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

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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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Article Information

Corresponding Author: Gene Sung, MD, MPH, University of Southern California, 2051 Marengo St, IPT A4E111, Los Angeles, CA 90033 (gsung@usc.edu).

Accepted for Publication: June 15, 2020.

Published Online: August 3, 2020. doi:10.1001/jama.2020.11586

Author Contributions: Dr Sung had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Greer and Shemie contributed equally to this work and are co–first authors.

Concept and design: Sung, Greer, Shemie, Lewis, Torrance.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Greer, Shemie, Lewis, Torrance, Sung, Alexandrov, Goldenberg, Pope, Baldisseri, Hoppe, Silvester, Bernat, Jacobe, Souter, Bleck, Thomson, Citerio, Manara, Topcuoglu, Quayum, Dawson, Nakagawa, Varelas.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: Sung, Greer, Shemie, Lewis, Torrance.

Supervision: Sung, Greer, Shemie, Lewis, Torrance.

Conflict of Interest Disclosures: Dr Shemie reported being the medical advisor for deceased donation at Canadian Blood Services, a government-funded nonprofit organization tasked with producing clinical practice guidelines for death determination and organ donation in Canada. Dr Varelas reported receiving a grant from the Gift of Life of Michigan Foundation for Brain Death Simulation courses. Dr Souter reported receiving funding from Lifecenter Northwest outside the submitted work. Dr Nakagawa reported receiving royalties from Wolters Kluwer and UpToDate. Dr Timmons reported current and past leadership positions in several neurosurgical societies/organizations, including the American Association of Neurological Surgeons (AANS) and the Joint Section of Neurotrauma and Critical Care of the AANS and Congress of Neurological Surgeons. She did not participate in these organizations' review of the manuscript for endorsement of educational content, as part of our normal recusal processes. Authors are debarred from participating in reviews. No other disclosures were reported.

Additional Information: This project has been endorsed by the following world federations: World Federation of Critical Care Nurses (WFCCN); World Federation of Intensive and Critical Care (WFICC); World Federation of Neurology (WFN); World Federation of Neurosurgical Societies (WFNS); World Federation of Pediatric Intensive and Critical Care Societies (WFPICCS). This project has been endorsed by the following medical societies: 1. Bangladesh Society of Critical Care Medicine (BSCCM); 2. Brain Injury Evaluation Quality Control Center (BQCC), National Health Commission of China; 3. Canadian Neurological Sciences Federation (CNSF) [represents the Canadian Neurological Society (CNS), Canadian Neurosurgical Society (CNSS), Canadian Society of Clinical Neurophysiologists (CSCN), Canadian Association of Child Neurology (CACN) and the Canadian Society of Neuroradiology (CSNR)]; 4. Colombian Association of Critical Medicine and Intensive Care / Asociación Colombiana de Medicina Critica y Cuidada Intensivo (AMCI); 5. Critical Care Society of Southern Africa (CCSSA) (represents South Africa, Botswana, Namibia, Lesotho, Zambia, Zimbabwe, Mozambique, Swaziland); 6. Czech Society of Anaesthesiology and Intensive Care Medicine / Česká společnost anesteziologie resuscitace a intenzivní medicíny (CSARIM); 7. European Society of Intensive Care Medicine (ESICM); 8. Faculty of Intensive Care Medicine (FICM), UK; 9. German Interdisciplinary Association of Critical Care and Emergency Medicine / Deutsche Interdisziplinäre Vereinigung für Intensiv-und Notfallmedizin (DIVI); 10. IberoAmerican Stroke Organization / Sociedade Iberoamericana de Enfermidades Cerebrovasculares (SIECV); 11. Indian Society of Critical Care Medicine (ISCCM); 12. Intensive Care Society (ICS), UK; 13. Intensive Care Society of Ireland; 14. International Pan Arab Critical Care Medicine Society (IPACCMS); 15. International Society for Donation and Procurement (ISODP); 16. Japanese Society of Intensive Care Medicine (JSICM); 17. Korean Neurocritical Care Society (KNCS); 18. Latin American Brain Injury Consortium (LABIC) ; 19. National Association of Specialists in Neuroanesthesia and Neurocritical Care, Russia; 20. Nepalese Society of Critical Care Medicine (NSCCM); 21. Neurocritical Care Society (NCS); 22. Sociedad Argentina de Terapia Intensiva (SATI-Argentine Society of Intensive Care); 23. Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor (SEDAR); 24. Sociedad Española de Neurocirugía (SENEC-Spanish Society of Neurosurgery); 25. Sociedad Española de Neurologia (SEN-Spanish Society of Neurology); 26. Society for Neuroscience in Anesthesiology and Critical Care (SNACC); 27. Society of Critical Care Medicine (SCCM). The following societies reserve the term endorsement only for those guidelines that adhere to clinical practice guideline methodologies such as GRADE/AGREE; for guidelines that are evidence-based consensus-driven, other terminology are used. “The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.” “The American Association of Neurological Surgeons/Congress of Neurosurgical Surgeons Joint Section for Neurotrauma and Critical Care affirms the educational benefit of this document.” “Although the Canadian Critical Care Society reserves societal endorsement for clinical practice guidelines that have been developed through comprehensive guideline methodology (1) such as GRADE, the CCCS, the CCCS recognizes the importance of this document and looks forward to working with local, provincial, and national bodies to adapt the concepts that are presented in the World Brain Death Document to our national context.”

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Determination of Brain Death/Death by Neurologic CriteriaThe World Brain Death Project

Standardizing Brain Death Globally

Is There a Right to Delay Determination of Death by Neurologic Criteria?

Brain Death: Moving Beyond Consistency in the Diagnostic Criteria

Patient Information: Brain Death