The clinical criteria of brain death throughout the world

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The use of neurological criteria of death rather than cardiorespirato-

ry criteria of death is a fascinating chapter in the history of medicine and

neurology [1]. 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.,

encephalitis, intoxications).

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’ [2]. The recognition of

loss of all brainstem reflexes including apnea was first described in a com-

prehensive manuscript by Mollaret and Goulon [3]. 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 [4].


The views expressed with absolute freedom in this paper should be understood as

representing the views of the author and not necessarily those of the Pontifical Academy

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 Gold Standard

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 [5]. 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.

This influential document also determined that the brainstem is the main

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) [4]. Much of the work on brain

stem death in the United Kingdom should be credited to Pallis [6].





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-

tion with 100% oxygen followed by 10 minutes disconnection was deemed

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




Surveyed Countries (No. of countries)

United States of America




Central and South America






Middle East






introducing acute hypocarbia resulting in CSF acidosis that in turn maxi-

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. 

The number of physicians required to diagnose brain death varied sig-

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

professor level).

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 [4]. 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.

Remaining Concerns

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

vasopressors and vasopressin.

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 [7]. 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 [8] 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.


1. Wijdicks E.F.M, Brain Death, Philadelphia: Lippincott Williams &

Wilkins, 2001.

2. Wijdicks E.F.M., The neurologist and Harvard criteria for brain death,

Neurology 2003;61:970-976.

3. Mollaret P., Goulon M., Coma Depasse, Rev Neurol (Paris) 1959;101:3-15.

4. Wijdicks E.F.M., Brain death worldwide: accepted fact but no global

consensus in diagnostic criteria, Neurology 2002;58:20-25.

5. A definition of irreversible coma, Report of the Ad Hoc Committee of

the Harvard Medical School to Examine the Definition of Brain Death,

Jama 1968;205:337-340.

6. Pallis C., ABC of brain stem death. The position in the USA and else-

where, Br Med J (Clin Res Ed) 1983;286:209-210.

7. Powner D.J., Hernandez M., Rives T.E., Variability among hospital policies

for determining brain death in adults, Crit Care Med 2004;32:1284-1288.

8. Wang M.Y., Wallace P., Gruen J.P., Brain death documentation: analysis

and issues, Neurosurgery 2002; 51:731-735; discussion 735-736.



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