"Brain death"
A lie destined to die

THE FALACIES OF  THE  CONCEPTS AND CRITERIA 

OF   BRAIN DEATH

As already mentioned, the philosophical  assumption (7,8) from  which  the concept of brainstem death was derived considered human  death to be “ a state in which there is irreversible loss of the capacity for  consciousness combined with irreversible loss of capacity to breathe  spontaneously “ the concept of brainstem death was further supported  by the fact that those patients would inevitably die in a matter of hours or days ( 5.7)

This belief was based on earlier studies ( 10.11.12 ) carried out with the technologies of the sixties and seventies When scientists struggled hard to make a clear – cut decision about brain death . when  brainstem death was well established,  its victims were never given the chance to let die, probably because they were treated as potential  organ- donors in most centers all over the world later studies however revealed that it was possible to outlast this period by several weeks or months when that deemed necessary (13.14)

A young lady in her 24 th week of gestation suffering from brainstem failure was kept alive  for nine weeks to ensure the viability of her baby After birth the lady was then sacrificed (13)

For these reasons recent studies (15) tend to refer to brainstem death as brainstem failure It is now evident that there is no  single anatomical site in the brain responsible for consciousness as it was discovered that  there are substantial interconnections among the brainstem, subcortical structures and neocortex ( 15) these  are essential for integrating  consciousness (3,4). So a new classification of consciousness now appears . Consciousness is now universally  accepted to consist of two components : arousal and awareness(16,17)

Arousal : Normal consciousness requires arousal ; autonomic- vegetative brain functions subserved  by ascending stimuli from the pontine tegmentum, posterior hypothalamus and thalamus that activate  “ wakefulness “ (18) .        Arousal  depends on the integrity of physiological mechanisms that take their origin in the  ascending reticular activation system ( ARAS), arising from nonspecific populations of neurons located in the  mid brain and thalamus (19) Additional important pathways  participating in arousal have been recently recognized (17) . They  originate in the brain stem, hypothalamus and basal forebrain projecting  monosynaptically  to cerebral cortex without relaying  through the thalamus.

Experimental  studies have verified that an almost complete  destruction of the thalamus does not block cortical activation (16,20)  Arousal is due to several ascending systems  stimulating the cerebral  cortex and thalamus in parallel . Thus thalamo cortical transmission is not necessary to produce cortical activation(16)

Awareness : ( content of consciousness ), represents the sum of cognitive and affective mental functions and denotes the knowledge of existence and recognition of internal and external worlds(16) . Plum et  al. (19) have defined  not two but three components of normal consciousness subdividing awareness into two levels or components .According to these authors, the second level of component, which  importantly regulates the sustained behavioral state function of affection, mood, attention, cognitive integration and psychic energy depends on the integrity of the limbic structures including the hypothalamus, the basal  forebrain, the amygdala, the hippocampal complex, the cingulum  and the septal area. The third component is considered by Plum et al .; as the cerebral level, along with the thalamus and basal ganglia . This component is related to the process of higher levels of perception, self- awareness, language motor skill, and planning. Memory  can be impaired by injury of  either cerebral or limbic levels.

Awareness is mainly ( but not totally ) the function of  the cerebral cortex The basal  functional unit of the neocortex  is a vertically oriented group of cells extending across the cellular layers and heavily interconnected in the vertical direction (21) . These functional units or columns are interconnected by local circuits and represent  information – processing modules. It seems that the brain operates in “ parallel processing “ because cortical regions are linked  in parallel networks with each other and with subcortical structures. Thus a specific component of a certain cognitive function  is scattered among  interconnected regions, each one implicated in a distinct  aspect of  the cognitive ability

( 17.22) Thus awareness is not only related to the function of the neocortex

( although it is primarily important ) but to complex physical and psychological mechanisms due to the interrelation of the  ARAS, limbic system and the cerebrum (19)

From the above considerations it is clear that there is no single anatomical place of the brain necessary and sufficient for consciousness (23)

As already mentioned  trying to attribute “ consciousness “ to the function of a localized area of the brain, as the brain stem or otherwise is very wrongful and irrational.  Likewise, trying to establish or to claim the irreversibility of coma in such cases is equally  wrongful and irrational  As a matter of fact, Hassler et al (24) used deep brain stimulation in cases with “ coma vigil “     ( persistant vegetative  state due to insult of cerebral hemispheres ) and actually succeeded in awakening his patients with an undoubted recovery of awareness ( recognition of their families and emotional expressions) this proves the reversibility of this type of coma which had long been regarded as irreversible. Likewise brainstem coma (which was also regarded as irreversible ) might turn to be reversible in the future.

Getting   back to the philosophical concept which assumes that human death is “ a state in which there is  irreversible loss of the capacity for consciousness” the above mentioned data seem to contradict  the  essence of this concept  as far as the capacity for consciousness in brain  stem failure patients is concerned. This is particularly so if we keep in mind that it is possible to sustain their lives for  much longer period of time (13) than it had been claimed ( 10.11) .      For these reasons recent  studies (15)  tend to refer to brainstem death as brainstem failure. Had brainstem failure “patients been granted the proper length of time, the recent technological tools of management and above all regarded as patients rather than cadavers, and potential organ donors, how many of these patients would have survived?

DIGNOSIS  OF  BRAINSTEM  DEATH

Table 7 (5)

Three steps are involved in making a diagnosis of brainstem  death :

·        Ensuring that certain preconditions have  been met.

·        Excluding reversible causes  of apnoeic coma.

·        The clinical examination confirming brainstem areflexia and documenting persistent apnoea ( table 8)

Preconditions:

Table 8 (5)

Two preconditions are necessary:

·        That the patient is in apnoeic coma – that is, unresponsive and on a ventilator.

·        That  the cause is irremediable structural brain damage due to a “ disorder which can lead to brain death”

A positive diagnosis of  a disorder that lead to brain death depends on standard methods of history taking clinical examination, and special investigation Severe head injury  and subarachoid haemorrhage ( which together account for about 80% of cases of brainstem death ) are examples of cause of structural brain damage .

       The objective is not only to diagnose a condition that could damage the brain but to establish that it has in fact done so irremediably . The irremediable nature of the damage is only partly assessed by the severity  of the clinical features ( apnoeic coma is always a critical state ) .In theory  irremediable means  that no treatment  may reasonably be expected to change  the condition . In practice it also means that no therapeutic endeavours ( such as resuscitation or measures directed at controlling cerebral oedema ) have changed the patient’s  condition during an adequate period of observation and that further endeavours are therefore unlikely to be effective.

  The responsible  disorder may be thought of as structural when it is not due to such functional – that is , potentially reversible- causes  such as drug intoxication, hypothermia, or metabolic or endocrine disturbance            Table (10)

Table 9 (5)

      A thorough history taking and medical examination can suspect or exclude drug intoxication, hypothermia and  metabolic or endocrine disturbances. It can also readily detect loss of brainstem function

 ( listed in table 11) as well as the absence of  brainstem reflexes

( table 12) . The absence of brainstem reflexes can be elicited by a number of bedside tests and a number of ancillary confirmatory tests.                                                                                

Table 10 ( 5)

Table  11( 5)

A.Bedside Tests:

These include

·        Absent  brainstem reflexes ( the vestibulo – ocular reflex  and the occuocephalic or doll’s  eyes reflex are described in table (13) (25)

·        Apnoea ( disconnection ) test ( table 14) (25 )

Table (12) : doll’s eyes reflex and  cold caloric response

Table (13) : performing the apnea test (25)

Table (14) : continue.

B.Ancillary ( Confirmatory Tests )

These tests are primarily confiratory tests (8) intending to :

1-Detect the presence  ( or the adequacy ) of  cerebral blood flow

    ( angiography; contrast and radionuclide, and Doppler ultrasonography   

     and magnetic resonance imaging ).

2- Elicit an electroencephalic response  after cerebral nerve  stimulation 

     ( e.g. auditory evoked potentials ).

3- Detect metabolic and hormonal markers.

4- Detect any residual electric activity in the brain ( electro –   

      encephalography ).

The validity and  limitations of these  tests are discussed below.

 Tests  for demonstrating  absent blood flow:

I. Contrast medium angiography

  Throughout  the 1950 s and 1960 s neuroradiologists repeatedly showed the phenomenon of cerebral circulatory arrest . It was commonly found in patients with head injury, cerebral haemorrhage, or other structural brain lesions, particularly if there had been respiratory  complications. The basis of such a finding was the reduction of cerebral perfusion as a result of cerebral oedema or the loss of cerebrovascular  autoregulation, or both. Tentorial pressure cones also contributed .The main problem was that it was not uncommon for there to be  vertebral flow without carotid flow and vice versa it was also found that it was possible for there to be electroencephalographic activity after demonstration of “ absent cerebral circulation “ (26,27) Again the reduction  of intracranial pressure by removing a haematoma or by  hyperventilation and the administration of mannitol sometimes resulted in the restoration of blood flow.

The question was how “ blocked “ did the cerebral circulation have to be  before you could conclude that the whole brain was dead? In a review of the problem Bricolo  et al. reported patients with non- filling and silent electroencephalograms who had “ clear signs of cerebral life” and the reversal of no flow situations  after removal of a tumour or haematoma or hyperventilation(28) In infants and the newborn in whom the diagnosis of brain death is notoriously difficult digital subtraction angiography has been suggested. A report  indicates it may be of value in demonstrating lack of cerebral flow (29) Nevertheless, these techniques have considerable drawbacks and better methods are continually being sought (5)

II.Isotope angiography

       Isotope angiography ( radionuclide cerebral perfusion scintigraphy ) is based on the assumption that cerebral blood flow at levels too low to be detected by  this technique is insufficient to maintain the metabolic requirements of the brain. Radionuclide imaging has been shown in many studies to be capable of equaling conventional angiography of supratentorial structures, especially if technetium – 99 m hexamethy 1- propylenamine oxime ( 99 m Tc- HMPAO ) is used and the results have equated well with clinical evidence of brainstem death (30-33) .It should be noted that it was discovered at an early stage that isotope angiography was not suitable for demonstrating  the vertebrobasilar vasculature. Hence the demonstration of brainstem  blood flow could not be relied on with this technique . If studies  with single position emission computed tomography (SPECT) are carried out as well then flow in both infratentorial and supratentorial structures can be examined. Neverheless, in those studies where some residual flow coexisted with clinical evidence of brainstem areflexia, all patients developed asystole. The primary use of the tests is in "both the mitigation of uncertainty due to factors interfering with the clinical examination and  in expediting the correct diagnosis of brain death". However, the tests suffer from the same drawbacks as contrast angiography - raised intracranial pressure will interfere with the distribution  of  isotopes (5).

iii.    Transcranial doppler flow imaging

If arteries supplying the brain can be examined by ultrasonic means by using doppler techniques, flow through relevant Arteries should be assessable. It has been found that in "brain dead" patients there is absence or reversed diastolic flow or small early systolic spikes in more than one intracranial artery ^(34,35). Transcranial Doppler methods will show flow through the middle cerebral   and   basilar arteries.

iv. Magnetic resonance imaging

Flow sensitive gradient-echo sequences on magnetic resonance imaging (MRI) and demonstrate the absence of' flow in the cerebral circulation⁽³⁶⁾. The further place of^. this technique is still uncertain. As the scanners are not bedside instruments there are major logistical problems of moving ill patients and maintaining their ventilation in the confines of an MRI tube.

Brainstem auditory evoked potentials

The application of brainstem auditory evoked potentials has been the subject of a great deal of research. Much of this has been directed at efforts to determine levels of consciousness. This method has been widely studied in determining alterations in brainstem activity in, for instance, anaesthesia. It has the advantage of' being a bedside technique. In essence acoustic stimuli are applied and the resulting activity of the brainstem is recorded with modified electroencephalographic techniques. The pattern of waves on the tracing and the presence or absence of some or all waves are directly related to levels of brainstem activity. The results are not affected by sedative drugs so the technique can be used in those patients ⁱⁿ whom residual drug effects may be influencing diagnosis as when the administration of barbiturate is being used as part of the "treatment" of the cerebral condition. It is important to remember that previous deafness can render the test useless and that the presence of a petrous fracture must be excluded. This test is potentially useful (37,38). An investigation of 33 patients in Ankara with brainstem auditory evoked potentials and radionuclide and brain perfusion studies showed a close correlation in the results ⁽³⁹⁾. All those patients with absent brainstem auditory evoked potentials showed a "blocked cerebral circulation" and this, added to the clinical findings, resulted in a diagnosis of brain death. Similar results have been reported elsewhere ^(40). Anoxia may cause a reversible loss of brainstem auditory evoked potentials components  (41).

Metabolic and hormonal markers

Great efforts have been made to dertermine whether the presence or absence of various biochemical markers could be of value in the diagnosis of brain death: Thus thyrotropin releasing hormone may be used to demonstrate lack of thyrotropin and prolactin secretion in brain dead patients⁽⁴²⁾. It has been asserted that changes in levels of hypothalamic hormones, the presence or absence of glucose metabolism, and the production of excess lactate are relevant in determining brain death. Reduction in the concentration of antidiuretic hormone and the subsequent diabetes insipidus are a common occurrence in severe brain damage, but estimation of the concentrations of the relevant hormones has proved disappointing prognostically . like so many investigations  the results of  most of these tests are, at best, equivocal and require highly skilled interpreters(5)

The electroencephalogram:

The main argument about electroencephalogram is conceptual not just technical⁽⁵⁾ To what overall concept of death does it relate? To those who advocate brainstem death, its presence only reflects the activity of parts of the brain other than the brainstem. This makes it irrelevant⁽⁴³⁾ to them. On the other hand, those who insist upon "death of the whole brain find its presence relevant because it indicates viability of some parts of the brain above the brainstem reflecting the presence of residual sentience(44). Actually, we do not know what persisting EEG activity may  be  trying to tell us about continuing brain function at some  level – even, perhaps, about the persistence of something akin to consciousness ( however defined) in  some rudimentary from in some remote. Untestable, part of that most complex and truly wonderful organ. (45)