Journal of Taibah University Medical Sciences (2013) 8(1), 1–6

Taibah University

Journal of Taibah University Medical Sciences

www.sciencedirect.com

Editorial

Brain death: Criteria, signs, and testsq

Omar Hasan Kasule

Faculty of Medicine, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

Received 30 June 2012; revised 10 November 2012; accepted 14 December 2012

KEYWORDS Abstract Objective: This paper identified ethical issues relating to brain death and analyzed them
Brain death definition; according to the purposes of the Law, maqasid al shari’at, and principles of the law, qawa’id al fiqh,
Criteria; to reach conclusions of practical importance.
Guidelines; Methods: Issues arising in brain death were selected from articles retrieved from PUBMED over
Tests; a 10-year period. Practical and conceptual issues identified in the articles were analyzed using maqa-
Organ harvesting sid al shari’atand qawa’id al fiqh.
Results: Early determination of death by use of brain death criteria was motivated by the need to
harvest transplantation organs earlier, to save intensive care resources by earlier cessation of life
support, and to obtain tissues for research before deterioration. These motives would violate the
principle of intention which requires that actions be judged by underlying intentions and that the
end does not justify the means. In this case the nobility of the ends and their public interest were
overriding considerations. The requirements, by the principle of certainty, of evidence-based proof
of death were partially fulfilled by brain death criteria, tests, and examinations. The principle of cus-
tom was partially fulfilled because there was no universal consensus on criteria of brain death; the
criteria varied by country, by institution, and over time.
Conclusions and recommendations: Brain stem death, determined by clinical examination with or
without instrumental confirmation, should remain the mainstay of death definition. Legal rulings
on brain death should be reviewed every 3 years to take into consideration new developments in
medical knowledge and technology.
ª 2013 Taibah University. Production and hosting by Elsevier Ltd. All rights reserved.

Introduction dead. There is a need to determine a point on the timeline of

the death process that defines a point of no return after which
Death is a process with a time line and cannot be envisaged as the patient enters a rapid irreversible course to ultimate death.
a one-time event with 2 dichotomous states, dead and not Death in essence is failure of the cardio-respiratory system that
q
Presented at a joint physician-jurist seminar on brain death held in Riyadh on April 16, 2012.
Corresponding author: Faculty of Medicine, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia. Tel.: +966 12889037.
E-mail: omarkasule@yahoo.com
Peer review under responsibility of Taibah University.

Production and hosting by Elsevier

1658-3612 ª 2013 Taibah University. Production and hosting by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jtumed.2013.02.001
2 O.H. Kasule

transports chemical nutrients and oxygen needed for the con- as well as three principles of the Law qawa’id al fiqh6: the prin-
tinued life and metabolism of cells. The sensitivity of cells to ciple of motive, qa’idat al qasd, the principle of certainty,
oxygen deprivation varies; brain tissue is the most sensitive qa’idat al yaqiin, and the principle of custom, qa’idat al ‘aadat.
and its cells will die earlier that those of other tissues. When
the cardio-respiratory system fails to deliver enough oxygen Results
and nutrients to the brain, brain cells will die earlier that those
of the heart and blood vessels making brain death an earlier The underlying motives of brain death criteria
indicator of death than death of the cardiovascular and respi-
ratory systems. Death of the brain and its vital centers that
Underlying motives for defining legal death as brain death
control the respiratory and the cardiovascular systems leads
need to be recognized as required by the principle of intention,
to death of these two systems. We thus end up with a perfect
qa’idat al qasd, that states that matters are to be considered
cyclic chicken and egg situation. An exception to this scenario
according to their underlying intentions, al umuur bi maqasidi-
is brain death due to an electric shock1 or cranial trauma that
ha, and not the outward expression of objectives, al ‘ibrat fi al
destroys the brain directly.
maqasid wa al ma’aani la al alfaadh wa al mabaani (Al Majallat
From the earliest human history, three indicators of death
Articles No 2 & No 3). There was pressure to recognize brain
were known as failure of the vital systems of the body: neurolog-
death as the earliest indication of death as a legal definition of
ical, respiratory, and cardiac. Failure of the neurological system
death. The ethical problem arising from this pressure was that
was recognized as loss of consciousness or coma. The Qur’an de-
the outward and expressed purpose of using brain death crite-
scribed death of the neurological system in several verses as sak-
ria was divergent from the underlying motive. This pressure
rat al mawt,2 ghashiyat al mawt3 and ghamrat al mawt.4 Stopping
arose from three sources: organ transplantation, artificial life
of chest respiratory movements and lack of air exit from the nose
support, and research.
or mouth were indicators of respiratory failure. Lack of a heart
Organ transplantation teams want to declare death early to
beat or a pulse were considered indicators of cardiovascular
harvest organs from heart beating patients before organ dete-
failure. It was also known that loss of consciousness preceded
rioration due to increasing lack of oxygen and nutrients7,8 as
respiratory and cardiovascular failure. Modern recognition of
well as accumulation of toxic metabolic waste. The motivation
brain death as an early indicator of death is therefore not
of the 1968 Harvard criteria for brain death could have been
entirely new. Modern indicators of death are extensions and
procuring organs for transplantation.9 Acceptance of brain
refinements of these three using modern medical knowledge.
death as legal death enabled harvesting organs,10 made it easy
The ‘modern’ indicators are not static they keep changing with
for health care workers to make decisions related to organ
development of new technologies. New indicators are able to de-
donation,11 and encouraged families to consent to donation
tect the point of irreversible vital organ failure earlier. As new
if misconceptions were removed about brain death.12
knowledge and technology develop the point in time at which
The use of artificial life support systems deprived physicians
death can be pronounced is earlier than before.
of the use of cardio-respiratory arrest as a sign of death, leav-
The brain generally dies before other organs because it is
ing only brain death as the sole determinant. Physicians caring
very sensitive to injury and has no potential for recovery or tis-
for terminal patients would like to recognize death earlier so
sue replacement after severe injury. Irreversible death of the
that they do not waste resources on patients who are dying;
brain will in time result in the death of all other organs because
this is an important ethical consideration even if the family
the brain is the command, coordination, and communication
or the society were affluent and could afford such care.13 This
(C–C–C) center of the bodily functions. Without a functioning
partly explained the coincidence of the adoption of the brain
brain all bodily functions will in time disintegrate. The dilem-
death criterion with advances in artificial ventilation.14,10
ma of modern medical technology is that it can ‘take over’ the
Researchers especially those working on neural tissues
C–C–C functions of the brain by continuing bodily functions
would like to declare brain death earlier so that they can ob-
after death of the brain. This gives rise to many ethico-legal is-
tain organs and tissues for research before they deteriorate.15
sues the central one being the contrast between ‘supporting
life’ versus ‘a dead corpse with a beating heart’.
Brain death criteria
This paper will analyze current practice regarding the deter-
mination of brain death from the perspective of methodologi-
cal tools based on the purposes of the Law, maqasid al shari’at, Brain death criteria do not reach the level of absolute certainty,
and axioms of the Law, qawa’id al fiqh, and will derive general yaqiin, but could be considered to be predominant conjecture,
rules that can be applied to various situations of and changing ghalabat al dhann, for defining legal death. The first criteria were
criteria. published in 1968 under the title ‘A Definition of Irreversible
Coma’ in the Journal of the American Medical Association by
the Ad Hoc Committee of the Harvard Medical School. They
Materials and Methods defined a permanently non-functioning whole brain (irreversible
loss of function of the whole brain). The criteria given for brain-
Issues arising in brain death were selected from articles re- death syndrome were: apneic coma with no evidence of brain
trieved from PubMed over a 10 year period by using the key stem or spinal reflexes and a flat electroencephalogram over a
words: ‘brain death’ with ‘diagnosis’, ‘definition’, ‘determina- period of 24 h. The report implied that death was brain death
tion’, ‘guidelines’, ‘criteria’, ‘organ donation’. The practical and recommended withdrawal of life support. In 1973, brain
and conceptual issues identified in the articles were analyzed stem death was identified as the point of no return and the Uni-
using two purposes of the Law, maqasid al shari’at5: protection ted States Uniform Determination of Death Act was enacted
of life, hifdh al nafs, and protection of resources, hifdh al maal permitting organ procurement from heart-beating donors. The
 Brain death: Criteria, signs, and tests
Harvard criteria were controversial from the start until our day
raising the issue of uncertainty because according to the princi-
ples of the Law doubt does not void a certainty, al yaqiin la yazu-
ulu bi al shakk (Majallat Article No. 4). In this case life is a
certainty and brain death is a doubt.
Five objections to the Harvard criteria were raised.16 The
first was that brain death was not followed by disruption of
the integrity and coordination of the living organism. The sec-
ond was that the criteria of brain death could not pinpoint the
exact moment on the death time line when death occurs. The
third objection was that brain death criteria for a person with
a beating heart ignored psychosocial, cultural, and religious as-
pects of death. The fourth objection was that autopsy did not
consistently validate the brain death criteria by findings of irre-
versible brain stem ischemic injury or necrosis. The fifth objec-
tion was that the criteria could not distinguish among various
states on the spectrum that starts with coma through various
states of loss of consciousness (coma, akinetic mutism/
locked-in syndrome, minimally conscious state, vegetative
state) and ends with brain death.
There was consensus world-wide on the clinical signs of brain
stem death but no such consensus existed with regard to the cri-
teria of brain death or the confirmatory tests among different
countries and among institutions in the same country.10,17 Deci-
sions based on professional consensus have the force of law
according to the principle that custom is a basis for legal rulings,
al ‘aadat muhakkamat (Al Majallat Article No. 36). New knowl-
edge and development of new technologies result in frequent
revisions of guidelines of brain death determination and proce-
dures at the local, national, and even international levels.17,18
These changes are valid according to the principle that rulings
can change with time, la yunkar taghayyur al ahkaam bi tag-
hayyur al azmaan (Al Majallat Article No. 39).
Clinical determination of brain death
Clinical signs of brain stem death enjoyed a wide consensus
fulfilling the requirements of the principle of custom, qa’idat
al ‘aadat, that what is customary has the force of law, al ‘aadat
muhakkamat (Al Majallat Article No. 36) and also that what is
customary is what is widespread and dominant, innama yu’uta-
bar al ‘aadat idha atradat aw ghalabat (Al Majallat Article No.
41), wide spread and not rare, al ‘ibrat li al ghaalib al shai’u la
al naadir (Al Majallat Article No. 42). The uncertainty in clin-
ical signs may arise from deficient clinical experience of the
examiner or presence of confounding factors. In cases of
uncertainty, extra confirmatory tests have to be undertaken.
Also normally the examination is repeated after an interval
of time to confirm the initial findings.
In 1995 The American Academy of Neurology published
guidelines on determining brain death based on coma, absent
brainstem reflexes, and apnea, as well as the exclusion of
reversible confounders with ancillary tests being carried out
in case of uncertainty.19
The first step was to exclude causes of reversible coma or
unconsciousness that could be confused with brain stem death.
These included hypotension, hypothermia, drugs that depress
the nervous system, and metabolic disturbances.20 Presence
of drugs that depressed the central nervous system could be de-
tected using chromatographic methods21,22 but their elimina-
tion could be delayed requiring monitoring.23
3
The second step was to identify a plausible cause of brain
stem death. The clinical signs could not be interpreted cor-
rectly in the absence of knowledge of a possible cause of brain
death. Knowledge of such a cause enabled elimination of con-
founding causes of the signs such as intoxication, metabolic
alterations, major facial injury, infra-tentorial lesions, and cer-
vical spinal cord injury.24
The third step was to elicit clinical signs of brain stem
death: (1) Absence of pupillary reflexes (constriction of pupils
when light is shorn in them). (2) Fixedly-dilated pupils. (3) Ab-
sence of the corneal reflex (blinking when cornea is stimu-
lated). (4) Absence of eye movements. (5) Absence of the
orbicularis oculi or blink reflex when eyes are illuminated by
a strong light.25 (6) Absence of the vestibule-ocular reflex
which is absence of eye movement when the external auditory
meatus is flushed with 20 ml of ice cold water, (7) Absence of
motor response to stimulation in the area of cranial nerve dis-
tribution such as absence of grimacing on applying firm pres-
sure above the eye socket. (8) The apnea test (lack of
spontaneous respiration on disconnecting the respirator). (8)
Absence of cephalic reflexes, (9) Absence of motor response
to pain. (10) Absence of the cough reflex and the gag reflex
(coughing or gagging when a catheter is passed down the
airway).
The apnea test was based on the absence of spontaneous
respirations when carbon dioxide accumulated to a level that
should trigger respiration. The patient was made to breathe
oxygen and then the respirator was disconnected long enough
for carbon dioxide to accumulate in the lungs to trigger spon-
taneous breathing. Rather than relying on elapsed time, a spe-
cific level of pCO2 could be defined as the required stimulus for
triggering breathing.26 The apnea test was criticized because of
low sensitivity and specificity, causation of brain stem death
due to increased intra cranial hypertension/baropressure
caused by hypercabia,27 and other complications.28
Confirmation of brain death required a second examina-
tion after an interval that varied according to institution.
An argument in favor of early organ harvesting was that
the second examination was not necessary because empirical
research showed that none of those declared brainstem dead
ever recovered and the wait for the second examination was
associated with loss of organs and more refusals of organ
harvesting.29
Confirmatory instrumental tests of brain death
The primary diagnosis of brain death was based on clinical exam-
ination followed by confirmatory instrumental tests that were of
two kinds: measurement of brain electrical activity and measure-
ment of brain blood flow. These tests related to whole brain death
and were not specific for brain stem death. There were questions
about the diagnostic utility of these tests more and above those
of clinical tests. Using clinical criteria these tests might be false po-
sitive or false negative. The tests indicated brain death when path-
ologic studies still found viable brain tissue.30
Laboratory tests relied on chemical methods. One of these
tests was measurement of oxygen saturation in the cutaneous
jugular bulb.31
Neurophysiological tests depended on measuring electrical
activity of the brain. Electroencephalography (EEG)32 was
one of the earliest tests. It could be quantified as a range from
4 O.H. Kasule
isoelectric = 0 to fully awake = 100.33 Evoked potentials were
measurements of electrical activity after sensory stimulation
for example the auditory brain-stem responses (ABRs) and
somatosensory evoked potentials (SEPs).34 Monitoring of
brain stem evoked potentials over time in comatose patients
was more useful because their loss meant brain stem death.35
The trend and not the cessation of the auditory evoked poten-
tial might be more meaningful.36
Imaging techniques improved brain death diagnosis. Cere-
bral angiography was an invasive investigation that showed
cerebral circulatory arrest. Computed Tomographic Angiogra-
phy (CTA)37,38 was a non-invasive examination that indicated
cessation of blood circulation by showing pooling of blood in
cerebral blood vessels. Its reliability was questioned when com-
pared to EEG39 and it was observed to diverge from cerebral
angiography.40 Trans cranial Doppler was a cheap and easy
non-invasive bedside examination41 but its reliability varied
with time from brain death42 and there were debates about
its reliability.43 Other techniques used were: cerebral perfusion
scintillography,44 single photon computed tomography,45 and
magnetic resonance imaging.46
Discussions
The major purpose of the law relevant to brain death is protec-
tion of life, maqsad hifdh al nafs. It requires that death should
not be declared in a living person without evidence-based cer-
tainty because the declaration will be followed by measures
with irreversible consequences such as cessation of life support,
organ harvesting, and burial. Mistaken diagnosis has therefore
very severe consequences.
The purpose of protecting resources, maqsad hifdh al mal, is
fulfilled by earlier determination of death using brain death cri-
teria to stop expensive life support in the intensive care unit.
Costs related to long ICU hospitalization are direct such as
salaries and costs of equipment and supplies. There are indirect
costs to the family who have to leave their work and travel dai-
ly to the hospital. Since the protection of life takes precedence
over protection of resources, death cannot be declared on the
basis of expense of ICU care. It should be evaluated on its own
criteria. However once death is confirmed with certainty any
further ICU care is a waste of resources.
The principle of intention, qa’idat al qasd, states that ac-
tions are judged by their underlying motivation, al umuur bi
maqasidiha. The quest to define death as brain death has
underlying motives that may not be in the best interests of
the patient but may be in the interests of others. In ancient
times there was no pressure to recognize the earliest point in
time at which death occurred. In modern times there is pres-
sure to recognize death earlier to enable organ harvesting.
While the ultimate objective is noble, we should not violate
the principle that the ends do not justify the means, al wasail
laha hukum al maqasid47. The determination of death should
ethically be independent of other considerations like organ
harvesting, cost control, or research.
Organ harvesting was recognized as a major motivator for
early brain death diagnosis so that organs can be harvested be-
fore deterioration. Some observations cast doubt on this
assumption. Doubts were expressed about organ deterioration
for patients in the ICU48 and in any case active donor resusci-
tation could prevent or minimize the deterioration.49
The underlying motivations for adopting brain death crite-
ria had benefits for individuals who are recipients of organs.
They might have benefits for families who are saved paying ex-
tra expenses in ICU care. They might also have public interests
in saving health care resources or advance of medical knowl-
edge. Therefore rare errors in declaring death in an individual
could be mitigated by consideration of the public interest of
protecting the lives of many organ recipients by use of brain
death criteria. This is justified by the principle that individual
harm could be sustained to prevent public harm, yutahammal
al dharar al khaas li daf’e dharar ‘aam (Al Majallat Article
No. 26). Even in this situation we still have to face an ethical
issue of deception because outwardly death is declared on
the basis of brain death criteria but there is an unstated motive
of seeking organs for transplantation. If the motivation for
declaring brain death is under pressure from a known specific
organ recipient we may have a major ethical problem because
of causing potential harm to a donor to benefit a recipient
which would violate the principle that prevention of harm
has precedence over getting a benefit, dariu al mafasid awla
min jalbi al masaalih (Al Majallat Article No. 30).
The principle of certainty, qa’idat al yaqiin, requires that
recognition of death be based on clear evidence. The evidence
is facts that can be established by empirical observation. Inter-
pretation of the evidence to reach conclusions about the occur-
rence of death requires consideration of the evidence according
to consensus criteria. There are problems about reaching con-
sensus on the criteria.
The Harvard death criteria generated controversy since
they were first formulated. The objection that brain death
did not lead to disintegration of the body was difficult to test
in practice because normally patients were put on artificial life
support and there was no need for bran coordination of vital
functions. When the support was withdrawn the patient suc-
cumbed inevitably to death but at varying intervals depending
on the extent of the brain damage. The inability of the criteria
to pinpoint the exact moment on the death was conceptually
valid but was not relevant practically in an irreversible death
trajectory. The objection that the criteria ignored non-medical
aspects was a valid criticism of modern medical practice that is
based on the biomedical model and marginalizes psychosocial
and religio-cultural aspects. The marginalized aspects were vir-
tually impossible to operationalize but were taken care of when
the consent of the family is sought in decisions about organ
donation and withdrawal of life support. The fact that autopsy
findings did not always validate the criteria raised serious is-
sues about the certainty of brain stem death but a mitigating
factor was that in the experience of virtually all clinicians no
patient properly diagnosed as brain stem dead has ever re-
turned to normal life. The criteria were unable to distinguish
among various states on the spectrum that started with coma
through various states of loss of consciousness (coma,
akinetic mutism/locked-in syndrome, minimally conscious
state, and vegetative state) and ended with brain death. The
problem was that one of these states can be confused for brain
death.
A sixth objection that could be added is that the Harvard
criteria envisaged whole brain death and did not distinguish
between cerebral cortex (higher brain death) and brain stem
death. Cerebral death meant cessation of higher intellectual
functions with preservation of vital cardio-respiratory function
in what is called a vegetative state. The brain stem contained
 Brain death: Criteria, signs, and tests
the vital respiratory and circulatory centers and its death was
recognized as definitive death by a consensus of many jurists.
Brain stem death was easy to diagnose clinically but difficult
to confirm using instrumental confirmatory tests that de-
pended on whole-brain function.
According to the principle of custom, a professional con-
sensus on criteria of death and determination of death is leg-
ally binding, al ‘aadat muhakkamat (Majallat Article No. 36).
The condition is that this consensus be by a preponderant
majority of the professionals and not by a minority. It also
must have stood the test of time. In the situation of brain death
the consensus on clinical signs of brain stem death seems uni-
versal but the same consensus is not found for confirmatory
instrumental tests. This means that clinical tests will remain
a main stay of diagnosing brain stem death.
A sub principle of the principle of custom, that legal rulings
change with time, la yunkir taghayyur al ahkaam bi taghayyur
al azmaan (Majallat Article No. 39), is the basis for the legal
validity of changing definitions of death with developments
in medical knowledge and technology. The definition and cri-
teria of death change with new knowledge and new technolog-
ical capabilities. They also change according to underlying
motivations such the need to declare legal death early in order
to save artificial life support resources or to harvest organs for
transplantation. This sub principle allows for change of con-
sensus without condemning as wrong previous consensus.
We may speculate that it is possible that death of the brain
as measured using available technology today misses out on
other unknown functions of the brain that may continue after
its ‘perceived’ physical death.
Conclusions
The criteria and determination of brain death do not fully con-
form to principles of intention, certainty, and custom. Consid-
erations of organ harvesting, ICU costs and research have
been a driving force behind development of brain death crite-
ria. These criteria have been changing with development of
knowledge and technology and have not reached the level of
universal consensus having variation by country and by insti-
tution. There is consensus about the reliability of clinical tests
of brain stem death but there is no such consensus on the reli-
ability of the instrumental confirmatory tests.
Recommendations
Brain stem death should remain the mainstay of death defini-
tion notwithstanding the uncertainties that have been dis-
cussed above because the public interest inherent in organ
harvesting and saving ICU resources overcomes these con-
cerns. Legal rulings, fatwa, on brain death should be reviewed
every 3 years to take into consideration new developments in
medical knowledge and technology.
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