Qu'est ce que la mort cérébrale / What is brain death ?

Vous trouverez ci-dessous l'article de A. Halevy et de B. Brody :
"Brain death: Reconciling definitions, criteria and tests". Annals of Internal medicine: 1993; n°119, p. 519-525

Cet article montre en substance que parler de "mort" est complètement inadéquat, n'existent que des stades du processus de mort.



MEDICINE AND PUBLIC ISSUES
Brain Death
Reconciling Definitions, Criteria, and Tests
Amir Halevy and Baruch Brody
15 September 1993 | Volume 119 Issue 6 | Pages 519-525

"Brain death has been discussed extensively for the last 25 years.Most investigators now believe that requiring death of the entire brain as the criterion for brain death in the Uniform Determination of Death Act and the standard clinical tests of brain death outlined in the Report of the Medical Consultants to the President's Commission have produced a satisfactory resolution of the issues surrounding the determination of death. However, we show that satisfying the standard medical tests does not guarantee that all brain functions have actually ceased and that there is tension between the legal criterion and the standard clinical tests. After considering and rejecting six possible reconciliations, we present an alternative approach that does not acknowledge any sharp dichotomy between life and death and incorporates the proposition that the questions of when care can be unilaterally discontinued, when organs can be harvested, and when a patient is ready for the services of an undertaker should be answered independent of any single account of death.



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The development of machines that mechanically sustain the life functions of respiration and circulation forced the medical community and society in general to re-evaluate the accepted definition, criterion, and tests of death. In certain cases, the classic definition of death as the permanent cessation of the flow of vital bodily fluids was no longer consonant with the classic criterion of death as the irreversible cessation of spontaneous respiration and circulation [1]. In addition, newly developed organ transplantation programs required a definition, criterion, and test of death that would facilitate the procurement of organs before they deteriorate.
Thus, the medical community began to develop alternative, brain-based accounts of death. The Harvard Report [2], published in 1968, was the first formal attempt to meet this need. Continued efforts to reach a consensus regarding brain death culminated in a report from the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research [3] and in two resulting documents, the clinical report of the medical consultants to the President's Commission [4] and the Uniform Determination of Death Act [5]. These efforts were largely successful, although doubts about the appropriateness of this brain-based account continued to be expressed in some countries [6,7] and in some religious communities [8].

The President's Commission considered three possible criteria for death: a nonbrain criterion, a whole-brain criterion, and a higher-brain criterion Table 1. The first criterion was most consonant with the definition of death as the permanent cessation of the flow of vital bodily fluids, the second with the definition of death as the permanent cessation of the integrated functioning of the organism as a whole, and the third with the definition of death as the permanent loss of what is essential to the nature of man (consciousness). Although the Commission chose to emphasize legislation derived from criteria rather than from definitions [3], it did refer in its justification to the brain's primacy in integrating body functions as well as in sponsoring consciousness. To quote the Commission: "This view gives the brain primacy not merely as the sponsor of consciousness (since even unconscious persons may be alive), but also as the complex organizer and regulator of bodily functions.Only the brain can direct the entire organism" [3].


Table 1. Alternative Definitions of Death

The whole-brain criterion was selected for practical reasons as well. From a practical standpoint, the higher-brain criterion suffered because no agreement could be reached about what portions of the brain are required for cognition and consciousness and because "even when the sites of certain aspects of consciousness can be found, their cessation often cannot be assessed with the certainty that would be required in applying a statutory definition" [3]. Moreover, adoption of a higher-brain criterion was too radical a departure from the traditional criterion and "one would desire much greater consensus than now exists before taking the major step of radically revising the concept of death" [3].

The Uniform Determination of Death Act provided the legal articulation of the whole-brain criterion of death as "irreversible cessation of all functions of the brain, including the brainstem" [5]. The choice of the word "functions" rather than "activity" reflected the view that "bodily parts, and the subparts that make them up, are important for the functions they perform" [3]. The President's Commission explicitly recognized that electrical and metabolic activity of groups of cells within an organ may continue after that organ has ceased functioning. However, the Commission stipulated that cellular activity is considered functioning when it is "organized and directed" [3]. We consider below still stronger requirements for when activity is considered functioning.

Less clear are the medical tests necessary to establish that the legal criterion is met. The Uniform Determination of Death Act stated that a "determination of death must be made in accordance with accepted medical standards" [4], but what are these standard tests? To meet the challenge of developing standard tests that clinicians could use to establish that the criterion of death had been met, the President's Commission created a panel of medical consultants.

The standard tests proposed by the medical consultants to the President's Commission are clinically based. The brain functions considered are cerebral and brain stem functions. Cessation of cerebral function is attested by deep coma without clinical response to any physical stimuli. Brain stem function is assessed by testing for cranial nerve function, including pupillary, corneal, oculocephalic, oculovestibular, and oropharyngeal reflexes, and by carrying out an apnea test to determine respiratory function. Irreversibility is determined by identifying the cause of the coma to exclude drug intoxication and hypothermia and by observing the patient for a specified period of time. Such tests as an electroencephalogram, a brain stem evoked potentials study, or a cerebral blood flow study are considered desirable when objective documentation is needed to substantiate these clinical findings but are not generally necessary for the determination of brain death.

We show that the standard clinical tests proposed by the advisors to the President's Commission do not ensure that all brain functions have actually ceased and do not therefore ensure that the whole-brain criterion of death has been met. We also show that many possible solutions to this discrepancy are unsatisfactory. We conclude by suggesting that an alternative approach is needed to deal with troubling cases.

The Problem

A review of published reports about brain death shows that many patients who meet the standard clinical tests for brain death still maintain some brain functioning and therefore do not satisfy the whole-brain criterion of death. Three areas of persistent functioning are neurohormonal regulation, cortical functioning as shown by significant nonisoelectric electroencephalograms, and brain stem functioning as shown by evoked responses.

Neurohormonal Functioning

The first evidence for continued brain functioning despite a patient's meeting the standard clinical tests for brain death is found in analyses of neurohormonal regulation. Anterior pituitary hormone levels have been studied by several investigators; much of the research has been motivated by a desire to optimally manage brain-dead donors. In one of the earliest studies, by Schrader and colleagues [9], normal hormonal levels were found, although other studies [10] have reported different results. Provocative testing provides the best evidence of intact neurohormonal regulation. Schrader and coworkers [9] evaluated several patients "with signs of brain death including the criteria set forth by the Ad Hoc Committee of Harvard". In two cases, an insulin-induced hypoglycemia test was done, and one of the patients showed a decrease in the glucose level that was associated with an immediate growth hormone response.

Posterior pituitary function, specifically antidiuretic hormone secretion, provides the best documented evidence of preserved brain function. If the hypothalamus and neurohypophysis, structures on the brain side of the blood-brain barrier, were nonfunctional, then the patient should develop clinically apparent central diabetes insipidus because of the lack of antidiuretic hormone regulation. However, not all patients meeting the standard clinical criteria of brain death develop the syndrome. Mollaret and Goulon [11] in their original paper on "coma depasse" observed polyuria that behaved like diabetes insipidus in some of the cases. Grenvik and colleagues [12] reported that only 8.5% of their cases had the clinical manifestations of diabetes insipidus. Two series on the incidence of diabetes insipidus in children meeting the standard clinical tests of death showed clinical manifestations of diabetes insipidus in 87% [13] and in 38% [14] of patients. Further reducing the percentage of such patients with true central diabetes insipidus is evidence from two groups that assayed for antidiuretic hormone [15,16]. Hohenegger and colleagues assayed antidiuretic hormone in 11 patients meeting the standard tests of brain death who had clinical manifestations of central diabetes insipidus and found normal-to-increased levels in all 11 cases, effectively excluding the diagnosis of central diabetes insipidus.

This residual neurohormonal regulation is the most troubling of the three forms of functioning for three reasons. First, it is apparently found in most patients presumed to be brain dead using the standard tests. Moreover, this residual neurohormonal regulation clearly represents functioning and not merely activity. As noted above, the definition of functioning offered by the President's Commission was "organized and directed cellular activity," and this regulation certainly meets that definition. Bernat [17] proposed that only clinically observable (as opposed to measurable in the laboratory) activity that contributes to the functioning of the whole organism counts as functioning. In another report [18], he has suggested that only neuronal activity that executes the functions of the organism as a whole counts as functioning. A failure of neurohormonal regulation of antidiuretic hormone secretion certainly presents itself clinically at the bedside, and the preservation of that regulation is certainly essential to the functioning of the whole organism; therefore, neurohormonal regulation is functioning, even according to the most demanding accounts of functioning, and not merely activity. Finally, it is a component of the integrative role of the brain in regulating the rest of the body, the very role that is emphasized in the whole-brain definition of death.

Cortical Functioning

Second, electroencephalographic findings that indicate cortical functioning can continue in patients who meet the standard clinical tests for brain death. Rodin and coworkers [19] reported the case of a 71-year-old woman who met the standard clinical tests for brain death after surgery for a cerebellopontine angle tumor. Her electroencephalogram was "compatible with survival.... Except for unresponsiveness to external stimuli, it was of a type one finds in stuporous, or semicomatose patients and even showed suggestions of sleep spindles.... The electroencephalographic state would suggest that if there was cognition at all it would probably have been in the realm of dream type rather than waking reality". Deliyannakis and colleagues [20] described a patient who was in deep coma, was ventilator dependent with nonreactive pupils, and showed no response to any stimuli but had an electroencephalogram showing delta, theta, and alpha waves. Autopsy showed nearly complete destruction of the brain stem with relative sparing of the cortex. These two cases are now supplemented by a large series of 56 consecutive patients who met the clinical tests of brain death, including formal apnea testing [21]. Eleven patients had persistent electrical activity. Two patients had electroencephalographic findings resembling physiologic sleep patterns, in one case up to 168 hours after the standard clinical tests for brain death had been met. Autopsies on both patients showed extensive ischemic necrosis of the brain stem, with relative sparing of the cortex.

Thus, some unusual patients can meet all of the standard clinical tests for brain death and still have significant cortical functioning as shown by electroencephalograms. Although this functioning does not lead to any clinically apparent interaction with the environment, it clearly satisfies the definition of functioning offered by the President's Commission because it represents organized and directed cellular activity and is referred to by the medical advisors to the President's Commission as functioning [4].

Stem Functioning

Third, brain stem function, as shown by evoked potentials, can continue despite a patient's meeting the standard clinical tests for brain death. Brain stem evoked potentials, recommended by the medical consultants to the President's Commission [4] to assess "brain stem functions (italics supplied)" in certain cases, assess the functional integrity of the auditory and visual pathways, from the receptors through the stem to the cortex. Several cases have been reported in which patients met the standard clinical tests for brain death while exhibiting preserved evoked responses. Barelli and coworkers [22], using the standard clinical tests for brain death and isoelectric electroencephalography for 2 hours, reported two such cases. In the first case, a 28-year-old woman had cardiopulmonary arrest and, for a brief period, preservation of her central auditory pathways. In the second case, a 60-year-old woman had monaural persistence of some centrally originated waves up to 72 hours after determination of brain death by the standard clinical tests. Ferbert and colleagues [23] reported a case in which a 46-year-old man met the standard clinical tests for brain death. His electroencephalogram showed a slow alpha rhythm, and normal visual evoked potentials were elicited on flash stimulation.

Again, these evoked potential findings are evidence of brain stem functioning, which certainly satisfies the definition of functioning offered by the President's Commission (organized and directed cellular activities) and which was explicitly referred to as functioning by their consultants.

In summary, many patients meeting all of the standard clinical tests for brain death still have some cortical, midbrain, or stem functioning. Included in this residual functioning is some of the significant integrative functioning of the brain, the very functioning stressed by the President's Commission when providing its philosophical foundation for the whole-brain criterion of death. The issue then is deciding how to reconcile these clinical facts, the standard clinical tests currently used for determining brain death, and the intent and the philosophical foundation of the current legal criterion for brain death.

Six Possible Responses

Some investigators [17,18] have responded by redefining the concept of functioning so that some of the clinical phenomena we have described are not considered to be indicative of functioning. This strategy of redefinition does not work. In part, this is because neurohormonal regulation, the most prevalent of the clinical phenomena we have described, represents functioning according to these redefinitions. For example, neurohormonal regulation constitutes clinical functioning (one of the redefinitions) because its absence is strongly suggested by clinical examination. More crucially, it is because, as Veatch [24] has pointed out, no conceptual or moral basis exists for these redefinitions, so "holders of this view are already on a precarious slippery slope with no principled way to distinguish neurologic integration outside the brain from that inside the brain, and no obvious difference between one set of functions and another".

We consider six responses, each of which has certain advantages and disadvantages. We ultimately reject all of them in favor of an alternative solution that we find more satisfactory.

Too Few Exceptions

The first suggestion claims that we can ignore the problem because the discrepancies are found in only a few cases. Given that this is so, we should see the discrepancies simply as a reminder that the best clinical tests do not work in every case and that, in this imperfect world, we must settle for tests that work in the overwhelming majority of cases. There is one major difficulty with this suggestion. The evidence that we have described shows that neurohormonal functioning (which is the clearest example of residual functioning) is found in a significant number of cases after the standard clinical tests for brain death have been satisfied.

The Consensus Works

The second suggestion claims that we can ignore the problem because of 1) the pragmatic success of the current consensus and 2) the fact that no dissonance exists between the actual language of the current legal criterion (as opposed to its intent) and the standard clinical tests because the statute refers to "accepted medical standards" for determining brain death.

There are two major difficulties with this second suggestion. If we maintain the whole-brain criterion of death while ignoring clearcut examples of residual functioning, we make it difficult to respond to such advocates of the higher-brain criterion as Veatch [24], who call for disregarding all noncortical functioning. As Youngner [25] recently noted, the best argument for the higher-brain criterion is that the current consensus represents "a superficial and fragile consensus". Moreover, as he also notes, summarizing his earlier data [26], the fragile nature of the current consensus is responsible for great confusion about brain death among health care professionals involved in organ transplantation and "may be one of the factors impeding effective communication with families about their option to donate organs" [25]. Both of these problems indicate the difficulties that one encounters when one pretends that real problems do not exist.

Adding Tests

The third suggestion resolves the problem by adding additional tests to the standard clinical tests. As Barelli and coworkers have suggested [22], we could add a negative auditory evoked potential test before declaring patients brain-dead. More important, we could test for neurohormonal functioning. But there are prices to be paid for following this suggestion. First, the various envisaged tests and the resulting prolongation of the determination of death are expensive and their use as standard parts of the testing for brain death would add to the costs of an already overburdened health care system. Second, organ procurement would be hindered because more organ deterioration would occur while awaiting the satisfaction of the strengthened tests. Both of these problems would be worsened by continued technological advances. As new tests of brain functioning are developed, we would be forced to add them to the standard clinical tests, worsening both of the problems.

Poor Prognosis

The fourth suggestion, advocated by British investigators such as Pallis [27], resolves the problem by claiming that the satisfaction of the standard clinical tests means that the stem has ceased functioning, that no consciousness is therefore possible because of the destruction of the reticular activating system, and that asystole will occur within days. There is, however, one major difficulty with this "brain stem death" suggestion. Neither of its legitimate points ensure that the criterion of whole-brain death has been met. That there is no consciousness present simply means that the higher-brain criterion has been met, not the whole-brain criterion. That asystole will occur within days means only that the patient will be dead on all accounts within days; it says nothing about whether the patient is dead now.

The best way to understand the suggestion provided by Pallis [27] is to see it as offering another criterion for death, the "brain stem" criterion as opposed to the higher-brain criterion and the whole-brain criterion. The trouble is that these other criteria are supported by the justifying definitions presented earlier in our report, but no analogous definition of death has been developed to justify this brain stem criterion.

Only Respiration Counts

The fifth suggestion, advocated by the Israeli Chief Rabbinate in its recent decision to allow heart transplants [28], is a variation on Pallis' suggestion. According to this suggestion, because patients meeting the standard clinical tests of brain death have irreversibly lost the capacity to attempt to breathe on their own as a result of the destruction of their brain stems, they are dead because part of the classic criterion for death (irreversible cessation of spontaneous respiratory function) is met. The fact that they have continued functioning by other parts of the brain (for example, hormonal regulation) and by other parts of the body (for example, continued circulation) is therefore irrelevant.

The problem with this approach, as with Pallis' approach, is its lack of a justifying definition. It cannot appeal to the classic definition because the continued circulatory functioning means that a permanent cessation of the flow of vital bodily fluids has not occurred. This approach has no other justifying definition. It lacks any grounding except for those, such as the Israeli Chief Rabbinate, who can ground it in a long-standing legal tradition to which they adhere.

Higher-Brain Criterion

The final suggestion focuses on the fact that the whole problem relates to functioning that is independent of consciousness. We can resolve it by adopting a higher-brain criterion for death that requires only the irreversible cessation of conscious functioning. Given that the standard clinical tests ensure that such functioning has irreversibly ceased, they are adequate to ensure that death has occurred, according to this higher-brain criterion, even if considerable brain functioning is still present. This suggestion was advocated, even before the report of the President's Commission, by such investigators as Engelhardt [29] and Veatch [30]; since the report, it has been advocated by Youngner and Bartlett [31] and by Smith [32].

This suggestion, unlike Pallis' suggestion, can be supported by a justifying definition of death--the definition of death as the permanent loss of what is essential to human beings. This could be loss of personhood or loss of consciousness. There are many different conceptions of personhood, but all, except those that identify personhood with mere biologic functioning, require cortical functioning. Alternatively, this suggestion may deny the linkage with personhood but may assert that death consists of loss of conscious activity because that activity is what is essential to humans. Green and Wikler [33] have also attempted to support that criterion by appealing to the theory of personal identity, but that attempt has been appropriately challenged [34].

The difficulties with this proposal are not new, so we review only some of them. As Youngner and Bartlett [31] themselves recognize, adopting their approach means at least a theoretical willingness to bury or cremate vegetative patients who have lost all conscious functioning but who still breathe on their own. They provide various primarily aesthetic explanations about why we might not actually adopt such a practice. Many, however, might conclude that the objection is more than just aesthetic and rests on an intuitive understanding that such patients are not dead, even if they have lost their conscious functioning. Second, this suggestion has to struggle with how to understand patients like that of Rodin and colleagues [19], who had no stem functioning but some cortical functioning. Just how much cortical death is required before a patient is dead? How can this question be resolved in a nonarbitrary fashion? Finally, as one of us has argued elsewhere [35], it is unclear why humans have to maintain conscious functioning to be alive, given that members of many species are alive without ever having conscious functioning.

A New Proposal

The problem we have identified with the current consensus about brain death is not easily resolved. We believe that this difficulty is an indication of a fundamental misunderstanding in the current consensus, one that was first identified by Morison [36] 20 years ago during the initial debate about brain death. The consensus presupposes a sharp line between life and death and tries to identify that line with one or another criterion for death. The data we have presented challenge this consensus by showing that different aspects of brain functioning cease at many different times. Thus, any sharp dichotomy between life and death based on brain functioning, although convenient and appealing, is biologically artificial. We need an approach that recognizes this fact. This is the theoretical basis for our proposal.

There is, moreover, a practical reason for such an approach. The varying criteria for brain death were developed in response to the emergence of life support systems and transplantation technology. Three basic clinical questions emerged. One question is old: When is a patient ready for the services of the undertaker rather than those of the clinician? Two questions are new: When is it appropriate to unilaterally stop supporting patients (as opposed to stopping support at the request of a patient or surrogate)? and When can organs be obtained for transplantation? The creation of the varying criteria for brain death was an attempt to answer all three clinical questions (plus many other social questions about rights, roles, and responsibilities) with a single response based on a sharp life-death dichotomy. The problem of such a single answer to all three clinical questions is as follows: With loss of brain functioning on a continuum rather than at a discrete point, choosing an arbitrary point to call brain death and using it as the basis for a single answer creates undesirable results. For example, the loss of conscious functioning is one point at which some would be willing to unilaterally withhold support but at which few would be willing to accept burial or cremation. On the other end of the continuum, irreversible cessation of all functioning of the brain, including the brain stem, is a point at which nearly all would be willing to accept burial or cremation (after discontinuation of support and the resulting asystole), but adopting that point as an answer to all three questions, in view of the data we have presented, effectively eliminates organ transplantation as a viable option and forces society to needlessly expend limited resources. These practical reasons reinforce our theoretical reasons for denying, contrary to Kass [37], that death is an event that sharply differentiates between the living and the dead and provides a single answer for several different questions.

We propose a revision in the way in which we think about life and death. Rather than struggling with the impossible task of creating a single theoretically satisfactory and practically relevant criterion of death, we propose that each of the three above-mentioned clinical questions be answered on its own merits, with the realization that the three answers are not necessarily the same. We repudiate the attempt to answer all of them with a single definition of death. Table 2summarizes our answers. Let us elaborate on the rationale for them.


Table 2. Summation of the New Approach

The difficulties with the first question, which involves the point at which care can be unilaterally withheld or withdrawn, are highlighted by the recent Wanglie case [38]. Various reasons have been put forward about why, in certain cases (such as those involving vegetative patients), medical care can be withheld or withdrawn without patient or surrogate consent. Some investigators [39] argue that care can be withheld or withdrawn in these cases because it is futile. However, if the goal of a patient or family is to prolong mere biologic life, then care even of a vegetative patient accomplishes that limited goal and is not futile [40,41]. Others [38] assert that such care is not medically appropriate, but this stance begs the question of how to define appropriate care. Attempts to solve this problem by offering a different criterion for death are not, as we have argued, supportable.

We feel that, given the finite resources available for health care, appropriate use of social resources should serve as the justification for the unilateral withholding or withdrawing of care. For example, irreversible cessation of conscious functioning is a point on the continuum where the need to rationally use societal resources outweighs the desires of some persons for unlimited care. In such cases, the question of the unilateral withholding or withdrawing of care can be answered without any appeal to a criterion for death.

Our approach, unlike approaches based on some single criterion for death, allows for the appropriate consideration of the stewardship of social resources in unilateral decisions to withhold or withdraw care.

The second question concerns the donation of organs. The shortage of available organs has led to the consideration of using organs from vegetative patients [42] and to the proposal that we use organs from anencephalic infants [43]. It might be suggested that organs can be obtained from such patients if we adopt a new criterion for death. We rejected that argument above. But we also feel that the criterion for death is not where the discussion should be centered. For us, it should center around the attempt to balance the advantage of lives saved through increased organ availability (which argues for harvesting organs in such cases) against the need for public acceptance of organ donation (which may require forgoing harvesting organs in such cases). We feel, in view of these considerations, that the combination of irreversible cessation of conscious functioning with apnea is the appropriate point on the continuum for organ harvesting.

This is, in fact, close to the point at which we currently harvest organs, using the whole-brain criterion and the standard clinical tests. Our suggestion emerges from neither a new criterion for death nor some resolution of the dissonance between the whole-brain criterion and the standard clinical tests but from a practical attempt to balance saving lives and maintaining public acceptance of organ transplantation.

We feel that the question of when the patient is ready for the services of the undertaker involves a tradeoff between concern for family sensitivities and concern for preserving social resources. In view of the answers we have provided, the tradeoff is made easier. If medical care, including artificial hydration and nutrition, is unilaterally withheld or withdrawn, the vegetative patient will satisfy the classic criteria of irreversible cessation of respiration and circulation within 7 to 14 days, whereas the patient who is in addition apneic will satisfy the criterion within an hour. Little is to be gained in terms of conserving social resources by using the services of the undertaker before the classic criterion is met because the social costs of minimal care are relatively low and do not outweigh respecting the intuitive social feeling that breathing bodies should not be cremated or buried. This approach to the third question is advocated not as a theoretical account of death but as a practical solution to a balancing problem.

Each of these answers to the three questions has been widely advocated or adopted; what we have provided is a theoretical basis for combining them into one systematic approach, which has been lacking until now. We believe that such a theoretical basis is required for these proposals to be accepted by clinicians, ethicists, lawyers, and reflective members of society at large. We feel that medical care, including artificial nutrition and hydration, can be unilaterally withdrawn from vegetative patients. Organs may be harvested from eligible donors when the standard clinical tests are satisfied. In all cases, however, the undertaker's services should not be used until asystole occurs. Each of these key clinical decisions should be made at a discrete point, which we have justified above as the relevant point for making that decision; however, the point in time for each decision will not be the same because no sharp dichotomy exists between life and death. The possibility of combining these three positions rests on accepting Morison's insight that the sharp dichotomy between life and death is biologically artificial because death is a process rather than an event [36].

Acknowledgments: The authors thank Robert Arnold, MD, and Stuart Youngner, MD, for advice and support.

From Baylor College of Medicine, Houston, Texas.
Requests for Reprints: Amir Halevy, MD, General Medicine Section, Ben Taub General Hospital, 1504 Taub Loop, Houston, TX 77030.

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