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BRAIN DEATH

The Medical Determination of Death

History

The role of the physician in the diagnosis of death began only toward the end of the eighteenth century, and it increased throughout the nineteenth century, From about 1850 or so, several countries and large cities introduced statutory requirements for a declaration or verification of death by a medical practitioner. A medical critic wrote in 1818: Doctors are rarely called in to certify death, This important responsibility is left to mercenaries or individuals who have no knowledge whatsoever of the human anatomy, When a doctor cannot save a man's life, he avoids being in his home after he had died, and all practitioners seem totally convinced of the axiom of the great philosopher that it is not seemly for a doctor to visit the dead.

In the recent copious literature about death and dying, it is often said or implied that from the earliest stages of humankind, people have been terrified of death and of its premature pronouncement and their interment. It is difficult to know how death was regarded by prehistoric peoples, Comparisons with the concepts of existing primitive cultures are not necessarily reliable or accurate, There are significant differences in the attitudes and practices among the cultures of today.The attitudes of both prehistoric and contemporary societies probably modified their practices gradually as they underwent fundamental structural changes, Death may have been regarded not as a termination of one's existence but as a translation to a different form or to a different world. No doubt the immediate family and friends expressed grief at their loss, but the attitude of dying persons may have reflected an assurance of the transformation of their lives. The caves of Lascaux display a shaman, and similar figures appear in other wall paintings in widely scattered areas. Curiously, the people regarded today as the oldest and purest representative of primitive culture, the Australian aborigines, have a shaman in a dress quite similar to the one appearing in Lascaux. Perhaps in the Neolithic age, and even earlier, the shaman played the role not only of healer but of guide or assistant in conveying the dying person to a new form. The sites of Neanderthal and Cro-Magnon burials often display the evidence of reverence.

In the twelfth century B.C., the spread of the Dorian culture from east central Europe throughout the Peloponnese and into Crete resulted in the replacement of burial by cremation. This was a relatively short-lived change in the West, but in northern Europe and in southern Asia the cremation of the body effectively separated the old life from the one to be assumed by the dead person or from the world of the dead.

The religion of ancient Egypt expressed a belief in constant rebirth. The Greeks modified the concept of rebirth into another form. There was life to death to life once again, young to old and old to young, as illustrated by the lines of Empedocles in the fifth century B.C.: "Once on a time a youth was I, and I was a maiden. A bush, a bird, and a fish with scales that gleam in the ocean." The form of a society and its religion and ways of existence probably molded and refined the beliefs in immortality, in rebirth, and in transformation to another world of existence. A small food­gathering and hunting society is likely to have a different set of beliefs about death from a stable, sedentary agrarian society that persists over several centuries. The attitudes toward death and the customs related to dying and death have undergone several significant changes in western Europe from the Middle Ages to the present.

The fundamental element shared by all Western societies is the fear of death as a feature of the untamed destructive forces of nature, which are not only unpredictable but are also constant reminders of human weakness and vulnerability. Aries believes that love and death are the greatest of the natural forces that excite human emotions. Their uncontrolled character is potentially destructive to the integrity of a society. He suggests that it is the threat to society which, until recently, dictated the forms of belief and ritual related to death. Only within the modern period has emphasis shifted to a primary concern about the death of an individual, as illustrated by the literature of the romantic movement, the literature of various disciplines and twentieth century fiction.

As taboos were developed to control the disorder associated with love, particularly to assure legitimate inheritance of property and position, so too death became depersonalized-ritualized and regulated by the society. In sharp distinction is the heroic literature of ancient times, of Homer and of the sagas. In the earliest narrative we know, the Gilgamesh epic, probably dating from before 2000 B.C., the grief of Gilgamesh for the death of his friend Engidu is depicted:

Then I began to be afraid. . .
Fear of death seized upon me.
Therefore I make a way over the steppes
The fate of my friend weigheth me down; . . .
My friend, whom I love,
Hath turned into earth.
Must not I too, as he, lay me down,
And rise not up again
Forever and for ever?

The reply he receives asks whether man is to be immortal, and if any compact of immortality exists between man and God. The emphasis in the epics was placed on the tragedy of the individual's death.

The death of the self was restored to its earlier significance by the religious beliefs that had evolved from more primitive traditions; the earlier concept is said to have first reappeared in the early Middle Ages, with the doctrine of the duality of the body and the soul and the idea of a direct transition from life to death, without an intervening period of sleep or a persistence of some degree of sensibility. In earlier periods of the Christian era, and again the late Middle Ages and well into modern times, there was a persistent belief that death was a gradual process. The soul did not leave the body all at once. There was a state of sleep, a stage in the process of dying that resembled death, during which there was no breath or movement but the hair and nails continued to grow.

The Protestant revolution and Catholic reformation and the slow but continued introduction of scientific knowledge in the sixteenth and seventeenth centuries considerably weakened the struggle to contain the intrusion of the awareness of death into society. Its force showed once again that regardless of the great technologic achievements, increasingly buttressing society against the other ravages of nature and creating a sense in some that humankind was gaining control of its own destiny, death was the reminder that all must die, that the fundamental punishment of the God of Genesis still remained unchallenged. The fear, horror, and power of death were displayed in both art and literature. The depiction of the dance of death in this period differs significantly from the same theme in the Middle Ages. The belief in the gradual nature of dying became exaggerated. Phantoms and fantastic creatures, often grotesque images of the dying and of the soul, were depicted.

With the emphasis once again shifting back to the individual in the West, and with the presence of renewed fear and the emergence of the Enlightenment, customs arose to prevent the premature burial of the body, which, though life was absent, was believed to be not yet a cadaver. A body would be left on display and undisturbed for two or more days, often until decomposition became evident. There often followed a temporary entombment, followed by burial after several weeks or months, as depicted in Shakespeare's Romeo and Juliet. A person's will, previously given orally by the dying person, would specify the length and conditions of each phase of care. Accidental declaration of death was guarded against by several commonly prescribed measures. The most common and oldest was the conclamatio-the calling of the person's name three times-employed in ancient Rome and today still performed on the death of a Pope. The scratching or cutting of the skin to determine sensibility and the cutting of a blood vessel to demonstrate absence of bleeding were commonly prescribed.

When Winslow was preparing his book in the eighteenth century, there were many anecdotes in circulation of people who had been prematurely declared dead and entombed or buried. The stories invariably ended with the supposedly dead person regaining consciousness and being restored to life or with the evidence, found on exhumation, of a fruitless and terrible struggle within the grave. There was little evidence to support any of these tales, but Winslow's book reinforced public fears and lent credibility to the popular superstitions and fantasies.

Mary Shelley's Frankenstein, or the New Prometheus displayed the various aspects of fear, phantasm, and the belief in the power of science to restore life to the not-yet dead. Medical doctors and scientists of the age added to the fears. Many legends and folk tales contain depictions of the appearance of death or its premature declaration. During the early years of the romantic movement, the Grimm brothers collected and published many of the stories of Germany, and the burgeoning of interest in the old myths and cultures brought to public attention and reconfirmed the belief in the slow transition of life to death and the false appearance of death, as portrayed in the mixtures of eroticism and death in, for example, Sleeping Beauty and Snow White. The romantic association of cancer and tuberculosis, and perhaps AIDS today, with death and attributes associated with the affected one are described in other works.

During the fourteenth century, the bodies of people of wealth and social importance who died far from their desired burial place were preserved by embalming. In the fifteenth century this custom was extended to many others, but during the next two centuries the wills of many people specifically ordered their bodies to be left undisturbed, without embalming. This was not only from fear of premature burial but also to serve as a precaution against secret and illegal exhumation for dissection in the houses of medical doctors or of intellectuals seeking to acquire knowledge of the human body. It was thought not only that leaving a body undisturbed for 2 to 3 days would establish the true presence of death but that leaving it unembalmed would probably protect it from the "resurrectionists." The practice of grave robbing was so common and lucrative that some cemeteries experienced multiple thefts of the newly interred every night. Many educated people were motivated by a genuine desire to learn something of human anatomy. but one can imagine the stench of the decaying corpse left in the house of Vesalius and others for a week or longer.

It was during this period, the late eighteenth and early nineteenth centuries, that some temporary repositories for bodies were established to allow the continuous observation of the body until decomposition had commenced. These repositories, of German origin, were the first funeral homes of the West and were termed vitae dubiae azilia, or shelters for doubtful life.

Partly because of public fears and the criticisms of physicians, the medical practitioner became more and more involved in the pronouncement of death. This development was also promoted by the attitudes generated by science and the Enlightenment, the growth of medical knowledge, the gradual democratization of society, the beginning of romanticism, and the increased numbers of physicians and of hospitals serving not only to house mendicants, condemned criminals, and the insane but also the physically ill. There also was the simultaneous public reaction against the church and its doctrines. The doctor came to be regarded as the preserver of life, for a few effective remedies were becoming available. The gap between alchemy and medical science was being bridged. The services of the physician, previously reserved for wealthy and titled families, became available to the public. If in spite of his efforts death supervened, he was expected to continue to look after the welfare of his patient after all obvious signs of life had vanished. Winslow's book probably played an important role in leading people and governments to enlist the doctor to play an important role in the declaration of death.

For centuries, a coroner or the equivalent was required to determine whether or not a sudden death was due to foul play and to collect in the English court the taxes due to the crown. This regulation is usually attributed to William the Conqueror. In England, a law relating to the certification of death was enacted in 1836 and amended in 1874. A registered medical practitioner who had attended the deceased during the last illness was required to provide a certificate giving the cause of death. In 1893 a committee of the House of Commons recommended certain changes. A doctor was to inspect the body to confirm the presence of death, whether or not he had attended the deceased during life. If he could not inspect the body, he was to obtain a statement from neighbors verifying the fact of death.

It was not until the end of the nineteenth century that most doctors came to regard the stories of premature burial as bona fide. No doubt some instances of premature burial did occur. Certainly in war and during epidemics of infectious diseases, some people who could have recovered from their injury or illness were buried while alive, along with scores of hundreds of the dead, often in mass graves. However, there were doctors who published accounts of patients they were called to attend or declare dead who suffered from obscure illnesses that created the appearance of death, but who recovered, even if only temporarlly.

At the beginning of the twentieth century, although recognizing that premature declaration of death and premature burial did occur, most physicians recounting such experiences prefaced their remarks with the statement that the problem was uncommon, although they cautioned their colleagues against false appearances.

In an article of 1901, Schultze mentioned the specific conditions of catalepsy and lethargy that could be confused with death. He stated that lethargy might resemble coma and might present with marked relaxation of the muscles, apparent arrest of breathing and heart action, and even a reduction of body temperature and absence of reflexes. Oppenheim, in 1911, equated lethargy with "hysterical stupor," notably described earlier in the nineteenth century, largely by French physicians. He confirmed that some patients could manifest these symptoms and achieve a state he termed hysterical suspended animation. He mentions one patient who was reported not to have manifested any signs of life for 48 hours. This illness, seemingly the chief cause of confusion with death, appears to have been a phenomenon of the later nineteenth century and has now almost entirely disappeared, at least in the West, as have most of the other complex varieties of hysteria. However, lethargy of the same magnitude is described as possibly the last stage of acute infectious disease, of epilepsy, of African sleeping sickness, and of head injury.

Two additional states were noted as potentially resembling death: apnea of the newborn and the apnea of victims of drowning, who may be unconscious for half an hour. The clinical limitations of diagnosis are mentioned, including pupillary responses to light and the spasmodic facial twitching that continues after decapitation. (A victim of decapitation surely is seldom likely to be confused with the living! However, the analogy of decapitation with brain death is currently used to justify the acceptance of brain death in some religious thought.). Schultze noted the unmistakable manifestations of death: total muscular relaxation before the appearance of rigor mortis, profound lowering of the body temperature, discolorations of the skin, superficial alterations of the appearance of the eyes and lips, and several other changes clearly evident in the cadaver. This approach to clinical certainty is hardly convincing and is more in keeping with the prolonged display of the body prescribed in the sixteenth and seventeenth centuries and revived in the late eighteenth century. A more recent author mentions the occasional mistaken diagnosis of death in patients suffering from alcoholic coma or in markedly hypothermic or debilitated patients. These are the only states that appear to have occasioned mistaken determination of death. It is interesting that apart from the alcoholic condition, drug intoxication is not mentioned in the earlier literature.

By the twentieth century, physicians seem to have had sufficient self-confidence to believe they were quite competent to distinguish life from death. In earlier periods they had accepted the belief that death was gradual. They believed there were two kinds of death: that which occurred when a person ceased to show signs of life and that which occurred when the body began to display signs of decomposition. Death did not intrude on life, but rather, life intruded on death. This concept was discarded and replaced with the idea that death occurs at a single precise moment.

The belief in a single and exact moment of death was challenged earlier in 1809 by the physician Xavier Bichat, who claimed that in the slowly aging and deteriorating person death occurs slowly. Using the term natural life, he maintained that it was encroached on by the slow disintegration of parts of the "organic life" of a person. The brain, eyes, heart, limbs, and other organs and systems underwent deterioration and death, slowly affecting the integrity of the natural life of the body and mind. As Bichat was a highly respected physician in Paris, his ideas received wide acceptance. His concept reversed the prevailing notion: people may die slowly, not instantaneously at an exact time which can be recorded. Death advanced on life and encroached on it, not the reverse. His concept, based on both animal experimentation and clinical observations, was kept alive for most of the nineteenth century. The idea was perpetuated in fiction as well. and occasionally in association with the other erotic elements of death and necrophilia. In a classic example, Emily Bronte describes the graveyard scene of Heathcliffe and Catherine in her novel Wuthering Heights. and much later the idea is described in a poem by Valery.

By the end of the nineteenth century, Bichat's theories were still evident. There could be irreversible cardiac or pulmonary arrest or cessation of both functions from a lesion of the brain. When one organ ceases to function, so do the others. The brain, heart, and lungs are essential to one another. They are the three centers from which all the secondary phenomena, both "organic" and "natural," take their origin, and the cessation of their function results in the death of the human being: "every kind of sudden death commences, in fact, by the interruption of circulation and respiration or of the action of the brain."

This concept is repeated in an article of 1901, in which the author states:

The causes which result in the permanent suspension of circulation and respiration operate directly upon their mechanism, or remotely through the nerve centers which regulate their action. So important indeed to the proper continuance of their functions is the maintenance of an uninterrupted action of the nerve centers or organic life that it is customary to adopt the classification of Bichat and to speak of death beginning at the heart. death beginning at the lungs, and death beginning at the head.

Brouardel also restated the persisting argument that death does not occur at a particular instant. His treatise relates examples of instances in which even the stoppage of the heart was not a certain sign of death, and of other instances of clinical confusion about apparent and real death and certain causes of the former.

Although one may discern the beginnings of a concept of brain death in the writings of Bichat and French, the primary clinical concern early in this century were how to avoid mistakenly making the diagnosis of death. Philosophical and religious concepts about the nature of death as an event or process still continue, recognition being given to the legal and medical needs to treat it as an event.

In the same encyclopedia of medical practice in which the passage quoted above appears, another entry mentions that by 1901. In several states and major cities of the United States as well as other nations, laws requiring death certificates had been promulgated, and all were similar in their requirements. In Austria. for example, each commune was required to nominate a Beschauer, a physician or surgeon who must examine the body of the deceased to determine whether or not the person was truly dead. The same requirement existed in Belgium and Denmark. In Berlin the examiner was required to indicate what signs were found that indicated death.

It is recounted that in 1918 a law was passed in France specifying that an arteriotomy was to be performed to determine the presence or absence of blood flow and an injection of fluorescin given to disclose whether or not the conjunctivae and mucosa of the eyes became discolored within 30 min. This may be the only statute, until quite recently, to specify any tests to be used to diagnose death.

Brain Death: Definition

The concept of brain death appears to have been lost for about two generations. In the intervening years, the generally accepted common-law definition of death, as quoted in Black's law dictionary, related entirely to cessation of cardiac and pulmonary activities, and was the standard accepted by the legal and medical professions alike, as well as by authorities of the major religions. However, it was known by physicians that patients suffering respiratory arrest from some form of injury to the brain would shortly die, for there was no effective means of maintaining artificial ventilation. Cushing reported the instance of a patient in coma who ceased breathing and was "kept alive" 23 h by artificial ventilation in 1902, and he mentions similar experiences of Macewen, Horsley, and Hudson. The state of irreversible coma, or coma depasse, was described by Mollaret and colleagues in 1959 but had been recognized for many years.  Although the victims generally were able to continue to breathe spontaneously, this description included the loss of vegetative functions, including the loss of spontaneous respirations, and should not be confused with the persistent vegetative state.

The refinement of the means to determine death accurately has followed closely the evolution of medical technology. Probably the first of these means was the stethoscope in 1816, followed by the later methods to determine and record the pulse and its variations and the blood pressure, and finally by the electrocardiograph. Certainly all victims of fatal injury to or illness of the brain died of cardiopulmonary arrest and thus fulfilled the criteria of the common-law definition, It was only the absence of means to maintain sufficient sustained artificial ventilation and to meet the body's needs for water and electrolytes that made the theoretical concept of brain death impractical to apply. Even after their availability, brain death was not seriously and systematically studied until the formation of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death, which published its report in 1968.

Several critics have objected to the present definition of brain death. In some instances the concept of brain death is attacked because allegedly it was introduced to serve the needs of organ donation. In other instances, highly publicized cases of dead or dying patients used as organ donors had a great and adverse effect on both public and professional acceptance of brain death. In Sweden, the controversy began in 1964 when it became known that a dying woman had served as an organ donor. In 1968 the first cardiac transplant procedure that took place in Japan created a public storm of concern and political and professional reticence. It was never made clear whether the donor was determined to be brain dead. This was the fourth heart transplant to be performed in the world. It led to a legal inquiry, but no civil or criminal action was undertaken. The event created interest in the Japanese medical community, but though the occurrence was not condemned by the medical society, no professional or governmental action resulted for several years. In 1984, brain death criteria were employed in Japan in the case of a woman who died from cerebral hemorrhage, and from whom the kidneys, corneas, and liver were harvested. Criticism occurred because the medical records indicated that she had suffered from some form of mental disease and that no informed consent had been obtained. Once again, a formal complaint was lodged but no charges were filed. These events in Sweden and in Japan had deleterious effects on the acceptance of brain death and organ transplantation.

In 1967, a Kansas court decision was the first in the United States to implicitly accept brain death, but the matter was not directly litigated until the acquittal in 1972 of physicians charged with murder in the state of Virginia following the removal of heart and kidneys for transplant after determination of brain death. In 1970, Kansas became the first state to enact a death statute incorporating the concept of brain death applicable to the potential organ donor. The National Conference of Commissioners on Uniform State Laws formulated the Uniform Anatomic Gift Act which, enacted by many states, permitted the use of brain death for potential organ donors. This, however, led to the legal creation of two forms of death: the common-law definition for nondonors and inclusion of brain death for potential donors. Once again, the Uniform Law Commissioners attempted to rectify the legal ambiguity by creating the Uniform Brain Death Act in 1979, with concurrent support of the American Bar Association and the American Medical Association. By the autumn of 1981, 22 states had adopted one or more forms of the statute that allowed for the inclusion of brain death applicable to anyone.

The formulation of the criteria for determination of brain death commenced with the report of the Ad Hoc Committee of Harvard Medical School. Mohandas and Chou added the inclusion of irreversible loss of function of the brain stem. The President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research published its summary of criteria in 1981. There existed several sets of criteria to be used in the determination of brain death, and they are given in Tables-1 and 2. This led to confusion in many instances. However, the Uniform Brain Death Act did not address the criteria that were to be employed to make the determination. Several states, notably Illinois and New York, rely on court decisions. Texas revised its statute in 1989. An informative and useful commentary on the revision can be found in Hardy's paper, as well as recommendations to physicians in the application of clinical, laboratory, and radiographic criteria.

Inclusion of brain death was enacted into law in Sweden in 1988. Canada, by statute, recognizes brain death. Although the United Kingdom lacks a statutory definition of death, the brain death standard is used and accepted. The Danish Council of Ethics stated in 1989 that death has not occurred until respiration, circulation, and brain functions have "all totally and irreversibly ceased." If the person's brain has ceased functioning, the person is not yet dead, but is in an irreversible process of dying. Artificial means for the prolongation of dying should not be maintained because the patient has no interest in their continuation. Their removal does not cause the death, but only allows for the completion of the dying process. Parenthetically, it was recommended that removal of organs for transplantation from the dead be delayed for 48 h to allow completion of the process of death, thus eliminating matters of implied consent or proxy consent by the patient's relatives.

A good many countries of Europe have incorporated implied consent of a dead person to justify the harvest and use of organs. Advance directives are allowed by law in many states, but the wording varies. Missouri requires "clear and convincing" evidence of a patient's intentions. Texas law does not. Several state statutes apply only to adults. In Missouri and in other states whose statutes are vague or silent on this issue, a court order is deemed advisable to permit withdrawal of what is incorrectly but commonly termed "life support systems," but which in the dead are truly artificial perfusion systems, One author considers it not unethical to discontinue all means of "life prolonging" medical treatment if the patient's coma is beyond doubt irreversible and there are adequate safeguards to confirm the accuracy of the diagnosis, and one obtains the consensus of those responsible for the patient, except in instances of advance directives. A brief review for Texas physicians regarding guidelines for organ donation and transplantation can be found in the article by Francisco.

TABLE-1 Criteria for Cerebral Death (in Addition to Coma and Apnea) Based on Clinical Concepts


 
Author(s) Prerequisites Reflexes Time, h Confirmatory Tests
BeecherNo hypothermia or drugsAbsent reflexes24EEG
Mohandas and ChouKnown irreparable organic encephalopathyCephalic reflexes absent12 
Royal CollegesNo depressant or blocking drugs, normothermia, metabolic disturbances excluded, irreme­diable structural brain damage establishedBrain stem reflexes absent, pupils fixed and unresponsive, no corneal reflex, vestibulo-ocular reflex absent no gag reflex, no motor brain stem response, no respiratory effort after disconnection24EEG, if possible
Minnesota Medical AssociationNo reversible CNS dysfunction

Cerebral unresponsivity, absent brain stem reflexes, pupils more than 5 mm and fixed

 

12 
Working PartyIrremediable structural brain damageApneic coma (no respiration with PaCO2 > 50 mmHg), brain stem reflexes absentUnspecifiedIndependent certification by two physicians
Key: CNS, central nervous system; EEG, electroencephalography

TABLE-2 Criteria for Cerebral Death (in Addition to Coma and Apnea) Based on Clinical Concepts Plus Electroencephalographic or Cerebral Blood Flow Tests

Author(s) Prerequisites Reflexes EEG Time Applicable, h Confirmatory or Other Tests
Alderete et aLNormothermia, no drugsAreflexiaECS24 
Allegheny County AreflexiaECS2 
Barbard (cited by Walker)Normothermia, treatment ineffectivePupils fixed and dilatedECS1ECG flat. 1 h
Berkutov et aLBrain traumaCorneal and pupillary reflexes absentECS2 
Canadian Medical AssociationNormothermia, no drugsAreflexiaECS24 
CIOMSNormothermia, no drugs, not infantAreflexiaECS BP failing
Cooley (cited by Walker)NoneCephalic areflexiaECS BP failing
German Society of SurgeryBrain trauma or ICP increasePupils dilated and fixedECS, 1h12

Angiographic proof of no CBF for 30 min

Ingvar and WidenNoneAbsence of cerebral functions including brain stem reflexesECS Nonfilling of cerebral vessels two angiograms 25 min apart
IvanNo remediable conditionCephalic areflexiaECS6BP failing
Kaufer et alNoneAreflexia, dilated pupilsECS4 
LorenzDiagnosis knownAreflexiaECS24Atropine 1 mg without tachycardia
Collab, StudyHistory knownAreflexia, dilated pupilsECS BP failing
Schwab et al.Normothermia, no drugs, electrolytes normalAreflexiaECS24-72No change in pulse rate with ocular or carotid pressure
Solnitzky Cephalic areflexiaECS Angiography
SpannNormal electrolytesAreflexiaECS6BP failing
US. NavyDiagnosis known, no drugs, normothermiaCephalic areflexiaECS if possible13 
Wawersik Pupillary areflexiaECS12Or no CBF for 30 min
Key: BP, blood pressure; CBF, cerebral blood flow; ECS, electrocerebral silence; EEG, electroencephalogram; EKG, electrocardiogram.


It appears that with the introduction of the Uniform Brain Death Act and the publication of the guidelines of the President's Commission that acceptance of the concept of brain death was at hand; that most if not all states would soon enact the model statute; and that medical criteria for determination of brain death in adults would be adopted and used by most physicians. The guidelines were less certain and informative about infants and children, and resulted in the creation of a Task Force for the Determination of Brain Death in Children, which issued its report in 1987. Still, a good many publications have appeared in the past 2 decades that relate to philosophical, religious, and cultural questions about the definition of death. One author quotes Pliny, that "so uncertain is men's judgement that they cannot determine even death itself."  Capron sensibly states that the word coma implies a state of life, and the term should be avoided when defining the state of death.36 Agich and Jones4 argue that loss of all brain func­tion is a logically sufficient criterion for the determination of death. "Providing a definition of death is primarily a philosophical task and consists in saying what are the essential characteristics of death. Specifying a criterion (or criteria) is primarily a biomedical and clinical task that consists in saying what conditions must be met for the definition of death to obtain." The definition of death does not involve the criteria. Instead, "a definition of death should state what it is for an organism to die, not what it is for an organ­ism to be an individual or person." 4 This concern with defining death has led some to believe that it is also necessary to develop a legally consistent definition of life. Although this issue mainly relates to the use of fetal tissue and organ transplants, it extends as well to cultural and religious considerations.

According to Kimura, human life involves a rhythm in which all living things live together at the "same level."  Organ removal from a warm body is generally regarded by the Japanese public as the imposition of an unnatural end to life. The mind­spirit-body are integrated both in life and death. Organ removal disturbs the spiritual and corporeal unity. Thus, autopsies also are abhorred in Japan. Death itself disturbs the rhythm of all living things and should not be hastened. However, Tsuji, in reviewing the Buddhist beliefs regarding organ retrieval, states that the Sangha (the organization of followers of Buddhism in all countries) has not adopted a uniform position, and presents personal arguments from Buddha-Dharma that would support the transplantation of organs. The Buddhist belief that the spirit of the deceased remains in the physical world for 49 days would lead to the concern that removal of organs or tissue would disrupt the natural course of translation from life to death and the eventual passage of the dead one to his full merging with the community of the spirits to become an ancestor after the passage of 32 years.

Several authors trace the origins of the idea of the duality of mind-spirit and body to the ancient Greek philosophers, and see this and the later dualism of Descartes as forming the basis for the idea that death is an event terminating physical life, which in turn allows the evolution of criteria to determine the moment of death, including brain death, without regard to organ and tissue retrieval. This duality is foreign to the Japanese, as well as to Buddhism in general. We see in many areas of cultural conflict today the embodiment of what Kimura terms wakon-yosai or the mixing of Western technology with the Japanese spirit. He argues that there is still a strong resistance, coexisting with the adoption of Western advances in medicine and science, to the acceptance of Western values in place of indigenous, traditional cultural beliefs and practices. In a report from October 1987 of public opinion polls conducted by the Prime Minister's Office of Japan, only 23.7 percent of respondents accepted the concept of brain death, and only 17.8 percent would agree to offer organs for transplant. By 1990, 40 percent of respondents agreed with the donation of the organs of a relative under circumstances of brain death, 11 percent would limit the donation to a person known to the family, and only 16 percent would refuse. Both the Japanese government and Japanese medical societies have displayed great reluctance to take any formal action on the matters of acceptance of brain death criteria or organ donation from the dead. As late as June, 1988, the Japanese Society of Psychiatry and Neurology concluded that it is difficult to determine when brain function has ceased irreversibly. It was doubted that medical doctors alone should have the authority to diagnose brain death.

However, in August 1990, the Osaka University School of Medicine approved transplantation of the heart, liver, and kidneys from donors who fulfilled criteria for determination of brain death. The Japanese Ad Hoc Commission on Brain Death and Organ Transplantation issued its report in June 1991 and recommended that irreversible loss of brain stem functions be sufficient to diagnose death. It was anticipated at that time that after submission of its final report in January 1992, a full program of organ transplantation might begin, perhaps to incorporate several earlier recommendations, for example, those of the Special Task Force on Brain Death of the Ministry of Health and Welfare, that would require that determination of brain death be made by medical doctors who respect the patient's and families' sensibilities and wishes with regard to brain death and use a truly informed consent. The time of death would be recorded no later than 6 h after the initial determination of brain death.

A contrary opinion about acceptance of brain death was issued by the Japanese Federation of Bar Associations. The Bioethics Council of the Japanese Medical Association recommended in 1988 that the decision to accept either traditional or brain death criteria should be left to patients and families. Individual doctors may have used brain death criteria in earlier years without informing the families, but one author believes that the main reason for the medical profession's reluctance to use the criteria is its fear that physicians lack the authority and organization to establish and enforce any new and required medical standards. A common theme of the literature relating to the situation in Japan is the need for consensus, for a broad public and professional acceptance both of the concept of brain death and of cadaveric organ harvesting before their widespread implementation. Several excellent reviews provide more detailed information about the cultural, religious, and historic factors that have affected both use of brain death criteria and organ transplantation in Japan.

Parenthetically, the number of kidney transplants in Japan reached 757 in 1988, but 70 percent were from living, related donors. Cadaveric kidneys made up only 233 (30.8 percent). Ota reported that by the end of 1988, 88,534 patients in Japan were on maintenance hemodialysis and 15,000 patients were on the waiting lists for transplants. He also related the several leading reasons for public and professional reluctance to fully implement organ transplantation. A significant factor, he believed, was an insufficient amount of participation by the government and medical associations in preceding years.

The concerns of Japanese are not unique. They also are expressed in similar ways in Western and other countries. Earlier it was mentioned that in several countries, implied consent is used to obtain organs and tissues for harvesting. The importance of considering cultural and religious differences is highlighted by an article by Iyer regarding pending legislation in the Republic of Singapore, which subsequently has become law. Its Human Organ Transplant Act of 1986 is applicable to the harvesting of all organs, but in draft form it referred only to "the kidney of a human body." Presumed or implied consent for donation would apply to all citizens and permanent residents above the age of 21 and below the age of 60 years. For those younger than 21, consent of a parent or guardian would be required. The act also applied only to deaths resulting from accidents and other injuries. Prior formal individual written request for exclusion is provided for. The person can also withdraw the request for exclusion. Those who choose exclusion are assigned the lowest priority for organ transplantation. A committee would determine the priority of the recipients, using several criteria, one of which is anticipated to be the number of dependents of the potential recipient. Diagnosis of death would be based on the determination of the irreversible cessation of all functions of the brain. Iyer believed that the Ministry of Health might designate the criteria to be used. The implications for the United States in particular relate to the Singapore government's recognition of the ethnic, cultural, and religious differences in its country, a matter that has not been adequately studied and addressed in other countries. The author points out that Singapore is populated by a racial mixture of 76.4 percent Chinese, 14.9 percent Malays, and 6.4 percent Indians. Buddhists and Taoists make up 56 percent, Muslims 16 percent, Christians 10 percent, and Hindus 4 percent. Because of this diversity, the law had to make provision for individuals and families to "opt out" of the presumed consent.

With the notable and recent exception of the New Jersey statute and of regulations in the state of New York, no state or federal legislative notice has been given to diversities in the United States. These may be of much greater importance than has been recognized. Although it appears that both states have made provision for nonacceptance of brain death criteria for Orthodox Jews, the New Jersey statute in particular may have great relevance in helping to explain the difficulties in the passage of the Uniform Brain Death Act in several states, the shortage of organs and tissues from cadavers, and the reluctance of some doctors to use brain death criteria.

Akabayashi and Morioka remark that scientific technology has no national borders, but that bioethical issues require particular consideration in countries with differing political, economic, and social mores. They believe that certain issues, such as those involving brain death and the use of organs, should be resolved within a domestic framework but in an international context. Cushman and Holm stress that public debate is important in democracies and that the role of governmental bodies is to teach and to lead and not to use coercion by legislation, oversimplification, and "technical obfuscation" to build a false consensus in the name of political efficiency. Although it is recognized that consensus is much easier to achieve in countries with an essentially homogeneous culture than in the United States, the responsibility of government in a democracy to obtain consensus involves a continuing dichotomy between guiding and leading. It is  reminded increasingly in the United States that on many bioethical issues there is no consensus, and recourse is made to the courts, which has created significant delays, confusion, and contradiction.

Perhaps insufficient notice has been taken by the medical, allied-health, and legal professions of the cultural diversities in the United States. May reviews Western Christian religious traditions, and urges that we both accommodate such differences in matters of brain death and organ donation and obtain the informed consent of the family. Although the usual opinions expressed in the literature are that the determination of death is a medical decision and should not and does not require participation of the family, and this attitude is reflected in either statute or court decisions in almost every jurisdiction, it is probably both advisable and ethical for the physician to carefully and fully explain the nature of death by brain death criteria, even though the participation of the family or other responsible person is not required in making the diagnosis of death. Nevertheless, some doctors do ask permission to remove artificial perfusion systems from a dead person, which can lead to some families fearing later that they have caused or participated in the premature death of their loved one. Still, the New Jersey law requires a different approach.

Because the recent New Jersey statute was enacted from consideration of traditional Jewish law, it is worthwhile to briefly review the history and practices of Jewish law. Rosner explains that in Judaism, human life is of infinite worth. The taking or shortening of a human life is ethically wrong and is murder. Classically, the definition of death in Judaism requires that the absence of spontaneous respiration and heartbeat be demonstrated in a person who displays no bodily motion. A brief waiting period of a few minutes to half an hour after cessation of breathing is also required before death is pronounced.  Jewish law, Halachah, is based on both the Written Law (the Scriptures) and Oral Law (the Mishnah), which consists of legal declarations of early scholars and judges (the Tanzim) and the Gemarrah, which are later, more extensive discursive dialectic records of discussions and adjudications based on both Scriptures and Mishnah rendered by rabbis (Amoraim) of both Babylonian and Palestinian academies during the third through fifth centuries. The Talmudic Midrashim amplify the jurisprudential and philosophical pronouncements of the Mishnah and the Gemarrah, both of which together are the Talmud. Oral law extends beyond the Talmud and is meant to amplify, interpret, modulate, and make application to changing and novel conditions. Weiss noted in 1988 that in preceding months halachic opinion had begun to indicate an acceptance of the concept of brain death as the decisive or definitive marking of the termination of Iife. Rosner relates that some rabbis may accept the irreversible death of the brain stem as equivalent to the traditional acceptance of decapitation, but brain death is .still a source of intense debate in rabbinic circles.

The state of New York lacks a statute defining death, but relies primarily on a New York Court of Appeals decision of 1984 which states:

We hold that a recognition of brain-based criteria for determining death is not unfaithful to prior judicial definitions of "death," as presumptively adopted in the many statutes using that term. Close examination of the common-law conception of death and the traditional criteria used to determine when death has occurred leads inexorably to this conclusion.

The New York State Task Force on Life and the Law recommended the adoption of the brain-death standard, but, "recognizing the theological and moral dimensions of death, the Task Force believes that efforts should be made to accommodate the deeply held religious or moral beliefs of persons who object to the determination of death based on cessation of brain function."  Its report stressed the importance of notifying family members and/or other individuals legally responsible or personally involved with the patient regarding the presence of brain death, and recommended that the time of death be recorded as the time when the irreversible cessation of total brain function is confirmed. The Department of Health of the State of New York issued a memorandum on August 21, 1987, stating that the State Hospital Review and Planning Council promulgated Regulation 10 NYCRR 400.16, which provides that an individual is dead when either irreversible cessation of respiratory and circulatory functions or irreversible cessation of all function of the brain, including the brain stem, occurs. This is the present status in New York and is likely to remain so indefinitely. The regulation mandates that a hospital "make a reasonable effort to notify the next of kin or other person closest to the patient prior to the determination of death," and each hospital is to establish and implement a written policy that includes

(1) a description of the tests to be employed in making the determination,

(2) a procedure for notifying next of kin or other person closest to the patient, and

(3) a procedure for the reasonable accommodation of any religious or moral objection to the determination expressed by the patient beforehand or by the next of kin or other person closest to the individual.

The Department of Health recommended that its criteria for determination of brain death be employed. They are essentially those of the President's Commission.

The New York provision recognized the lack of acceptance of brain death by some, notably many if not most Orthodox Jews. However, the State of New Jersey enacted a Declaration of Death Act that was signed into law on April 8, 1991, that specifically provides exemption from brain death criteria for cases in which the practitioner is "knowledgeable about the individual's personal religious beliefs that such a declaration would violate the personal religious beliefs of the individual. In these cases, death shall be declared, and the time of death fixed, solely upon the basis of cardio-respiratory criteria. . ." This exception was directed primarily toward the religious beliefs of Orthodox Jews. It is the only statute in the United States to recognize and allow for nonacceptance of brain death criteria. Both this law, and, by inference, the regulation of the State of New York, affirms that "the neurologically dead patient is not legally dead and considers himself or herself to be alive."  The New York regulation is silent on its meaning of "reasonable accommodation" and the New Jersey law does not clarify what medical measures are required to be taken by health care providers to accommodate the religious exception.

Although enactment of the New Jersey statute was strongly encouraged and supported by several Orthodox Jewish organizations, its provision is applicable to anyone. As there is lack of uniformity of acceptance of brain death within the Jewish faith, the same is true for Muslims. The structure of Islamic law is similar to that of Jewish law. It is based on the Shari'a that incorporates the Quran and the Hadith or oral tradition and teachings of the Prophet, as well as fatwa or legal opinions that are pronounced by the mufti, imam, or religious scholars. One author states that Muslim scholars had not yet addressed the many ethical issues raised by recent medical and technological advances. Islam affirms the primacy of life. Rather than man being created in the image of God, the breath of God is blown into the "clay" to create a human being at about the 120th day following conception. In general, it appears that traditional and majority opinions are that death occurs when the breath of life is irreversibly lost and that any form of mutilation of a human cadaver, including removal of organs, represents a perversion. Another author refers to the several schools of Islamic law, which differ in several important respects.

The Hanafi school prohibits any defiling of the body. The Maliki school holds that the body is pure in both life and death, The Hanbali school regards the human body as pure when alive, defiled by death, but purified once again by the ritual ablution after death, One mufti is reported as stating that any removed organ from a purified body would be pure, The maslaha, or principle of public benefit, may possibly become in time the basis for acceptance of organ and tissue donation, for it is employed to promote new legal concepts for which the Shari'-a holds no reference. The acceptance of brain death by Muslims has not been resolved so far.

Epistemologic questions regarding the definitions of life and death retain importance for a goodly number of philosophers and biomedical ethicists, Sassower and Grodin stress the importance of a socially accepted definition of death. They make mention that the desire to be certain about the presence of death can lead to an "absurd infinite regress." Sass proposes the acceptance of human life and human death to be equivalent to brain life and brain death. Such questions and proposals are likely to continue to be made, especially in the light of suggestions that exception be made for anencephalic newborns, and broadening of the definition of death to include the loss of "personhood," as in the persistent vegetative state.

Brain Death: Criteria and Ancillary Tests

The first serious systematic study of the matter of brain death was undertaken by the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death, which published its report in 1968. French and German medical societies proposed criteria and published their reports the same year. These criteria place considerable emphasis on the demonstration by angiography of the absence of arterial filling of the intracranial vessels. The Swedish guidelines of 1972 had a similar emphasis, and the Japanese report of the next year, although it required a similar test, as had Mollaret and colleagues, included an additional one of a demonstrated fall in the arterial blood pressure. The criteria that make mandatory the use of angiography, or at least blood flow studies, do not allow for situations or locations in which angiographic facilities might be lacking. Early on, prior to the Harvard report of 1968, emphasis was placed on the utilization and significance of the electroencephalogram (EEG) in the presence of irreversible coma and on the flat, or isoelectric, tracing. The impact of the Harvard report, with its emphasis on the use of the EEG as an ancillary test for brain death, increased the focus of many authors on its importance, and it was recommended as a requirement for the determination of death of the brain. In several institutions, largely those most active in organ transplant surgery, the requirement of serial EEG recordings was adopted in the early years of the 1970s as they developed their own criteria for the determination of brain death. In some instances this was done out of concern for legal implications to the hospitals and physicians. The isoelectric EEG was termed electrocerebral silence (ECS).

Except in instances of hypothermia, drug intoxication, or some metabolic disorders, a flat or isoelectric EEG was found to be of great predictive value if made in strict accordance with specific parameters. The presence of electrocerebral silence is determined on the basis of a recording made with scalp electrodes 10 cm or more apart, with resistance between 100 and 10,000 Ω between any two electrodes, and without any activity greater than 2 µV. Walker provides a discussion of sources of artifacts and of the limitations of EEG use in determining brain death. The many sources of error led the American Electroencephalographic Society to recommend specific requirements for obtaining the most accurate recording, as follows:

I. A minimum of eight scalp electrodes and ear reference electrodes
2. Interelectrode resistance under 10,000 Ω but over 100 Ω
3. Test of the integrity of the recording system by the deliberate creation of electrode artifacts by manipulation
4. Interelectrode distances of at least 10 cm
5. Gains increased during most of the recording from 7.0 to 2.0 µV/mm
6. Use of 0.3 or 0.4 s time constants during part of the recording
7. Recording with electrocardiography and other monitoring devices, such as a pair of electrodes on the dorsum of the righ hand, to detect extracerebral potentials
8. Tests for reactivity to pain, loud noises, or light
9. A 30-min total recording time
10. Recording by a qualified technician
11. A repeat recording if the ECS is doubtful

In addition, telephone-transmitted EEGs are not considered appropriate for determination of electrocerebral silence. Walker adds that the recording must not be done during the initial phase of shock but only after the patient's status has stabilized, because of possible misinterpretation. In his summary of the value of the EEG in determining brain death, Walker reports the findings of Hughes that normal alpha activity may be present even when a patient is apneic and comatose and that electrocerebral silence may be present even when a patient shows clinical evidence of brain stem activity. Walker believes the evidence indicates that the EEG, when used alone to establish death, requires multiple isoelectric recordings over 2 to 3 days: "Brain death can only be assumed when all clinical and EEG criteria of a dead brain are met."

He mentions one important factor in the correct interpretation of an EEG performed in less than ideal circumstances. The unshielded environment of the intensive care unit and of locations other than the EEG laboratory can create artifactual changes to a degree that can lead an insufficiently experienced interpreter to believe that some brain electrical activity persists. Moreover, being uncertain of the conditions under which the recording is made, the exact clinical condition of the patient, and often the cause of the coma, the electroencephalographer may be reluctant to report electrocerebral silence even while believing it to be present, from fear of causing a premature declaration of death by the clinician. The unreliability of the EEG in establishing brain death is now widely recognized, especially in instances of barbiturate coma and when the cause of coma is unexplained or potentially reversible, and in the presence of hypothermia, any CNS depressant, a pacemaker, or a ventilator. Grigg and colleagues reported that 20 percent of clinically brain-dead patients had EEG activity persisting for up to 72 h. Others have reported continued EEG activity in the presence of clinical brain death, or even its absence in instances of severe insult to the brain but without clinical brain death. In summary, the EEG probably should be used only as an ancillary test in determining brain death.

The guidelines of the President's Commission were published in 1981 and gained broad acceptance by physicians in the United States. They state in part that:

An individual with irreversible cessation of all functions of the entire brain including the brainstem is dead. Cessation is recognized when evaluation discloses (the following) findings: (1) Cerebral functions are absent. There must be cerebral unresponsivity and unreceptivity. (2) Brainstem functions are absent. This includes pupillary light, corneal, oculo­cephalic, oculovestibular, oropharyngeal, and respiratory reflexes. Apnea is tested with nasal canula delivering oxygen and demonstrating failure of respiratory effort with PaCO2, more than 60 mmHg. True decerebrate or decorticate posturing or seizures are inconsistent with the diagnosis of death. Irreversibility is recognized when evaluation discloses (the following) findings: (1) the cause of coma is established and is sufficient to account for the loss of brain functions, (2) the possibility of recovery of any brain function is excluded, and (3) the cessation of all brain functions persists for an appropriate period of observation or trial of therapy. Confirmation of clinical findings by EEG is desirable when objective documentation is needed to substantiate the clinical findings.

Complete cessation of circulation to the normothermic adult brain for more than ten minutes is incompatible with survival of brain tissue. Absent cerebral blood flow, in conjunction with the clinical determination of cessation of all brain functions for at least six hours, is diagnostic of death. Complicating conditions (include) drug and metabolic intoxication, hypothermia, children, and shock.

Subsequent to the appearance of the above guidelines, in recognition of the difficulty of their application to infants and children, a Task Force for the Determination of Brain Death in Children published its guidelines in 1987. The report states in part:

It is generally assumed that the child's brain is more resistant to insults leading to death, although this issue is controversial and lacks convincing clinical documentation. The criteria outlined are useful in determining brain death in infants and children. In term newborns (38 weeks' gestation), the criteria are useful 7 days after the neurologic insult. The newborn is clinically difficult to evaluate after perinatal insults. This relates to many factors including the difficulties of clinical assessment, the determination of the proximate cause of coma, and the certainty of the validity of laboratory tests. Those problems are accentuated in a premature newborn... .

The critical initial assessment is the clinical history and examination. The most important factor is determination of the proximate cause of coma to insure absence of remediable or reversible conditions. Most difficulties with the determination of death on the basis of neurological criteria have resulted from overlooking this basic fact. Especially important are detection of toxic and metabolic disorders, sedative­hypnotic drugs. . . , paralytic agents, hypothermia, hypotension, and surgically remediable conditions. The physical examination is necessary to determine the failure of brain function.

Physical Examination Criteria

1. Coma and apnea must coexist. The patient must exhibit complete loss of consciousness, vocalization, and volitional activity.
2. Absence of brainstem functions as defined by:
    a. Midposition or fully dilated pupils which do not respond to light. Drugs may influence and invalidate pupillary assessment.
    b. Absence of spontaneous eye movements, those inducednby oculocephalic and caloric (oculovestibular) testing.
   c. Absence of movement of bulbar musculature including facial and oropharyngeal muscles. The corneal, gag, cough, sucking, and rooting reflexes are absent.
   d. Respiratory movements are absent with the patient off the respirator. Apnea testing using standardized methods can be performed. . but is done after other criteria are met.
3. The patient must not be significantly hypothermic or hypotensive for age.
4. Flaccid tone and absence of spontaneous or induced movements, excluding spinal cord events such as reflex withdrawal or spinal myoclonus should exist.
5. The examination should remain consistent with brain death throughout the observation and testing period.

Observation Periods According to Age

The recommended observation period depends on the age of the patient and the laboratory test utilized.

7 days to 2 months: The Task Force recommends two examinations and encephalograms (EEGs) separated by at least 48 hours.

2 months to 1 year: The Task Force recommends two examinations and EEGs separated by at least 24 hours. A repeat examination and EEG are not necessary if a concomitant radionuclide angiographic (CRAG) study demonstrates no visualization of cerebral arteries.

Over 1year: When an irreversible cause exists, laboratory testing is not required and the Task Force recommends an observation period of at least 12 hours. There are conditions, particularly hypoxic-ischemic encephalopathy, in which it is difficult to assess the extent and reversibility of brain damage. This is particularly true if the first examination is performed soon after the acute event. Therefore, in this situation, the Task Force recommends a more prolonged period of at least 24 hours of observation. The observation period may be reduced if the EEG demonstrates electrocerebral silence or the CRAG does not visualize cerebral arteries.

Laboratory Testing

Electroencephalography (EEG) to document electrocerebral silence should, if performed, be done over a 30-minute period, using standardized techniques for brain death determinations. In small children, it may not be possible to meet the standard requirement for a I0-cm electrode separation. The interelectrode distance should be decreased proportional to the patient's head size. Drug concentrations should be insufficient to suppress EEG activity.

A cerebral radionuclide angiogram confirms cerebral death by demonstrating the lack of visualization of the cerebral circulation. A technically satisfactory cerebral radionuclide angiogram that demonstrates arrest of carotid circulation at the base of the skull and absence of intracranial arterial circulation can be considered confirmatory of brain death, even though there may be some visualization of the intracranial venous sinuses. . . . The value of this study in infants under 2 months is under investigation. Contrast angiography can document lack of effective blood flow to the brain.

The Task Force recognizes that other tests, including xenon computed tomography (CT) . . . , digital subtraction angiography. . . , visualization of cerebral arterial pulsations by real-time cranial ultrasound, Doppler determination of cerebral flow velocity. . . , and evoked potentials, are under investigation.

Since the publication of the guidelines of the President's Commission and the Task Force, a number of authors have proposed additions, refinements, and alternatives to specific guidelines. The limitations of the EEG have already been noted. Sensory evoked potential studies may have some use as ancillary tests in the determination of death. Their limitations and usefulness remain uncertain. Hall and Tucker provide a good review. They recommend sensory evoked response testing for the acute management of brain injury, for it is noninvasive and safe, can be performed at the bedside, and is available today in many hospitals; also, artifacts that occur because of the environment can be minimized, and the results are relatively independent of the effects of central nervous system (CNS) depressant therapies. The authors do state, however, that "the ultimate clinical utility of sensory evoked responses is at this point unknown."  The persistence of cortical evoked potentials after clinical brain death has been noted by others. It does not appear at this time to be of more than perhaps supplemental confirmatory value, in cases in which it demonstrates total absence of responses.

The use of atropine has also been included by some to determine the effect on the heart rate. The atropine bolus test consists of the intravenous injection of 1.0 mg atropine to determine if the heart rate will increase. It would fail to respond if the brain were dead. Anecdotal accounts report a rise in pulse rate occurring after pronouncement of death when the organs of the presumed cadaver are being removed. This simple test may be of ancillary assistance, in particular in small children and infants.

Four-vessel cerebral angiography has also been employed in some centers, more commonly in Europe. It is awkward to employ and invasive, and possibly the use of the contrast agent could impair functioning of organs that might be harvested for transplantation. Computed tomography with enhancement has been found to be of assistance by some, as has intravenous digital subtraction angiography, but both are awkward to use and have not been adequately evaluated.  Errors have been reported. This is also true for magnetic resonance imaging.

Transcranial Doppler sonography records arterial blood flow at the base of the brain. With complete cessation of cerebral perfusion there occurs a reverberating flow pattern consisting of a counterbalancing forward systolic flow and backward diastolic reflux. The unequivocal presence of this phenomenon is essential if the finding is to be used to confirm the presence of brain death. Again, the test has not been employed enough for its accuracy to be known.

Ashwal and colleagues employed both computed tomography and stable xenon administration, but the primary criticism of this technique is that it measures only blood flow and not brain function. This may be a moot point after 10 min of apnea in a normothermic unsedated adult.

It appears that the most promising confirmatory test for brain death is the employment of radionuclide cerebral angiography making use of a new radioisotope agent, 99mTc HM-PAO, which is lipophilic and so crosses the blood-brain barrier and is taken up and retained by the brain parenchyma. The test employs a portable gamma camera, which means it can be performed at the bed­side. Single positron emission tomography studies appear to be the best method, but this modality is not available in many institutions. Instead, planar flow and equilibrium images are believed to suffice. Hardy states that the study may require repetition at 24 h until complete absence of all intracranial uptake is documented. Several authors have reported this methodology and their experiences. The isotope may be combined with 131I-labeled amphetamine. Galaske and colleagues recommended using static images at 7±3 min after injection for children. Presence of activity would be revealed by retention in any intact brain parenchyma. The polar isotope agents, such as 99mTc-DTPA do not cross the blood-brain barrier and thus would not be useful for determining the persistence of functioning brain parenchyma. van Bunnen and colleagues,  although regarding the HM-PAO technique as being a reliable test for brain death, caution that more study is required, because abnormally low body temperatures, hypotension, reduced cerebral blood flow, and sedatives such as barbiturates may affect its accuracy. They remark that even a 1 to 2 percent false-positive rate would render this or any test invalid and of no use.

de la Riva and colleagues reported in 1992 the results of 41 studies performed on 37 patients who were suffering from severe brain injury or under the effects of drugs or in whom other diagnostic tests had given equivocal results. The patients were 4 months to 75 years old. Both dynamic flow and 5-min static images were obtained. All patients showing no uptake met clinical criteria of brain death. There were no contradictory findings in the static images. All other patients showed at least some uptake in the brain stem. Of the five patients in whom dynamic studies gave equivocal results, four showed no uptake on static images. In an earlier series, three patients with the clinical criteria of brain death showed significant perfusion, and two of them ultimately survived. Reid and colleagues state that anesthetic agents can reduce but not abolish cerebral perfusion. The main limitations of the test are technical constraints on reconstitution of the isotope from its kit. Laurin and colleagues enumerate the interfering conditions that could affect the accuracy of the clinical examination. They include barbiturate coma, hypothermia, high doses of pancuronium, high doses of fentanyl, and pregnancy, which forbids testing for apnea. The 99mTc HM-PAO test, in their experience, was not influenced by any of these conditions. Of 17 patients in their series who had clinical criteria of brain death, 16 failed to show any cerebral or cerebellar uptake. Although more studies of the reliability of this test are required, it may be of great potential value and may gain wide usage in countries and institutions that have the required facilities.

Even if it proves to be completely reliable, however, it and other specific laboratory and radiologic criteria should not be mandated by law, for laws are difficult to alter in light of new and valid or outmoded standards of care. Furthermore, such specific statutory requirements would create serious differentials in the care required of both physicians and hospitals. It should be left to individual hospitals, specialties, and physicians to develop and modify their own guidelines or criteria to confirm the presence of brain death, perhaps in the context of the more general criteria adopted by, for example, the Department of Health of the State of New York. A few states, notably Florida, specify which special ties are allowed to declare brain death. It is reported that Canada requires two physicians not associated with a transplant team to certify death. In the context of the guidelines of the President's Commission, and given the fact that they were intended to be modified as necessary to fit given institutions or locations as well as to accommodate future refinements, Black reminds us that "the fact that different institutions may use different techniques does not mean that the condition being diagnosed is different. . . . These are all different ways of looking at the same problem, and it appears that this is also the case with brain death."

In the face of the several guidelines that have been proposed over the past 35 years, and the recognition that some components have proven to be inaccurate or relatively unreliable while others are too new to have been evaluated adequately, it appears that those of the Regional Organ Bank of Illinois may be the most reasonable, practical, current, and comprehensive. They are provided in Table-3. They are applicable to both children and adults. With allowances made for the demonstrated limitations of EEG and radionuclide cerebral blood flow studies, they should be of great value to every physician and hospital, for they are applicable to almost every institution. They give details for the apnea test. A debate may remain for some time regarding use of the EEG. At least two authorities have maintained that it is not required. Given national and cultural differences, it appears likely that the criteria used in other contexts will differ somewhat, perhaps with Japan adopting the use of radiologic procedures, as may occur also in some institutions in Europe and the United States. The aim of all the criteria is to accurately determine the presence of death. Although the needs of organ procurement have played a significant role in the development of the recent concept of brain death, they are not the primary motivation, which, as in the past, is to determine the presence of death and prevent the unnecessary prolongation of suffering of families. One author discusses in the context of the determination of brain death the inherent impossibility of validation of criteria. He notes that to validate any set of criteria would require so large a number of subjects as to make any prospective study impossible. The essential problem for the physician lies in the determination of irreversibility. In the adult, when the cause of coma is known and the proposed criteria are carefully employed, a premature declaration of death should not occur. The difficulties arise in the cases of newborns, infants, children, and adults in whom the cause of coma is not known.

There continue to be public and professional misunderstandings about brain death. Except for the New Jersey statute and the regulation of New York, the many state laws do not require the families and friends to be consulted before the determination of brain death. Black reminds us that the diagnosis of brain death is a medical decision. However, he recommends that the doctor describe to the affected parties the events involved in brain death and the actions that ensue, such as the discontinuation of artificial ventilation. He feels that, "except in very unusual circumstances, it is inappropriate to ask the family for permission to stop the ventilator in this setting." It is advisable whenever possible for the physician to explain the nature of brain death to the family, for a goodly portion of the population does not comprehend it adequately. Kirkland discussed the situation where the family refuses to accept diagnosis of brain death. He asked, Should artificial ventilation be continued? In the discussion that followed his presentation, one discussant observed that some families confuse brain death with the persistent vegetative state. The physician must be satisfied that the family understands that the patient is both clinically and legally dead. However, another discussant, recognizing the strong emotional need to regard death as a clearly defined event, describes it to families as being a process affecting first organ systems, then organs, and finally cells.

Table-3 Brain Death Protocol

Re: Suggested Guidelines for the Diagnosis of Brain Death

Brain Death in the States of Illinois and Indiana is defined as the complete and irreversible cessation of all functions of the Brain, including the Brain Stem. The determination must be made in accordance with accepted medical standards.

These guidelines reflect a compilation of current medical literature and have been established to assist the physician in the diagnosis of brain death. The pronouncement of death is, by law, a medical act and therefore consent is nor required nor is it to be requested from the next­of-kin. However, the patient's family should have full information concerning this certification process.

I. All of the following Clinical Criteria for Brain Death are necessary and sufficient to diagnose brain death:

a. The patient must be in deep coma-unresponsive to verbal or painful stimuli.
b. No brain stem reflexes (spinal reflexes may be present)
c. No spontaneous respirations
d. No spontaneous movement or posturing

i. The cause of coma must be established and sufficient to account for the loss of brain functions.

ii. Criteria for Brain Death are not valid where the effects of CNS depressants greater than therapeutic levels are present. When clinically indicated, a drug screen must be performed to excluded this possibility.

iii. Criteria for Brain Death are not valid if the patient's temperature is below 32.2°C (90°F)

iv. These criteria must be met at the time of a repeat evaluation (e.g., 2 h apart). If gross irreparable brain trauma is present this interval may be reduced.

v. There is a widely held belief that young children may be more resistant to anoxia and more likely than adults to survive severe brain insults. Therefore, for children under 2 months, it is recommended that two examinations and EEGs be performed at least 48 hours apart. In those patients two months to I year, two examinations and EEGs separated by at least 24 hours. A repeat examination and EEG are not necessary if a concomitant cerebral radionuclide angiographic study demonstrates no visualization of cerebral arteries.

II. Procedures for Clinical Examination:

A. Coma-No spontaneous movement and no response to painful stimul

B. No Reflexes

  1. The pupils are fixed and do not respond to a direct source of bright light.

  2. External ocular movements are absent in response to:

     a. head turning (doll's eyes)

     b. irrigation of the external auditory meatus with ice water for 20 seconds

 3. Corneal reflexes are absent

 4. Gag, swallowing, jaw and cough reflexes are absent

 5. Spinal reflexes MAY BE present (deep tendon reflexes, triple flexion)

C. Apnea-Because the respiratory drive is the most caudal of the brain stem responses, an apnea study should be considered. This can be performed as follows:

  I. Ventilate the patient with 100% oxygen.

  2. Disconnect the ventilator (if the patient becomes unstable, reconnect the ventilator immediately).

  3. Passively administer oxygen via T -piece or oxygen cannula via the trachea at 6 liters per minute.

  4. Observe the patient for any respiratory activity.

  5. An ABG should be drawn before reconnecting the ventilator to document a PaC02 greater than 60 mmHg.

  6. Failure of spontaneous respiration to occur after the arterial PC02 is 60 mmHg or greater, confirms the presence of brain stem death.

It is recornized that some patients may develop malignant rhythm disturbances when the respirator is disconnected, and a formal apnea test may be impractical.

 D. No movement or posturing. Some peculiar movements of upper limbs have been noted to occur in the confirmed brain death patient and collectively are termed the Lazarus sign.This could be confused with postural responses.

I. No postural activity. (Decerebrate/Decorticate)

2. Blinking, swallowing, yawning, coughing and vocalization are absent.

III. Other Tests

It is generally agreed that an EEG may not be helpful in the determination of brain death and, where indicated, a cerebral blood flow study may be helpful. The preferred method of establishing the diagnosis of brain death is conformity with the clinical criteria listed (II) and a positive apnea study. If an apnea study is not feasible, then the clinical evaluation should be repeated after 6-12 hours; if the patient continues to meet the clinical criteria for brain death, he may be pronounced dead.

1. EEG: Contrary to popular belief, the Harvard Criteria did not require an EEG (or two EEGs), but recommended it as a confirmatory test. The most widely accepted current standards are the Guidelines for the Determination of Death, set forth by the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Therein, laboratory tests are optional and do not replace the clinical examination. In recent years, reliance on the EEG to determine brain death has fallen from favor because of well-documented false positive and false negative results. Absence of brain waves despite "brain life" has been demonstrated in patients with preserved brainstem reflexes and in patients with reversible encephalopathy due to drug overdose. Conversely, EEG waves have been seen despite overwhelming evidence of brain death, leading to prolonged "life support."

2. Radionuclide Brain Scan: Cerebral blood-flow studies have proven useful for confirmation of brain death. Demonstrable absence of cerebral blood flow for more than a few minutes is incompatible with brain survival and is, therefore, with appropriate clinical findings, immediately diagnostic of brain death, even when the etiology is unknown, or metabolic/drug intoxication is present. In brain-dead individuals, radionuclide angiography will normally demonstrate no flow above the cervical portion of the internal carotid artery. It should be reemphasized, however, that brain death can usually be diagnosed on clinical grounds, and blood flow studies are not always needed.

There should be little difficulty diagnosing brain death if standard criteria are followed. The three most likely pitfalls are: failure to test for apnea, failure to exclude drug overdose, and lack of an established cause of coma sufficient to account for loss of all brain functions.

 When the patient has fulfilled the above criteria it is the responsibility of the attending physician or his designee to:

1. Write an official pronouncement of death not in the progress notes stating date and exact time of pronouncement.

2. Inform the family of the circumstance.

3. Notify Coroner when appropriate.

4. Call the local Organ Procurement Organization and allow the transpoant coordinator to suggest organ donation to the next-of­kin.

5. Complete death certificate.

Once again, like other authors mentioned earlier, he asserts that "the moment of death is not solely a medical judgment, but is critically dependent upon values and beliefs."  It probably is best for a physician and hospital to include in their guidelines provision for what medical services if any would be provided to the dead person in the event that the family refuses to accept brain death criteria. In one review of 1989, only 64 percent of the parents of 106 brain-dead children are said to have known that cessation of brain function is a definition of death. Of these, 73 percent had obtained information about organ transplantation from the mass media, and only 37 percent had received it from medical personnel. The authors note ethnic differences in acceptance of the concept of organ donation.  Ethnic differences in the understanding of both brain death and organ transplantation appear to have been inadequately appreciated and studied and would offer valuable information.

Wheeldon reports that the number of organ transplant procedures appears to have plateaued between 1987 and 1991, reflecting the worldwide shortage of donor organs.  Although federal law in the United States requires that the family or responsible individual be offered the opportunity to donate the organs of the deceased, the practice is still restrained. The reasons are complex.

In the instance of the diagnosis of brain death in children, a survey by Lynch and Eldadah in 1992 revealed that 77 percent of physician respondents thought that a second clinical examination is required within 12 to 24 h of the initial determination, and in 80 percent of 49 pediatric intensive care units a second physician was required to confirm the diagnosis. This situation appears to reflect the uncertainty of the accuracy of diagnosis even when the guidelines of the Task Force are used. Darby and colleagues, for example, documented absence of blood flow in the posterior circulation and persistent reduction in the anterior circulation, in conjunction with an EEG displaying brain activity but with all clinical criteria of brain death met. Another case is reported of a newborn who manifested no evidence of brain function initially but recovered fully and had normal subsequent development.

An important publication reported the results of a survey of the opinions of 34 percent of the 3600 members of the American "ssociation of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS)," which helps to clarify some of the concerns of members. One-half of the respondents practiced in teaching hospitals. Almost all accepted the value of organ transplantation, and 87 percent believed that all families should be offered the opportunity to donate the organs of the dead. Almost all believed that the neurosurgeon should be involved in diagnosing brain death and explaining it to the family. Surprisingly, only 40 percent felt that no more than half of the public would give consent, but 36 percent thought that 50 to 80 percent would agree.

A Gallup Poll of 1990 reported that 89 percent of adults would agree to organ donation if the loved one had requested it. This situation is provided for in the advance directives or living wills accepted by many states, but the durable power of attorney statute of Texas would apply only if the guardian had executed the document prior to the death.

In the AANS-CNS survey, about 25 percent thought that brain death should be declared only with the prior consent of the family, and about 50 percent allowed for a conscience clause or exemption. No single set of criteria to determine brain death was employed by more than one-third of the doctors. Individualized hospital criteria or guidelines were employed by 53 percent, 34 percent used the older Harvard criteria, 6 percent used the even older criteria of the NIH Cooperative Study, and 11 percent applied those of the President's Commission. Forty-one percent thought that there are no valid criteria for patients under the age of 5 years. In the case of older children and adults, 58 percent made routine use of the EEG, and no more than 23 percent employed a measure of cerebral blood flow. Less than half of the neurosurgeons reported they had participated in the development of their hospital's brain death criteria. A sizeable percentage believed that the existing state statutes that provide for brain death do not adequately protect the neurosurgeon from possible legal liability; only 30 percent believed that they do. Thirty-two percent did not believe they bore a responsibility to facilitate organ procurement, although 20 percent expressed their strong commitment. As a group, older physicians expressed slightly more support for organ donation than did younger ones. The reasons for reservations may be summarized as follows:

1. Perception of how families may feel about the donor process
2. Questions about the effectiveness of organ transplantation
3. Potential conflict between their patient care and management of the donor procedures
4. Concerns about legal liability
5. Negative experiences with transplant coordinators and/or transplant surgeons
6. Belief that the organ donation process is too time-consuming.

Recognizing the extensive shortage of organs for transplantation as well as the diverse practices and views of neurosurgeons and other practitioners, a great effort must still be made to inform doctors of the validity of criteria to determine brain death, to encourage their participation in the development of their hospitals' criteria or guidelines and policies and the applicable state statutes and decisions, and to inform them of the results of organ transplantation and the extent of organ shortages. Organ transplant organizations and personnel must play an even greater role both in the education of lay people and professionals and in facilitating organ donation and harvesting.

Wheel don reviewed the acute mortality associated with the use of transplanted hearts and other tissues and organs that have undergone storage. Although the requirement for storage is not governed solely by the hospital or physician involved in the determination of brain death, both parties perhaps could reduce the need for storage and thus improve the success of transplants.

Although Ota reports several of the reasons he surmises make the Japanese reluctant to accept brain death, most would appear to apply to many societies. He enumerates six:

I. Lack of understanding of the concept
2. Special emotional attachments to the dead person
3. Loss of confidence in the medical profession
4. Ethical questions related to earlier organ transplant procedures
5. Repeated denunciation of the concept of brain death by third parties
6. Perceived insufficient participation of government and medical associations

All of these issues must be reviewed and addressed.

Although somewhat outside the scope of this review, it is worth noting that a significant number of physicians and biomedical ethicists have expressed the desirability of extending the definition of death to incorporate those suffering from neocortical death or the persistent vegetative state. Although I cite only one reference, this debate is accumulating an increasing literature. The idea generally seems to derive from the belief of some that either state has resulted in the loss of personhood in the face of permanent and irreversible loss of consciousness. A society can alter its acceptance of what constitutes death, but Rothenberg uses a quotation from Hegel to remind us that "what is useful is right" is not a sufficient justification for attempting to fan societal enthusiasm for and hasten the acceptance of a new or expanded definition of death.

In summary, it would seem today that much greater attention must be given to understanding the public and professional perceptions of brain death, to educating both groups, to assisting in the development of improved and appropriate medical criteria and in the enactment of laws by all the states still lacking adequate statutory provision of brain death, perhaps to assuring legal and ethical exemption for those who by reason of conscience cannot accept the concept of brain death.

Ethical, Legal, and Medical Aspects of Fetal and Neonatal Tissue and Organ Transplants

The lifting of the federal ban in the United States on research on and use of fetal tissue transplantation may have made more timery and imperative the consideration of the many ethical, legal, and medical aspects of the subject, though few if any of these issues have been resolved. We may find the same to be true a decade from now. Nevertheless, considerable literature has evolved in the past 10 years that raises many questions and suggestions for resolution. The medical aspects here will be limited to anatomic, physiologic, and clinical observations and opinions about the development of the fetus and the status of the neon ate and especially of the anencephalic newborn.

Akabayashi and Morioka review the present feasible medical uses of a brain-dead body. As a medical resource, it could be used as ­
1. a donor for organs for transplantation, including marrow;
2. for storage purposes, for example, for the preservation of organs for transplant and of rare blood types;
3. a factory, for example, to produce hormones and antibodies.

They also list several uses with medical applications:

1. For experimentation
a. in basic medicine, for example, to help determine physiologic functions in humans, in place of animal experimentation, and
b. in clinical medicine­
i. to serve as disease models, for example, for AIDS and carcinoma; for trials of experimental drugs and determinations of toxicity,
ii. for use in technological development, for example, of artificial hearts or new diagnostic methods or for trials of new surgical procedures, and
iii. for use in preliminary tests of new drugs after completion of animal tests and before application to humans.
2. For educational purposes, for example, in practical training and anatomic dissection

No doubt other applications can be conceived, not only for brain­dead bodies but for tissues and organs from those not dead. The latter condition at present would consist in the use of fetuses and anencephalic newborns. Schoen notes that, historically, viability has been equated with the "quickening" of the fetus, which usually occurs about the 10th week following conception, or with the initial movements perceived by the mother, which may not take place until the 4th or 5th month of pregnancy. (Thumb sucking commences toward the end of the 11th week.) At 17 weeks, the lungs are not yet able to exchange gases. A fetus born between the 20th and 28th weeks of gestation has but a 10 percent chance of survival. At 24 weeks, the lungs usually are not sufficiently well developed to permit survival. The United States Supreme Court in its decision re: Roe v. Wade referred to the ability of a fetus to sustain life outside the womb as beginning at the 28th week plus or minus 4 weeks. By the 26th through 29th weeks, the fetus has gained sufficient brain development to direct rhythmic breathing. At 32 weeks it still requires an incubator; by 34 weeks it can distinguish light and dark, and by 35 weeks it shows spontaneous orientation to light. It is regarded as full-term at 38 weeks. A fetus is regarded by some as being a living human being when it acquires all of the characteristic functions of life, in particular a normally functioning brain.

Sass reviews normal fetal cortical development. On the basis of the development at about the 54th day after conception of the stationary neurons that form the early cerebral cortical plate, he believes that cortical brain life can be dated from this time and that human life should be treated as the equivalent of brain life. He writes:

In general, the shift to a brain-oriented definition of death has major advantages: (1) Human life that can no longer communicate or feel pain need no longer be supported; severe moral, emotional, cultural, social, and economic costs that would have been associated with the artificial extension of the life of such entities are thus avoided. (2) Organs then become available for patients who would otherwise die or face severe suffering, hardship or inconvenience. (3) There is a single criterion for death, prior to which human life enjoys full, uncompromised legal protection and moral recognition, and after which it is not legally protected or morally recognized in the ways we protect or recognize each other.

He believes that the point of cortical development is the point after which fetal life should be morally recognized and legally protected, because "even the biological preconditions for being an 'imago Dei' or 'zoon logan echon' are otherwise not present."  He allows that the termination of pregnancy after the 54th day after conception "will have to be based on moral considerations other than the absence of brain life" (by which he means early cerebral cortical development).

Sass also reviews the arguments against designating a specific time point in embryonic development as the start of life, the most common being that of "potentiality," or the potential to become a person, and provides an excellent review of the several viewpoints for and against. The interface of science with societal acceptance and law becomes of paramount importance. Sass relates that the Federal Republic of Germany legally protected abortion under certain easily met criteria up to the end of the 90th day after conception, but introduced an "embryo protection law" that made it a criminal offense to do research on the pre-embryo during the first 14 days after conception. He notes the various laws governing abortion in the United States.

Kearney and colleagues discuss the text and implications of a United States Congressional Bill to fund some fetal tissue research, which would require the woman willing to donate the tissue to certify that she did not undergo an abortion with the intention of making the donation. If she were to refuse to make the certification, in several of the states she could be denied an abortion. The Bill does not provide for confidentiality. The government should state the reasons for the requirement.

Rosner and colleagues provide an excellent, thorough review of the debates about equating attainment of "brain life" with life itself. Although the paper is in the context of the status of anencephalic fetuses and newborns as organ donors, they relate the proposal of Michael Harrison that a definition of death be provided for those with an absent brain. The concept of the nonbeing of the anencephalic fetus was first put forth by Beller and Quakernack in Germany in 1980. Schoen provides a thorough review of both legal and legislative approaches to answering the question of when life begins and when it ends. Like many others, he recognizes the need to apply a legally consistent definition of life to both its beginning and its end.

Who should define life? Should life be precisely defined? There is no consensus at this time. Even if one task of law is to define a common denominator of public morality, it is probably expecting too much of legislators and many other governments to ask them to undertake it now, except for a limited locality. Even this would be a formidable job and could result in many disparate laws and predicaments, at least the United States. The Supreme Court decision in re: Roe v. Wade refused to rule on the question of when life begins. As of 1990, Minnesota and 15 other states had "implicitly granted personhood by 'feticide' laws that permit prosecution for homicide when a fetus is killed in a criminal attack on the mother."  Minnesota defines the unborn child as a "human being conceived but not yet born." Fetal abuse laws in existence in 18 states in 1990 recognized maternal responsibility for the health of the fetus. In re: Doe v. Bolton, the United States Supreme Court held that a state may not limit physicians to considering only the possibility of serious danger to a mother's life or health or the risk of fetal defects, but must allow them to consider all relevant factors.

Although lack of development of brain functions in anencephalic newborns has been the subject of much debate, Rosner and colleagues point out that no one has yet proposed that those born with hypoplastic lungs or heart be included in a comprehensive definition of death. As mentioned earlier, the state of Missouri defines life as "beginning at conception," and this criterion is applicable to all unborn children at every stage of biological development." Schoen notes the inherent contradictions with the Missouri brain death statute. Similar discrepancies may exist in the laws of other states. In Germany, any anencephalic fetus is legally regarded as stillborn, but a Board of the West German Physicians ruled that "a termination of pregnancy after the 22nd week is no longer permitted in the Federal Republic of Germany." In Canada, fetal tissue has the same legal status as other tissues and organs from human beings, with provision for both informed consent of the motor and confidentiality. In Great Britain, reference is made to the Peel Report and the guidelines established by the British Medical Association and the Medical Research Council. Approval was granted for the use of tissue and for experimentation on a "previable" fetus, defined as one that has not attained a gestational age of 20 weeks and does not exceed 400 g in weight. The fetus can only be obtained by "natural processes or lawful means." Informed consent must be obtained from the mother, and when practicable from the father. There must not be any financial incentive or reward involved. A complete record of the usage of fetal tissue and organs must be maintained. The responsibilities of clinicians and researchers are to be clearly delineated and separated. In 1984, Molnar reviewed the prevailing status in France. A 1976 law allowed the tissues and organs of an aborted fetus to be used if the fetus had died a natural death. The entire subject remained in widespread debate.

The situation in the United States is reviewed by Deutsch. When allowed by law, the use of fetal tissue or organs requires the informed consent of the parents or mother and also a demonstrated need or sound medical basis for the use and a positive benefit/risk ratio. Much of the debate in the United States has centered on the use of tissues and organs from anencephalic neonates. Several authors have noted that organs and tissues are useless when there has been in utero death or spontaneous abortion. The success rate for the transplantation of fetal or neonatal organs is greatest when the organs are removed immediately and thus are viable and is almost zero when removal is delayed by the present legal requirement that the brain death of the anencephalic neonate be determined. Rosner and colleagues provide a very valuable review of the history of donor procedures for anencephalic newborns, the clinical results of organ transplantation from 1966, and the many ethical and legal questions involved. Fost believes that the present whole-brain death criteria need not be applied and, in fact. cannot be applied to infants less than 7 days old. He urges a moratorium on the use of anencephalic infants as a source of tissues or organs, for the subject requires more debate. "Just as war is too important to leave to generals, transplantation policy is too important to leave to physicians."

Walters reports that of the 2 million babies born in California over a 5-year period, 888 were anencephalic. Of these, 58 percent were born alive, but 65 percent died within 24 h, an additional 30 percent died within the first week, and two lived approximately 2 months. He states that all anencephalic infants are "born dying."  Walters observes that all viable neonates are registered and receive constitutional protection of their lives. He believes that a handicapped newborn must possess a reasonable potential for minimal personal capacities to have a unique claim to life, including personal awareness and not just physiologic functions. Otherwise, parents should be free to choose the option of nontreatment for these infants.  Earlier, he and Ashwal regarded it as ethically and medically appropriate for certain liveborn anencephalic infants to be assisted with ventilation to allow the later determination of brain death. The use of ventilation was deemed an appropriate measure within the existing law toward meeting the severe shortage of neonatal organs and, presumably, tissues.

Shewmon provides a good review of epidemiologic and neurological data about anencephaly. Prenatal screening is becoming much more common and results in discovery of most instances of the malformation, which gives the opportunity for therapeutic abortion when allowed by law. The incidence of anencephaly in the 1950s was 1.93/1000 births, but it had fallen to 0.3/1000 in 1988. The estimated number of live anencephalic neonates in 1988 was 304. The use of both ultrasound and maternal alpha-fetoprotein studies contributed to the decline. He stated that nearly all cases of anencephaly would be detected during the second trimester of pregnancy, and most likely cause a further substantial decline in the numbers born. Anencephalic infants tend to be born prematurely (53 to 58 percent) at a mean gestational age of 33 to 36 weeks, and 50 to 80 percent have a birth weight less than 2500 g. Shewmon estimated that one-third to one-half of these infants suffer from a gross malformation of at least one other organ system, including the heart in 15 percent and the liver in 25 percent. He projected that the incidence of anencephalic births would proceed an overall 3 percent annual decline. On the basis of these data, he suggested that the overall annual availability of usable organs from anencephalic infants would be 25 kidneys, 12 hearts, and seven livers. For these reasons, he argued against the proposal of several authors to attempt to change the existing statutes regarding brain death to exempt anencephaly.

The Transplant Policy Center argued that anencephalic infants are so different from other neonates and have such different futures that it should be permissible with full free and informed consent to allow the removal of any and all useful organs and tissues. Walters and Ashwal in 1988 reported that they and others were attempting to develop ethical and medical protocols within the context of existing laws, and presented their protocol. The epidemiology and several medical aspects of anencephaly are reviewed as mentioned earlier, stresses that the rate of success of transplantation of organs from anencephalic infants is greatest when the infants are viable and is essentially zero after declaration of brain death. McGillivray also reports on the high incidence of additional anomalies found in anencephaly, and estimates that most anencephalic fetuses will be identified before 20 weeks gestation. He suggests that an infant who is to serve as an organ donor should ideally have reached a weight of 2000 g and a gestational age of 30 to 32 weeks.

Rosner and colleagues believe that "if viable anencephalic organs can be retrieved when total brain death occurs, their use may be ethically and legally acceptable." 132 They recognize the lack of concensus about medical criteria regarding determination of brain death in the liveborn anencephalic infant. They quote Capron:

Medical ingenuity should be directed toward finding ways to care for dying anencephalic (and other) babies so that when they become brain dead, they can be organ donors (with their parents' permission). Medicine should not embark on a course of sacrificing living but incompetent patients for the admitted good of transplanting organs.

A second major area of disagreement to a proposed legal exception for anencephalic live newborns concerns the "slippery slope" issue. The opponents to the creation of legal provision to exempt anencephalic newborns from the present standards of determination and declaration of death argue that the exemption might in time be expanded to cover other situations and medical conditions. These could include infants with cortical brain death or a persistent vegetative state, and possibly other handicapped infants among others. Fost and others are opposed to making such an exemption. He believes that a consensus first must be reached through "the broadest possible debate." Other opponents include Willke and Andrusko and Arras and Shinnar. Thorough reviews of the arguments for and against are provided by Rothenberg and several others. After considering these arguments, several have supported the proposal.The arguments in favor of the exemption of viable anencephalic newborns are presented by Rothenberg, Walters, and Zaner. These arguments include the following:

1. There is a serious need for solid organ donors.
2. It provides the opportunity to save another's life.
3. The saved life would probably repay the costs of the procedure via future earnings, taxes, etc.
4. Both the parents and recipients benefit from a sense of benevolence.
5. The "best interests" of the anencephalic infant, who is doomed to die, would be served.
6. As the legal right for a person to forego life-sustaining treatment is recognized by many courts, the anencephalic infant's consent should be allowed by way of a surrogate.
7. Many laws at present provide the moral framework on which a people's social fabric is established. There should be recognition and acceptance of an autonomous right of control over one's own body.
8. The anencephalic newborn has not and cannot attain "personhood."

Rothenberg reviews the California data concerning survival of anencephalic neonates and infants. Of 205 anencephalic infants born between 1987 and 1982, 7.8 percent survived 1 week to 1 month, and 1 percent survived 3 months. Their birth weights were in excess of 2500 g. He notes that others have reported survivals as long as 5.5 to 14 months. Such long, though rare, survivals are perhaps related to the varying forms of anencephaly noted by Shewmon. Baird and Sadovnick have also reported figures of survivability.

The arguments against exemption include the following:

1. A threat to public support from the need for a new and modified definition of death
2. Possible misdiagnosis of anencephaly
3. Opening of the door for inclusion of other medical conditions, such as persistent vegetative state
4. The position that the usefulness as such of a set of organs should not dominate lawmaking
5. The absence of an adequate evaluation of the degree and rate of success of such transplants
6. Fear that guilt-inducing arguments or economic incentives might be used to persuade a mother to either terminate a pregnancy or delay termination until the fetal organs were mature enough to be useful for transplantation
7. The fact that third-trimester abortion remains at best a topic of extreme controversy or is illegal
8. The great difficulty of achieving clear and enforceable public policy and law at this time

Walters states that today some hold to a "genetically based motion of persons, some [hold] to a personality based definition of human values and most of us are intuitively drawn toward features of both." Two editorials appeared in the New England Journal of Medicine in 1989. One argued that anencephaly is a "special case in which removal of organs would be permitted without regard for criteria of brain death." The second editorial opposed this view. Brody would justify using the organs of viable anencephalic newborns on the basis that functional maturation of the brain constitutes personhood.

Waiters reported in 1991 the results of a selective survey he conducted in 1990 of clinicians and bioethicists. He received replies from 70 percent of the 119 people surveyed. The purpose of the survey was to investigate the attitudes and beliefs of individuals with a special interest in the question of using anencephalic newborns as a source for organs. He found that 57 percent of clinicians felt it would be intrinsically moral; only 13 percent said it would not. Of the bioethicists, 72 percent indicated support and 6 percent disagreement. Thirty percent of respondents gave qualified answers, mainly stressing the importance of considering the parents' desires, and 37 percent of clinicians and 30 percent of bioethicists thought that the use of organs before brain stem death is confirmed should remain illegal. The survey offered several choices on the question of whether and how laws should be changed. The clinicians, 32 percent would change the law from death of the entire brain to cerebral death; 37 percent of bioethicists would do so. Of the clinicians, 49 would modify the law to allow exemption for the anencephalic infant, but only 32 percent of the bioethicists proposed other alterations. Of the 58 percent who felt that organ use should be legalized, 38 percent thought that cerebral death should be incorporated in the law and 13 percent thought that the only exception should be for anencephaly. Regarding the "slippery slope" argument, the clinicians and bioethicists gave quite similar responses: 63 percent of clinicians and 58 percent of bioethicists felt that the argument had no relevance, but an almost equal percentage (54 percent and 53 percent, respectively) felt that it held considerable importance for society. The "current" law regarding brain death was thought to be morally right and good by 37 percent of clinicians but only 5 percent of bioethicists; 63 percent of physicians believed the current law could be medically validated with a high degree of accuracy; somewhat surprisingly, 68 percent of bioethicists also did. On personal philosophies regarding death, 38 percent of clinicians and an equal percentage of bioethicists accepted that death is equivalent to the irreversible cessation of all brain functions, but 51 percent of the clinicians and 60 percent of the bioethicists regarded cerebral death as equivalent to death. Approximately 10 percent of both groups were opposed to the use of anencephalies as donors or organs. The results of the above survey reflect a degree of uncertainty with regard to anencephaly similar to that shown by the recent surveyor neurological surgeons reported in the preceding section.

The use of fetal tissues in neurosurgery is reviewed by Erwin Deutsch of Germany. He states that it is mandatory to obtain the informed consent of an adult patient or parent (mother) whenever an organ or tissue is to be used for any purpose. He cites the 1988 ruling for the adult plaintiff by the California Court of Appeal that concerned the unauthorized use of the patient's spleen and other tissues (Moore v Regents of the University of California,  Cal Rptr , California Court of Appeal, 21 July 1988). He states that if the fetus has been aborted, the fetal tissues do not belong to the clinic or the doctor. The NIH guidelines require that both parents, or at least the mother, give informed consent for any use; otherwise the fetus must be destroyed or otherwise disposed of. The fetus has no legal standing, never having become a person, and is treated as being a former part of the mother. If the mother is married, it appears that the majority opinion would require informed consent from both parents. He cites the case of destruction of in vitro-fertilized eggs by a hospital that failed to obtain consent. The district court of the Southern District of New York held that the parents were entitled to compensation [Del Zio v The Presbyterian Hospital, United States District Court, Southern District of New York, 1978 (74 Civ 3588)]. There may be significant differences in other jurisdictions. It would be considered unethical to prolong a pregnancy that is to be aborted to allow further growth and maturation of tissues. It would also be unethical to allow any financial profit to result from either the donation or brokering of such tissues. Much of the present use of fetal tissue is experimental. Deutsch believes that when transplantation involves human subjects, there must be a positive benefit/risk ratio. "In this respect the lawyer has to step aside and leave the podium to the doctor. The lawyer's task is only to draw the outer limitations of this novel medical procedure, not to pass judgement on the medical indications." One can only hope this occurs.

Marshall reviewed the Canadian regulation of the medical use of fetal tissue in both research and therapy. He noted that in the United States, all human experimentation has been regulated since 1975 (Code of Federal Regulations title 46, subpart B, US Government Printing Office, Washington, 1985). He remarked on the ethical concerns of some that fetal tissue use would encourage abortion and abuse. "Few, if any, people have difficulty with research that uses tissue obtained from spontaneous abortions. However, if such research is to continue, its goals must never be a factor in advice about or a decision for abortion. In other words, regulations or guidelines must be established through law that clearly separate the two issues. ,, In Canada, as of 1990, fetal tissues obtained from either spontaneous or induced termination of pregnancy have the same legal status as other organs and tissues from human beings, and require both consent and confidentiality. Marshall noted that at the meeting of September 14-16, 1988, the majority of members of the Human Fetal Tissue Transplantation Research Panel in the United States "tentatively" concluded that the use of fetal tissue obtained from legally performed abortions were acceptable.

Garry and colleagues in a recent editorial in the New England Journal of Medicine note that tissue obtained from ectopic and spontaneously aborted pregnancies is not suitable for most uses. Neural tissue must usually be obtained from fetuses of less than 12 weeks gestational age. Some cell lines may be developed from the yolk sac or the placenta, which lacks class II major histocompatibility antigens. An accompanying editorial by Kassirer and Angell expresses support for the use of fetal tissues from elective abortions. They are critical of the prevailing attitude of government that it has the right to evaluate the motives of citizens relative to elective abortions despite the absence of any legal basis or justification. They estimate that more than 1 million people in the United States suffer from Parkinson's disease and believe that their needs and potential benefit from tissue transplantation must be given attention.

Garry and colleagues note that small samples of tissue may be obtained from the placenta or amniotic fluid without abortion through villus sampling and amniocentesis. Biopsy of the yolk sac raises significant ethical questions, because it is not safe and is not needed for diagnosis. It may become possible to engineer cells obtained via amniocentesis performed for diagnostic purposes to produce insulin, neurotransmitters, and other chemicals. The yolk sac could serve as a source of hemopoietic stem cells, and possibly such cell cultures might become an alternative to the use at fetal liver cells. However, these "would at best be rare and unpredict­able sources of normal, viable fetal tissue." Allowance must also be made for the fact that harvested cells and tissues are frequently abnormal and thus could pose a risk to recipients of the transplants. At present, chromosomal analysis requires 10 days, which means that genetic defects could not be found before transplantation took place.

Germ-line gene therapy and its ethical implications are reviewed by Feltcher and Anderson. They quote the early opinion of 1972 of the theologian Paul Ramsey:

. . . to know fully who a fellowman essentially is, which should be known only to God and on record in his counsels. Before us then opens up the dizzy, abysmal prospects that men can be present where the foundations of the world were laid. Piece by piece of information may destroy our sense that, for all the genetic corruption, God made the world and the human creature and they are good.

Arguments about the implications of genetic research continued throughout the 1970s. The President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research published its report Splicing Life in 1982. It strongly defended the continuation of DNA research. A Human Gene Therapy Subcommittee was created in 1984. The authors state the 1992 position of the Recombinant DNA Advisory Com­mittee of the National Institutes of Health and the Subcommittee, that they

. . . will not at present entertain proposals for germ line alterations but will consider for approval protocols involving somatic cell gene therapy. The purpose of somatic cell gene therapy is to treat an individual patient, e.g., by inserting a properly functioning gene into a patient's somatic cells. In germ-line alterations, a specific attempt is made to introduce genetic changes into the germ (reproductive) cells of an individual, with the aim of changing the set of genes passed on to the individual's offspring.

The Council of Europe has passed three recommendations in 1982,1986, and, in 1989. The latter would permit investigations to be conducted on viable embryos in vitro only

-for applied purposes of a diagnostic nature or for preventive or therapeutic purposes

-if their non-pathological genetic heritage is not interfered with. . .

It is impermissible in Europe to undertake experiments with embryos only for the purpose of research. It is illegal in Germany, where the authors note that a scientist can be jailed for up to three years for any kind of human embryonic research. By contrast, the guidelines governing research on human embryos within the United Kingdom" state that research projects will be considered

. . . on a case by case basis but certain types will not be approved, e.g., modification of the genetic constitution of a pre-embryo: the placing of a human pre-embryo in the uterus of another species for gestation: cloning of pre-embryos by nuclear substitution.

Scientific bodies appear in general to have recognized the importance and ethical applications of somatic gene therapy. Increasingly, other individuals have proposed and accept the extension of these techniques to germ-line research and therapy. The authors quote, as one example, the comments of Gregorius, Metropolitan Greek Orthodox Bishop of Delhi": one cannot seen anything intrinsically forbidden or evil in gene therapy, whether somatic or germ-line. Infinite possibilities of power are open to humanity. The ethical problem is not in the acquisition of this power, but in its wise use.

Fletcher and Anderson offer several important questions to the continuing debate about germ-line experimentation." They believe that a "solid societal consensus should undergird the first attempts at germ-line therapy," for the therapy would affect future generations and its social impact is immeasurable. They relate the five ethical principles for biomedical research: respect for persons, beneficence, nonmaleficence, proportionality (the duty to balance risks and benefits and employ the procedure of least harm and most benefit), and justice (the distribution of benefits and burdens fairly and equally). The goals for biomedical research "should be set primarily to cure and prevent the greatest sources of human suffering and premature death, and to relieve the pain and suffering caused by these disorders." Within the constraints of ethics and law, they believe that the United States Congress would support these goals.

They estimate that 22 percent of newborn deaths in developed nations are due to congenital malformation of genetic disorders. Approximately one-third of the children admitted to pediatric units in Western nations require treatment for the complications of genetic disorders, congenital defects, or mental retardation. Nearly half of all implanted embryos die in spontaneous abortions in the first few weeks following fertilization. They report surveys of Americans that demonstrate that a majority would support therapy to "correct a gene 'that would carry the disease to future generations.' " Fletcher and Anderson believe that' 'society ought not to draw a moral line between intentional germ-line therapy and somatic cell therapy (but that) a moral line should be drawn between both of these modes of gene therapy-directed toward disorders with the greatest magnitude of suffering, pain, and early death­and efforts at 'enhancement' by either mode of therapy. They ask if it is possible for a line to be drawn and respected between germ-line interventions to cure and prevent serious genetic disorders or susceptibility and efforts to enhance individual traits like height, memory, skin, hair color, etc. They believe it is essential for a consensus to be reached on both public policies and ethically acceptable strategies. Thus far, many of these issues have not been adequately discussed or addressed by scientists, bioethicists, policy makers, and the public.

In an important, detailed, and recent review of the legal status of cryopreserved embryos, Perry and Schneider note that no one and no state of the United States has any guidelines regarding their ownership. By extension, one may be equally concerned about the legal and ethical issues relating to ownership of in vitro embryos in general, when they are to serve as sources of cells for genetic manipulation and other uses in both basic research and human application. Informed consent on the part of the donors would seem essential. The drafting of the requisite statutes and regulations by the federal and state governments may require many years, especially in the present context of widespread opposition to the unrelated issue of abortion. It is possible that repositories of embryos will be created for research and subsequent clinical use and that one day techniques may be developed to allow the cultivation of embryos into the fetal stages. In this event, statutes and ethical principles must be formed to address the fundamental question of the commencement of life. No doubt most people will expect and even demand that the data from the human genome project be employed for the relief of suffering. However, as almost every author has indicated, the broadest education and debate must be undertaken. As with the matter of brain death, it may not be possible to obtain a consensus for many years. Matters of such import will probably be resolved only through slow, repeated deliberations and tentative conclusions.

Authors notice about brain dead patients:

1.In dead patients with removed bony flaps, the brain persist to pulsate indicating that the circulation still persisting even with brain dead patients.

2.Diabetes insipidus disappear after brain death and the dead stopped needing Minirin to control if he progressed such a condition before death.

Skyra MRI with all clinical applications in the run since 28-Novemeber-2013.


Inomed Riechert-Mundinger System, with three point fixation is the most accurate system in the market. The microdrive and its sensor gives feed back about the localization.


Inomed MER system

Leica HM500

Leica HM500
The World's first and the only Headmounted Microscope.
Freedom combined with Outstanding Vision, but very bad video recording and documentation.

TRUMPF TruSystem 7500

After long years TRUMPF TruSystem 7500 is running with in the neurosuite at Shmaisani hospital starting from 23-March-2014

 

 

 

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