Clinical and pathomorphological parameters of brain death: from the origins of the concept to its use in organ transplantation

Authors

  • V. O. Tumanskyi Zaporizhzhia State Medical University, Ukraine,
  • L. M. Tumanska Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1237.2020.1.203850

Keywords:

brain death, cardio-respiratory center, standards for brain death, pathology, organ transplantation

Abstract

 

The criteria for brain death (BD), the parameters of their clinical and pathomorphological determination and use in organ harvesting for transplantation are being clarified in different countries to date.

Objective: analysis of the formation and clinical and pathological characteristics of brain death.

The review provides retrospective analysis of the formation and improvement of the medical concept of BD: the concepts of “death of the whole brain” (including the brain stem) and “death of the brain stem”. Based on our own data, the main pathomorphological forms of BD are described (total necrosis of the brain, subtotal necrosis of the brain stem and cerebellum), their development mechanisms, and diagnostic pathological parameters. It has been established that the main criterion for the development of human biological death, which determines irreversible cardiac arrest and the impossibility of restoring spontaneous respiration, are irreversible destructive changes in the nuclei of the pons and medulla oblongata, which make up the cardio-respiratory center that regulates heart rate, vascular tone and blood pressure, and generating rhythm and breathing patterns. The modern standards of clinical diagnosis of BD and their real application in different countries during organ transplantation, as well as the prerequisites for the revival of the concept of "circulatory death" in the era of organ transplantation are highlighted.

Conclusions. The applied three standards of human death have insufficiently studied medical aspects and unresolved ethical problems.

 

References

De Georgia, M. A. (2014). History of brain death as death: 1968 to the present. Journal of Critical Care, 29(4), 673-678. https://doi.org/10.1016/j.jcrc.2014.04.015

Mollaret, P., Bertrand, I., & Mollaret, H. (1959). Coma depasse et necroses nerveuses centrales massives. Revue Neurologique (Paris), 101, 116-139.

Kramer, W. (1963). From reanimation to deanimation (Intravital death of the brain during artificial respiration). Acta Neurologica Scandinavica, 39(2), 139-153. https://doi.org/10.1111/j.1600-0404.1963.tb05315.x

Towbin, A. (1973). The respirator brain death syndrome. Human Pathology, 4(4), 583-594. https://doi.org/10.1016/S0046-8177(73)80067-X

Moskopp, D. (1971). Das Konzept des Hirntodes wurde in Europa zwischen 1952 und 1960 entwickelt. Eine Übersicht zur Historie [The compendium of cerebral death developed in Europe between 1952 and 1960. Review to history]. Nervenheilkunde, 36, 423-432. [in German].

Adams, R. D., & Jéquier, M. (1969). The brain death syndrome: Hypoxemic panencephalopathy. Schweizerische Medizinische Wochenschrift, 99(3), 65-73.

Schwab, R. S., Potts, F., & Bonazzi, A. (1963). EEG as an aid in determining death in the presence of cardiac activity ethical, legal, and medical aspects. Electroencephalography and Clinical Neurophysiology, 15, 147-148.

Haid, B. (1958). Religioes-sittliche Fragen betreffend die Wiederbelebung (Resuscitation, Reanimation). Der Anaesthesist, 7, 241-243. [in German].

Pius XII (1957). Discours en réponse à trois questions de morale médicale sur la reanimation. Acta Apostolica Sedis, 49, 1027-1033.

Lynn, J. (1981). Guidelines for the determination of death. Report of the medical consultants on the diagnosis of death to the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Jama-Journal of the American Medical Association, 246(19), 2184-2188.

Machado, C. (2007). Conceptual Approach to Human Death on Neurological Grounds. In : C. Machado. Brain Death. A Reappraisal. Springer, New York, NY. https://doi.org/10.1007/978-0-387-38977-6_3

Russell J. A., Epstein L. G., Greer D. M., Kirschen M., Rubin M. A., & Lewis A. (2019). Brain death, the determination of brain death, and member guidance for brain death accommodation requests. Neurology, 92(5), 228-232. https://doi.org/10.1212/WNL.0000000000006750

Wijdicks, E. F. M., Varelas, P. N., Gronseth, G. S., & Greer, D. M. (2010). Evidence-based guideline update: Determining brain death in adults: Report of the quality standards subcommittee of the American Academy of Neurology. Neurology, 74(23), 1911-1918. https://doi.org/10.1212/WNL.0b013e3181e242a8

Nakagawa, T. A., Ashwal, S., Mathur, M., Mysore, M., Kolinski, L., Retford, L., … Jaeschke, R. (2011). Clinical report - Guidelines for the determination of brain death in infants and children: An update of the 1987 task force recommendations. Pediatrics, 128(3), e720-e740. https://doi.org/10.1542/peds.2011-1511

Jain, S., & DeGeorgia, M. (2005). Brain death-associated reflexes and automatisms. Neurocritical Care, 3(2), 122-126. https://doi.org/10.1385/ncc:3:2:122

Saposnik, G., Maurino, J., Saizar, R., & Bueri, J. A. (2005). Spontaneous and reflex movements in 107 patients with brain death. American Journal of Medicine, 118(3), 311-314. https://doi.org/10.1016/j.amjmed.2004.09.013

Beckmann, Y., Ciftci, Y., Incesu, T. K., Secil, Y., & Akhan, G. (2014). Spinal reflexes in brain death. Acta Neurologica Belgica, 114(4), 303-306. https://doi.org/10.1007/s13760-014-0284-0

Domi, R., Sula, H., Ohri, I., & Laho, H. (2013). Pathophysiologic changes after brain death and organ preservation: The intensivist’s and anesthesiologist’s role. Journal of Anesthesia and Clinical Research, 4(3). https://doi.org/10.4172/2155-6148.1000302

Gordon, J. K., & McKinlay, J. (2012). Physiological changes after brain stem death and management of the heart-beating donor. Continuing Education in Anaesthesia, Critical Care and Pain, 12(5), 225-229. https://doi.org/10.1093/bjaceaccp/mks026

Permiakov, N. K., & Tumanskii, V. A. (1984). Postreanimatsionnaya entsefalopatiya [Postresuscitation encephalopathy]. Arkhiv patologii, 46(9), 5-16. [in Russian].

Permiakov, N. K., Khuchua, A. V., & Tumanskii, V. A. (1986). Postreanimatsionnaya entsefalopatiya [Postresuscitation encephalopathy]. Moscow: Meditsina. [in Russian].

Tumanskii, V. A., & Tumanskaya, L. M. (1996). Sindrom smerti mozga: patogenez, ekspertnaya otsenka rannikh stadii razvitiya, patologoanatomicheskie formy [Brain death syndrome: pathogenesis, expert evaluation of the early stages of development, pathological forms]. In Reanimatologiya na rubezhe XXI veka. Moscow. [in Russian].

Tumanskii, V. A., & Tumanskaya, L. M. (1998). Sindrom smerti mozga: morfogenez i kriterii patologoanatomicheskoi diagnostiki [Brain death syndrome: morphogenesis and criteria for pathological diagnosis]. Sudynni i onkolohichni zakhvoriuvannia: morfohenez ta ekolohichnyi patomorfoz. Vinnytsia. [in Russian].

Schneider, H., Masshoff, W., & Neuhaus, G. A. (1969). Klinische und morphologische Aspekte des Hirntodes. Hin Wochenschr, 47(16), 844-859.

Schneider, H. (1970). Der Hirntod. Begriffsgeschichte und Pathogenese. Nervenartz, 41(8), 381-387.

Lyudkovskaya, I. G., & Popova, L. M. (1978). Morfologiya i patogenez "smerti golovnogo mozga" pri insul'te. [Morphology and pathogenesis of "brain death" in stroke]. Arkhiv patologii, 40(9), 48-54. [in Russian].

Walker, A. E. (1978). Pathology of brain death. Annals of the New York Academy of Sciences, 315, 272-280. https://doi.org/10.1111/j.1749-6632.1978.tb50345.x

Bernat, J. L. (1992). Brain-death - occurs only with destruction of the cerebral hemispheres and the brain-stem. Archives of Neurology, 49(5), 569-570. https://doi.org/10.1001/archneur.1992.00530290161027

Maith J. M. (2009). Der Hirntod des Menschen: Forensische Neuropathologie (Doctoral dissertation). Kiel.

Schneider, H., & Matakas, F. (1971). Pathological changes of the spinal cord after brain death. Acta neuropathologica, 18(3), 234-247.

Schroder, R. (1983). Later changes in brain-death - Signs of partial recirculation. Acta Neuropathologica, 62(1-2), 15-23. https://doi.org/10.1007/bf00684915

Machado, C., Valdes, P., Garcia, O., Coutin, P., Miranda, J., & Roman, J. (1993). Short latency somatosensory evoked potentials in brain-dead patients using restricted low cut filter setting. Journal of Neurosurgical Sciences, 37(3), 133-140.

Korein, J., & Machado, C. (2004). Brain death - Updating a valid concept for 2004. Brain Death and Disorders of Consciousness, 550, 1-14.

McCormick, W. F., & Halmi, N. S. (1970). The hypophysis in patients with coma dépassé (“respirator brain”). American Journal of Clinical Pathology, 54(3), 374-383. https://doi.org/10.1093/ajcp/54.3.374

Ujihira, N., Hashizume, Y., & Takahashi, A. (1993). A neuropathological study on respirator brain. Clinical Neurology, 33(2), 141-149.

Wijdicks, E. F. M., & Pfeifer, E. A. (2008). Neuropathology of brain death in the modern transplant era. Neurology, 70(15), 1234-1237. https://doi.org/10.1212/01.wnl.0000289762.50376.b6

Wijdicks, E. F. M. (2015, April 1). The clinical determination of brain death: Rational and reliable. Seminars in Neurology. Thieme Medical Publishers, Inc. https://doi.org/10.1055/s-0035-1547531

Wagner, W., Ungersböck, K., & Perneczky, A. (1993). Preserved cortical somatosensory evoked potentials in apnoeic coma with loss of brain-stem reflexes: case report. Journal of Neurology, 240(4), 243-246. https://doi.org/10.1007/BF00818712

Varelas, P. N., Brady, P., Rehman, M., Afshinnik, A., Mehta, C., Abdelhak, T., & Wijdicks, E. F. (2017). Primary Posterior Fossa Lesions and Preserved Supratentorial Cerebral Blood Flow: Implications for Brain Death Determination. Neurocritical Care, 27(3), 407-414. https://doi.org/10.1007/s12028-017-0442-3

Mohandas, A., & Chou, S. N. (1971). Brain death. A clinical and pathological study. Journal of Neurosurgery, 35(2), 211-218. https://doi.org/10.3171/jns.1971.35.2.0211

Tumanskii ,V. A., Darii, V. I., Tumanskaya, L. M., Tertyshnyi, S. I., & Evseev, A. V. (2005). Kliniko-morfologicheskaya kharakteristika kardio-respiratornogo tsentra stvola golovnogo mozga v dinamike postreanimatsionnoi bolezni i tserebralnogo polusharnogo insulta, oslozhnennogo vtorichnym stvolovym sindromom [Clinical and morphological characteristics of the cardio-respiratory center of the brain stem in the dynamics of postresuscitation disease and cerebral hemispheric stroke complicated by secondary stem syndrome]. Pathologia, 2(3), 82-91. [in Russian].

Tumanskaya, L. M. (1976). Dinamika submikroskopicheskikh izmenenii neironov i glii retikulyarnoi formatsii stvola golovnogo mozga posle ostroi gipoksicheskoi gipoksii [Dynamics of submicroscopic changes in neurons and glia of the reticular formation of the brain stem after acute hypoxic hypoxia]. In Strukturno-funktsionalnye osnovy organizatsii mozga (pp. 153-156). Moscow. [in Russian].

Tumanskaya, L. M. (1978). Ultrastruktura dendritov neironov retikulyarnoi formatsii stvola golovnogo mozga pri ostroi gipoksicheskoi gipoksii [Ultrastructure of neurons dendrites of the reticular formation of the brain stem in acute hypoxic hypoxia]. Arkhiv anatomii, gistologii i embriologii, 74(3), 67-72. [in Russian].

Gordon, J. K., & McKinlay, J. (2012). Physiological changes after brain stem death and management of the heart-beating donor. Continuing Education in Anaesthesia, Critical Care and Pain, 12(5), 225–229. https://doi.org/10.1093/bjaceaccp/mks026

Merkulova, N. A., Inyushkin, A. N., Belyakov, V. I., Zainulin, R. A., & Inyushkina, E. M. (2007). Dykhatel'nyi tsentr i regulyatsiya ego deyatel'nosti suprabul'barnymi strukturami [Respiratory center and regulation of its activity by suprabulbar structures]. Samara: Izd-vo ‘Samarskii universitet’. [in Russian].

Citerio, G., Crippa, I. A., Bronco, A., Vargiolu, A., & Smith, M. (2014). Variability in Brain Death Determination in Europe: Looking for a Solution. Neurocritical Care, 21(3), 376-382. https://doi.org/10.1007/s12028-014-9983-x

Stulin, I. D., Musin, R. S., Solonsky, D. S., & Sinkin, M. V. (2014). Sovremennaya kliniko-instrumental'naya diagnostika smerti mozga [Modern clinical and instrumental diagnosis of brain death]. Transplantologiya, (1), 24-35. [in Russian].

Verkhovna Rada of Ukraine. (2019, December 20). Pro vnesennia zmin do deiakykh zakonodavchykh aktiv Ukrainy, shcho rehuliuiut pytannia transplantatsii anatomichnykh materialiv liudyni : zakon Ukrainy 20.12.2019 No 418-IX. https://zakon.rada.gov.ua/laws/show/418-20?lang=en

Chua, H. C., Kwek, T. K., Morihara, H., & Gao, D. (2015, April 1). Brain death: The asian perspective. Seminars in Neurology. Thieme Medical Publishers, Inc. https://doi.org/10.1055/s-0035-1547539

Greer, D. ., Wang, H. H., Robinson, J. D., Varelas, P. N., Henderson, G. V., & Wijdicks, E. F. M. (2016). Variability of brain death policies in the United States. JAMA Neurology, 73(2), 213-218. https://doi.org/10.1001/jamaneurol.2015.3943

Wahlster, S., Wijdicks, E. F. M., Patel, P. V., Greer, D. M., Hemphill, J. C., Carone, M., & Mateen, F. J. (2015). Brain death declaration: Practices and perceptions worldwide. Neurology, 84(18), 1870-1879. https://doi.org/10.1212/wnl.0000000000001540

Citerio, G., & Murphy, P. G. (2015, April 1). Brain death: The European perspective. Seminars in Neurology. Thieme Medical Publishers, Inc. https://doi.org/10.1055/s-0035-1547533

Australian and New Zealand Intensive Care Society. (2013). The ANZICS Statement on Death and Organ Donation (Edition 3.2). Melbourne: ANZICS.

Smith, M. (2015). Brain death: The United Kingdom perspective. Seminars in Neurology, 35(2), 145-151. https://doi.org/10.1055/s-0035-1547534

Cameron, E. J., Bellini, A., Damian, M. S., & Breen, D. P. (2016). Confirmation of brainstem death. Practical Neurology, 16(2), 129-135. https://doi.org/10.1136/practneurol-2015-001297

Norris, S. (2014). Organ Donation and Transplantation in Canada. Legal and Social Affairs Division: Parliamentary Information and Research Service. Publication no.: 2011-113-E. http://www.lop.parl.gc.ca/content/lop/researchpublications/2011-113-e.pdf

Manyalich, M., Nelson, H., & Delmonico, F. L. (2018). The need and opportunity for donation after circulatory death worldwide. Current Opinion in Organ Transplantation, 23(1), 136-141. https://doi.org/10.1097/MOT.0000000000000486

Bernat, J. L., Capron, A. M., Bleck, T. P., Blosser, S., Bratton, S. L., Childress, J. F., … White, D. B. (2010). The circulatory-respiratory determination of death in organ donation. Critical Care Medicine, 38(3), 963-970. https://doi.org/10.1097/CCM.0b013e3181c58916

How to Cite

1.
Tumanskyi VO, Tumanska LM. Clinical and pathomorphological parameters of brain death: from the origins of the concept to its use in organ transplantation. Pathologia [Internet]. 2020May25 [cited 2024Nov.23];(1). Available from: http://pat.zsmu.edu.ua/article/view/203850

Issue

Section

Review