THROUGHOUT THE WORLD
EELCO F.M. WIJDICKS
ry criteria of death is a fascinating chapter in the history of medicine and
neurology . This paradigm change came when patients with an acute
brain injury could be resuscitated in emergency departments and inten-
sive care units and survived. Apnea would not lead to asystole and the
brain lesion could go on to further cause catastrophic damage while the
rest of the body was artificially supported. In most cases this resulted in
development of brain edema, shift, and eventually massive increase in
intracranial pressure that would stop the blood flow at the entrance of the
skull base. This would then result in total necrosis of the brain. In other
situations, brain and brainstem would become destroyed directly (e.g.,
Pathologists noted a necrotic brain never seen before (‘respirator brain’)
but there was no good clinical correlate, only fragmentary observations. Most
likely, an isoelectric EEG was the first clinical observation that the brain has
lost its function – ‘Isoelectric EEG with a Heartbeat’ . The recognition of
loss of all brainstem reflexes including apnea was first described in a com-
prehensive manuscript by Mollaret and Goulon . This paper was hardly
noticed at the time, but should now be considered a landmark paper. It was
followed almost 10 years later by ‘the Harvard Criteria’ written by an Ad Hoc
committee in 1968, consisting of representatives of several Harvard schools.
Symposia were organized in Sweden, the United Kingdom, and Australia
that tried to formulate brain death on the basis of neurologic criteria. Brain
death examination became a prerequisite to allow organ donation and its
concept has been fully accepted. However, until recently, it was largely
unknown how brain death criteria had been codified in different parts of the
world. In this paper, I will discuss the results of a recent survey .
The views expressed with absolute freedom in this paper should be understood as
of Sciences. The views expressed in the discussion are those of the participants and not
necessarily those of the Academy.
The Signs of Death
Pontifical Academy of Sciences, Scripta Varia 110, Vatican City 2007
The Harvard Committee, appointed by the Dean of the Harvard
Medical School and chaired by anesthesiologist Henry Beecher included
multiple specialties including a transplant surgeon and transplant immu-
nologist . Their presence has been criticized by some and conflict of
interest has been suggested. The guideline was written mostly by the neu-
rologists Schwab and Adams, who in only a few drafts within four
months completed an important document that included neurologic eval-
uation of the patient with no brain function. There was a desire to pro-
duce a brief but succinct document but also to work swiftly because of a
pressing need in the community to provide guidelines. The transplant
physicians commented on this document but left the final say to the neu-
rologists. The document was also important because for the first time it
clearly mentioned the confounding effect of CNS depressants and
hypothermia. The Harvard criteria remain an example of simplicity.
The criteria were as follows.
1. Unreceptivity and unresponsivity.
2. No movements or breathing.
3. No brainstem reflexes.
4. Flat electroencephalogram.
5. With all of tests repeated at least 24 hours with no change and
exclusion of hyperthermia (below 90° degrees F or 32.2 °C) or central
nervous system depressants.
There have been modifications to the clinical examination of the brain dead
patient. Undoubtedly, the influential paper by the Harvard Ad Hoc Committee
has been the basis of many hospital policies throughout the United States of
A few years later, the conference of Medical Royal College in the United
Kingdom further defined criteria by describing further details on brainstem
examination and determined a target for PaCO
to assess breathing drive.
part of the brain to be tested and lead to the term ‘brainstem death’. It is
noticeable that the somewhat subtle differences between the UK and the
US criteria permeate throughout the world, particularly in those countries
that were prior colonies of the UK (eg. India) . Much of the work on brain
stem death in the United Kingdom should be credited to Pallis .
EELCO F.M. WIJDICKS
Brain Death Criteria throughout the World
I had the opportunity to survey the brain death throughout the world.
Through helpful neurologists and neurosurgeons and other physicians, I
was able to obtain the original brain death documents of 80 countries
throughout the world, representing all major continents (Table 1). There is
global acceptance of the concept of brain death. There are no concerns with
the validity of the concept and physicians all over the world recognize –
without a scintilla of doubt – that when the clinical criteria of brain death
are met, the patient has died. However there were major differences in the
technical procedures used to arrive at the clinical diagnosis. No major dif-
ferences were noted when the methods of examination of brainstem reflex-
es were compared with each other; but there were marked differences in
how the apnea test was performed. The presence of apnea using a PaCO
target value was used in only 59% of all guidelines. In others, preoxygena-
sufficient. There was no evidence that the insufficient apnea testing was a
result of failure to obtain timely arterial blood gasses or a general reluc-
tance to do the test. In Central and South America countries, a large pro-
portion of patients were either examined with disconnection from the ven-
tilator only, or criteria or guidelines for the apnea test were not present.
This is potentially concerning because apnea can only be determined after
United States of America
Central and South America
mally stimulates the respiratory centers. Ten minutes disconnection in a
patient with a baseline hypocarbia (not uncommon after induced hyper-
ventilation for increased ICP) could potentially show apnea with a PaCO
not reaching a target value.
nificantly throughout the world. In 44%, one physician was required
(including Canada); 34%, 2 physicians; and 16%, more than two physi-
cians. In 6%, the number of physicians was not specified. Confirmatory
tests were required in 40% of the 80 nations of the world. The complexi-
ty of criteria did not seem to be influenced by cultural differences. There
was no difference between Eastern and Western civilizations, and the dif-
ferences were largely already apparent in one single continent. In some
countries, an academic grade was needed to perform the test (associate
The type of confirmatory tests and the need for confirmatory tests has
been different throughout many countries. The choice of confirmatory tests
seems to be very arbitrary, with Sweden as a notable exception. In this
country, a cerebral angiogram has to be performed twice with an adequate
period of observation in between documenting an absent of flow to the
brain . Surprisingly, in many countries stricter criteria (confirmatory
test) were present when organ donation was considered. This is a common
qualifier in guidelines throughout the world.
In at least half of the surveyed nations in the world and in several US
States, confirmation of brain death requires examination by a second
physician. This remains very reasonable, but there is no data to suggest cri-
teria should go beyond two physicians. However having two physicians
available in order to determine brain death may lead to logistic problems,
but, in most modern neurological intensive care units, this could be done
by a designated neurologist or neurointensivist, a neurosurgeon, or anes-
thesiologist. The documentation of absence of respiratory drive remains
essential in the diagnosis of brain death. Although the outcome is likely
similar, the apnea testing should not be deferred. Documentation of
destroyed respiratory centers is the most important test of medulla oblon-
gata destruction; however, it almost always coincides with marked hypoten-
sion. Loss of medulla oblongata function results in loss of vascular tone
that only temporarily can be supported with high and incremental doses of
It should be emphasized that in many civilized countries the cultural
attitudes and religious attitudes are very supportive towards brain death
and organ donation. There is no evidence to suggest that cultural values
play a major role in further complicating the determination of brain death
such as multiple observations, multiple confirmatory tests, with multiple
physicians. It may simply be a consequence of collective decisions of task
forces. Variability among hospital policies may also be present and was
recently documented by Posner . We can easily assume that similar dif-
ferences can be found throughout the world when different hospital poli-
cies would have been surveyed. There also is a lingering concern on the
accuracy brain death documentation. A study by Wang  from the
University of California examined patients declared brain dead at Los
Angeles County General Hospital and found there were major problems
with chart documentation. Cornea reflex was not documented in 43% of
the cases, and motor examination was not documented in 34% of the
patients. It remains unclear whether this is truly a problem of documenta-
tion or a lapse in performing a clinical examination of brain death. The
organ donation procurement organizations may play an important role in
fact checking these examinations. The accuracy of documentation of brain
death in countries outside the US is not known.
When reviewing the complex guidelines of brain death determination
and preparation for organ donation, one can only conclude that consensus
is needed. This would require a task force that reviews the data and provide
evidentiary tables. Acceptance of uniform criteria of brain death would
then lead to a more uniform policy for brain death determination. Many
countries have come to their own judgment in how to solidify these crite-
ria. Usually special committees have been formed but the members of the
committee may not always have been most qualified, active practitioners or
major specialties have been missing. Complicating the diagnosis with addi-
tional laboratory tests must have been driven by a concern that inaccurate
assessment of these fatally injured patients may occur. However, more
physicians and more confirmatory tests cannot solve that. What remains
needed is appropriate education of staff, introduction of checklists in inten-
sive care units, and brain death examination by designated neurologists
who have documented proficiency in brain death examination. A qualifying
examination should be considered.
There is broad medical and legal acceptance of the concept of brain
death throughout the world. The acceptance of brain death and organ
donation permeates throughout countries with different religious values.
All major religions have embraced this concept and it allows organ dona-
tion (the ultimate gift of life). There are procedural differences that could
delay declaration of death and a consensus should be desirable.
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