Advancing neuroscience research in brain death An ethical obligation to society Journal of Critical Care xxx (2016) xxx–xxx Contents lists available at ScienceDirect Journal of Critical Care j ourna l[.]
Journal of Critical Care xxx (2016) xxx–xxx Contents lists available at ScienceDirect Journal of Critical Care journal homepage: www.jccjournal.org Letter to Editor Advancing neuroscience research in brain death: An ethical obligation to society☆,☆☆,★,★★,☆☆☆,★★★ To the Editor Recently, the “Reanima Project,” a nonrandomized, open-labeled, interventional study, was initiated in India to document the feasibility of reversibility of brain death after traumatic brain injury with diffuse axonal injury (ClinicalTrials.gov Identifier: NCT02742857) [1] Several commentators have criticized the Reanima Project on brain death as being “unscientific,” “quackery,” “unethical,” “exploiting religious sentiment,” or “illegal” [2,3] The study enrollment was suspended in November 2016 In these commentaries, it was argued that (1) “dead means dead” [2] and (2) “[t]here is no scientific basis for the notion that someone can be brought back from the dead” [3] We agree that all human researches must adhere to accepted scientific, ethical, and legal standards However, we challenge the underlying suggestion in these commentaries that any brain death research would be unethical because death by neurologic criteria (DNC) “is well-acknowledged by the medical, legal, and ethical communities to constitute legal death” [2] Based on that premise, empirical knowledge would be nonfalsifiable Commentators would be correct if and only if the concept and criteria of DNC can be scientifically validated However, neuroscientists and scholars have frequently challenged the scientific and philosophical validation for equating DNC with biologic death Currently, diagnostic testing predominantly depends on clinical demonstration of absent motor reflexes of cranial nerves and respiratory drive [4] Absence of motor reflexes of cranial nerves does not conclusively prove irreversible absence of capacity for consciousness [5] In fact, to date, no specific tests exist that can reliably demonstrate irreversibility of cessation of capacity for awareness or consciousness Although time is an important confounder of reversibility, the exact length of time to irreversibility in brain death is unknown This, in part, might be due to the time constraint dictated by the need for expediting organ procurement or the desire for discontinuing life-support treatment Portions of the postmortem human brain have been demonstrated to retain capacities for electrophysiologic responsiveness [6] As Lewis and Caplan [2] pointed out, “[b]y definition, DNC requires irreversible cessation of all functions of the entire brain, including the brainstem.” The ☆ Ethics approval and consent to participate: Not applicable ☆☆ Consent for publication: Not applicable ★ Availability of data and material: Not applicable ★★ Competing interests: The authors declare that they have no competing interests ☆☆☆ Funding: None ★★★ Authors' contributions: MYR and JLV have made substantial contributions to (i) the concept and design, (ii) the drafting of the manuscript or revising it critically for important intellectual content, and (iii) the final approval of the version to be published American Academy of Neurology assigned to the updated practice recommendations for brain death determination the lowest level of scientific evidence “U = [d]ata inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven)” [4] In the United States, the validity of American Academy of Neurology practice recommendations for brain death determination has come under scrutiny and legal challenge in the Jahi McMath case [7] Neuroscientists have urged for more empirical research to better understand and characterize brain death [8] In absence thereof, global ethical and legal challenges to DNC will persist The US President's Council on Bioethics concluded that there is a lack of biologic and clinical-pathologic evidence to substantiate uniformity and validity of the DNC [9, pp 39-42, pp 52-57, and pp 69-72] With some members opposing [9, p95 and p107], the Council considered DNC criteria philosophically but not scientifically justifiable [9, pp 44-45 and pp 59-65] Advances in neuroscience research can be applied for both empiric characterization and potential therapy in different phenotypes of disorders of consciousness [10] The medical community is obligated to promote further scientific research to ensure patient's safety and avoid premature decisions to proceed with organ donation or to discontinue further treatment after a brain death diagnosis Mohamed Y Rady BChir, MB (Cantab), MA, MD (Cantab), FRCS (Eng&Edin) FRCP (UK), FCCM⁎ Department of Critical Care Medicine, Mayo Clinic Hospital, 5777 East Mayo Blvd, Phoenix, Arizona 85054, USA ⁎Corresponding author E-mail address: rady.mohamed@mayo.edu Joseph L Verheijde PhD, MBA, PT Department of Physical Medicine & Rehabilitation, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, Arizona 85259, USA E-mail address: jverheijde@mayo.edu Available online xxxx References [1] ClinicalTrials.gov identifier: NCT02742857 Non-randomized, open-labeled, interventional, single group, proof of concept study with multi-modality approach in cases of brain death due to traumatic brain injury having diffuse axonal injury Available at: https://clinicaltrials.gov/ct2/show/NCT02742857?term=bioquark&rank=1 [Accessed December 8, 2016] [2] Lewis A, Caplan A Response to a trial on reversal of death by neurologic criteria Crit Care 2016;20(1):377 [3] Srinivasan S, Johari V Response to proposed research to reverse brain death: more than regulatory failure Indian J Med Ethics 2016;1(3):134–7 http://dx.doi.org/10.1016/j.jcrc.2016.12.011 0883-9441/© 2016 The Authors Published by Elsevier Inc This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article as: Rady MY, , Advancing neuroscience research in brain death: An ethical obligation to society, Journal of Critical Care (2016), http://dx.doi.org/10.1016/j.jcrc.2016.12.011 Letter to Editor [4] Wijdicks EF, Varelas PN, Gronseth GS, Greer DM Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology 2010;74(23):1911–8 [5] Rady MY, Verheijde JL American academy of neurology guidelines and the neurologic determination of death JAMA Neurol 2016;73(6):760–1 [6] Rouleau N, Murugan NJ, Tessaro LWE, Costa JN, Persinger MA When is the brain dead? Living-like electrophysiological responses and photon emissions from applications of neurotransmitters in fixed post-mortem human brains PLoS ONE 2016; 11(12):e0167231 http://dx.doi.org/10.1371/journal.pone.0167231 [7] Yanke G, Rady MY, Verheijde JL When brain death belies belief J Relig Health 2016; 55:2199–213 [8] Peterson A, Norton L, Naci L, Owen AM, Weijer C Toward a science of brain death Am J Bioeth 2014;14(8):29–31 [9] The President's Council on Bioethics Controversies in the determination of death: a white paper by the President's Council on Bioethics Available at: https://bioethicsarchive.georgetown.edu/ pcbe/reports/death/; 2008 [Accessed November 27, 2016, 2016] [10] Sinai L, Owen AM, Naci L Mapping preserved real-world cognition in severely braininjured patients Front Biosci (Landmark Ed) 2017;22:815–23 Please cite this article as: Rady MY, , Advancing neuroscience research in brain death: An ethical obligation to society, Journal of Critical Care (2016), http://dx.doi.org/10.1016/j.jcrc.2016.12.011 ... Sinai L, Owen AM, Naci L Mapping preserved real-world cognition in severely braininjured patients Front Biosci (Landmark Ed) 2017;22:815–23 Please cite this article as: Rady MY, , Advancing neuroscience. .. Letter to Editor [4] Wijdicks EF, Varelas PN, Gronseth GS, Greer DM Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American... 2017;22:815–23 Please cite this article as: Rady MY, , Advancing neuroscience research in brain death: An ethical obligation to society, Journal of Critical Care (2016), http://dx.doi.org/10.1016/j.jcrc.2016.12.011