Introduction: Brain death is a conept which is in present seen from multiple angles in the medical practice having more definitions. The clear definition and the establishing the medical teams which are involved from medical, legal and ethic point of view.

Objectives: We want to highlight the different definition of brain death, to see the existent protocols existing in the world toward the brain death, as also the organ donation this involving multidisciplinary teams.

Material and methods: We read the existing literature in Romania in this field and in the existing publications in the world.

Discutions: The brain death is a diagnostic, and death must be understood as a progressing proces in wshich are involved more organs which are loosing their functions.

Conclusions: Brain death must be seen in multidisciplinary teams in which are involved neurologists, neurophysiologists, intensive care specialists, and other specialities beeing an improtant border for the families, doctors and society.

Brain death in children is a diagnosis more rarely met in our hospitals.It’s a diagnosis wich will be routinelly met in our hospitals where are trained multidisciplinary teams to determine it.

At the one hand the methods of resuscitation and vital support experienced a higher explosion and the patient can be maintained in life and brought back to life (sometimes with subsequent very good functional parameters) in longer or shorter time, and on the other hand the patient can save lifes trough organ donation. That’s why the responsibility of the persons which are formulating this diagnosis is very high and we try to present the existing protocols in this field.

The death of a human being, defined in a biological point of view, is not instantly but it is an evolutionary process during which various organs are losing their functions and which is finished when the cells of the hole body cease irreversibly to function. (12) Although death is accepted as a process, society is requiring doctors not only to confirm the biological death of a patient but also to establish the exact hor of the event. (12)

In the hospitals with great adressability neurologists are formulating this diagnosis 25-30 times/year. (1) It exists a great difference between severe brain injury and cerebral death. (2)

The incidence of cerebral death in the intensive care unit at greater children is 0,6-1,2% from the hospitalised children. In one study cerebral death represented 31,4% from all deaths of children more than one month old and 6,3% from the deaths of the newborn. (2)

In 1987 were established the guidelines for the determination of brain death in children and wre published by a task force. (9) The first nation which defined brain death legally was Finland in 1971. (8)

In 1564 Versalius a famous anatomist was required to lead an autopsy at a noble which was before his patient. This autopsy was in the presence of a great assistance formed by the citizens from the town and when the thorax of the noble was opened the heart was beating toward. After this event Versalius needed to move from Spain. This and other episodes like this were necessary to for the doctors to elaborate the criteria of defining death.(8)

Cerebral death is defined when there are not existing clinically any more functions of the brain and the brainstem.(8) The bain of a patient is in cerebral death is an organ which has lost all its neurological functions. Despite this some specific neurological functions (for instance the neuroendocrine) can persist for a short time. (12)

But for to demonstrate that the brain is in cerebral death there were supplementary investigations like:

• Electroencephalograme
• Multimodal evoked potentials
• Transcranian Eco-Doppler
• 4 vessels Arteriogrphy
• Studies with radioactive contrast substances (12,8)
• IRM (10)

The determination of brain death is infrequent done in the emergency department. Ideal criteria for brain death are including the following:

1. Normotermia
2. The cause of the brain death
3. Non-responsiveness (the absence of responses)
4. The absence of brain stem responses
5. Apneea (10)

After Zota, (12) we have:

Preliminary criteria and premises necessary for the establishment of the diagnosis of brain death:

1. Preliminary condition: coma of unknown etiology
2. Necessary premises:

• Normal medium arterial blood pressure
• Absent of severe hypotermia ( temperture of the body > 35 Celsius degrees )
• The absence of the effects nerodepressing medication
• The absence of the effects of neuromuscular blockers
• The absence of the effects of anticholinergic medication

a. It’s essential to exclude all the factors which could affect the pacient like induced hypotermia ( brain death is often associated with spontaneous hypotermia )

b. The anterior administration of antidepressants and neuromuscular blockers. It’s important to mention that the administration of benzodiazepines (e.g. midazolam), barbiturates (thiopental, fenobarbital) anticholinergic drugs (atropine), neuromuscular blockers can determine a similar symptomatology to cerebral death. In the case of the medication that can be antagonised, it’s recomended to give the antagonic medication (flumazemil for example). It is waited until the medication make his effect and is eliminated.

c. In the case of doubts are recommended functional explorations: investigations which must certify the cessation of cerebral activity ( conventional arteriography, cerebral scanning with isotopes, Doppler transcranial ultrasonography) and/or multimodal evoked potentials. ( 12 )

When declaring brain death it’s important to coexist coma with apneea. (9). When we have doubts in establishing the criteria of brain death it is recommended to extend the evaluations to 24-48 hours (9). For children the protocols for different ages are separated in evaluations for the children age under 1 year and the children aged between 1-18 years (9).

In USA, in children, as cause of brain death the child abuse is more frequent then motor vehicle accidents and asfixic events (1).

The raised intracranial pressure higher than the medium blood pressure is incompatible with life (1). All the reversibile causes of coma must be excluded including hypotermia ( core temperature lower than 33 Celsius degrees), drug intoxication, hypotension, neuromuscular blockade, and sedative medication (8).

The cascade of brain death: Neuronal injury – the swelling of neurons – raised intracranial pressure – decreased intracerebral perfusion (1). The children found in brain death develop in proportion of 38-88% central diabetes insipidus due to the distruction of the neurons from the hypothalamus (5).

The cerebral death due to meningitis is seen in children which develop rapidly cerebral oedema and the onset of herniation in 12-24 after hospitalisation (2). Other causes of brain death include rare metabolic diseses, perioperative lesions of the CNS and acute obstructive hydrocephalia. (2)

President’s Commission – Determination of Cerebral Death (5)

An individual with irreversible cessation of all functions of the entire brain, including the brain stem, is dead if the following are true:

• Cessation of all brain function is recognized
• Cerebral functions are absent (ie, unresponsiveness)
• The following brainstem functions are absent: pupillary light reflex, corneal reflex, oculocephalic/oculovestibular reflex, oropharyngeal reflex, and respiratory (apnea using an accepted apnea testing procedure)
• Irreversibility of brain function cessation is recognized
• The cause of coma is established and is sufficient to account for the loss of brain function
• The possibility of recovery of any brain function is excluded
• Cessation of brain function persists for an appropriate period of observation or trial of therapy
• Complicating conditions are excluded, such as the following: drug and metabolic intoxication, hypothermia, age younger than 5 years, and circulatory shock
• The patient has been monitored for an appropriate observation period
• Without confirmatory tests: (1) 12 hours when the etiology of the irreversible condition is well established or (2) 24 hours for anoxic injury to the brain

With confirmatory tests (may reduce the observation period): (1) EEG: irreversible loss of cortical functions with electrocerebral silence (ECS), together with the clinical findings of absent brainstem functions, confirms the diagnosis of brain death; (2) cerebral blood flow (CBF): absent CBF demonstrated by radionuclide scanning or intracranial 4-vessel cerebral angiography in conjunction with clinical determination of absence of all brain function for at least 6 hours is diagnostic of brain death (5)

The Protocole of the Clinic Exam elaborated to confirm the Brain Death after Zota (12)

Non-responsiveness means the absence of reponse to any applied stimulus (score from 3 on the Glasgow Coma Scale). The presence of the withdrawal reflexes typically found at the lower extremities, do not hinder the diagnosis of brain death as the withdrawal reflexes can be spinal mediated (10)

Pupilar reflexes

Are more difficult to be tested at neonates and for children in incubator, due to corneal lesions, retinal hemorrhages and other anatomic factors likelocal swelling of the eyelides or partial fusion of the eyelids.

Corneal reflex

Although the corneal reflex is the easiest to examine brain stem reflex, is often the least reliable in newborn and infants. The contact irritations, corneal dehydration and maceration as the use of lubricating drops, eyes glued patches that are put when doing phototherapy when combat hyperbilirubinemia, the use of local analgesics, affects often the surface sensitive endings of the cornea and adversely affect the test. However it is important to test it, because its presence indicates thekeeping of the brain stem function.

Oculocephalic reflex

It is revealed by rapid an vigorous return at 90 degrees on both sides of the head. The normal response is with the deviation of the eyes on the opposite side from the side on which the head is turned. In brain death the oculocephalic reflex are absent and eye movements do not occur in response to movement of the head (8).

Vestibuloocular reflex

It is revealed by raising the head at 30 degrees and the irrigation of both tympanic membranes with 50 ml of salt water or clean water: in brain death the vestibuloocular reflexes are absent and there not appears any eye deviation in response to the irrigation of the inne ear (8).

The apneea test

The normal physiological treshold for the apneea test ( the minimal carbon dioxide pressure at which respiration starts ) for children is considered the same as that in adults ( PCO2 greater than 60 mm Hg ). Testing technique for apneea is similar in children like that in adults using apneic oxygenation after disconnecting from the device (2).

EEG

The term electrocerebral inactivity (ECI) is often used instead of ECS electrocerebral silence (5). The registration of EEG for 30 minutes wth amplification characteristics of 2 microV/mm, frequency bands between 0,3-30 Hz, electrodes placed at least 10 cm from each other, situated in the frontal, temporal, occipital and prietal region associated with painful stimulation of the patient will show whether there are brain electrical activity (12).

Data suggest that the EEG and the cerebral blood flow tests are of similar value. The cerebral radionucleotide testing of the cerebral flow are techniques with a more extensive use replacing EEG as a complementary test in newborns and infants (9).

The interval between two examinations EEG differ by age, at children aged between 7 days – 2 months the interval between two examinations EEG must be 48 hours, and at a child aged between 2 months -1 year this inteval must be 24 hours (5,2,9).

Evoked potentials

Can be useful as confirmatory tests. Auditory evoked potentials mus demonstrate the VIII-th nerve conduction (wave I ) and it is necessary to demanstrate for the evaluation of other responses of the brain stem (wave II-VII ). Wave II can be present in brain death because it can originate in the proximal end of the auditory nerve (5).

Four-vessel cerebral angiography

Is the gold standard for determining absence of CBF. This test can be difficult to perform in infants and small children, may not be readily available at all institutions, and requires moving the patient to the angiography suite potentially increasing risk of exacerbating hemodynamic and respiratory instability during transport of a critically ill child outside of the intensive care unit (9).

In hypoxic-ischemic encephalopathy need to monitoring is a 24 hours minim interval (5). In particular pathologies like perpheric acute fulminating polineuropathies as acute inlammatory demyelinating poliradiculopathy and botulismus are necessary confirmatory tests with EEG and tests demonstrating the existence of the cerebral blood flow (5).

It is important to identify the patients which, due their neurological status, are evolving to brain death. Classification of the degree of coma on the Glasgow scale represent an excellent marker of the neurological status and can be usefull for the determination of the prognosis of the patient to brain death especially when the GCS is or lowe than 5 (11).

In the long periods of electric inactivity observed on the brains in which then electrical activity reappears it might be due to loss of connections between neurons. One type of coma like the coma described in new experiments can protect better the neuronal tissue, maintaining a minimal activity in the brain.

The researchers reproduced profound coma on cats with medication, and after the cats were brought in coma with isoelectric line, increasing the doses of the used medication the researchers found the recurrence of a new type of electrical cerebral activity (3). The impulses originate in the hippocampus. This impulses generated in the hippocampus have reverberated and spread out to other cerebral structures (4).

Long periods of brain deth were studied for example on a child 3 months old and which has had the criteria for pediatric brain death established in 1987 by the Task Force, but he presented 2-3 irregular breaths after the 43-th day of hospitalisation and the death occured in the 71-th day from hospital admission. The question is if this irregular breaths can be considered a return of the respiratory function and if it can be considered an „improvement” in the absence of other brain stem functions (2).

Allowing the families to be present during the clinical exam for the diagnosis of brain death, as also to the apneea testing and to the confirmatoy tests for brain death are methods for the family support which such will understand that their child’s death occured (9).

Qualified clinicians include: pediatric intensivists and neonatologists, pediatric neurologists and neurosurgeons, pediatric trauma surgeons, and pediatric anesthesiologists with critical care training. (9)

Brain death is a diagnosis which have not to be made any too hasty but also not long-winded existing multiple medical, ethic, economic, social and cultural implications, the correct approach to it reflecting the maturity and the professionalism of the medical staff.

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