• Local academic highlights cases of withdrawing life support and retrieving organs from patients with irreversible neurological damage 

• Notes need for uniform global framework for determining brain death that is acceptable to medical community and public

  BY Ruwan Laknath Jayakody  Since the determination of brain death, the withdrawal of life support, and organ transplantation are intricately intertwined, it is time to disentangle and critically re-evaluate these fundamental issues separately, and establish legal mechanisms for the withdrawal of life support and organ retrieval from patients with irreversible neurological damage who are conceptually alive but unlikely to survive.  This point was made by U.K. Ranawaka (attached to the University of Kelaniya’s Medical Faculty) in an article on “What is death in the 21st Century?” which was published in the Ceylon Medical Journal 66 (1) in July 2021.  Diagnosing death: The evolution of different criteria Death can be diagnosed using three different sets of criteria: somatic (the features visible upon the external inspection of a corpse such as rigour mortis or decomposition, per D. Gardiner, S. Shemie, A. Manara and H. Opdam’s “International perspective on the diagnosis of death” – which is a criteria useful in diagnosing death in a community setting, especially after some delay), circulatory (use of the stethoscope, which is relevant when death is determined immediately afterwards, especially in a hospital setting) and neurological (the concept of brain death, where “irreversible coma” was defined as the new criterion for death, and thereby, the diagnosis of death required, per the Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death on “A definition of irreversible coma”, the “abolition of function at the cerebral, brainstem [the distal and posterior stalk like part of the brain that connects the cerebrum (largest and uppermost portion of the brain) with the spinal cord, that helps regulate breathing, the heart rate, blood pressure, and several other important functions], and often the spinal level”). In the US’ Uniform Determination of Death Act of 1981, death was defined as the “irreversible cessation of circulatory and respiratory functions or the irreversible cessation of all functions of the entire brain, including the brainstem”. According to Gardiner et al. and the Report of the Quality Standards Subcommittee of the American Academy of Neurology on “Evidence-based guideline update: Determining brain death in adults” by E.F.M. Wijdicks, P.N. Varelas, G.S. Gronseth and D.M. Greer, the currently accepted criteria consists of three essential components: an aetiology capable of causing irreversible brain damage, the exclusion of reversible causes, and the clinical demonstration of deep coma, absent brainstem reflexes and apnoea (temporary cessation of breathing).  Diagnosing death: Many controversies  The circulatory criteria remains the most appropriate for diagnosing death outside an intensive care unit setting, but considerable variation is seen in their application, per J.L. Bernat’s “Controversies in defining and determining death in critical care”. Ranawaka explained that a minimum observation period of apnoea and asystole (flatline – the cessation of electrical and mechanical activity of the heart) is required in order to confirm death following cardiac respiratory arrest. However, Ranawaka observed that it is baffling that there is no agreement even on this; the observation period varies from two minutes in the US and Australia, five minutes in the UK and Canada, to 10 minutes in several European countries (per Gardiner et al., and Bernat). Recommendations for a minimum observation period are made with the caveat that no attempts at resuscitation should be made during this period (per Gardiner et al.), which Ranawaka noted, perhaps is in itself an admission that it is clearly inadequate.  Determining death by neurological criteria was endorsed by at least 70 countries as of 2015 (E.F. Wijdicks’s “Brain death worldwide: Accepted fact but no global consensus in diagnostic criteria”), yet there is continued debate regarding the concept of brain death, the criteria used and their application (Gardiner et al., and in the US, and in countries in Asia and the Pacific, amongst others).  The concept of brain death: Are you dead, if you are brain dead? Patients who fulfil the criteria for brain death continue to show traditional signs of life, such as warm and moist skin, cardiac rhythm and respiration with ventilator support (per I.H. Kerridge, P. Saul, M. Lowe, J. McPhee and D. Williams’s “Death, dying and donation: Organ transplantation and the diagnosis of death”). If sustained with artificial respiration, they maintain diverse bodily functions such as wound healing, growth and sexual maturation in children, and the gestation of healthy foetuses in pregnant women (Kerridge et al., and M. Nair-Collins’s “Clinical and ethical perspectives on brain death”). They continue to show the preservation of varied brain functions: osmoregulation via antidiuretic hormone secretion, thermoregulation, the secretion of hypophysiotropic (acting on or stimulating the pituitary, the latter an endocrine gland) hormones, and preserved electroencephalogram activity (persistent in 20% of patients declared brain dead, per M.M. Grigg, M.A. Kelly, G.G. Celesia, M.W. Ghobrial and E.R. Ross’s “EEG activity after brain death”) and sensory or brainstem evoked potentials (Kerridge et al., Nair-Collins, and C.J. Doig and E. Burgess’s “Brain death: Resolving inconsistencies in the ethical declaration of death”). These findings, Ranawaka explained, are inconsistent with a concept of “whole brain death”.  The criteria for brain death: Are they the same across the world?  There is a lack of global consensus on even what constitutes death. Some countries consider brainstem death as death (13% of countries in an international survey, e.g., the UK, Canada, and India), whereas most countries (including the US, Australia, and Japan) require the demonstration of whole brain death (Gardiner et al.; Bernat; A. Lewis, A. Bakkar, E. Kreiger-Benson, A. Kumpfbeck, J. Liebman, S.D. Shemie, G. Sung, S. Torrance and D. Greer’s “Determination of death by neurological criteria around the world”; and Nair-Collins). However, Ranawaka pointed out that the current criteria and tests used for the diagnosis of brain death relate primarily to the brainstem function, and are incapable of excluding “higher brain” functions. Surveys in the 21st Century, Ranawaka reiterated, have consistently highlighted marked international variation in the criteria, protocols and guidelines used in the determination of brain death. Significant disparities are reported in apnoea testing, the observation period before the declaration of death, the number of tests required, the number and expertise of physicians required to be present, and the use of ancillary testing (Gardiner et al., and D.M. Greer, S.D. Shemie, A. Lewis, S. Torrance, P. Varelas, F.D. Goldenberg, J.L. Bernat, M. Souter, M.A. Topcuoglu, A.W. Alexandrov, M. Baldisseri, T. Bleck, G. Citerio, R. Dawson, A. Hoppe, S. Jacobe, A. Manara, T.A. Nakagawa, T.M. Pope, W. Silvester, D. Thomson, H.A. Rahma, R. Badenes, A.J. Baker, V. Cerny, C. Chang, T.R. Chang, E. Gnedovskaya, M.K. Han, S. Honeybul, E. Jimenez, Y. Kuroda, G. Liu, U.K. Mallick, V. Marquevich, J. Mejia-Mantilla, M. Piradov, S. Quayyum, G.S. Shrestha, Y.Y. Su, S.D. Timmons, J. Teitelbaum, W. Videtta, K. Zirpe and G. Sung’s “Determination of brain death/death by neurological criteria: The World Brain Death Project”). In a survey of 80 countries, Wijdicks (2002) found that apnoea testing was required in only 59% of the countries, while the observation period before the confirmation of death varied from two to 72 hours, and more than one physician was required for the confirmation in half of the guidelines. In 2020, Lewis et al. reported similar variation in brain death protocols in 83 countries: the assessment of coma was not mentioned in 10% of the protocols, apnoea testing was not listed as a requirement in 9%, computed tomography scan or magnetic resonance imaging required before determining brain death was there in only 27%, and the observation period varied between one to 72 hours. A 100% consensus, per Lewis et al., was not seen regarding any aspect of brain death determination among the protocols studied. In a survey of 91 countries (S. Wahlster, E.F.M. Wijdicks, P.V. Patel, D.M. Greer, J.C. Hemphill the IIIrd, M. Carone and F.J. Mateen’s “Brain death declaration: Practices and perceptions worldwide”), only five did not require ancillary testing (the UK, Ghana, Malta, Jamaica, and Trinidad and Tobago), while ancillary tests were mandatory in 22 countries and optional in others.  In Sri Lanka, per the Transplantation of Human Tissues Act, No. 48 of 1987 and the Health Ministry's General Circular Number 01-37/2010, the determination of brain death requires the loss of “all functions of the brain”, should be made by two doctors independently on two occasions, and “should not be considered until at least six hours after the onset of coma”, while on the other hand, ancillary tests are not mandatory. Application of the accepted criteria: More variation Even with the criteria for determining brain death well established, Ranawaka added that the application of these criteria can vary considerably. In a study of brain death determination in organ donors in the USA (C.N. Shappell, J.I. Frank, K. Husari, M. Sanchez, F. Goldenberg and A. Ardelt’s “Practice variability in brain death determination: A call to action”), apnoea testing was completed in only 73% and was not even attempted in 21%; 7% of decedents without apnoea testing were declared brain dead without confirmatory testing, and only 45% of death determinations complied with the existing guidelines. In an international survey (Wahlster et al.), 53% of the respondents deviated from the established criteria. The failure to adhere to established criteria may, according to Ranawaka, reflect a lack of training. In a study of physicians and nurses involved in organ transplantation (S.J. Youngner, C.S. Landefeld, C.J. Coulton, B.W. Juknialis and M. Leary’s “Brain death’ and organ retrieval. A cross sectional survey of knowledge and concepts among health professionals”), among a group that is expected to have better than average knowledge on brain death, two thirds were unable to correctly identify the legal and medical criteria. Brain death: For organ transplantation? From the time of its introduction, the concept of brain death has attracted criticism for being a move to facilitate organ retrieval for transplantation. Wijdicks acknowledged the “perpetuating concern that the transplant physicians on this Committee (Harvard) played a decisive role in the definition of brain death”. Wijdicks commented: “I am uncertain… whether an alleged agenda of facilitating transplantation through a new construct of death existed”. In his “The neurologist and Harvard criteria for brain death”, Wijdicks narrated that the Harvard Committee Chair has commented: “Can society afford to lose organs that are now being buried?”. In an international survey (Wahlster et al.), the existence of a transplantation network was found to be more important than the per capita income level of a country in determining the presence of a brain death protocol.  There are well documented reports (G.A.V. Norman’s “A matter of life and death. What every anaesthesiologist should know about the medical, legal, and ethical aspects of declaring brain death”) of organs being removed from patients with intact spontaneous respiration yet declared brain dead, which are unlikely to enhance public confidence in the process of organ transplantation. Community surveys (Norman) have consistently highlighted public anxiety of not being dead at the time of organ collection, and people were more likely to donate the organs of relatives (82%) than their own (43%). Hence, Ranawaka noted: it is indeed debatable if society would accept a patient with a beating heart as “suitably dead” for burial or cremation, if he/she was not a candidate for organ donation.  What is death in the 21st Century? Death should be an unequivocal diagnostic entity, but a simple and straightforward answer to the question “What is death?” appears elusive. Society requires a clear definition of death. It is therefore inconceivable that there is no global consensus on such a fundamental concept, and hence, a unifying definition of death is clearly an imperative.  The lack of a global consensus has resulted in tremendous variation in the way brain death is determined. Ranawaka noted that we currently have a situation where one may be pronounced dead in one country but considered alive in another. This would indeed be comical, if not for the profound medical, legal and ethical implications of the transition from life to death. A recent Court case (J.L. Bernat and D. Larriviere’s “Areas of persisting controversy in brain death”, and J.S. Grisolia’s “The World Brain Death Project: Answering the wrong questions”) involving the death of a 13-year-old child following ear, nose, and throat surgery in the US brought into focus the persisting dilemmas regarding the determination of brain death, where the child was kept alive for more than five years after the initial brain death declaration. Are we ready, in the 21st Century, to rely on a diagnostic method with less than 100% sensitivity and specificity, and to accept a “false positive” diagnosis, in such a fundamental event as death? Ranawaka queried.  There is therefore a clear need for a uniform global framework for determining brain death that is at the same time, accepted by the medical community as well as the public. The World Brain Death Project’s consensus statement in August 2020, acknowledges the “confusion and dilemmas”, “inconsistencies in concept, criteria, practice, and documentation of brain death” and the “wide variance in practice internationally and within countries” and hence recommends abandoning the terms “whole brain death” and “brainstem death”, and calls for consistency in using the term “brain death/death by neurological criteria (BD/DNC)”. It thereby recognises the potential for a false positive diagnosis of death when “brainstem” criteria are used in primary brainstem or posterior cerebral circulation pathology, and the need for ancillary testing in such situations before brain death is confirmed. It also provides clarity on several contentious issues based on consensus, while acknowledging the lack of high quality data from randomised clinical trials to guide its recommendations, and conceding that all countries may not be able to adhere to the recommendations made, and that the determination of brain death “will always be influenced by local factors including religious, societal and cultural perspectives, legal requirements and resource availability”. In conclusion, Ranawaka maintained that the world is still a long way from settling the age-old controversy of whether a state of “as good as dead” is good enough to be labelled as “dead”.