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REFLECTIONS ON THE FIRST INTERNATIONAL SYMPOSIUM ON BRAIN DEATH.
(Havana, September 22-25, 1992)

By: CALIXTO MACHADO, President of the Organizing Committee

Correspondence: Dr. CALIXTO MACHADO
Instituto de Neurologia y Neurocirugia
29 y D, Vedado, Habana 4
Ciudad de La Habana 10400
Apartado Postal 4268
CUBA
Fax: 53-7-336321
E.mail: braind@.ceniai.cu

The "FIRST INTERNATIONAL SYMPOSIUM ON BRAIN DEATH" was held at the International Conference Center, Havana, between September 22 and 25, 1992.

Delegates from twenty-one countries attended this sunny and Caribbean city to discuss many controversial issues concerning brain death and other related states. Argentina provided the biggest delegation (22 attenders).

The Opening Ceremony was highlighted by the performance of the National Chorus of Cuba. The singing of beautiful cuban songs prepared the delegates for the words of welcome given by the Organizing Committee, emphasizing that even in such a scientific context, there would be opportunities to discuss human dignity, and life as well as death.

On the morning of September 22, delegates enjoyed four striking opening lectures. Like Olympic Gold Medallists, Earl Walker (U. S. A.), Christopher Pallis (U. K.), Gaetano Molinari (U. S. A.) and Daniel Wikler (U. S. A.) followed one another to the rostrum.

In his address "Dead or Alive" Earl Walker presented much of the basic material derived from the Collaborative Study of Cerebral Survival sponsored by the National Institute of Neurological and Communicative Diseases and Stroke (1). For ages, people had considered life to exist as long as an individual was breathing. It was later realized that respiration was a means of maintaining the heart which circulated the blood. Life was then attributed to cardio-respiratory action. As long as such activity maintained the nutritional needs of the brain, the individual was alive. But, in the middle of this century, physicians became aware that the brain required much more energy than other organs and, if its needs were not met, it would cease to function, while other parts of the body (requiring less energy) might remain viable and even regain their activity provided the circulation was maintained. The result would be a dead brain in a viable body. Is such a preparation alive or dead? Before answering that question, one had to establish the general principles upon which the diagnosis of a dead brain could be made. The cause of the coma had to be known, so that it could be remedied, if possible. If the condition was not remediable, the state of the brain (underlying all sets of brain-death standards) had to be determined. The clinical status could be ascertained by standard neurological examination. Testing was, however, often complicated by factors such as wounds, which could render it difficult to carry out or difficult to interpret. Other confirmatory examinations then had to be relied upon to establish the death of the brain. But these confirmatory tests had limitations too, some related to the quality of the examination (such as electroencephalo-graphy) and others quantitative aspects (such as isotopic angio-graphy). But with the recognition of these limitations, the available yardsticks provide a satisfactory estimate of the state of the brain. In the rare case in which the clinical and confirmatory test seem to be at variance, observation of the subject for a longer period of time provided clarification of the issue. The validity of these criteria under such circumstances as infancy, concomitant intoxications and impaired cardiovascular status had been questioned. Having established the clinical states of the subject, the physician usually had no problem in certifying death. Problem cases required a careful consideration of medical, religious and legal factors.

The second lecture "Brainstem death. Evolution of the Concept", proved a detonator for future discussions. Pallis (2, 3, 4) emphasized that most controversies concerning the criteria for diagnosing death had sprung from a reluctance to define death. Discussions about the validity of different criteria could not meaningfully take place in a philosophical vacuum. What we did (or did not or did not do) in the Intensive Care Unit had to flow from explicitly formulated philosophical premises. "There was only a kind of human death: the irreversible loss of the capacity for consciousness, combined with the irreversible loss of the capacity to breathe (and hence to sustain a spontaneous beat)". All death, in this perspective, was brainstem death. But whereas there was only one death there were clearly several ways of dying. The commonest, by far, was circulatory arrest. But this only proved lethal if it persisted for long enough for the brainstem to sustain irreversible anoxic damage. Circulatory arrest of briefer duration either had no sequelae, or cause slight, moderate or severe neurological damage, the most pronounced form of which was PVS (persistent vegetative state). The death of the brainstem was nearly always the infratentorial repercussion of supratentorial events. It implied the death of the "brain as a whole". A diagnosis of brainstem death had two fundamental implications. The first, pragmatic, was that the heart would inevitably stop, within a relative short period. This was an empirically validated observation, to which no exception had as yet been recorded. The second, philosophical, was that quite independently of the cardiac prognosis an individual with a dead brainstem was already dead (because irreversible unconscious and irreversible apnoeic).

The distinctions between "whole brain death" (death of every neuron in the intracranial cavity) and "brainstem death" (death of the "brain as a whole") were, both philosophically and in practice, of minor significance. There were fundamental differences, however, between both of these concepts and the various "higher brain" formulations currently being proposed and discussed mainly by philosophers (5, 6, 7). Their views implied that an individual might be declared dead even if still breathing. We would undoubtedly lose public support for transplantation (and rightly so) if such a proposition were ever seriously put forward.

Gaetano Molinari (U. S. A.) was the third on the scene. He emphasized that: "still prohibiting unanimity among physicians worldwide were only some unfortunate but persisting choices of words". Terms like brain death (BD), whole brain death, brainstem death, neocortical death served only to confuse a basic issue, namely, that heartbeat, blood pressure, and even body temperature had lost significance as evidence of life in modern intensive care units. In situations in which spontaneous respirations had stopped but heartbeat persisted, death must be pronounced "neurologically". Comparing the "whole brain" and "brain as a whole" formulations of death, he stated that the only situation in which the British Criteria (8) might declare persons dead while the cerebrum retained functional capacity was the possibility and demonstration in three cases in the American Study (1), and subsequently by others (9), of apnoeic coma with absent cephalic reflexes due to primary brainstem lesions (suggesting death) while electroencephalograms might indicate some residual biological activity (10).

The fourth speaker in this marathon was Daniel Wikler, presenting some remarks on "The Philosophical Considerations on Death". Wikler was included as a philosopher, on the professional staff of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (11). He asked: "Should we consider a further revision in the definition of death, one which would define death as permanent loss of consciousness? This change would permit physicians to pronounce dead patients in a PVS. Today we lack the ability to diagnose this condition with certainty, so a further change in the law would be unwise. Nevertheless, we might wish to be prepared for the day when physicians acquire the ability to diagnose PVS with certainty, at least for some types of patient. Should such patients be considered dead or alive?

A thought experiment suggested the need for a further redefinition. Suppose that, at some future date, doctors became capable of maintaining function in severed heads and decapitated bodies. One poor man, careless in his use of an electric saw, suffers a complete decapitation. His head is carried in an ambulance to the Head Hospital; his body is carried to the Body Hospital in the next town. Since no one can be in two places at once, we must ask: Where is the patient? Is he in the Body Hospital or the Head Hospital? All of us would answer, if we had to make a choice, that he was in the Head Hospital. Now, to continue the story, suppose that the head dies, but that the patient's body continues to live. Is he alive or dead? We cannot say he is alive, since that would imply that at the time his head died he magically switched his location to the Body Hospital. Therefore we must say: he died. At this point in the story, we have his living body, in the Body Hospital, but the patient is not alive. But this is what we have with a patient in PVS; and therefore we ought to say that such a patient is not alive either. In the future, however, we will have to address the problem of those patients who remain in an unconscious state for many years. As an issue in bioethics, the definition of death has been put to rest, but it has not yet expired. In this remarkable lecture Daniel wikler introduced the Symposium to the concept of "higher brain formulations of death" (5, 6, 7).

The lunch break was taken up in further discussion: three lunch panels were presented: "Famous Trial Cases" (in relation to BD and persistent vegetative state) was moderated by Gaetano Molinari; "Persistent Vegetative State (PVS)" by R. Firshing (Germany) and "Do not Resuscitate Orders", by Daniel Wikler and Stuart Youngner (U. S. A.).

The afternoon of Tuesday, September 22, proved an interesting session in which brain death criteria in different countries were compared. We presented the "Cuban Criteria for Brain Death Diagnosis" (12, 13). These involved a sequential approach for brain death diagnosis, using multi-modality evoked potentials (MEPs) and electroretinography (ERG) as a key step. When reviewing literature it was clear that most sets of criteria had not presented considering such a sequential approach. MEPs and ERG were not usually included as confirmatory tests. The combination of of both a sequential approach, and the application of a test battery comprising MEPs and ERG, could overcome the difficulties posed by conditions traditionally considered as excluding a diagnosis of brain death, and could facilitate clinical practice, in establishing a precise and early diagnosis of BD, which was also fundamental for organ transplantation (14).

Christopher Pallis again took the rostrum (he was always expected by the auditorium) and presented the U. K. code (8). The majority of the delegates thought that he had been a member of the Commission that had drawn up the U. K.Code, but we were to learn from him that although the U. K.Code had a brainstem orientation in its concept of death, his own contributions in this field had been due to personal interest and commitment. Pallis stressed that the main emphasis of the U. K. code was the all important question of "context". Unless strict preconditions had been fulfilled, and certain conditions specifically excluded, a diagnosis of brain death could not even considered. He likened the picture to a patient having to pass through two tight sieved, before been tested for brain death.

This point had seldom been grasped by those criticizing the code. The scheme outlined was scientifically sound and clinically easy to use. Terminological problems remained however. The memorandum produced by the Conference of Medical Royal Colleges and their Faculties was entitled "The Diagnosis of Brain Death" (8). The document stated, however, that it was the "permanent functional death of the brainstem that constituted death". This is unexceptionable, if taken to mean that death of the brainstem prevented any kind of meaningful functioning of the "brain as a whole". The title of the document remained, however, open to misunderstanding.

A different view concerning the U. K. code (8) was presented by a german delegate, Dr. R. Firsching, a close collaborator of R. A. Frowein's. In Germany, death of the entire brain was required and brainstem death alone had not in general been accepted as death of the individual. Firsching emphasized that as recommended by the "Bundersfrztekammer" in Germany, prerequisites for the declaration of brain death were a primary or secondary brain lesion and the exclusion of drug effects, hypothermia or endocrine disorders.

After the association of apnoeic coma and cranial nerve arreflexia had been confirmed (in cases of primary supratentorial lesions) four options were available: (1) a waiting period of 12 hours; (2) electrocortical silence as revealed by EEG; (3) step wise abolition of brainstem auditory evoked potentials in sequential investigations; (4) the demonstration of intracerebral circulatory arrest, either by angiography or by transcranial Doppler sonography. In primary infratentorial lesions cortical function might be preserved by hours or days. The demonstration of electrocortical silence by EEG was therefore mandatory.

An interesting paper was then presented by a group of colleagues from Argentina. A retrospective analysis of 630 potential donors showed that their average age was 31. There was a net predominance of males (71,4 %). Head injury (46,65 %) and cerebrovascular diseases (44,6 %) were the most common aetiologies among the potential donors. Consent for organ donation was obtained in 58 % of the cases.

Preliminary results from a prospective study on BD, were then presented by neurologists from the National Institute of Neurology and Neurosurgery, in Mexico.

A warm evening proved a pleasant background to the "Welcome Party". There was plenty of cuban music, rum and friendship.

The morning of September 23, began with interesting presentations on: "Neurophysiological Tests and other Confirmatory Techniques in Brain Death and Related States" and "Legal Considerations on Brain Death and Related States".

I presented a paper on the "Early Diagnosis of Brain Death Using Multi-modality Evoked Potentials (MEPs) and Electroretinography (ERG)" (14, 15, 16, 17). MEPs and ERG were highly resistant to factors such as: drug intoxication, barbiturate narcosis, the use of anaesthetics, hypothermia, and so on. They had been shown to be reliable in the Intensive Care Unit environment. Considered as single tests, they had their limitations and they had been not routinely included as confirmatory tests for the diagnosis of BD. We applied a battery of tests (including MEPs and ERG) to thirty brain-dead patients. For brain stem auditory evoked potentials (BAEPs), three patterns of abnormality were observed: (1) no identifiable waves (73.34 %); (2) an isolated bilateral wave I (16.66 %) and (3) an isolated unilateral wave I (10 %). For short latency somatosensory evoked potentials (SSEPs) a characteristic pattern was found: absence of N20 and later responses in the scalp-cephalic record with preservation of all or some of the so-called subcortical components in the rest of the derivations. An interesting dissociation appeared in which some SSEP components were still present in neck-cephalic and spine while absent in scalp-non cephalic leads. Our data further suggested that all components after P13-N13 (recorded with restricted filter bandpass) also recognized two or multiple distinct generator sources. Rostral generators were probably located in the brainstem and/or thalamus, but a significant part of these SSEP components seemed to be generated at the lowest part of the medulla oblongata (dorsal column nuclei) and/or at the level of the upper cervical spine.

Visual evoked potentials (VEPs) and the ERG were elicited and recorded simultaneously, using cephalic and non-cephalic references. In all cases in which a non-cephalic reference was used the ERG did not change (either in latency or in morphology) while the VEP channel showed no response. In only two cases (using the VEP derivation with a non-cephalic reference) was it possible to record waves that indicated a spread of the ERG to the occipital area. These results suggested that although contamination of the VEP recordings by the possible spread of the electroretinogram to the occipital area might occur, when using a non-cephalic reference it was easy to confirm the absence of a true cortical visual response in brain-dead patients.

It was suggested that the test battery we proposed would permit the assessment of several sensory pathways, in brain-dead patients, thereby considerably increasing diagnostic reliability. Taking into account that these techniques are highly resistant to hypothermia, drug intoxication, the use of anesthetics, etc., resort to this battery as confirmatory tests might considerably diminish the time of observation needed to establish a definitive diagnosis of BD. This was of course a fundamental prerequisite to organ transplantation. MEPs and ERG were considered as confirmatory tests in the Cuban Criteria for Brain Death Diagnosis (12).

R. Firsching from Germany continued the session, presenting an interesting paper about "Evoked Potentials and Brainstem Reflexes in BD". In Germany registration of brain stem auditory evoked potentials (BAEPs) had been recommended as a confirmatory test of brain death under certain conditions. The author's group investigated 100 patients who exhibited apnoeic coma and cranial nerve arreflexia after primary brain lesions and who finally met all the criteria of brain death. BAEPs, somatosensory (SEP) and visual evoked potentials (VEP) and, in addition, transcranial magnetic (TmgMEP) and electric (TelMEP) motor evoked potentials were registered. In no patient with apnoeic coma and cranial nerve arreflexia could preserve BAEPs, SEP, VEP or TmgMEP or TelMEP. Brainstem reflexes were also abolished with the exception of seven cases with a preserved R1 response of the blink reflex immediately after apnoea had been documented. Registration of evoked potentials as a confirmatory test added safety to the diagnosis of brain death, as they were particularly resistant to drugs. They proved practicable for the declaration of brain death in one third of our patients. Brain stem reflexes required further research.

Hilmar Prange, also from Germany, continued the session with some remarks concerning the reliability of several technical investigations for the confirmation of BD. Fifty consecutive patients with suspected brain death were included in his study dedicated to evaluate the reliability of different diagnostic techniques. The techniques employed comprised clinical examination, apnoea testing, EEG, extracranial Doppler ultrasonography (ECD), brainstem acoustic evoked potentials (BAEP) and arterial digital subtraction angiography (DSA). In 39 cases these were no discrepancies in the results of the different techniques used to confirm brain death. With the remaining 11 patients the findings were not exactly concordant or, at least, permitted varying interpretations. For example, in six cases doubts existed as to whether or not the EEG was isoelectric. In four patients BAEP findings were compatible with brain death two to three days before intracranial circulatory arrest was documented. Finally, in two patients with isoelectric EEG and absent BAEP, arterial DSA showed residual cerebral flow. The significance of the mentioned technique for brain death diagnosis was discussed in the light of their conceptual differences implicit in the term brain death.

A beautiful lady from Chile, then proved that women were to be respected in neurophysiology. Nelly Chiofallo had worked with Professor Earl Walker during the seventies in an International Commission on Brain Death. She emphasized that when since clinical criteria were only partially realized and there was not total certainty concerning suspected brain death, certain non-invasive electrophysiological tests could provide objective evidence as to whether or not the cerebrum was active. Monitoring EEG and computer-average Evoked Potentials (EP) were among these confirmatory methods. EEG methodology was highly important in relation to both false negatives or false positives findings. (The author's experience with corpses was reported). Dr. Chiofalo presented 132 brain-dead patients studied by EEG, in a three year period, taking into consideration: age-sex distribution, primary diagnosis, consciousness state on admission, time elapsed until respiratory arrest, time elapsed from isoelectric EEG to asystole, etc. She also discussed the utility of topographic brain mapping in a controversial paedriatic case. Minimal EEG activity in few channels were related to artifacts. Mapping-histograms defined the presence of true bioelectrical activity.

Flying thousand of miles, A. Erbengy came from Turkey to the Pearl of the Antilles (Cuba). He stressed that although the determination of brain death was fundamentally a clinical diagnosis, conditions that might interfere with diagnostic accuracy required assessment by at least one ancillary test. In his institution (Hacettepe University Medical School) they had found that brain stem auditory evoked potentials (BAEPs) was the most reliable technique. They had also performed radionuclide angiography and brain perfusion studies, whenever they had felt it was necessary. More than 150 brain-dead patients had been studied by BAEPs and 30 by radionuclide angiography and brain perfusion. A highly significant correlation was found among BAEPs and radionuclide study results. None of the patients with absent BAEPs had showed cerebral perfusion. BAEP records, with or without radionuclide studies, had been found to be very reliable adjunct to a clinical diagnosis of brain death. Besides the determination of brain death, radionuclide studies also provided valuable information on the current status of the organs to be used as grafts in organ transplantation (kidneys, liver, heart, etc.)

The chairman of this session, Arnold Starr (U. S. A.), had in 1976 reported original data in 1976 about the use of auditory brainstem responses in brain death (18). He now presented a nice lecture entitled "Averaged evoked brain potentials and brain death". The averaging of electrical events in the brain (time-locked to sensory events) revealed a sequence of components reflecting activity at different levels of the pathway from receptor to cerebral cortex. The generators of these components varied, and examples that had been defined included activity in nerve fibers at points of an impedance change or activity in neuronal clusters. In comatose patients, the pattern of potential loss could be used to define the level of brain dysfunction. Brain death had been equated with the loss of central brain or brainstem activity while receptor function could be preserved. Among theoretical problems engendered by these assumptions was the fact that averaging required synchrony of brain activity time-locked to the sensory stimuli. Pathological processes might lead to a loss of this synchrony. Thus even though the brain was viable, averaged evoked potentials might be absent. A pathological process might result in the loss of function of nerve fiber pathways sparing neurons. Averaged evoked potentials would be absent in this scenario, since the neurons would not be receiving input yet the brain would be viable. Compromised receptor function might impair sensory pathway responses in a viable brain. Alternative activation of sensory pathways had to be developed for this situation as it had to be developed with peripheral nerve stimulation for somatosensory evoked potentials.

The lunch break proved not only a moment to enjoy cuban food. Three equally attractive lunch panels reported. As a final game for the World Crown in Chess, Christopher Pallis (U. K.) and Earl Walker (U. S. A.) moderated a discussion on the "Brain as a Whole and Whole Brain formulations of death on neurological grounds". Stuart Youngner (U. S. A.) chaired a group of discussion of: The "Higher Brain Formulations of Death". Meanwhile R. Dierkens (Belgium) was accompanied by enthusiastic delegates wanting to discuss "Medical Decisions in Terminal Cases".

From Oslo, Marianne Forsman, an interesting nordic lady, presented some remarks about the effect of nimodipine on cerebral flow and cerebrospinal fluid pressure after cardiac arrest. Fifty-one patients were included in a blind randomized study to evaluated whether the Ca-blocker nimodipine could influence cerebral blood flow (CBF) or cerebrospinal fluid pressure (CSFP) during the cerebral hypoperfusion period that followed resuscitation from cardiac arrest and to determined whether changes in CBF correlated with neurologic outcome. CBF (measured 1 to 4 hours after arrest with the use of intravenous 133Xe) was significantly greater with nimodipine than with placebo, There was no clinical evidence of seriously increased CSFP in any patient in either group during the first 48 hours. Mean arterial pressure was significantly lower, and antiarrhythmic drugs were used significantly less frequently in the nimodipine group than in the placebo group. Twelve patients in each group eventually regained consciousness. There was no significant difference in neurologic status between the two groups at any point, and no positive correlation between CBF in the hypoperfusion period and neurologic outcome.

From my group, Dr. Orlando Garcia presented the results of a study dealing with heart rate variability (HRV) in coma and brain death. Thirty-three comatose patients were studied serially by HRV and Glasgow Coma Scale (GCS), as were 40 normal subjects to document our normative data. HRV values were considered for different GCS scores. For GCS from 7 to 9, the HRV achieved its maximum values. We considered these in relation to a functional disconnection of the defense hypothalamic area with a normal functioning brainstem, such results apparently not been previously reported in the literature. HRV showed a significant tendency to decrease with low GCS values (3-6). For high GCS scores (10-15), the HRV also showed a significant tendency to decrease. With these results a non-lineal correlation between HRV and GCS was defined. Fourteen brain-dead patients were also studied and were found to present the lowest values for HRV (significantly different from normals). During the atropine test no significant changes in the HRV were found for brain-dead patients.

An enthusiastic group of neurologists and neurosurgeons from the Neurological Center of the French Hospital in Buenos Aires, (Argentina) presented three papers dealing with the application of neurophysiological techniques to study brain-dead patients. They described a patient diagnosed as brain dead who had preservation of the spinal (somatosensory) evoked potential at L5-S1. These results might be used to explain the finding of the Lazarus's Sign in brain death. In another paper, they described a series of 30 patients, studied by multi-modality evoked potentials and EEG, finding patterns which confirmed absence of cerebral function. All cases showed a electrocerebral silence, except three patients, who showed preservation of rudimentary but recordable EEG. They discussed the possible mechanisms of EEG preservation in such patients, in relation to the intracranial pathology and to the timing of the EEG study in relation to the clinical evolution, since brain death was established. The colleagues from Argentina were in fact defending the "brain as a whole" (brainstem death) formulation of death. The third paper consisted in the presentation of a patient who developed a cardiac arrest during a study of the brainstem auditory evoked potential. Several changes in evoked responses were noted, that confirmed the diagnosis of brain death.

The session devoted to discuss the "Legal Considerations on Brain Death and Related States" was chaired by Professor R. Dierkens, President of the World Association of Medical Law. Dierkens emphasized that the wishes of the patient had to be considered, but in a context in which the medical opinion was also important. The deontological code in Belgium proposed the cessation of treatment when the clinical diagnosis was hopeless. The Catholic Church in this country had also proposed to discontinue treatments progressively in terminal patients, but without abandoning nurse care, pain relief and psychological support.

From my group, Dr. Jesus Parets, a young lawyer, continued with "Legal Considerations on Brain Death Diagnosis and the Moment of its Occurrence" . The old Civil Code in Cuba (1942) had stated that "death was diagnosed by physicians confirming an irreversible cessation of cardio-respiratory functions". In 1985 a new Civil Code altered this, starting that "death is diagnosed by physicians in relation to criteria defined by the Ministry of Public Health". This view defended a position in which the relevant criteria were not included in any law. New criteria could thus be included at any time. The Ministry of Public Health had then organized a national commission which every year reviewed and updated the criteria to be applied in our country. A ministerial resolution had validated the use and application of the "Cuban Criteria for Brain Death Diagnosis" (19).

DONAR (the Spanish for to donate) is an organization from Santa Fe, Argentina. Its President, Dr. Pedro Zukas, emphasized that "Time is too short for egoism". Dr. Zukas read a paper whose main author was Dr. Cesar Rey Leyes (Argentina). Article 103 of the Argentinean Civil Code emphasized that death made it impossible to have human rights. The diagnosis of death was accepted in relation to medical criteria, but this had to be done independently of any decision concerning organ transplantation. The patient's relatives could give or refuse permission regarding organ donation. The law had to facilitate medical development, and not impede it.

A controversial session (Bioethical Considerations on Brain Death and Related States) began in the morning of thursday 24. It was chaired by Daniel Wikler and Stuart Youngner (U. S. A.)

An expected lecture was presented by the chairman, Daniel Wikler: "Why Brain-dead Patients are Dead? The President's Commission Explanations After One Decade". Daniel Wikler's presentation was a discussion of the definition of death provided by the President's Commission for the study of Ethical Problems in Medicine and Biomedical and Behavioral Research (11). This commission had been appointed in 1979, by the President of the United States. It had produced eleven reports which had proven influential in American and international bioethics. The President's Commission report addressed three topics: (a) What concept of death should be used? (b) What legal statute should be adopted? (c) How should brain death be diagnosed? However, only (a) was the official product of the Commission. The statute had been written in collaboration with the American Medical Association and the American Bar Association (among others). It gave a legal definition of death as either whole-brain death or cardio-respiratory death. The Commission's report provided (c) as a public service in an Appendix (not endorsed by the Commission itself) its recommendations on diagnosing death. These had been formulated by an expert panel, including Dr. Walker and Dr. Molinari. In its comments on the concept of death (a), the Commission had argued that patients who suffered whole-brain death should be viewed as dead. The primary reason was that the brain (and in particular the brainstem) was the integrator of the body's major organ systems. Without this integration, the Commission reasoned, continued functioning of the patient's major organ systems (in an ICU) did not constitute organismic life. The Commission rejected a "cortical-death" definition, pointing out that such a definition of death would seem to endorse the burial of a patient with a spontaneously beating heart. The Commission's findings had resulted in a change in the definition of death in nearly every one of the states in the U. S. A. (where defining death is a matter of state, rather than federal, law). Philosophers, however, had questioned the logic of the Commission's central argument, pointing out that the major organ systems in a well-maintained brain-dead patient, interacted so as to sustain the main non-cognitive bodily functions.

Dr. Stuart Youngner (Associate Professor of Medicine, Psychiatry and Biomedical Ethics at the Case Western Reserve University School of Medicine and Director of the Clinical Ethics Program of the University Hospitals of Cleveland) presented a paper on "Brain Death and Organ Transplantation: Confusion and Its Consequences" (20). He argued that despite the rapid and widespread embrace of so-called "brain death" in the United States, confusion about its meaning and implications remained a problem. He gave several examples of evidence of this confusion. First, the criterion of brain death, i.e the irreversible loss of all brain function, was accepted for practical reasons (without a wide agreement on exactly why patients who had lost all brain function were dead). The practical reasons were: (1) in the hands of a competent neurologist, neurosurgeon, or critical care physician, brain death was a relatively easy diagnosis to make; and (2) that once the diagnosis of brain death had been made the prognosis was certain that the patient would never regain consciousness and would develop asystole within a short time, despite continued aggressive intervention. The diagnostic certainty and uniformly dismal cardiac prognosis for brain-dead patients facilitated the acceptance of policies aimed at treatment withdrawal and organ retrieval.

A study by Youngner and his colleagues (20) at Case Western Reserve University had, however, indicated that physicians and nurses working in critical care and operating room settings accepted brain death for different reasons. Some thought brain-dead patients were dead because they would never wake up again. Others accepted them as dead because they had lost the integrating functions of the brainstem. Still others indicated that they did not really believe the patients were dead, saying that the patients were "going to die very soon despite aggressive treatment" or that their "quality of life was unacceptable."

Further evidence of confusion was the stubborn persistence of the term "brain death" itself. Health professionals consistently referred to patients who had lost all brain function as brain-dead (rather than, simply dead). It is also common to hear them say that the brain-dead patient "died" after life support had been removed. Of course you can not die if you are already dead. The persistence of term brain death may well reflect an inevitable conflict between reason (which told us that brain-dead patients were dead) and emotions. The latter were stimulated by the many signs of "life" still shown in brain-dead patients. These were of particular concern to nurses who took care of brain-dead patients. Intensive Care Unit nurses reported feelings of discomfort at calling patients "dead" who require aggressive treatment (including resuscitative efforts if the "dead" patient develop a cardiac arrests) at a time when clearly living and conscious patients, in the same unit, fell into the "do not resuscitate" category. In the operating theater, nurses sometimes felt that the patient's spirit was in the room during organ retrieval surgery, and only departed when the ventilator was turned off and the patient came to complete rest. These examples of confusion were inevitable when we were willing to call patients dead when so much life persisted. This confusion pointed not only to the need for more ongoing education about brain death, but also for wide debate and consensus among various elements of society (including not only doctors, but the legal and religious communities, and especially the lay public) before policies are implemented and enforced. To do otherwise was to foment distrust and suspicion of medical science, perhaps undermining the worthwhile goal of saving more lives by getting more persons to donate their organs.

Dr. E. Bochiardo from DONAR (Argentina) presented a paper "Brain Death", in which he emphasized that until some time ago the determination of death was relatively easy: confirming the irreversible absence of cardio-respiratory function. In the sixties, the development of reanimation and other intensive care techniques, forced physicians to confront the concept of brain death. A man had to be considered dead when his brain functions disappeared. He considered that the decision (made by patient's relatives) to donate organs was a transcendental and admirable token.

The results of an interesting survey were then presented by Dr. Eduardo Fermin, a delegate of the Cuban group. The subject of the survey was related to the decisions and feelings of the physician, who had to decide what to do in a brain-dead patient, when transplantation was not envisaged. The survey described to the attitudes of 50 specialists in intensive care medicine. This survey was anonymous, assessing the concepts of life and death, euthanasia, as well as the methods used in the process of diagnosing brain death. Many interesting results had arisen: for example, the confusion about methods and criteria for diagnosing death, concerns about the legal protection of physicians, doubts about when to turn-off the respirator, mistakes in the concepts of BD and euthanasia, etc. Many physicians had expressed religious opinions in this context.

Two cuban specialists in psychiatry (Drs. Jose A. Hernandez and Carlos M. Notario) ended this session presenting a paper entitled: "Attention to Near-Death-Patients". They appreciated the classic study of Dr. Klubler-Ross and particularly her description of the psychological stages in dying persons. They paid attention to the medical custom which sought to prolong, in all possible ways, the life of hopelessly ill patients, while accepting that medical procedures should be directed to relieve the pain of the dying and allowing a decorous death. They stated that their purpose was to stimulate a discussion about this subject in our country and to exchange opinions with foreign experts, but always keeping their patients in the forefront of their minds.

Three interesting lunch panels joined delegates with providing food for thought. "Near-death Experiences" was chaired by the Reverend Douglas Lynn (Canada), "Organ Marketing" by Dr. Raul Herrera (Cuba) and "Transplant Alternatives" by Dr. Noel Gonzalez (Cuba).

"Brain Death in Children" is always a controversial subject. This session was chaired by Dr. Kimio Sainio from Finland. He opened the session with a study of the patients with suspected brain death seen in the Children's University Hospital of Helsinki, during a ten year period (1983-1992). The study correlated clinical, neuroradiological and EEG data. A total of 36 patients were studied, ranging in age from 0 days to 11 years (mean = 1.9). Brain death was diagnosed in 21 patients. The diagnosis was confirmed in three patients by cerebral angiography and in four patients by colour flow Doppler ultrasound examinations. The EEG was inactive in 19 patients. Two patients showed minimal EEG activity two to five days before brain death was confirmed. The diagnosis of BD was not confirmed in 15 patients. Five of these cases had either flat or burst-suppression EEGs. Four of them died and one survived with major neurological sequelae. The inactivity of the EEG was due to barbiturate medication in two patients; both survived with major neurological sequelae. Both EEG and Doppler examinations were compatible with brain death, while clinically some brainstem function persisted in these two cases; both developed asystole within 24 hours. Of the remaining 6 patients, five died and one survived, a child who had inactive EEG at the age of 0 days and later developed major neurological damage. The ultrasound Doppler examination reliably confirmed the diagnosis of BD in these patients. The inactive EEG often preceded clinical and Doppler signs of brain death. An inactive EEG in patients that were not brain-dead was associated with poor prognosis.

A psychopedagogical view of organ transplantation was presented by Daniel De Greef (DONAR, Argentina) in his paper: "The Child and his Death and Organ Transplantation". The speaker considered that to be prepared for the moment of death, it was necessary to educate people to achieve a new culture about the need for organ transplantation. In this context, people would be psychologically prepared when facing the death of a relative, to give their concern to donate organs. This was a message that we should learn since the child-hood in our schools. Organ transplantation allows a dead person to offer life to another.

A cultural night (on Thursday evening) gave us a marvelous opportunity to listen to cuban music.

Two important sessions took place on the last day: "BD and Organ Transplantation" and "Philosophical, theological, cultural, historical and sociological considerations on BD and related issues".

"Brain Death and Organ Transplantation" was chaired Professor Noel Gonzalez, pioneer of cardiac transplantation in Cuba, and Raul Herrera, Director of the National Institute of Nephrology.

Professor Noel Gonzalez presented an overview of the evolution of organ transplantation in Cuba, emphasizing cardiac transplantation. Professor Gonzalez had organized the Cuban National Program for Transplantation.

Dr. Raul Herrera described the Cuban experience in relation to renal transplantation. The first renal transplantation took place on February 24, 1970 in Cuba. This initiated the development of transplantation surgery in our country. The total number amount of renal transplants, up to 1992, had been 1809.

Dr. Antonio Marrero, a member of Professor Gonzalez's group, described the coordination of organ and tissue transplants. He described the medical and psychological problems encountered in obtaining adequate number of donors and viable organs and tissues. He also described the care of the donor in the Intensive Care Unit, the anaesthetic and surgical techniques employed, etc. Dr. Marrero also commented on the group's experience in cardiac transplantation. He analyzed data relating to 307 possible donors processed between 1985 and 1991, emphasizing the cause of brain death, age, sex, number of extracted organs, blood groups, causes of no acceptance, and the average ischaemia time, among other elements. He explained the selection criteria in donors for cardiac transplants, and summarized the technique used for organ harvesting.

A cuban lady, Sofia Sanchez, emphasized the important roll of the psychologist in the Intensive Care Unit, in managing patients' relatives. She described the medical-psychologic stages in the comprehension of the patient's relatives. She also described the organization of the Cuban National Program for Transplantation at the "Hermanos Ameijeiras" Hospital, showing the national statistics for multi-organ donors between December 1985 and December 1991.

This session was ended with a round table involving specialists from the Intensive Care Unit of the "Hermanos Ameijeiras" Hospital.

The session devoted to "Philosophical, Theological, Cultural, Historical and Sociological considerations on BD and related issues" was chaired by Douglas Lynn, Senior Pastor and President of the Crossroad Cathedral International Ministries and Dorita Caballero, also Pastor of the Crossroad Cathedral (Canada). Reverend Lynn began the session with these remarks: "The Human race had been caught up in a unique moment of wold history precipitated by man's tremendous advancements in medicine and science. Technology had outstripped the development of man himself, so that the two were no longer synchronized. What man "can do" was out of step with our knowledge of "who man is", which had resulted in an ever increasing tension and a multitude of unanswered questions. This had been further complicated by the interdisciplinary nature of bioethics which extended these questions beyond the field of medicine to the philosopher, the ethicist and the theologian. He proposed, in his paper to delineate the contours of this tension by examining fundamental questions like, "What determines humanity?", "What are the components of personhood?, "What defines the dignity and value of a human being?", "Is there a difference between human life and biological life?", "What does life as defined by a holy world View where our judgments are based on deep-seated absolutes to which are added precepts based upon experience?". Reverend Lynn came to this exchange as a fellow inquirer sharing some of the uncertainties common to us all. As an Evangelical Christian, his aim was to set forth what many of the great philosophers of the last 300 years had verbalized, namely, that without resort to a concept of God (variously under-stood) and to an understanding of the purpose of life which is provided by the great religions of the world, it was not possible to justify the rules of living which had been the guiding principles of our world. He believed we were more than the products of random accidents without purpose and meaning.

The Jewish position was defended by Rabby Dr. Moshe Tendler, Chairman of the Bioethics Committee of the Rabbinical Council of America and Professor of Medical Ethics and Biology at New York's Yeshiva University. Since decapitation was regarded by the Talmud as the only applicable model for brain death, Tendler and Rabbi Yigai Shafren had performed an interesting experiment: a pregnant ewe, close to delivery, was decapitated and organ viability was maintained by a ventilator. The decapitated sheep was kept in this condition for several hours with heart action and blood pressure remaining within normal values. A live lamb was them delivered by Caesarean section. Dr. Tendler emphasized that this experiment proved that neither a beating heart nor a live foetus were a signs of life when an animal was on respiratory support. The critical condition required by Rabbi Auerbach, one of the leading halachic arbiters in Israel, was a 30 seconds cessation of heart beat after the respirator had been disconnected from a brainstem-dead patient. Transplant surgeons could accept this condition when it involved the use of a kidney, liver, lung and pancreas, but it considerably reduced the success rate in cardiac transplants. Dr. Tendler considered that the heart could be removed from the brainstem-dead donor while it it was still beating. Tendler disputed the belief held by many Jews that they would be denied entrance to Paradise or resurrection after death unless they were buried with all their organs. If a man's leg was amputated, should it be buried so that its being above ground did not defile the Priestly Tribe? The greatest guarantee of Paradise was having donated organs to save another person's life. Dr. Moshe Tendler had called on all rabbis and Jews to accept brainstem death and to actively promote organ donation.

"DONAR" went again to scene. Dr. Zukas stated that death compelled man to face the mystery of his own life. Pope Pio XII had stated that the diagnosis of death was a subject of Medicine and not of the Church. Nowadays, what characterized death was the irreversible damage to the brain, with the disappearance of personhood. A "patient" in this state was a corpse. But was it not possible to offer life from these cadavers? Juan Pablo II had emphasized that organ transplantation was like the resurrection of Christ, who after his death continued to offer life: "Because I was thirsty, you gave me water; because I was hungry, you gave food to eat; because I was blind, you gave your corneas; because my heart was sick, you gave yours, before mine stopped; because I was on a dialysis machine, you gave your kidney; because of this I came to share the kingdom of God".

Dr. Orlando Garcia (from my group) and Dorita Caballero (Pastor of the Crossroad Cathedral, Canada) presented "One Body, Many Lives". Science and modern technology had made possible a dream that had caused wonder to humanity from the oldest times: organ transplantation. Today the lack of available organs constituted a major problem for thousands of people who remained on waiting lists. Medical activity could be an areas of deep meaning, and co-creating activity in the relation between man and God in a context of humanized structures, but such activity can also be adulterated, for example by the criminal practice of organ marketing. A theological understanding of the body was (and by far) more communitarian than individualistic. We belonged to one another. This derived from an understanding of Creation by God, and of a life project in Jesus Christ open to humanity. As part of their theological mission, churches could support a donation system and contributed to the public dialogue. "Look for a new heart, why should you die?...I will give you a new heart and will put a new Spirit within you, and I will take away from your flesh the heart of stone, and I will give you a heart of flesh". These words from the prophet Ezequiel had a special resonance in this context. The cuban hero Jose Marti said: "to die is to close one's eyes the better to see ...". The vision he was referring to so profoundly did not depend on our sense organs or the corneas which otherwise could restore the sight to others.

May be, for the first time, a group of Cuban Yoruba Theologians participated in an event like this. Spanish and African emigrations had provided the main core to cuban nationality. From a region of Africa, which is now Nigeria, had come numerous groups of slaves, who practiced what is known as the Yoruba Religion. The mixture of the Yoruba conceptions with catholicism and (less important) with animismism, defined the religious practice known as "Regla de Ochoa" or "Santeria"). A group of theologians from this religion, participated in the Symposium to present their philosophical views in relation to brain death. They emphasized that a brain-dead patient was not able to code the communication between the material and spiritual components of a human being, because it was in the brain that there existed the energetic centres to develop such a communication. In a living body with a dead brain, it was therefore impossible to communicate with God. They accepted this state as equivalent to death. They also considered that organ transplantation was both ethically and philosophically a valid way of helping people.

Final remarks. From the presentations and discussions during the Symposium, it was clear that discussing about brain death were not over. The persistence of the use of the term brain death could well reflect an inevitable confusion, namely that there were "different types of deaths". As Dr. Youngner (20) emphasized, the stubborn persistence of the words brain death in everyday language was not simply a slip of the tongue or ignorance of the facts. It reflected an underlying confusion about the true state of patients whose brains had stopped functioning, but whose other cells, tissues, organs, and organ systems continued to live, integrated, however modestly, by the machines and staff of our modern intensive care units. This confusion pointed out only to the need for more ongoing education about brain death, but also for wide debate and consensus among various elements of society, including not just the medical community but also philosophers, theologians, lawyers, sociologists, psychologists, etc. This Symposium had been a clear example of a multi-disciplinary approach of this subject.

There were still controversies about how much of the brain needed to be dead before a person could be declared dead on neurological grounds (2, 3, 4). The "whole brain" criterion meant the irreversible cessation of hemispheric and brainstem neuronal functions (11). It had been accepted by our society mainly for practical reasons, i. e., physicians had constructed batteries at bedside tests (and of confirmatory laboratory procedures) to show that this criterion of death had been satisfied. Nevertheless, persistence of certain hypothalamic neuroendocrinal functions and (rudimentary but recordable) EEG activity in patients otherwise fulfilling the "whole brain" criteria, emphasized the controversy concerning the "critical number of neurons" that had permanently to cease functioning before the essential activities of the hemispheres, diencephalon and brainstem ceased to integrate the functions of the organism as a whole? (2, 9, 10, 21).

The "brain as a whole" (brainstem) criteria powerfully defended, both clinically and philosophically, by Professor Christopher Pallis (2, 3, 4), were criticized by the German delegation, because they held that "it was not possible to exclude the possibility" that deeply comatose patients fulfilling all brainstem criteria of death, with destroyed brainstems but preserved cerebral hemispheres, might be capable of thinking, feeling and so forth. To this Dr. Pallis had responded that in the vast majority of cases the dead brainstem was the infratentorial repercussion of massive supratentorial pathology. In the debate it was notable that some colleagues talked about "consciousness" but without considering its two components described physiopatologically by Plum and Posner (22): the capacity ("arousal") and the content of consciousness. For example, when Pallis had spoken in his definition of human death (2, 3, 4), he had always talked about "the irreversible loss of the capacity for consciousness...". In PVS patients, the capacity for consciousness was preserved (a predominantly brainstem function), while the possibility of endowing the capacity with an affective or cognitive content is lost.

The distinctions between "whole brain" and "brainstem definitions" were, both philosophically and in practice, of minor significance (2, 3, 4). There were fundamental differences, however, between either of these two and the various "higher brain" formulations currently being proposed and discussed, mainly by philosophers (5, 6, 7). During the past two decades a group of philosophers and physicians had advocated replacing the "whole brain" criterion of death with the "higher brain " concept of death. "Higher brain" formulations proposed defining death as "the loss of that which is significant to the nature of man" (23). "Higher brain" constructionists held that irreversible loss of perception, sentience and cognition were necessary and sufficient for diagnosing death (5, 6, 7, 23). Again, a confusion might arise, because patients fulfilling the "higher brain" criteria of death might preserve the capacity for consciousness, although all (or virtually all) content might be lost. Using the "higher brain" criterion, patients in the persistent vegetative state, others with advanced forms of dementia, and anencephalic infants would be classified as dead. (24). There were many obstacles that rendered difficult the generalized acceptance of the "higher brain" criterion of death in PVS patients (2, 3, 4, 11, 24): it would imply a radical redefinition in the concept of death; it was arbitrary to define the degree of hemispheric brain damage necessary to diagnose death; there were no reliable criteria or generally accepted confirmatory tests to confirm the diagnosis; to assess prognosis (with an adequate degree of certainty) required weeks or months of observation, and it was inherently distasteful that that physicians should observe patients for many months to confirm the diagnosis of death; practical problems would arise concerning burial practices in "dead" patients that still exhibit breathing, heart beat, gagging, coughing, and sleep/wake cycles. In last years, it had become an increasing acceptable practice to permit the termination of medical treatments in such hopeless conditions such as PVS. A new question, then would arise: was one considering the PVS patients as "dead"? Or was one permitting them to "die"? In fact, the philosophical discussion about the concept of death was clearly not over.

Several authors defended the use of confirmatory tests (evoked potentials, cerebral blood flow, etc.) for an early diagnosis of BD. Others considered clinical examination sufficient for this purpose. I considered that multi-modality evoked potentials and electroretinography suitable procedures to test patients suspected of being brain-dead (12-17). These techniques were non-invasive, posed no risk to the patient and reliable recordings were feasible in an Intensive Care Unit environment. They provided an objective electrophysiological assessment of brainstem and hemispheric functions Furthermore, these techniques were highly resistant to any confusing factor (such as CNS depressant drugs, hypothermia, anoxia, and so on). It was easy to confirm that MEP and ERG were actually safe and rapid BD confirmatory tests that could be performed at the patient's bedside. Nonetheless, although the main reason behind the efforts made elsewhere to develop a safe and early diagnosis of BD was transplantology, I thinked that this was a matter of human dignity.

When considering the legal considerations on BD, and related states, most delegates endorsed the need to have laws that protected physicians, nurses, etc., in the difficult process brain death diagnosis and organ transplantation. Discussions also took place concerning the increasing acceptable practice (in U. S. A.) of permitting the termination of medical treatments hopeless states states, such as the PVS.

All the theologians and religious people attending the Symposium expressed their acceptance of the concept of brain death and of organ transplantation. Different views (mainly rejections) emerged from their comments concerning the acceptance of "higher brain formulations of death". If one accepted this concept of death future management of patients with advanced forms of dementia would prove very difficult and controversial.

PROPOSALS

One of the most important achievements of this Symposium was the proposal to organize an international Group or Commission on this field. The main objectives of this body could be:

These are merely preliminary ideas. Further contacts and discussions are needed. Delegates suggested an approach to different sources for sponsorship. There was a general agreement to the proposal that I should coordinate the organization of this group. The delegates also proposed to hold future Symposia on BD in different countries. Argentina was proposed to host the Second International Symposium on Brain Death.

The Closing Ceremony was memorable. Two young guitar players, conveyed by the delegates the real feeling of classic Cuban music. Colleagues from Argentina, as the leading delegation, elected Professor Christopher Pallis as "most popular delegate" (although the discussion was difficult taking in consideration other participants such as Professor Walker, Molinari, Wikler, Youngner, Dierkens, Lynn, etc.). In the name of the Organizing Committee, I emphasized that we had really committed ourselves in making a reality our dream: "the holding of the First International Symposium on Brain Death", in an atmosphere of friendship and understanding.

The Farewell Party lived up to expectations. With the help of "mojito" (a famous Cuban cocktail popularized by Hemingway) and Cuban "cerveza" (beer), foreign and cuban delegates were soon dancing "son" and "rumba". At the end, we all sang "La Guantamera" (famous Cuban song), with a mixture of happiness (at the thought of the pleasant and informative days we had enjoyed) and sadness, because the moment to say "hasta luego" (so-long) had arrived.

REFERENCES

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