No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Development of the concept of brain death: international data review
Abstract
The concept of brain death was introduced in the late 1960s and continues to develop. The article presents a brief history of the evolution of the idea of death by neurologic criteria. The concept is accepted worldwide, but there is still considerable variability in brain death determination protocols. New treatments for critical patients change the preconditions for brain death testing. The refinement of diagnostic techniques improves the capabilities of confirmatory tests. Controversial cases of determination of brain death cause public resonance and justified criticism of opponents of the concept. All these factors lead to review of some concept statements, terminology and update diagnostic protocols. In 2020, an international expert working group presented the minimum clinical standards for determination of brain death/death by neurologic criteria with guidance for various clinical circumstances. Some countries have already started to implement international recommendations and revise national diagnostic protocols. The extensive debate accompanying this process is an important contribution to the improvement of the concept of brain death.
ResearchGate has not been able to resolve any citations for this publication.
Background
Computed tomography angiography (CTA) has been investigated as a confirmatory study (CS) for the diagnosis of brain death (BD). International consensus regarding its use, study parameters, and evaluation criteria is lacking. In the German BD guideline, a CTA protocol was first introduced in 2015.
Methods
The authors obtained a comprehensive dataset of all BD examinations in adults from the German organ procurement organization to investigate implementation, results, and impact of CTA on BD determination during the first 4 years.
Results
In 5152 patients with clinically absent brain function, 1272 CTA were reported by 676 hospitals. Use of CTA increased from 17.2% of patients in the first year to 29.7% in the final year. CTA replaced other CS such as electroencephalography without increasing overall CS frequency. Technical failure was rare (0.9%); 89.3% of studies were positive. Negative results (9.8%) were more frequent with secondary brain injury, longer duration of the clinical BD syndrome, or unreliable clinical assessment. Median time to diagnosis was longer with CTA (2.6 h) versus other CS (1.6 h). CTA had no differential impact on the rate of confirmed BD and did not improve access of small hospitals to CS for BD determination.
Conclusions
CTA expands the range of available CS for the diagnosis of BD in adults. Real‐world evidence from a large cohort confirms usability of the German CTA protocol within the guideline‐specified context.
Background and Objectives
The purpose of this guideline is to update the 2010 American Academy of Neurology (AAN) brain death/death by neurologic criteria (BD/DNC) guideline for adults and the 2011 American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine guideline for infants and children and to clarify the BD/DNC determination process by integrating guidance for adults and children into a single guideline. Updates in this guideline include guidance related to conducting the BD/DNC evaluation in the context of extracorporeal membrane oxygenation, targeted temperature management, and primary infratentorial injury.
Methods
A panel of experts from multiple medical societies developed BD/DNC recommendations. Because of the lack of high-quality evidence on the subject, a novel, evidence-informed formal consensus process was used. This process relied on the panel experts' review and detailed knowledge of the literature surrounding BD/DNC to guide the development of preliminary recommendations. Recommendations were formulated and voted on, using a modified Delphi process, according to the 2017 AAN Clinical Practice Guideline Process Manual.
Major Recommendations
Eighty-five recommendations were developed on the following: (1) general principles for the BD/DNC evaluation, (2) qualifications to perform BD/DNC evaluations, (3) prerequisites for BD/DNC determination, (4) components of the BD/DNC neurologic examination, (5) apnea testing as part of the BD/DNC evaluation, (6) ancillary testing as part of the BD/DNC evaluation, and (7) special considerations for BD/DNC determination.
This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists’ Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.
This multidisciplinary consensus statement was produced following a recommendation by the Faculty of Intensive Care Medicine to develop a UK guideline for ancillary investigation, when one is required, to support the diagnosis of death using neurological criteria. A multidisciplinary panel reviewed the literature and UK practice in the diagnosis of death using neurological criteria and recommended cerebral CT angiography as the ancillary investigation of choice when death cannot be confirmed by clinical criteria alone. Cerebral CT angiography has been shown to have 100% specificity in supporting a diagnosis of death using neurological criteria and is an investigation available in all acute hospitals in the UK. A standardised technique for performing the investigation is described alongside a reporting template. The panel were unable to make recommendations for ancillary testing in children or patients receiving extracorporeal membrane oxygenation.
Background:
Brain death/death by neurologic criteria (BD/DNC) guidelines are routinely analyzed, compared and updated in the majority of countries and are later implemented as national criteria. At the same time, extensive works have been conducted in order to unify clinical procedures and to validate and implement new technologies into a panel of ancillary tests. Recently evaluated computed tomography angiography and computed tomography perfusion (CTA/CTP) seem to be superior to traditionally used digital subtraction angiography (DSA), transcranial Doppler (TCD) and cerebral perfusion scintigraphy for diagnosis of cerebral circulatory arrest (CCA). In this narrative review, we would like to demonstrate scientific evidence supporting the implementation of CTA/CTP in Polish guidelines for BD/DNC diagnosis. Research and implementation process: In the first of our base studies concerning the potential usefulness of CTA/CTP for the confirmation of CCA during BD/DNC diagnosis procedures, we showed a sensitivity of 96.3% of CTA in a group of 82 patients. CTA was validated against DSA in this report. In the second study, CTA showed a sensitivity of 86% and CTP showed a sensitivity of 100% in a group of 50 patients. In this study, CTA and CTP were validated against clinical diagnosis of BD/DNC supported by TCD. Additionally, we propose our CCA criteria for CTP test, which are based on ascertainment of cerebral blood flow (CBF) < 10 mL/100 g/min and cerebral blood volume < 1 mL/100 g in regions of interest (ROIs) localized in all brain regions. Based on our research results, CTA/CTP methods were implemented in Polish BD/DNC criteria. To our knowledge, CTP was implemented for the first time in national guidelines.
Conclusions:
CTA and CTP-derived CTA might be in future the tests of choice for CCA diagnosis, proper and/or Doppler pretest might significantly increase sensitivity of CTA in CCA diagnosis procedures. Whole brain CTP might be decisive in some cases of inconclusive CTA. Implementation of CTA/CTP in the Polish BD/DNC diagnosis guidelines does not show any major obstacles. We believe that in next edition of "The World Brain Death Project" CTA and CTP will be recommended as ancillary tests of choice for CCA confirmation during BD/DNC diagnosis procedures.
Importance
There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries.
Objective
To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel.
Process
Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery.
Evidence Synthesis
Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed.
Recommendations
Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing. Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability.
Conclusions and Relevance
This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.
In this paper, I reviewed the case of Jahi McMath who was diagnosed as being in brain death (BD). Nonetheless, ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to “Mother Talks” stimulus. She was clinically in a state of unarousable and unresponsiveness, without evidence of awareness of self or environment, but full absence of brainstem reflexes, and partial responsiveness rejected the possibility of being in coma. Jahi was not a UWS, because she was not in a wakefulness state, and showed partial responsiveness. LIS patients are wakeful and aware, and although these cases are quadriplegic, they fully or partially preserve brainstem reflexes, vertical eye movements, and/or blinking, and respire by their own, rejecting the possibility of classifying her as a LIS patient. She was not a MCS because she did not preserve arousal, and only partially preserved awareness. The CRS-R resulted in a very low score, not corresponding with MCS patients. MCS patients fully or partially preserve brainstem reflexes, and usually breathe by their own. MCS has been always described as a transitional state between coma, UWS, but MCS has never been reported in a patient who has all clinical BD findings. This case doesn’t contradict the concept of BD, but brings again to discussion the needs of using ancillary tests in BD. I concluded that Jahi represented a new state of disorder of consciousness, non-previously described, that I have termed: “responsive unawake syndrome” (RUS).
Objective
To determine the optimal observation period (OBP) in adults with a clinical diagnosis of brain death (BD) using electroencephalography (EEG) or computerized tomography angiography (CTA).
Methods
We conducted a retrospective observational analysis of adult patients with a diagnosis of BD from January 2000 to February 2017. The optimal OBP was defined as the minimum time interval from the first complete clinical neurological examination (CNE) that ensures that neither a second CNE nor any ancillary test (AT) performed after this period would fail to confirm BD.
Results
The study sample included 447 patients. In the supratentorial group, the first AT confirmed BD in 389 cases (98%), but in 8 (2%) cases the complementary test was incongruent. In this group, 8 of 245 patients in whom the first AT was carried out within the first 2 h after a complete CNE had a non-confirmatory test of BD versus none of 152 in whom the first AT was delayed more than 2 h (3.0% vs 0.0%; p = 0.026). In the infratentorial group, we found a higher probability of obtaining a first non-confirmatory AT of BD (34% vs 2%; p = 0.0001) and an OBP greater than 32.5 h was necessary to confirm a BD diagnosis.
Conclusions
We found important differences in the confirmation of BD diagnosis between primary supratentorial and infratentorial lesion, and identified an optimal OBP of 2 h in patients with supratentorial lesions. By contrast, in primary posterior fossa/infratentorial lesions, the determination of an optimal OPB remains less accurate and hence more challenging.
This report summarizes the results of the first phase in the development of international guidelines for death determination, focusing on the biology of death and the dying process, developed by an invitational forum of international content experts and representatives of a number of professional societies.
Precise terminology was developed in order to improve clarity in death discussion and debate. Critical events in the physiological sequences leading to cessation of neurological and/or circulatory function were constructed. It was agreed that death determination is primarily clinical and recommendations for preconditions, confounding factors, minimum clinical standards and additional testing were made. A single operational definition of human death was developed: 'the permanent loss of capacity for consciousness and all brainstem functions, as a consequence of permanent cessation of circulation or catastrophic brain injury'. In order to complete the project, in the next phase, a broader group of international stakeholders will develop clinical practice guidelines, based on comprehensive reviews and grading of the existing evidence.
To characterize the present state of brain death (BD) determination in actual practice relative to contemporary American Academy of Neurology (AAN) guidelines.
We reviewed the charts of all adult (16 years and older) BD organ donors during 2011 from 68 heterogeneous hospitals in the Midwest United States. Data were collected across 5 categories: guideline performance, preclinical testing, clinical examination, apnea testing, and use of ancillary tests. Practice within categories and overall adherence to AAN guidelines were assessed.
Two hundred twenty-six BD organ donors were included. Practice exceeded recommendations in guideline performance but varied widely and deviated from AAN guidelines in all other categories. One hundred two (45.1%) had complete documentation of brainstem areflexia and absent motor response. One hundred sixty-six (73.5%) had completed apnea testing. Of the 60 without completed apnea testing, 56 (93.3%) had ancillary tests consistent with BD. Overall, 101 (44.7%) strictly and 84 (37.2%) loosely adhered to contemporary AAN guidelines.
There is wide variability in the documentation of BD determination, likely reflecting similar variability in practice. This is a call for improved documentation, better uniformity of policies, and comprehensive and strategically targeted educational initiatives to ensure consistently contemporary approaches to BD determination in every patient.
The data reviewed here suggest the possibility that a global reduction of blood supply to the whole brain or solely to the infratentorial structures down to the range of ischemic penumbra for several hours or a few days may lead to misdiagnosis of irreversible brain or brain stem damage in a subset of deeply comatose patients with cephalic areflexia. The following proposals are advanced: 1) the lack of any set of clinically detectable brain functions does not provide a safe diagnosis of brain or brain stem death; 2) apnea testing may induce irreversible brain damage and should be abandoned; 3) moderate hypothermia, antipyresis, prevention of arterial hypotension, and occasionally intra-arterial thrombolysis may contribute to good recovery of a possibly large subset of cases of brain injury currently regarded as irreversible; 4) confirmatory tests for brain death should not replace or delay the administration of potentially effective therapeutic measures; 5) in order to validate confirmatory tests, further research is needed to relate their results to specific levels of blood supply to the brain. The current criteria for the diagnosis of brain death should be revised.
We have a reason to value the Uniform Determination of Death Act (UDDA). Since enactment, the UDDA has been of paramount importance to US citizens, families of comatose patients, and the health care professionals who care for them. The UDDA sets forth two standards for determining death and leaves to the medical community to elaborate criteria by which physicians can determine when those standards have been met. Neurologists and neurocritical care experts always have been center stage in this effort. Perfectly established, why change it? What ignited the recent review of the UDDA were lawsuits questioning medical (neurological) authority leading to the wording and accuracy of the UDDA being revisited. The major objections to the language of the UDDA by several groups led a committee appointed by the Uniform Law Commission to consider several substantial changes in the Act. After several years of discussion without reaching a consensus, the committee’s chair suspended the effort. Upending the UDDA will lead to a legal crisis and confusion across the states. We present our main arguments against revising this statute and argue that the committee’s failure to revise the UDDA should actually be seen as a necessary success.
Jahi McMath was diagnosed brain dead on 12/12/2013 in strict accordance with both the pediatric and adult Guidelines, reinforced by 4 isoelectric electroencephalograms and a radionuclide scan showing intracranial circulatory arrest. Her magnetic resonance imaging scan 9 1/2 months later surprisingly showed gross integrity of cortex, basal ganglia, thalamus, and upper brainstem. The greatest damage was in the white matter, which was extensively demyelinated and cystic, and in the lower brainstem, most likely from partial herniation that resolved. The apparent integrity of gray matter and the ascending reticular activating system may have provided a potential structural basis for the reemergence of some limited brain functions, while the white matter and lower brainstem lesions would have caused severe motor disability, brainstem areflexia and apnea. The findings indicate that there could never have been a period of sustained intracranial circulatory arrest. Rather, at the time of brain death diagnosis, low blood flow below the detection threshold of the radionuclide scan was sufficient to maintain widespread neuronal viability, though insufficient to support synaptic function. Her case represents the first indirect confirmation of the reality and clinical relevance of global ischemic penumbra, hypothesized in 1999 as a generally unacknowledged and possibly common brain death mimic.
Objective
To identify similarities and differences in protocols on determination of brain death/death by neurologic criteria (BD/DNC) around the world.
Methods
We collected and reviewed official national BD/DNC protocols from contacts around the world between January 2018 and April 2019.
Results
We communicated with contacts in 136 countries and found that 83 (61% of countries with contacts identified, 42% of the world) had BD/DNC protocols, 78 of which were unique. Protocols addressed the following prerequisites and provided differing instructions: drug clearance (64, 82%), temperature (61, 78%), laboratory values (56, 72%), observation period (37, 47%), and blood pressure (34, 44%). Protocols did not consistently identify the same components for the clinical examination of brain death; 70 (90%) included coma, 70 (90%) included the pupillary reflex, 68 (87%) included the corneal reflex, 67 (86%) included the oculovestibular reflex, 64 (82%) included the gag reflex, 62 (79%) included the cough reflex, 58 (74%) included the oculocephalic reflex, 37 (47%) included noxious stimulation to the face, and 22 (28%) included noxious stimulation to the limbs. Apnea testing was mentioned in 71 (91%) protocols; there was variability in the technique and target across protocols. Ancillary testing was included as a requirement for all determinations of BD/DNC in 22 (28%) protocols.
Conclusions
There is considerable variability in BD/DNC determination protocols around the world. Medical standards for death should be the same everywhere. We recommend that a worldwide consensus be reached on the minimum standards for BD/DNC.
From the start, I followed the case of Jahi McMath with great interest. In December 2013, she clearly fulfilled the diagnostic criteria for brain death. As a neurologist with a special interest in chronic brain death, I was not surprised that, after she was flown to New Jersey, where she became statutorily resurrected and was treated as a comatose patient, Jahi's condition quickly improved. In 2014, her family reported that she sometimes responded to simple motor commands. I shared the general skepticism regarding these reports, assuming that the family was in denial and was misinterpreting spinal myoclonus (a rapid, involuntary twitch generated by the spinal cord) as volitional. The family had noticed that when Jahi's heart rate was above eighty beats per minute, she was more likely to respond, as though the heart rate reflected some sort of inner level of arousal. So they began to make video recordings. I have been privileged to be entrusted with copies of these recordings, forty‐eight of which proved suitable for assessing alleged responsiveness. All have been certified by a forensic video expert as unaltered. The first thing that struck me was that the great majority of the alleged responses were not spinal myoclonus. In fact, they did not resemble any type of spontaneous, involuntary movement described in patients paralyzed from high spinal cord lesions.
This article clarifies some issues raised by Dr. Ariane Lewis in her recent “Current Opinion/Arguments” article on the case of Jahi McMath. Review of case materials. Jahi’s case most likely represents an instance of global ischemic penumbra (GIP) mimicking brain death (BD), with intracranial blood flow too low to support neuronal function or to be detected by radionuclide scan but sufficient to prevent widespread necrosis. Her MRI scan 9 months after the ischemic insult showed gross preservation of cortical and internal structures, incompatible with there ever having been a period of completely absent blood flow. Regarding Jahi’s alleged intermittent responsiveness, the set of videos, unsystematic as they are, constitutes convincing evidence that her movements in seeming response to command are not of spinal cord origin and are indeed voluntary responses, placing her in the category of minimally conscious state (MCS). In the absence of serial examinations by experts in MCS, the benefit of the doubt should be given. Unfortunately, her death on June 22, 2018, 4½ years after the diagnosis of BD, precludes such examinations. During those 4½ years, Jahi underwent menarche, with three documented menstrual periods, and ongoing pubertal development. Her case is an important example of false-positive diagnosis of BD, demonstrating the inability of current diagnostic standards to distinguish true BD from potentially reversible brain nonfunction due to GIP. The incidence of such mimicry is impossible to determine, because in most cases a BD diagnosis becomes a self-fulfilling prophecy.
Background:
The case of Jahi McMath has captured the attention of the public, healthcare professionals, and ethicists. Jahi was declared brain dead in late 2013, but her family transferred her to New Jersey to continue organ support. A lengthy legal battle has been ongoing since then. Jahi's family and two neurologists, Drs. Calixto Machado and Alan Shewmon, believe that she is not brain dead. Her family and Dr. Shewmon think that she is capable of following commands, thus making her minimally conscious.
Methods:
Review of case materials.
Results and conclusion:
Because brain death is an irreversible coma, one of three conclusions must be drawn: 1) Jahi was never dead; 2) Jahi met the criteria for brain death, but she isn't dead now; or 3) Jahi's movements are not purposeful responses, and she has been brain dead since 2013. The possibility that a person who was declared brain dead is now following commands threatens to erode the notion that brain death should be considered legal death. The discordant ideas that Jahi is brain dead and is following commands can only be reconciled if a formal evaluation for determination of death is repeated by reputable examiners.
Background:
Patients with primary posterior fossa catastrophic lesions may clinically meet brain death criteria, but may retain supratentorial brain function or blood flow. These patients could be declared brain-dead in the United Kingdom (UK), but not in the United States of America (USA). We report the outcome of adult patients with primary posterior fossa lesions without concurrent major supratentorial injury.
Methods:
Henry Ford Hospital database was reviewed over a period of 88 months in order to identify all adult patients with isolated brainstem or posterior fossa lesions. We excluded patients with concurrent significant supratentorial pathology potentially confounding the clinical brain death examination. One more patient from a different hospital meeting these criteria was also included.
Results:
Three patients out of 161 met inclusion criteria (1.9% of all brain deaths during this period). With the addition of a fourth patient from another hospital, 4 patients were analyzed. All four patients had catastrophic brainstem and cerebellar injuries meeting the clinical criteria of brain death with positive apnea test in the UK. All had preserved supratentorial blood flow, which after a period of 2 h to 6 days disappeared on repeat testing, allowing declaration of brain death by US criteria in all four. One patient became an organ donor.
Conclusions:
Patients with primary posterior fossa catastrophic lesions, who clinically seem to be brain-dead, evolve from retaining to losing supratentorial blood flow. If absent cerebral blood flow is used as an additional criterion for the declaration of death by neurological criteria, these patients are not different than those who become brain death due to supratentorial lesions.
Although the concept of brain death is accepted by the majority of physicians, lawyers, ethicists and society at large, controversies about determination of death by neurological criteria persist, and often reach the public eye. In this article, we examine four prominent controversial brain death cases from 2013-2016. We review current controversies, including protocol variability, recognition of the American Academy of Neurology (AAN) criteria for brain death as an accepted medical standard, and management of objections to discontinuation of organ support after determination of brain death. Brain death remains conceptually and legally valid, and it is vital that these issues are solved. We argue that medical societies and governmental regulatory bodies must support the AAN criteria in order to decrease protocol variability, and must fully endorse the validity of these criteria as accepted medical standards.
Importance
Brain death is the irreversible cessation of function of the entire brain, and it is a medically and legally accepted mechanism of death in the United States and worldwide. Significant variability may exist in individual institutional policies regarding the determination of brain death. It is imperative that brain death be diagnosed accurately in every patient. The American Academy of Neurology (AAN) issued new guidelines in 2010 on the determination of brain death.Objective
To evaluate if institutions have adopted the new AAN guidelines on the determination of brain death, leading to policy changes.Design, Setting, and Participants
Fifty-two organ procurement organizations provided US hospital policies pertaining to the criteria for determining brain death. Organizations were instructed to procure protocols specific to brain death (ie, not cardiac death or organ donation procedures). Data analysis was conducted from June 26, 2012, to July 1, 2015.Main Outcomes and Measures
Policies were evaluated for summary statistics across the following 5 categories of data: who is qualified to perform the determination of brain death, what are the necessary prerequisites for testing, details of the clinical examination, details of apnea testing, and details of ancillary testing. We compared these data with the standards in the 2010 AAN update on practice parameters for brain death.Results
A total of 508 unique hospital policies were obtained, representing the majority of hospitals in the United States that would be eligible and equipped to evaluate brain death in a patient. Of these, 492 provided adequate data for analysis. Although improvement with AAN practice parameters was readily apparent, there remained significant variability across all 5 categories of data, such as excluding the absence of hypotension (276 of 491 policies [56.2%]) and hypothermia (181 of 228 policies [79.4%]), specifying all aspects of the clinical examination and apnea testing, and specifying appropriate ancillary tests and how they were to be performed. Of the 492 policies, 163 (33.1%) required specific expertise in neurology or neurosurgery for the health care professional who determines brain death, and 212 (43.1%) stipulated that an attending physician determine brain death; 150 policies did not mention who could perform such determination.Conclusions and Relevance
Hospital policies in the United States for the determination of brain death are still widely variable and not fully congruent with contemporary practice parameters. Hospitals should be encouraged to implement the 2010 AAN guidelines to ensure 100% accurate and appropriate determination of brain death.
To assess the practices and perceptions of brain death determination worldwide and analyze the extent and nature of variations among countries.
An electronic survey was distributed globally to physicians with expertise in neurocritical care, neurology, or related disciplines who would encounter patients at risk of brain death.
Most countries (n = 91, response rate 76%) reported a legal provision (n = 63, 70%) and an institutional protocol (n = 70, 77%) for brain death. Institutional protocols were less common in lower-income countries (2/9 of low [22%], 9/18 lower-middle [50%], 22/26 upper-middle [85%], and 37/38 high-income countries [97%], p < 0.001). Countries with an organized transplant network were more likely to have a brain death provision compared with countries without one (53/64 [83%] vs 6/25 [24%], p < 0.001). Among institutions with a formalized brain death protocol, marked variability occurred in requisite examination findings (n = 37, 53% of respondents deviated from the American Academy of Neurology criteria), apnea testing, necessity and type of ancillary testing (most commonly required test: EEG [n = 37, 53%]), time to declaration, number and qualifications of physicians present, and criteria in children (distinct pediatric criteria: n = 38, 56%).
Substantial differences in perceptions and practices of brain death exist worldwide. The identification of discrepancies, improvement of gaps in medical education, and formalization of protocols in lower-income countries provide first pragmatic steps to reconciling these variations. Whether a harmonized, uniform standard for brain death worldwide can be achieved remains questionable.
© 2015 American Academy of Neurology.
To review and revise the 1987 pediatric brain death guidelines.
Relevant literature was reviewed. Recommendations were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
1) Determination of brain death in term newborns, infants, and children is a clinical diagnosis based on the absence of neurologic function with a known irreversible cause of coma. Because of insufficient data in the literature, recommendations for preterm infants <37 wks gestational age are not included in this guideline. 2) Hypotension, hypothermia, and metabolic disturbances should be treated and corrected and medications that can interfere with the neurologic examination and apnea testing should be discontinued allowing for adequate clearance before proceeding with these evaluations. 3) Two examinations, including apnea testing with each examination separated by an observation period, are required. Examinations should be performed by different attending physicians. Apnea testing may be performed by the same physician. An observation period of 24 hrs for term newborns (37 wks gestational age) to 30 days of age and 12 hrs for infants and children (>30 days to 18 yrs) is recommended. The first examination determines the child has met the accepted neurologic examination criteria for brain death. The second examination confirms brain death based on an unchanged and irreversible condition. Assessment of neurologic function after cardiopulmonary resuscitation or other severe acute brain injuries should be deferred for ≥24 hrs if there are concerns or inconsistencies in the examination. 4) Apnea testing to support the diagnosis of brain death must be performed safely and requires documentation of an arterial Paco2 20 mm Hg above the baseline and ≥60 mm Hg with no respiratory effort during the testing period. If the apnea test cannot be safely completed, an ancillary study should be performed. 5) Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. Ancillary studies may be used to assist the clinician in making the diagnosis of brain death a) when components of the examination or apnea testing cannot be completed safely as a result of the underlying medical condition of the patient; b) if there is uncertainty about the results of the neurologic examination; c) if a medication effect may be present; or d) to reduce the interexamination observation period. When ancillary studies are used, a second clinical examination and apnea test should be performed and components that can be completed must remain consistent with brain death. In this instance, the observation interval may be shortened and the second neurologic examination and apnea test (or all components that are able to be completed safely) can be performed at any time thereafter. 6) Death is declared when these criteria are fulfilled.
To provide an update of the 1995 American Academy of Neurology guideline with regard to the following questions: Are there patients who fulfill the clinical criteria of brain death who recover neurologic function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? What is the comparative safety of techniques for determining apnea? Are there new ancillary tests that accurately identify patients with brain death?
A systematic literature search was conducted and included a review of MEDLINE and EMBASE from January 1996 to May 2009. Studies were limited to adults.
In adults, there are no published reports of recovery of neurologic function after a diagnosis of brain death using the criteria reviewed in the 1995 American Academy of Neurology practice parameter. Complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead. There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly. Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing. There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain.
Lack of cerebral circulation is an important confirmatory test for brain death (BD). Conventional angiography remains the standard imaging method, but CT angiography (CTA) is emerging as an alternative. France accepts BD diagnoses relying on a score based on lack of opacification of 7 intracerebral vessels in CTA images. The purpose of this study was to validate the efficiency of this score and to evaluate the sensitivity of a novel 4-point CTA score in confirming BD.
A prospective multicentric study was conducted during 12 months with 105 patients referred for CTA to confirm a clinical diagnosis of BD. Clinical data were recorded. CTA images were interpreted first by local radiologists at the referent center, resulting in a 7-point score based on lack of opacification of the pericallosal and cortical segments of the middle cerebral arteries (MCAs), internal cerebral veins (ICVs), and 1 great cerebral vein per patient and, second, by a consensus panel of 3 expert radiologists, blinded to the initial scores, resulting in novel 4-point scores based on the lack of opacification of the cortical segments of the MCAs and ICVs.
Injection of contrast medium did not alter renal function. With the initial 7-point score, sensitivity was 62.8%. With the simplified 4-point score, sensitivity was 85.7% and specificity was 100%. Opacification of ICVs was absent in 98.1% of patients.
Lack of opacification in the cortical segments of the MCAs and internal veins in CTA is efficient and reliable for confirming BD.
One rationale for equating "brain death" (BD) with death is that it reduces the body to a mere collection of organs, as evidenced by purported imminence of asystole despite maximal therapy. To test this hypothesis, cases of prolonged survival were collected and examined for factors influencing survival capacity.
Formal diagnosis of BD with survival of 1 week or longer. More than 12,200 sources yielded approximately 175 cases meeting selection criteria; 56 had sufficient information for meta-analysis. Diagnosis was judged reliable if standard criteria were described or physicians made formal declarations. Data were analyzed by means of Kaplan-Meier curves, with treatment withdrawals as "censored" data, compared by log-rank test.
Survival probability over time decreased exponentially in two phases, with initial half-life of 2 to 3 months, followed at 1 year by slow decline to more than 14 years. Survival capacity correlated inversely with age. Independently, primary brain pathology was associated with longer survival than were multisystem etiologies. Initial hemodynamic instability tended to resolve gradually; some patients were successfully discharged on ventilators to nursing facilities or even to their homes.
The tendency to asystole in BD can be transient and is attributable more to systemic factors than to absence of brain function per se. If BD is to be equated with death, it must be on some basis more plausible than loss of somatic integrative unity.
“Brain death” was analyzed in 25 moribund patients with regard to the clinical evaluation of the patients and the significance of segmental reflexes and electroencephalographic recordings. It is concluded that a state of brain death in a patient with known irreparable pathology can be established solely on clinical grounds.
To survey brain death criteria throughout the world.
The clinical diagnosis of brain death allows organ donation or withdrawal of support. Declaration of brain death follows a certain set of examinations. The code of practice throughout the world has not been systematically investigated.
Brain death guidelines in adults in 80 countries were obtained through review of literature and legal standards and personal contacts with physicians.
Legal standards on organ transplantation were present in 55 of 80 countries (69%). Practice guidelines for brain death for adults were present in 70 of 80 countries (88%). More than one physician was required to declare brain death in half of the practice guidelines. Countries with guidelines all specifically specified exclusion of confounders, irreversible coma, absent motor response, and absent brainstem reflexes. Apnea testing, using a PCO(2) target, was recommended in 59% of the surveyed countries. Differences were also found in time of observation and required expertise of examining physicians. Additional provisions existed when brain death was due to anoxia. Confirmatory laboratory testing was mandatory in 28 of 70 practice guidelines (40%).
There is uniform agreement on the neurologic examination with exception of the apnea test. However, this survey found other major differences in the procedures for diagnosing brain death in adults. Standardization should be considered.
From brain death to brain stem death
- C Pallis
Pallis C. ABC of brain stem death. From brain death to brain stem death // Br
Med J (Clin Res Ed). -1982. -Vol. 285, № 6353. -P. 1487-1490. https://doi.
org/10.1136/bmj.285.6353.1487.
13. Declaration of Calixto Machado, M.D. URL: https://thaddeuspope.com/images/2014-10-14_Signed_Declaration_of_Dr_Calixto_Machado.pdf
(accessed 24.12.24).
Miracle' teen recovering after Leek van crash
- Bbc News
BBC News: 'Miracle' teen recovering after Leek van crash. 25.04.2022. URL:
https://www.bbc.co.uk/news/uk-england-stoke-staffordshire-61220154 (дата
обращения: 08.12.24.).
Additional FICMPAS Guidance for Decompressive Craniectomy and Diagnosing Death using Neurological Criteria (DNC) // Critical Eye
- D Gardiner
Gardiner D. Additional FICMPAS Guidance for Decompressive Craniectomy
and Diagnosing Death using Neurological Criteria (DNC) // Critical Eye. -2022, Issue 21. -P. 38-39. URL: https://www.ficm.ac.uk/sites/ficm/files/documents/2022-03/Critical%20Eye%2021%20Winter%202022.pdf (дата обращения: 24.12.24).
24) 37. Practice parameters for determining brain death in adults (summary statement)
- E F Wijdicks
- P N Varelas
- G S Gronseth
Wijdicks E. F., Varelas P. N., Gronseth G. S. et al. Evidence-based guideline
update: determining brain death in adults: report of the Quality Standards
Subcommittee of the American Academy of Neurology // Neurology. -2010. -Vol. 74, № 23. -P. 1911-1918. https://doi.org/10.1212/WNL.0b013e3181e242a8.
52. 2025 Code of Practice for the diagnosis and confirmation of death. URL:
https://www.aomrc.org.uk/2025-code-of-practice-for-the-diagnosis-and-confirmation-of-death/ (дата обращения: 15.12.24)
37. Practice parameters for determining brain death in adults (summary statement). The Quality Standards Subcommittee of the American Academy
of Neurology. Neurology, 1995, vol. 45, no. 5, pp. 1012-1014. https://doi.
org/10.1212/wnl.45.5.1012.
Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death
A definition of irreversible coma. Report of the Ad Hoc Committee of the
Harvard Medical School to Examine the Definition of Brain Death. JAMA, 1968,
vol. 205, no. 6, pp. 337-340. https://doi.org/10.1001/jama.1968.03140320031009.
An appraisal of the criteria of cerebral death. A summary statement. A collaborative study
An appraisal of the criteria of cerebral death. A summary statement. A
collaborative study. JAMA, 1977, vol. 237, no. 10, pp. 982-986. https://doi.
org/10.1001/jama.1977.03270370054022.
Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project
- D M Greer
- S D Shemie
- A Lewis
Jahi McMath: a new state of disorder of consciousness
- C Machado
Machado C. Jahi McMath: a new state of disorder of consciousness. J Neurosurg Sci, 2021, vol. 65, no. 2, pp. 211-213. https://doi.
org/10.23736/S0390-5616.20.04939-5.
Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the
- E F Wijdicks
- P N Varelas
- G S Gronseth
Wijdicks E. F., Varelas P. N., Gronseth G. S. et al. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 2010, vol. 74,
no. 23, pp. 1911-1918. https://doi.org/10.1212/WNL.0b013e3181e242a8.
52. 2025 Code of Practice for the diagnosis and confirmation of death. URL:
https://www.aomrc.org.uk/2025-code-of-practice-for-the-diagnosis-and-confirmation-of-death/ (accessed 15.12.24).