David M. Greer, Sam D. Shemie, Ariane Lewis, Sylvia
Torrance, Panayiotis Varelas, Fernando D. Goldenberg, James L. Bernat, Michael
Souter, Mehmet Akif Topcuoglu, Anne W. Alexandrov, Marie Baldisseri, Thomas
Bleck, Giuseppe Citerio, Rosanne Dawson, Arnold Hoppe, Stephen Jacobe, Alex
Manara, Thomas A. Nakagawa, Thaddeus Mason Pope, William Silvester, David
Thomson, Hussain Al Rahma, Rafael Badenes, Andrew J. Baker, Vladimir Cerny, Cherylee
Chang, Tiffany R. Chang, Elena Gnedovskaya, Moon-Ku Han, Stephen Honeybul, Edgar
Jimenez, Yasuhiro Kuroda, Gang Liu, Uzzwal Kumar Mallick, Victoria Marquevich, Jorge
Mejia-Mantilla, MD, MSc35; Michael Piradov, Sarah Quayyum, Gentle Sunder
Shrestha, Ying-ying Su, Shelly D. Timmons, Jeanne Teitelbaum, Walter Videtta, Kapil
Zirpe, Gene Sung.
Determination of Brain
Death/Death by Neurologic Criteria.
World Brain Death Project.
Published online August 3, 2020. doi:10.1001/jama.2020.11586
There are inconsistencies in concept,
criteria, practice, and documentation of brain death/death by neurologic
criteria (BD/DNC) both internationally and within countries.
To formulate a consensus statement of
recommendations on determination of BD/DNC based on review of the literature
and expert opinion of a large multidisciplinary, international panel.
Relevant international professional societies
were recruited to develop recommendations regarding determination of BD/DNC.
Literature searches of the Cochrane, Embase, and MEDLINE databases included
January 1, 1992, through April 2020 identified pertinent articles for review.
Because of the lack of high-quality data from randomized clinical trials or
large observational studies, recommendations were formulated based on consensus
of contributors and medical societies that represented relevant disciplines,
including critical care, neurology, and neurosurgery.
Based on review of the literature and
consensus from a large multidisciplinary, international panel, minimum clinical
criteria needed to determine BD/DNC in various circumstances were developed.
Prior to evaluating a patient for BD/DNC, the
patient should have an established neurologic diagnosis that can lead to the
complete and irreversible loss of all brain function, and conditions that may
confound the clinical examination and diseases that may mimic BD/DNC should be
excluded. Determination of BD/DNC can be done with a clinical examination that
demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there
is no evidence of arousal or awareness to maximal external stimulation,
including noxious visual, auditory, and tactile stimulation; (2) pupils are
fixed in a midsize or dilated position and are nonreactive to light; (3)
corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is
no facial movement to noxious stimulation; (5) the gag reflex is absent to
bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to
deep tracheal suctioning; (7) there is no brain-mediated motor response to
noxious stimulation of the limbs; and (8) spontaneous respirations are not
observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the
clinical examination cannot be completed, ancillary testing may be considered
with blood flow studies or electrophysiologic testing. Special consideration is
needed for children, for persons receiving extracorporeal membrane oxygenation,
and for those receiving therapeutic hypothermia, as well as for factors such as
religious, societal, and cultural perspectives; legal requirements; and
Conclusions and Relevance
This report provides
recommendations for the minimum clinical standards for determination of brain
death/death by neurologic criteria in adults and children with clear guidance
for various clinical circumstances. The recommendations have widespread
international society endorsement and can serve to guide professional societies
and countries in the revision or development of protocols and procedures for
determination of brain death/death by neurologic criteria, leading to greater consistency
within and between countries.
Recommendations Issued for Brain Death/Death by Neurologic
The World Brain Death Project has released recommendations
regarding the minimum clinical criteria needed to determine brain death/death
by neurologic criteria (BD/DNC) in various scenarios.
The recommendations, which were developed by an
international, multidisciplinary panel of experts, include:
A neurologic diagnosis that can cause complete and
irreversible loss of all brain function should be established prior to
examining a patient for BD/DNC. Clinicians should rule out any conditions that
could confound clinical examination and any diseases that may resemble BD/DNC.
A clinical examination demonstrating coma, brainstem
areflexia, and apnea can determine BD/DNC, which occurs when:
There are no signs of arousal or awareness to maximal
external stimulation, including noxious visual, auditory, and tactile
Pupils remain fixed in a midsize or dilated position and do
not react to light.
There are no corneal, oculocephalic, and oculovestibular
No facial movement to noxious stimulation occurs.
The gag reflex does not respond to bilateral posterior
The cough reflex does not respond to deep tracheal
A brain-mediated motor response to noxious stimulation of
the limbs does not occur.
Spontaneous respirations do not occur when apnea test
targets reach a pH of less than 7.30 and partial pressure of carbon dioxide of
at least 60 mm Hg.
Ancillary testing with blood flow studies or
electrophysiologic testing may be considered if the clinical examination is
unable to be completed.
Special considerations are required in certain patients,
including children, individuals receiving extracorporeal membrane oxygenation,
and individuals receiving therapeutic hypothermia.
Other factors such as religious, societal, and cultural
perspectives; legal requirements; and resource availability should also be
taken into account.
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