Neurological Criteria Research Articles

Criteria for brain death in Denmark

In 1990, the Danish brain death legislation was adopted by the Danish Parliament. Each year, around 100 patients in Denmark fulfil criteria for brain death/death by neurological criteria (BD/DNC). In this review of current Danish criteria including the indication for ancillary investigation, which in Denmark is digital subtraction angiography (DSA), we conclude that the time has come to revise the national BD/DNC criteria. We propose that visible anoxic-ischaemic encephalopathy on brain CT after cardiac arrest does not require evaluation by ancillary testing, and that CT-angiography can be used instead of DSA.

Update in Pediatric Neurocritical Care: What a Neurologist Caring for Critically Ill Children Needs to Know.

Currently nearly one-quarter of admissions to pediatric intensive care units (PICUs) worldwide are for neurocritical care diagnoses that are associated with significant morbidity and mortality. Pediatric neurocritical care is a rapidly evolving field with unique challenges due to not only age-related responses to primary neurologic insults and their treatments but also the rarity of pediatric neurocritical care conditions at any given institution. The structure of pediatric neurocritical care services therefore is most commonly a collaborative model where critical care medicine physicians coordinate care and are supported by a multidisciplinary team of pediatric subspecialists, including neurologists. While pediatric neurocritical care lies at the intersection between critical care and the neurosciences, this narrative review focuses on the most common clinical scenarios encountered by pediatric neurologists as consultants in the PICU and synthesizes the recent evidence, best practices, and ongoing research in these cases. We provide an in-depth review of (1) the evaluation and management of abnormal movements (seizures/status epilepticus and status dystonicus); (2) acute weakness and paralysis (focusing on pediatric stroke and select pediatric neuroimmune conditions); (3) neuromonitoring modalities using a pathophysiology-driven approach; (4) neuroprotective strategies for which there is evidence (e.g., pediatric severe traumatic brain injury, post-cardiac arrest care, and ischemic stroke and hemorrhagic stroke); and (5) best practices for neuroprognostication in pediatric traumatic brain injury, cardiac arrest, and disorders of consciousness, with highlights of the 2023 updates on Brain Death/Death by Neurological Criteria. Our review of the current state of pediatric neurocritical care from the viewpoint of what a pediatric neurologist in the PICU needs to know is intended to improve knowledge for providers at the bedside with the goal of better patient care and outcomes.

Verification of Death by Neurologic Criteria: A Survey of 12 Organ Procurement Organizations Across the United States.

The Center for Medicare and Medicaid Services requires Organ Procurement Organizations (OPOs) to verify and document that any potential organ donor has been pronounced dead per applicable legal requirements of local, state, and federal laws. However, OPO practices regarding death by neurologic criteria (DNC) verification are not standardized, and little is known about their DNC verification processes. This study aimed to explore OPO practices regarding DNC verification in the United States. An electronic survey was sent to all 57 OPOs in the United States from June to September 2023 to assess verification of policies and practices versus guidelines, concerns about policies and practices, processes to address concerns about DNC determination, and communication practices. Representatives from 12 OPOs across six US regions completed the entire survey; 8 of 12 reported serving > 50 referral hospitals. Most respondents (11 of 12) reported comparing their referral hospital's DNC policies with the 2010 American Academy of Neurology Practice Parameter and/or other (4 of 12) guidelines. Additionally, most (10 of 12) reported independently reviewing and verifying each DNC determination. Nearly half (5 of 12) reported concerns about guideline-discordant hospital policies, and only 3 of 12 thought all referral hospitals followed the 2010 American Academy of Neurology Practice Parameter in practice. Moreover, 9 of 12 reported concerns about clinician knowledge surrounding DNC determination, and most (10 of 12) reported having received referrals for patients whose DNC declaration was ultimately reversed. All reported experiences in which their OPO requested additional assessments (11 of 12 clinical evaluation, 10 of 12 ancillary testing, 9 of 12 apnea testing) because of concerns about DNC determination validity. Accurate DNC determination is important to maintain public trust. Nearly all OPO respondents reported a process to verify hospital DNC policies and practices with medical society guidelines. Many reported concerns about clinician knowledge surrounding DNC determination and guideline-discordant policies and practices. Educational and regulatory advocacy efforts are needed to facilitate systematic implementation of guideline-concordant practices across the country.

Use of neurological criteria to declare death in children.

Accurate determination of death is a necessary responsibility of the medical profession. Brain death, or death by neurological criteria (DNC), can be legally declared after the determination of permanent loss of clinical brain function, including the capacity for consciousness, brainstem reflexes, and the ability to breathe spontaneously. Despite longstanding debates over the exact definition of brain death or DNC and how it is determined, most middle- and high-income countries have compatible medical protocols and legal policies for brain death or DNC. This review summarizes the 2023 updated guidelines for brain death or DNC determination, which integrate adult and pediatric diagnostic criteria. We discuss the clinical challenges related to brain death or DNC determination in infants and young children. We emphasize that physicians must follow the standardized and meticulous evaluation processes outlined in these guidelines to reduce diagnostic error and ensure no false positive determinations. An essential component of the brain death or DNC evaluation is appropriate and transparent communication with families. Ongoing efforts to promote consistency and legal uniformity in the declaration of death are needed.

Communicating About Death by Neurologic Criteria #479.

Communicating About Death by Neurologic Criteria #479.

Sowing “seeds of trust”: How trust in normothermic regional perfusion is built in a continuum of care

Normothermic regional perfusion (NRP) is a promising technology to improve organ transplantation outcomes by reversing ischemic injury caused by controlled donation after circulatory determination of death. However, it has not yet been implemented in Canada due to ethical questions. These issues must be resolved to preserve public trust in organ donation and transplantation. This qualitative, constructivist grounded theory study sought to understand how those most impacted by NRP perceived the ethical implications. We interviewed 29 participants across stakeholder groups of donor families, organ recipients, donation and transplantation system leaders, and care providers. The interview protocol included a short presentation about the purpose of NRP and procedures in abdomen versus chest and abdomen NRP, followed by questions probing potential violations of the dead donor rule and concerns regarding brain reperfusion. The results present a grounded theory placing NRP within a trust-building continuum of care for the donor, their family, and organ recipients. Stakeholders consistently described both forms of NRP as an ethical intervention, but their rationales were predicated on assumptions that neurologic criteria for death had been met following circulatory death determination. Empirical validation of these assumptions will help ground the implementation of NRP in a trust-preserving way.

Early Cardiac Evaluation, Abnormal Test Results, and Associations with Outcomes in Patients with Acute Brain Injury Admitted to a Neurocritical Care Unit.

Background: to examine factors associated with cardiac evaluation and associations between cardiac test abnormalities and clinical outcomes in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), spontaneous subarachnoid hemorrhage (SAH), spontaneous intracerebral hemorrhage (sICH), and traumatic brain injury (TBI) requiring neurocritical care. Methods: In a cohort of patients ≥18 years, we examined the utilization of electrocardiography (ECG), beta-natriuretic peptide (BNP), cardiac troponin (cTnI), and transthoracic echocardiography (TTE). We investigated the association between cTnI, BNP, sex-adjusted prolonged QTc interval, low ejection fraction (EF < 40%), all-cause mortality, death by neurologic criteria (DNC), transition to comfort measures only (CMO), and hospital discharge to home using univariable and multivariable analysis (adjusted for age, sex, race/ethnicity, insurance carrier, pre-admission cardiac disorder, ABI type, admission Glasgow Coma Scale Score, mechanical ventilation, and intracranial pressure [ICP] monitoring). Results: The final sample comprised 11,822 patients: AIS (46.7%), sICH (18.5%), SAH (14.8%), and TBI (20.0%). A total of 63% (n = 7472) received cardiac workup, which increased over nine years (p < 0.001). A cardiac investigation was associated with increased age, male sex (aOR 1.16 [1.07, 1.27]), non-white ethnicity (aOR), non-commercial insurance (aOR 1.21 [1.09, 1.33]), pre-admission cardiac disorder (aOR 1.21 [1.09, 1.34]), mechanical ventilation (aOR1.78 [1.57, 2.02]) and ICP monitoring (aOR1.68 [1.49, 1.89]). Compared to AIS, sICH (aOR 0.25 [0.22, 0.29]), SAH (aOR 0.36 [0.30, 0.43]), and TBI (aOR 0.19 [0.17, 0.24]) patients were less likely to receive cardiac investigation. Patients with troponin 25th-50th quartile (aOR 1.65 [1.10-2.47]), troponin 50th-75th quartile (aOR 1.79 [1.22-2.63]), troponin >75th quartile (aOR 2.18 [1.49-3.17]), BNP 50th-75th quartile (aOR 2.86 [1.28-6.40]), BNP >75th quartile (aOR 4.54 [2.09-9.85]), prolonged QTc (aOR 3.41 [2.28; 5.30]), and EF < 40% (aOR 2.47 [1.07; 5.14]) were more likely to be DNC. Patients with troponin 50th-75th quartile (aOR 1.77 [1.14-2.73]), troponin >75th quartile (aOR 1.81 [1.18-2.78]), and prolonged QTc (aOR 1.71 [1.39; 2.12]) were more likely to be associated with a transition to CMO. Patients with prolonged QTc (aOR 0.66 [0.58; 0.76]) were less likely to be discharged home. Conclusions: This large, single-center study demonstrates low rates of cardiac evaluations in TBI, SAH, and sICH compared to AIS. However, there are strong associations between electrocardiography, biomarkers of cardiac injury and heart failure, and echocardiography findings on clinical outcomes in patients with ABI. Findings need validation in a multicenter cohort.

An Update on Brain Death/Death by Neurologic Criteria since the World Brain Death Project.

The World Brain Death Project (WBDP) is a 2020 international consensus statement that provides historical background and recommendations on brain death/death by neurologic criteria (BD/DNC) determination. It addresses 13 topics including: (1) worldwide variance in BD/DNC, (2) the science of BD/DNC, (3) the concept of BD/DNC, (4) minimum clinical criteria for BD/DNC determination, (5) beyond minimum clinical BD/DNC determination, (6) pediatric and neonatal BD/DNC determination, (7) BD/DNC determination in patients on ECMO, (8) BD/DNC determination after treatment with targeted temperature management, (9) BD/DNC documentation, (10) qualification for and education on BD/DNC determination, (11) somatic support after BD/DNC for organ donation and other special circumstances, (12) religion and BD/DNC: managing requests to forego a BD/DNC evaluation or continue somatic support after BD/DNC, and (13) BD/DNC and the law. This review summarizes the WBDP content on each of these topics and highlights relevant work published from 2020 to 2023, including both the 192 citing publications and other publications on BD/DNC. Finally, it reviews questions for future research related to BD/DNC and emphasizes the need for national efforts to ensure the minimum standards for BD/DNC determination described in the WBDP are included in national BD/DNC guidelines and due consideration is given to the recommendations about social and legal aspects of BD/DNC determination.

Assessing Outcomes of Patients Subject to Intensive Care to Facilitate Organ Donation: A Spanish Multicenter Prospective Study.

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.

Aproximación bioética a la definición de persona a través del diagnóstico de muerte encefálica global. Importancia en el ámbito de los trasplantes de órganos

The acceptance of the diagnosis of death based on neurological criteria (brain death) was not quickly or unanimously accepted by the scientific community, nor by the philosophical world. The persistence of biological activity in the corporeality of human beings in brain death has served to refute this concept in the medical, anthropological and philosophical fields. In this study, characteristics of the different hierarchical levels of living organisms are established, focusing mainly on the uniqueness of complex biological structures (organic biotope), human corporality, and the person. A series of characteristics of each of these levels are described and it is evident how in the remaining corporality after brain death all the characteristics of the person have disappeared (rationality, self-awareness, moral conduct, freedom, manifestation, project). , identity of person, immanence of person, transcendence of person culmination, etc.) and exclusive of it. In a situation of whole brain death, only those characteristics that are inherent to it but comparable to what we could find in other developed living beings remain in the body, with those characteristics exclusive to the person having disappeared. It can be concluded that the irreversible cessation of all intrinsically neurological functions of the entire brain (whole brain death) is the death of the person due to the disappearance of all those essential and exclusive characteristics of the person, leaving only the activity of the organic biotope and human corporality.

Survey of Nationwide Organ Procurement Organization (OPO) Practices in Verification of Death by Neurologic Criteria (DNC) (P1-2.001)

Survey of Nationwide Organ Procurement Organization (OPO) Practices in Verification of Death by Neurologic Criteria (DNC) (P1-2.001)

Donation after Brain Death and Circulatory Death in Turkey: Current Status.

Tissue and organ transplantation is the best treatment option for end-stage organ failure. However, organ shortage still remains to be the greatest challenge facing the field of organ transplantation. Millions of people die and are buried with healthy organs, which could save the lives of many patients who continue to wait on transplant lists. Countries must aim to work towards a system of matching organs as much as possible with the deceased donation to meet the growing demand for organs. This action will not only result in the reduction of organ trafficking activities but shall also make an enormous difference to those patients awaiting transplants where living organ donors are not an option. Donation after circulator death (DCD) has gained much attention over the last decade as one of the accepted practices in order to expand the donor pool. DCD donation takes place after declaration of death using cardio-respiratory criteria in contrast to donation after brain death (DBD) where neurological criteria are used. Although DCD remains a focus of interest and contributes to donor numbers in many countries, it also poses many challenges medically, ethically and legally.

(445) - Longer Time from Death Determination Using Neurologic Criteria (DNC) to Cross Clamp is Associated with Worse Cardiac Transplant Outcomes

(445) - Longer Time from Death Determination Using Neurologic Criteria (DNC) to Cross Clamp is Associated with Worse Cardiac Transplant Outcomes

The importance of public engagement in clinical xenotransplantation

AbstractOver the past several decades, significant scientific progress in xenotransplantation has brought the field to the threshold of clinical trials. In the past 3 years in the United States, experimental pig kidney and heart xenotransplantation have been performed on human subjects recently declared dead by neurological criteria (decedents). In addition, two pig heart transplants have been carried out in living patients under the United States Food and Drug Administration's expanded access guidelines. However, though there has been a flurry of activity there remain unanswered questions regarding how the public views xenotransplantation, what concerns may exist, and how to address these concerns in a meaningful way. This paper aims to underscore the importance of public engagement in xenotransplantation, emphasizing the ongoing need for studies to assess public opinions. The current evidence on public engagement studies is reviewed and gaps in our understanding are identified. We propose practical steps to advance this field. Additional studies to determine the extent of racial/ethnic differences in attitudes to xenotransplantation should be conducted. Empirical and descriptive analysis of certain religious viewpoints—especially minority faiths—would be valuable. As public engagement is an important aspect of public acceptance of novel research that is accompanied by risk, we suggest that xenotransplantation biotechnology companies might consider leading the way in funding this research.

Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline: Report of the AAN Guidelines Subcommittee, AAP, CNS, and SCCM

Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline: Report of the AAN Guidelines Subcommittee, AAP, CNS, and SCCM

New developments in guidelines for brain death/death by neurological criteria.

The declaration of brain death (BD), or death by neurological criteria (DNC), is medically and legally accepted throughout much of the world. However, inconsistencies in national and international policies have prompted efforts to harmonize practice and central concepts, both between and within countries. The World Brain Death Project was published in 2020, followed by notable revisions to the Canadian and US guidelines in 2023. The mission of these initiatives was to ensure accurate and conservative determination of BD/DNC, as false-positive determinations could have major negative implications for the medical field and the public's trust in our ability to accurately declare death. In this Review, we review the changes that were introduced in the 2023 US BD/DNC guidelines and consider how these guidelines compare with those formulated in Canada and elsewhere in the world. We address controversies in BD/DNC determination, including neuroendocrine function, consent and accommodation of objections, summarize the legal status of BD/DNC internationally and discuss areas for further BD/DNC research.

Brain death/death by neurologic criteria: What you need to know.

Since the beginning of time, man has been intrigued with the question of when a person is considered dead. Traditionally, death has been considered the cessation of all cardiorespiratory function. At the end of the last century a new definition was introduced into the lexicon surrounding death in addition to cessation of cardiac and respiratory function: Brain Death/Death by Neurologic Criteria (BD/DNC). There are medical, legal, ethical, and even theological controversies that surround this diagnosis. In addition, there is no small amount of confusion among medical practitioners regarding the diagnosis of BD/DNC. For families enduring the devastating development of BD/DNC in their loved one, it is the duty of the principal caregiver to provide a transparent presentation of the clinical situation and clear definitive explanation of what constitutes BD/DNC. In this report, we present a historical outline of the development of BD/DNC as a clinical entity, specifically how one goes about making a determination of BD/DNC, what steps are taken once a diagnosis of BD/DNC is made, a brief discussion of some of the ethical/moral issues surrounding this diagnosis, and finally the caregiver approach to the family of a patient who had been declared with BD/DNC. It is our humble hope that with a greater understanding of the myriad of complicated issues surrounding the diagnosis of BD/DNC that the bedside caregiver can provide needed closure for both the patient and the family enduring this critical time in their life.

Uncontrolled organ donation after out-of-hospital cardiac arrest. Literature review

Organ transplantation is the best therapy for terminal and irreversible organ failure. The global development of organ transplantation as a type of medical care is inextricably linked to the establishment of neurological criteria for declaring human death (brain death). In the early evolutionary period of transplantation, organs were used, mainly kidneys, obtained from donors whose death was ascertained in accordance with the generally accepted criteria of cessation of blood circulation and respiration. As this type of organ donation developed, numerous terms were used in the world literature to designate it, such as ‘asystolic donors’, ‘non-heart beating donors’, ‘donors after cardiac death’, etc. In Russia, there is an established practice of dealing with donors after cardiac death (DCD), but the active development of Russian transplantology in the last 20 years is primarily associated with brain-dead organ donation. However, countries with the most active and advanced organ donation practices have in recent years been successfully dealing with donors who have suffered sudden out-of-hospital cardiac arrest (OHCA). Previously, this type of donation was considered inaccessible due to the unacceptable warm ischemia time and consequently severe damage to donor organs. Due to the development of new technologies in emergency medical care, it became possible to transport a patient with clinical death that occurred in an outof-hospital setting, to the hospital, while providing cardiopulmonary resuscitation by means of automatic chest compression and artificial ventilation. The article presents historical aspects of donation after cardiac death, and the most actualized definitions and practices of dealing with such donors.

Resolving the Problem of Defining Death by Prioritizing the Neurological Criterion

One of the major complicating factors when evaluating death by the cardiological criteria is the advent of ventilators and their widespread adoption in recent decades. A person who once was considered dead can now continue take in oxygen and perfuse blood throughout the body. However, use of the neurological criteria instead has its own detractors, with many say the criteria do not fully evaluate brain function. In this article, Turner suggests that the neurological criteria is necessary to avoid the ambiguity brought on by new technologies and that, rather than combining criteria in any way, cardiological criteria should be abandoned entirely in favor of a primary focus on brain death.

Moral Certitude in Brain Death Diagnoses in Light of OrganEx and BrainEx

Death by neurological criteria has been at the center of ethical debates. I argue that brain death is a valid determination of death. This follows from an understanding that the brain is the effective integrator of the body and that following the death of the brain the body stops functioning as an integrated whole. Questions regarding this certainty have been reignited, however, by a study out of Yale that demonstrated synthetic perfusates, such as the compounds dubbed BrainEx and OrganEx, could restore cellular and even organ function in a porcine body and brain after death. Through analyzing medical, scientific, and theological literature I argue that even in the face of developing scientific technology moral certitude in brain death determinations is secure.