Journal of Taibah University Medical Sciences (2013) 8(1), 16

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
Brain death denition;
Criteria;
Guidelines;
Tests;
Organ harvesting

Abstract Objective: This paper identied ethical issues relating to brain death and analyzed them
according to the purposes of the Law, maqasid al shariat, and principles of the law, qawaid al qh,
to reach conclusions of practical importance.
Methods: Issues arising in brain death were selected from articles retrieved from PUBMED over
a 10-year period. Practical and conceptual issues identied in the articles were analyzed using maqasid al shariatand qawaid al qh.
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 fullled by brain death criteria, tests, and examinations. The principle of custom was partially fullled 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 conrmation, should remain the mainstay of death denition. Legal rulings
on brain death should be reviewed every 3 years to take into consideration new developments in
medical knowledge and technology.
2013 Taibah University. Production and hosting by Elsevier Ltd. All rights reserved.

Introduction
Death is a process with a time line and cannot be envisaged as
a one-time event with 2 dichotomous states, dead and not

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

the death process that denes a point of no return after which
the patient enters a rapid irreversible course to ultimate death.
Death in essence is failure of the cardio-respiratory system that

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 2013 Taibah University. Production and hosting by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jtumed.2013.02.001

O.H. Kasule

transports chemical nutrients and oxygen needed for the continued life and metabolism of cells. The sensitivity of cells to
oxygen deprivation varies; brain tissue is the most sensitive
and its cells will die earlier that those of other tissues. When
the cardio-respiratory system fails to deliver enough oxygen
and nutrients to the brain, brain cells will die earlier that those
of the heart and blood vessels making brain death an earlier
indicator of death than death of the cardiovascular and respiratory systems. Death of the brain and its vital centers that
control the respiratory and the cardiovascular systems leads
to death of these two systems. We thus end up with a perfect
cyclic chicken and egg situation. An exception to this scenario
is brain death due to an electric shock1 or cranial trauma that
destroys the brain directly.
From the earliest human history, three indicators of death
were known as failure of the vital systems of the body: neurological, respiratory, and cardiac. Failure of the neurological system
was recognized as loss of consciousness or coma. The Quran described death of the neurological system in several verses as sakrat al mawt,2 ghashiyat al mawt3 and ghamrat al mawt.4 Stopping
of chest respiratory movements and lack of air exit from the nose
or mouth were indicators of respiratory failure. Lack of a heart
beat or a pulse were considered indicators of cardiovascular
failure. It was also known that loss of consciousness preceded
respiratory and cardiovascular failure. Modern recognition of
brain death as an early indicator of death is therefore not
entirely new. Modern indicators of death are extensions and
renements of these three using modern medical knowledge.
The modern indicators are not static they keep changing with
development of new technologies. New indicators are able to detect the point of irreversible vital organ failure earlier. As new
knowledge and technology develop the point in time at which
death can be pronounced is earlier than before.
The brain generally dies before other organs because it is
very sensitive to injury and has no potential for recovery or tissue replacement after severe injury. Irreversible death of the
brain will in time result in the death of all other organs because
the brain is the command, coordination, and communication
(CCC) center of the bodily functions. Without a functioning
brain all bodily functions will in time disintegrate. The dilemma of modern medical technology is that it can take over the
CCC functions of the brain by continuing bodily functions
after death of the brain. This gives rise to many ethico-legal issues the central one being the contrast between supporting
life versus a dead corpse with a beating heart.
This paper will analyze current practice regarding the determination of brain death from the perspective of methodological tools based on the purposes of the Law, maqasid al shariat,
and axioms of the Law, qawaid al qh, and will derive general
rules that can be applied to various situations of and changing
criteria.
Materials and Methods
Issues arising in brain death were selected from articles retrieved from PubMed over a 10 year period by using the key
words: brain death with diagnosis, denition, determination, guidelines, criteria, organ donation. The practical
and conceptual issues identied in the articles were analyzed
using two purposes of the Law, maqasid al shariat5: protection
of life, hifdh al nafs, and protection of resources, hifdh al maal

as well as three principles of the Law qawaid al qh6: the principle of motive, qaidat al qasd, the principle of certainty,
qaidat al yaqiin, and the principle of custom, qaidat al aadat.
Results
The underlying motives of brain death criteria
Underlying motives for dening legal death as brain death
need to be recognized as required by the principle of intention,
qaidat al qasd, that states that matters are to be considered
according to their underlying intentions, al umuur bi maqasidiha, and not the outward expression of objectives, al ibrat al
maqasid wa al maaani la al alfaadh wa al mabaani (Al Majallat
Articles No 2 & No 3). There was pressure to recognize brain
death as the earliest indication of death as a legal denition of
death. The ethical problem arising from this pressure was that
the outward and expressed purpose of using brain death criteria was divergent from the underlying motive. This pressure
arose from three sources: organ transplantation, articial life
support, and research.
Organ transplantation teams want to declare death early to
harvest organs from heart beating patients before organ deterioration due to increasing lack of oxygen and nutrients7,8 as
well as accumulation of toxic metabolic waste. The motivation
of the 1968 Harvard criteria for brain death could have been
procuring organs for transplantation.9 Acceptance of brain
death as legal death enabled harvesting organs,10 made it easy
for health care workers to make decisions related to organ
donation,11 and encouraged families to consent to donation
if misconceptions were removed about brain death.12
The use of articial life support systems deprived physicians
of the use of cardio-respiratory arrest as a sign of death, leaving only brain death as the sole determinant. Physicians caring
for terminal patients would like to recognize death earlier so
that they do not waste resources on patients who are dying;
this is an important ethical consideration even if the family
or the society were afuent and could afford such care.13 This
partly explained the coincidence of the adoption of the brain
death criterion with advances in articial ventilation.14,10
Researchers especially those working on neural tissues
would like to declare brain death earlier so that they can obtain organs and tissues for research before they deteriorate.15
Brain death criteria
Brain death criteria do not reach the level of absolute certainty,
yaqiin, but could be considered to be predominant conjecture,
ghalabat al dhann, for dening legal death. The rst criteria were
published in 1968 under the title A Denition of Irreversible
Coma in the Journal of the American Medical Association by
the Ad Hoc Committee of the Harvard Medical School. They
dened a permanently non-functioning whole brain (irreversible
loss of function of the whole brain). The criteria given for braindeath syndrome were: apneic coma with no evidence of brain
stem or spinal reexes and a at electroencephalogram over a
period of 24 h. The report implied that death was brain death
and recommended withdrawal of life support. In 1973, brain
stem death was identied as the point of no return and the United States Uniform Determination of Death Act was enacted
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 principles of the Law doubt does not void a certainty, al yaqiin la yazuulu 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
rst was that brain death was not followed by disruption of
the integrity and coordination of the living organism. The second 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 aspects of death. The fourth objection was that autopsy did not
consistently validate the brain death criteria by ndings of irreversible brain stem ischemic injury or necrosis. The fth objection 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 criteria of brain death or the conrmatory tests among different
countries and among institutions in the same country.10,17 Decisions 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 knowledge and development of new technologies result in frequent
revisions of guidelines of brain death determination and procedures 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 taghayyur al azmaan (Al Majallat Article No. 39).
Clinical determination of brain death
Clinical signs of brain stem death enjoyed a wide consensus
fullling the requirements of the principle of custom, qaidat
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 yuutabar al aadat idha atradat aw ghalabat (Al Majallat Article No.
41), wide spread and not rare, al ibrat li al ghaalib al shaiu la
al naadir (Al Majallat Article No. 42). The uncertainty in clinical signs may arise from decient clinical experience of the
examiner or presence of confounding factors. In cases of
uncertainty, extra conrmatory tests have to be undertaken.
Also normally the examination is repeated after an interval
of time to conrm the initial ndings.
In 1995 The American Academy of Neurology published
guidelines on determining brain death based on coma, absent
brainstem reexes, and apnea, as well as the exclusion of
reversible confounders with ancillary tests being carried out
in case of uncertainty.19
The rst 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 detected using chromatographic methods21,22 but their elimination could be delayed requiring monitoring.23

The second step was to identify a plausible cause of brain

stem death. The clinical signs could not be interpreted correctly in the absence of knowledge of a possible cause of brain
death. Knowledge of such a cause enabled elimination of confounding causes of the signs such as intoxication, metabolic
alterations, major facial injury, infra-tentorial lesions, and cervical spinal cord injury.24
The third step was to elicit clinical signs of brain stem
death: (1) Absence of pupillary reexes (constriction of pupils
when light is shorn in them). (2) Fixedly-dilated pupils. (3) Absence of the corneal reex (blinking when cornea is stimulated). (4) Absence of eye movements. (5) Absence of the
orbicularis oculi or blink reex when eyes are illuminated by
a strong light.25 (6) Absence of the vestibule-ocular reex
which is absence of eye movement when the external auditory
meatus is ushed with 20 ml of ice cold water, (7) Absence of
motor response to stimulation in the area of cranial nerve distribution such as absence of grimacing on applying rm pressure above the eye socket. (8) The apnea test (lack of
spontaneous respiration on disconnecting the respirator). (8)
Absence of cephalic reexes, (9) Absence of motor response
to pain. (10) Absence of the cough reex and the gag reex
(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 spontaneous breathing. Rather than relying on elapsed time, a specic level of pCO2 could be dened as the required stimulus for
triggering breathing.26 The apnea test was criticized because of
low sensitivity and specicity, causation of brain stem death
due to increased intra cranial hypertension/baropressure
caused by hypercabia,27 and other complications.28
Conrmation of brain death required a second examination 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
Conrmatory instrumental tests of brain death
The primary diagnosis of brain death was based on clinical examination followed by conrmatory instrumental tests that were of
two kinds: measurement of brain electrical activity and measurement of brain blood ow. These tests related to whole brain death
and were not specic 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 positive or false negative. The tests indicated brain death when pathologic 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 quantied as a range from

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 potential might be more meaningful.36
Imaging techniques improved brain death diagnosis. Cerebral angiography was an invasive investigation that showed
cerebral circulatory arrest. Computed Tomographic Angiography (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 compared 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 protection of life, maqsad hifdh al nafs. It requires that death should
not be declared in a living person without evidence-based certainty 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
fullled by earlier determination of death using brain death criteria 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 daily 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 conrmed with certainty any
further ICU care is a waste of resources.
The principle of intention, qaidat al qasd, states that actions are judged by their underlying motivation, al umuur bi
maqasidiha. The quest to dene 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 pressure 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 before 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 resuscitation could prevent or minimize the deterioration.49

The underlying motivations for adopting brain death criteria had benets for individuals who are recipients of organs.
They might have benets for families who are saved paying extra expenses in ICU care. They might also have public interests
in saving health care resources or advance of medical knowledge. 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 justied by the principle that individual
harm could be sustained to prevent public harm, yutahammal
al dharar al khaas li dafe 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 specic
organ recipient we may have a major ethical problem because
of causing potential harm to a donor to benet a recipient
which would violate the principle that prevention of harm
has precedence over getting a benet, dariu al mafasid awla
min jalbi al masaalih (Al Majallat Article No. 30).
The principle of certainty, qaidat al yaqiin, requires that
recognition of death be based on clear evidence. The evidence
is facts that can be established by empirical observation. Interpretation of the evidence to reach conclusions about the occurrence of death requires consideration of the evidence according
to consensus criteria. There are problems about reaching consensus on the criteria.
The Harvard death criteria generated controversy since
they were rst formulated. The objection that brain death
did not lead to disintegration of the body was difcult to test
in practice because normally patients were put on articial life
support and there was no need for bran coordination of vital
functions. When the support was withdrawn the patient succumbed 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 virtually 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
ndings did not always validate the criteria raised serious issues 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 returned 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 denitive death by a consensus of many jurists.
Brain stem death was easy to diagnose clinically but difcult
to conrm using instrumental conrmatory tests that depended on whole-brain function.
According to the principle of custom, a professional consensus on criteria of death and determination of death is legally 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 universal but the same consensus is not found for conrmatory
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 denitions of death with developments
in medical knowledge and technology. The denition and criteria of death change with new knowledge and new technological capabilities. They also change according to underlying
motivations such the need to declare legal death early in order
to save articial life support resources or to harvest organs for
transplantation. This sub principle allows for change of consensus 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 conform to principles of intention, certainty, and custom. Considerations of organ harvesting, ICU costs and research have
been a driving force behind development of brain death criteria. 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 institution. There is consensus about the reliability of clinical tests
of brain stem death but there is no such consensus on the reliability of the instrumental conrmatory tests.

2.
3.
4.
5.
6.
7.

8.

9.
10.
11.

12.

13.

14.

15.

16.

17.
18.

19.
20.

Recommendations
Brain stem death should remain the mainstay of death denition notwithstanding the uncertainties that have been discussed above because the public interest inherent in organ
harvesting and saving ICU resources overcomes these concerns. Legal rulings, fatwa, on brain death should be reviewed
every 3 years to take into consideration new developments in
medical knowledge and technology.

21.

22.

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