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-Evolution of brain blood flow in three hypothetical cases of increased intracranial pressure (ICP): influence of moderate hypothermia (33 o C) induced at 24-h survival. Simultaneous normalization of intracranial pressure observed during cooling to 33 o C (27) leads to recirculation of cases 2 and 3 whilst case 1 is unaffected. Remarkable absorption of brain edema during the next few hours of hypothermic treatment should prevent recurrence of ICP (27). For abbreviations see legend to Figure 1.
Source publication
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 areflexi...
Context in source publication
Context 1
... surprisingly good results were ob- tained despite the fact that the neurological conditions of the head trauma victims prob- ably further deteriorated from admission up to an average survival of 16 h, when a 24-h treatment with moderate hypothermia was initiated (25). The mechanisms that account for recov- ery from such a pre-mortal state may include a) avoidance of detrimental effects related to apnea testing (26), b) normalization of ICP (recirculation from GIP -see Figure 3) dur- ing cooling to 33 o C (27), c) regression of brain edema (27), d) inhibition of the detri- mental cascade of neurochemical events trig- gered by a transient ischemic insult (28), and e) prevention of intracranial thermal pooling that increases brain temperature to levels capable of damaging vascular and neuronal proteins (29). ...
Similar publications
Continuous monitoring of brainstem auditory evoked potentials (BAEPs) was carried out in 57 comatose patients for periods ranging from 5 hours to 13 days. In 53 cases intracranial pressure (ICP) was also simultaneously monitored. The study of relative changes of evoked potentials over time proved more relevant to prognosis than the mere considerati...
Citations
... In the setting of brain death or DNC, conserved vascular perfusion of the hypophysis may result from either extracranial circulation or an 'ischemic penumbra'. 24,25 Some scholars believe that urine production is a clinical function regulated by the brain, while others argue that preserved neuroendocrine function is an isolated neuronal activity that does not violate the whole-brain definition of death. 26 Neither current nor previous brain death or DNC guidelines require the clinical assessment of neuroendocrine function. ...
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.
... Although the judge refused to grant legal immunity in the matter, a consensus was reached among the parties that the doctor will not be prosecuted and an appropriate procedure be drawn up. [21] This very same case is also evidence of the second concern, that is, code of ethics. The presiding judge in this case called in several medical and religious-ethics experts to testify as to the ethical validity of an action to remove the life support systems the patient was on. ...
Objective:
The legal definitions of brain death are tantamount for legal dogmas and sometimes criminal intimidation of the treating doctors. The tests for brain death are only applicable to patients planned for organ transplantation. We intend to discuss the necessity of the "Do Not Resuscitate (DNR)" legislature in cases of brain death patients and applicability of tests for brain death irrespective of the intention for organ donation.
Methods:
A comprehensive review of the literature was performed till May 31, 2020 from the MEDLINE (1966 to July 2019) and Web of Science (1900 to July 2019). Search criteria included all publications with the MESH terms: "Brain Death/legislation and jurisprudence"[Mesh] OR "Brain Death/organization and administration"[Mesh] AND "India" [Mesh]. We also discuss the different opinions and implications of brain death versus brain stem death in India with the senior author (KG) who was responsible for South Asia's first multi-organ transplant after certifying brain death. Additionally, a hypothetical scenario of a DNR case is discussed in the current legal paradigm of India.
Results:
The systematic search yielded only five articles reporting a series of brain stem death cases with an acceptance rate of organ transplant among brain stem deaths being 34.8%. The most common solid organs transplanted were the kidney (73%) and liver (21%). A hypothetical scenario of a DNR and possible legal implications of the same under the current 'Transplantation of Human Organs Act (THOA)' of India remains unclear. A comparison of brain death laws in most Asian countries shows a similar pattern regarding the declaration of brain death and the lack of knowledge or legislature regarding DNR cases.
Conclusion:
After the determination of brain death, discontinuation of organ support requires the consent of the family. The lack of education and the lack of awareness have been major impediments in this medico-legal battle. There is also an urgent need to make laws for cases that do not qualify for brain death. This would help in not only realistic realization but also better triage of the health care resources while legally safeguarding the medical fraternity.
... 1,7 Bir patoloji çalışması, beyin sapı ve daha yüksek beyin yapılarının, BD tanısı alan hastaların sadece %34-68'inde orta ila şiddetli iskemik değişiklikler gösterdiğini, beyin içi dolaşım durmasının tüm vakalarda tam olmadığını göstermiştir. 11 Akut durum geçtikten sonra kafa içi basıncı azaldığı ve beyin kan akımı kısmen de olsa sürebileceği için bazı nöral doku bölgelerinin "iskemik penumbra" olarak tanımlanan işlevini kaybetmiş ama hâlâ yaşayabilir durumda olması fizyolojik olarak mümkün olabilir. İskemik penumbra kavramı, kan akışının klinik olarak saptanabilir işlevsellik ile uyumlu olmayan, ancak dokunun bir süre hayatta kalmasını sağlamak için yeterli bir dereceye düştüğü durumu ifade eder. ...
... How to diagnose and treat these in the setting of suspected BD is unclear, and would require study. Yet another confounder present in an unknown number of cases is the global ischemic penumbra (GIP), to be described later [190]. Second, acknowledged confounders to any part of the examination for BD Third, the apnea test is both contraindicated and poorly suited for purpose [i.e., the purpose of determining loss of medullary function] [189,190]. ...
... Yet another confounder present in an unknown number of cases is the global ischemic penumbra (GIP), to be described later [190]. Second, acknowledged confounders to any part of the examination for BD Third, the apnea test is both contraindicated and poorly suited for purpose [i.e., the purpose of determining loss of medullary function] [189,190]. The test is contraindicated because, in the setting of a raised intracranial pressure, a rise in PaCO2 can be expected to increase this pressure further, thus reducing cerebral perfusion and resulting in no-reflow phenomenon [189][190][191][192][193][194]. ...
... Second, acknowledged confounders to any part of the examination for BD Third, the apnea test is both contraindicated and poorly suited for purpose [i.e., the purpose of determining loss of medullary function] [189,190]. The test is contraindicated because, in the setting of a raised intracranial pressure, a rise in PaCO2 can be expected to increase this pressure further, thus reducing cerebral perfusion and resulting in no-reflow phenomenon [189][190][191][192][193][194]. This can convert ischemic penumbra tissue to irreversibly injured brain [190]. ...
Brain death has been accepted worldwide medically and legally as the biological state of death of the organism. Nevertheless, the literature has described persistent problems with this acceptance ever since brain death was described. Many of these problems are not widely known or properly understood by much of the medical community. Here we aim to clarify these issues, based on the two intractable problems in the brain death debates. First, the metaphysical problem: there is no reason that withstands critical scrutiny to believe that BD is the state of biological death of the human organism. Second, the epistemic problem: there is no way currently to diagnose the state of BD, the irreversible loss of all brain functions, using clinical tests and ancillary tests, given potential confounders to testing. We discuss these problems and their main objections and conclude that these problems are intractable in that there has been no acceptable solution offered other than bare assertions of an ‘operational definition’ of death. We present possible ways to move forward that accept both the metaphysical problem - that BD is not biological death of the human organism - and the epistemic problem - that as currently diagnosed, BD is a devastating neurological state where recovery of sentience is very unlikely, but not a confirmed state of irreversible loss of all [critical] brain functions. We argue that the best solution is to abandon the dead donor rule, thus allowing vital organ donation from patients currently diagnosed as BD, assuming appropriate changes are made to the consent process and to laws about killing.
... In 1999, neurologist Cicero Coimbra applied this concept to brain death, hypothesizing that something like a global ischemic penumbra may take place in some patients declared brain-dead (Coimbra 1999). This concept, including both localized and global penumbra, brings greater clarity to the pathophysiology of brain death: Because CPP decreases in a continuous fashion, negatively roughly proportionate to ICP as it rises in a continuous fashion, it follows that for every part of the brain, it will first go through a state of ischemic penumbra, then reach some threshold of viability, and finally it will either cross that threshold and become irreversibly damaged, or it won't. ...
Some patients who have been diagnosed as “dead by neurologic criteria” continue to exhibit certain brain functions, most commonly, neuroendocrine functions. This preservation of neurologic function after the diagnosis of “brain death” or “brainstem death” is an ongoing source of controversy and concern in the medical, bioethics, and legal literatures. Most obviously, if some brain function persists, then it is not the case that all functions of the entire brain have ceased and hence, declaring such a patient to be “dead” would be a false positive, in any nation with so-called “whole brain death” laws. Furthermore, and perhaps more concerning, the preservation of any brain function necessarily entails the preservation of some amount of brain perfusion, thereby raising the concern as to whether additional areas of neural tissue may remain viable, including areas in the brainstem. These and other considerations cast significant doubt on the reliability of diagnosing either “brain death” or “brainstem death.”
... Given the ethical ramifications at stake here, it is worth saying more to establish the clinical basis for the risk assessment. The insidious phenomenon outlined in the previous paragraph is best described by a consideration of global ischemic penumbra (Coimbra 1999). A patient lacking clinically overt brain function may still retain viable areas of very low blood flow that may be recoverable if brain blood flow can be enhanced. ...
The past decade has witnessed escalating legal and ethical challenges to the diagnosis of death by neurologic criteria (DNC). The legal tactic of demanding consent for the apnea test, if successful, can halt the DNC. However, US law is currently unsettled and inconsistent in this matter. Consent has been required in several trial cases in Montana and Kansas but not in Virginia and Nevada. In this paper, we analyze and evaluate the legal and ethical bases for requiring consent before apnea testing and defend such a requirement by appealing to ethical and legal principles of informed consent and battery and the right to refuse medical treatment. We conclude by considering and rebutting two major objections to a consent requirement for apnea testing: (1) a justice-based objection to allocate scarce resources fairly and (2) a social utility objection that halting the diagnosis of brain death will reduce the number of organ donors.
... Some authors have raised concerns of persisting cerebral perfusion in some patients. This could result in minimal chance of cerebral survival [4]. On the other hand, a majority of clinicians regard brain death determination as a valued instrument and the brain death concept is emphasized by the law in many countries. ...
... Most physicians regard apnoea testing as an integral part of brain death determination. Some authors have postulated an additional rise of ICP due to apnoea testing and therefore a potential hazard in patients with severe brain lesions [4]. Recently, we were able to show that ICP in brain death patients strongly correlates with mean arterial pressure (MAP) [7]. ...
Background:
Clinical investigations of brain death are supposed to prove absence of cerebral perfusion. However, only limited data are available documenting intracranial pressure (ICP) and cerebral perfusion pressure (CPP) during the development of brain death. Our study presents additional data to understand the course of ICP and CPP in patients developing brain death.
Material and methods:
We analyzed retrospective data of 18 patients with ICP monitoring during the development of brain death due to primary brain lesions. ICP and CPP values were continuously measured between two clinically defined time points: 1. non-reactive and widened pupils, 2. brain death determination. We analyzed ICP and CPP at the above-mentioned end points. Additionally, we investigated maximum ICP and minimal CPP values between these time points.
Results:
Patients developed fixed and dilated pupils with a median of 38 h before brain death determination. During brain death determination median ICP and median CPP were 103.5 and -2.5 mmHg, respectively. Maximum ICP before brain death determination was significantly higher and minimal CPP values were significantly lower compared to the time point of brain death. During the investigation period all patients experienced ICP values >95 mmHg and CPP < 10 mmHg. All but one patient had documented CPP values of ≤0 mmHg. This single patient had a minimum CPP of 8 mmHg with a maximum ICP of 145 mmHg.
Conclusion:
Cerebral perfusion pressure during brain death determination may be positive in some patients. Our results showed variable values of ICP and CPP. However, extremely elevated ICP values before or during brain death in combination with low CPP values suggest absence of cerebral perfusion. The occurrence of positive CPP values during brain death determination therefore depends on the time point at which brain death determination is performed.
... This is the range called the "ischemic penumbra," well known in the stroke field and hypothesized by Cicero Coimbra to occur globally as a mathematical necessity during the progression from normal to no flow in the pathogenesis of brain death. 7 Jahi's case may be the first indirect confirmation of Coimbra's hypothesis. 8 False positivity of the brain death diagnostic criteria and of "confirmatory" blood flow tests is not unprecedented. ...
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.
... Are the neurologic findings in these patients potentially reversible with time? Coimbra (1999) described the phenomenon of global ischemic penumbra to account for absent neuronal ischemia and brain necrosis in patients who were determined brain dead (Fig. 2). This phenomenon is characterized by a reduction in global blood flow to the whole brain that can result in suppression of supraspinal synaptic transmission in the cerebral cortex and brainstem without necessarily triggering irreversible ischemic neuronal damage. ...
... The temporal reversibility of the clinical findings of brain death associated with global ischemic penumbra in patient 2 is unknown. (Adapted from the original source by Coimbra (1999) of the cessation of all functions of the brain. In order to avoid ongoing controversies about the moment when a person has indeed died, Bernat (2013) has posited that the notion of ''irreversibility'' should be replaced by ''permanence.'' ...
The conception and the determination of brain death continue to raise scientific, legal, philosophical, and religious controversies. While both the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research in 1981 and the President’s Council on Bioethics in 2008 committed to a biological definition of death as the basis for the whole-brain death criteria, contemporary neuroscientific findings augment the concerns about the validity of this biological definition. Neuroscientific evidentiary findings, however, have not yet permeated discussions about brain death. These findings have critical relevance (scientifically, medically, legally, morally, and religiously) because they indicate that some core assumptions about brain death are demonstrably incorrect, while others lack sufficient evidential support. If behavioral unresponsiveness does not equate to unconsciousness, then the philosophical underpinning of the definition based on loss of capacity for consciousness as well as the criteria, and tests in brain death determination are incongruent with empirical evidence. Thus, the primary claim that brain death equates to biological death has then been de facto falsified. This conclusion has profound philosophical, religious, and legal implications that should compel respective authorities to (1) reassess the philosophical rationale for the definition of death, (2) initiate a critical reappraisal of the presumed alignment of brain death with the theological definition of death in Abrahamic faith traditions, and (3) enact new legislation ratifying religious exemption to death determination by neurologic criteria.
... specificity for the Uniform Determination of Death Act's (UDDA's) criterion of "irreversible cessation of all functions of the entire brain" [6, p. 73]; they merely represent the consensus of a group of experts who uniformly did not consider that global ischemic penumbra (GIP) could in principle mimic BD in every way [7]. The Guidelines require that, prior to embarking on a BD diagnosis, confounding mimics must be excluded. ...
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.
