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Special Communication
August 3, 2020

Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project

Author Affiliations
  • 1Boston University School of Medicine, Boston, Massachusetts
  • 2McGill University, Montreal Children’s Hospital, Montreal, Canada
  • 3Canadian Blood Services, Ottawa, Canada
  • 4NYU Langone Medical Center, New York, New York
  • 5Albany Medical College, Albany, New York
  • 6University of Chicago, Chicago, Illinois
  • 7Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
  • 8University of Washington, Seattle
  • 9Department of Neurology, Hacettepe University, Ankara, Turkey
  • 10College of Nursing, University of Tennessee Health Science Center, Memphis
  • 11University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
  • 12Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 13University Milano-Bicocca, Milano-Bicocca, Italy
  • 14Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
  • 15University of Sydney and Children’s Hospital of Westmead, Westmead, Australia
  • 16Southmead Hospital, Bristol, United Kingdom
  • 17University of Florida, Jacksonville
  • 18Mitchell Hamline School of Law, Saint Paul, Minnesota
  • 19University of Melbourne, Melbourne, Australia
  • 20University of Cape Town, Cape Town, South Africa
  • 21Dubai Hospital, Dubai, United Arab Emirates
  • 22Hospital Clinic Universitari, University of Valencia, Valencia, Spain
  • 23St. Michael’s Hospital, Unity Health Toronto and University of Toronto, Toronto, Canada
  • 24J.E. Purkinje University, Masaryk Hospital, Usti nad Labem, Czech Republic
  • 25Queen’s Medical Center, Honolulu, Hawaii
  • 26The University of Texas Health Science Center at Houston, Houston
  • 27Research Center of Neurology, Moscow, Russia
  • 28Seoul National University Bundang Hospital, Seoul, Republic of Korea
  • 29Sir Charles Gairdner Hospital, Nedlands, Australia
  • 30Texas A&M, College Station
  • 31Kagawa University, Kagawa, Japan
  • 32Capital Medical University, Beijing, China
  • 33National Institute of Neurosciences and Hospital, Dhaka, Bangladesh
  • 34Hospital Universitario Austral, Buenos Aires, Argentina
  • 35Fundación Valle del Lili, Cali, Colombia
  • 36The University of Toronto, Toronto, Canada
  • 37Tribhuvan University Teaching Hospital, Kathmandu, Nepal
  • 38Indiana University, Indianapolis
  • 39Montreal Neurological Institute, Montreal, Canada
  • 40National Hospital, Alejandro Posadas, Buenos Aires, Argentina
  • 41Ruby Hall Clinic, Pune, India
  • 42University of Southern California, Los Angeles
JAMA. 2020;324(11):1078-1097. doi:10.1001/jama.2020.11586
Abstract

Importance  There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries.

Objective  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.

Process  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.

Evidence Synthesis  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.

Recommendations  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 resource availability.

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.

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    2 Comments for this article
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    EEG Sensitivity and Specificity in the Diagnosis of Brain Death
    Francesco Lolli, MD, PhD | University of Florence, Italy
    In the text of table 2, the sensitivity/specificity of the EEG test in the diagnosis of brain death seems difficult to understand as indicated. The fifth column is entitled "Sensitivity/Specificity (%)." The value for the EEG test is reported as "53-80, 4/97". In ref. 41 (Paolin), sensitivity is 53%, but the specificity is not calculated as the article is a study of consecutive brain death patients. In ref. 71 (Grigg), the sensitivity is 80%, and it is also the study of a series of patients with brain death. None of the patients recovered. The specificity was not calculated or specified in the cited studies.
    CONFLICT OF INTEREST: None Reported
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    The World Brain Death Project Statement on BD/DNC
    Calixto Machado, MD, PhD | Institute of Neurology and Neurosurgery Department of Clinical Neurophysiology
    This is an outstanding paper formulating a consensus statement of recommendations on determination of brain death/death by neurologic criteria (BD/DNC) (1). Based on personal experience and research on this topic, including organization of eight “International Symposia on Brain Death and Disorders of Consciousness” since the early ‘90s (2), I agree with the authors that substantial variability in BD/DNC protocols worldwide remains, which might partially explain why quarrelsome cases have recently raised new disputes on accepting BD/DNC (3). I approve the recommendation that the terms “whole brain death” and “brainstem death” should be replaced with BD/DNC, mainly in the setting of an isolated posterior fossa lesion, when ancillary testing should be performed. In these circumstances, it is important to remark that “BD/DNC should not be diagnosed until supratentorial and infratentorial blood flow is lost, even if the clinical examination and apnea test are suggestive of BD/DN (1).”

    It is necessary to state that there are two groups of ancillary tests: those which show no cerebral blood flow (CBF) and those which demonstrate absence of bioelectrical activity (2,4). I don’t agree with the recommendation that “it is suggested that electrophysiologic testing with electroencephalography (EEG) no longer be used routinely as an ancillary test in adults.” On the contrary, I fully agree that “EEG should be used in conjunction with somatosensory and brainstem auditory evoked potentials”. I have recommended a test battery conformed by EEG and evoked potentials to confirm BD/DNC (4).

    In fact, the presence of primary posterior fossa lesions enforces the needs to align the criterion and tests for BD/DNC diagnosis. In some patients fulfilling clinical BD/DNC criteria, when a posterior fossa lesion does not provoke an important increment of intracranial pressure there may be not a full absence of CBF, explaining preservation of EEG activity, evoked potentials, and autonomic function in some cases (3).
     
    Some authors commented that in the case of isolated brainstem lesions, sparing the mesopontine tegmental reticular formation, this condition would theoretically lead to a fully apneic locked-in syndrome, which imitates the so-called “brainstem death”, with the possibility of retaining some degree of consciousness for some time, even fulfilling clinical BD criteria (5). This was the case in Jahi McMath (3).

    I applaud the effort of the World Brain Death Project to formulate a consensus declaration of recommendations on determination of BD/DNC, which will undoubtedly diminish confusion and variability on the worldwide acceptance of BD/DNC as  synonym of human death.

    REFERENCES

    1. Greer DM, Shemie SD, Lewis A, et al. Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project. JAMA. 2020.
    2. Machado C. Brain Death: A reappraisal. New York: Spinger Science+Bussiness Media, LLC; 2007.
    3. Machado C. Jahi McMath: a new state of disorder of consciousness. J Neurosurg Sci. 2020.
    4. Machado C. Multimodality evoked potentials and electroretinography in a test battery for an early diagnosis of brain death. J Neurosurg Sci. 1993;37(3):125-131.
    5. Walter U, Fernandez-Torre JL, Kirschstein T, Laureys S. When is "brainstem death" brain death? The case for ancillary testing in primary infratentorial brain lesion. Clin Neurophysiol. 2018;129(11):2451-2465.
    CONFLICT OF INTEREST: None Reported
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