Six hours after BD, serum sample and kidney tissues were collected for analyses. The levels of blood urea nitrogen (BUN) and serum creatinine significantly elevated in the BD group than in sham group. In all the EGb761-treated BD animals except for the BD + Gb 2 h group, the levels of BUN and serum creatinine significantly reduced (all P < 0.01). EGb761 attenuated tubular injury and lowered the histological score. In addition, the longer duration of drug treatment was, the better protective efficacy could be observed. EGb761 significantly reduced IL-1ß, IL-6, TNF-α, MCP-1, IP-10 mRNA expression and macrophage infiltration in the kidney. EGb761 treatment at 48 hour before brain death significantly attenuate the levels of p-JNK-MAPK, p-p38-MAPK, and p-STAT3 proteins (all P < 0.05, compared to BD group). In summary, our data showed that EGb761 treatment protected donor kidney from BD-induced damages by blocking SAPK and JAK-STAT signalings. Early administration of EGb761 can provide better protective efficacy.