Brain
death
Introduction
For as long as medical practice has existed, the layperson has required
of medical practitioners that they be knowledgeable about death. For
centuries, laypeople and doctors alike have accepted cessation of respiration
and heartbeat as the classical signs of death. Advances in cardiopulmonary
resuscitation and modern mechanical ventilation have made obsolete the
traditional clinical definition of death with a small but significant harvest of
irreversibly brain-damaged patients. The worst form of such damage led to the
concept of ‘coma depasse’, first defined by Mollaret and Goulon in 1959. As
the number of patients with artificially maintained ventilation and circulation
increased, they became to be regarded as a potential source of donor organs.
These two developments occurred parallel to but independently of each other, and
the diagnosis of brain death did not arise because of the need for donor organs.
The
presence of an irreversibly damaged brain in a body in which ventilation and
circulation were being maintained by artificial means presented a state in need
of a definition. Mollaret and Goulon were the first to investigate this state in
their paper ‘Le coma depasse’. Many terms for this and other states for
which it has been mistaken have been suggested or used, of which the following
ate the most commonly encountered: cerebral death, brainstem death, brain death,
coma depasse, irreversible coma, cortical death, persistent vegetative state
and locked-in syndrome.
The
high cost of maintaining patients in intensive therapy units (ITUs) and the
premium on such limited resources has led significantly to the re-evaluation and
management of such states. Nursing and medical staff morale, as well as the emotional
toll on relatives, ate very real considerations. As these patients may now be
potential essential organ donors their care has acquired medicolegal and ethical
significance. It is not the primary task of a doctor to provide organs for
transplantation but neither is it to deny patients in need of transplant
surgery. Before a patient can be considered as having suffered irreversible
brain damage, it is mandatory that a positive diagnosis be made of the
pathogenesis of this damage. To produce coma, pathological processes must affect
the brain diffusely or encroach upon its deep central structures.
Three
major groups of lesions can be differentiated:
• suptatentotial lesions;
• infratentorial lesions;
• metabolic disorders — which widely depress or interrupt brain
function, including anoxia, ischaernia, infections, toxins and essential
deficiencies.
The
disintegration of function following progressive herniation will end in
cessation of spontaneous respiration leading to hypoxic cardiac arrest. If
ventilation and circulation are maintained artificially, the heart, kidneys
and liver may continue to function for some hours or days but after btainstem
death has occurred, cardiac arrest will follow within 2 weeks.
Since
Mollaret and Goulon, several committees and reviewers have sought to establish
unequivocal and appropriate clinical and EEG criteria for brainstem death based
on retrospective analysis of patients who died. The first was the Harvard group
who included EEG as part of their criteria. This was later deemed unnecessary by
both the Minnesota and British Groups. The latter are as follows.
Before
diagnosing brain death several preconditions should be satisfied:
• there should be no doubt that the patient’s condition is due
to irremediable brain damage of known aetiology (Fig.
• the patient should be in a coma on a ventilator because spontaneous
respiration has been inadequate or ceased altogether;
• conditions and drugs
which simulate brain death have to be excluded and, if necessary, drug levels
measured to ensure that there is no reversible cause for coma. Some drugs (e.g.
thiopentone) may take days to be cleared from the system.
Potentially reversible circulatory, metabolic and endocrine disturbances
must have been excluded as the cause for the continuation of unconsciousness. It
is recognised that circulatory, metabolic and endocrine disturbances are a
likely accompaniment of btainstem death (e.g. hypernatraemia and diabetes
insipidus) but these are the effect rather than the cause of that condition and
do not preclude the diagnosis.
The
tests should be performed by two physicians of not less than 5 years’
registration, who are not members of a transplant team and at least one of whom
is a consultant. The tests are designed to assess brainstem functioning as it is
the reticular activating system in the brainstem which is responsible for
activating the rest of the cerebrum.
2. There should be no corneal
reflex.
3. The vestibulo-ocular reflexes
should be absent. No eye movements should be observed while at least 50 ml of
cold water is infused over each eardrum. Clear access to the membrane must be
established by direct inspection.
4. No motor responses within the
cranial nerve distribution can be elicited by adequate stimulation of any
somatic area. There is no limb response to somatic pressure, bearing in mind
that movements mediated at a spinal level might still be possible.
5.
There is no gag reflex to
bronchial stimulation by a catheter placed down the trachea.
6. No respiratory movements appear
when the patient is disconnected from the mechanical ventilator. During this
test it is necessary for the arterial Cd2 to exceed the threshold for
respiratory stimulation, that is the PaCO2 should reach 6.65 kPa.
This should be ensured by measurement of the blood gases. The patient should
first be preoxygenated with 100 per cent 02 for 10 minutes (then with 5 per
cent CO2 in 02 for 10 minutes — if CO2 is available).
The ventilator should then be disconnected for 10 minutes while 6 litres per
minute 02 via a catheter is infused into the trachea.
If
no respiratory effort has been detected and other signs of brainstem dysfunction
have been demonstrated the patient may be considered brain dead.
Studies
of hundreds of patients in several countries have found that not a single body
displaying the criteria of brain death outlined gained any neurological
recovery. Despite full and repeated efforts at resuscitation all such reported
patients have suffered asystole within days or rarely weeks of the diagnosis.
Interestingly in 37 instances the EEG retained at least fragments of electrical
activity at a time when the patient was diagnosed as brain dead. In contrast to
this, Jennet has shown that of the patients surviving prolonged coma, none ever
met the criteria for brainstern death at any stage. Although not all agree, most
religious and ethical bodies have expressed themselves in sympathy with the
concept that death of the brain signifies death of the person. Pope Pius XII
proclaimed in 1958 that the pro- -nouncement of death was the responsibility of
the church, stating that when illnesses reached hopeless proportions, death
should not be medically opposed by extraordinary measures.
It
is imperative that conditions simulating brain death be excluded.
Drug
intoxication
CNS-depressant drug poisoning may cause total loss of cerebral function
and electrocerebral silence for more than 50 hours followed by complete
recovery. Self-induced drug poisoning often involves several drugs, frequently
in combination with alcohol. Toxicology screening is not always
Hypothermia
The core temperature tends to drop when the brainstem ceases to
function. That hypothermia may cause an isoelectric EEG is a theoretical
rather than a practical issue. What is important is that hypothermia should be
excluded as the cause rather than the result of the coma.
Electrical
injury
This may be an important cause of coma, apnoea and fixed pupils.
Brainstem
encephalitis
This is a rare form of encephalitis characterised by rapid
ophthalmoplegia, ataxia and areflexia with apnoea and coma in severe cases.
Although the clinical state may suggest brain death, these patients do not
comply with the basic prerequisite of an incontrovertible diagnosis and the
physician should be concerned with diagnostic and therapeutic measures rather
than speculating about irreversible coma.
Ancillary
tests
Ever since the concept of brain death arose, efforts have been made to
establish the diagnosis electrophysiologically, the reason being to seek an
objective nonclinical mode of diagnosis free of error or bias. These tests are
not available in all hospitals and those which have proved to be indisputable
indicators of brainstem death have usually occurred in patients in whom the
diagnosis was never in doubt. They are listed for completeness and not because
they replace clinical testing:
• EEG;
• scalp electrornyograms;
• evoked potentials;
• brainstem auditory evoked potentials;
• somatic evoked potentials;
• lower oesophageal contractility;
• arteriovenous 02 difference;
• cerebral blood flow;
• ocular microtremor.
There
is strong evidence that EEG silence for greater than 12 hours in a normothermic
patient having had no drugs is not compatible with neurological recovery.
Silverman reviewed 2560 isoelectric EEGs lasting for up to 24 hours. Only three
patients in this group, all of whom overdosed on CNS antidepressant drugs,
recovered cerebral function. Testing in an ITU setting is technically difficult
owing to interference. The presence of a few fragments of electrocerebral
activity is of dubious significance. Return of EEG activity after silence has
also been reported.
NB:
an EEG does not measure brainstem function. Drugs may cause coma with reversible
true electrocerebral silence.
Cessation
of cerebral blood flow in patients with raised ICP was first described by
Riishede and Ethelberg in 1953. It is a significant indicator of brain death
particularly where CT scanning is not available. It is caused by ICP rising
above the MAP and by progressive vascular obstruction caused by autolysis in
respirator brain (Fig. 35.49).
Ocular
microtrernor is one of three fixational eye movements measured using the
isoelectric strain gauge technique and is an indicator of brainstem activity.
Studies by Coakley and Bolger (1999) have shown that this tremor is absent in
patients with the diagnosis of brainstem death.
If
the viability of certain organs is to be maintained for possible harvesting,
mechanical ventilation can be continued and the circulation artificially
supported with a clear understanding, however, that these measures are not
therapeutic but continued in order to maintain a cadaver in a perfused state. A
member of the transplantation team is summoned and all further medical and
administrative care of the potential donor should be carried out by them. The
request for organ donation must come from the transplant team and not those
treating the primary pathology. The staff taking care of the patient declining
to brain death have a special responsibility towards the relatives who are
going through a very harrowing time. For the layperson it is still a macabre
concept to speak of death of a person in whom the heart is still beating.