152 Brain Death: The Asian Perspective Hoe Chin Chua, MBBS, MRCP, FRCP1 H irofum i Morihara, MD 3 Tong Kiat Kwek, MBBS, MMed (Anaesthesiology), FAMS2 Daiquan Gao, MD 4 1 Department of Neurology, National Neuroscience Institute, TanTock Seng Hospital, Singapore 2 Department of Anaesthesiology, Intensive Care and Pain Medicine, TanTock Seng Hospital, Singapore 3 Department of Neurosurgery, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore 4 Department of Neurology, XuanWu Hospital Capital Medical University, Beijing, China Address for correspondence Hoe Chin Chua, MBBS, MRCP, FRCP, Department of Neurology, National Neuroscience Institute, TanTock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433 (e-mail: hoe_chin_chua@nni.com.sg). Semin Neurol 2015;35:152-161. Abstract Keywords ► brain death ► Asia ► brainstem ► whole brain ► organ transplantation Asia is the largest and most populous continent in the world with people from many diverse ethnic groups, religions and government systems. The authors surveyed 14 countries accounting for the majority of Asia’s population and found that, although the concept of brain death is widely accepted, there is wide variability in the criteria for certification. Although most Asian countries have adopted the “whole-brain” concept of brain death, most countries with past colonial links to the United Kingdom follow the UK “brainstem ” concept of brain death. Despite this difference, most countries require only neurologic testing of irreversible coma and absent brainstem reflexes as criteria for certification of brain death. Variability exists in the number of personnel required, qualifications of certifying doctors, need for repeat examination, minimum time interval between examinations, and requirement for and choice of confirmatory tests. The concept of brain death has become an accepted fact in many countries since its first formal definition by an ad hoc committee at Flarvard Medical School in 1968.1,2 Flowever, there remains no accepted worldwide consensus on the criteria and procedures for certification of brain death in adults.2 This is a rather disconcerting state of affairs, given that brain death is being certified many times a day all over the world, with many critical decisions of organ donation or termination of organ support depending on the outcome of such certifications. Although the vast majority of countries have guidelines detailing the examination of brainstem reflexes in brain death certification, there is still a lack of clarity on the conduct of the apnea test, with only 59% of guidelines specifying a PaC02 target value.2,3 There is also no consensus on the need for a repeat examination and the optimal time interval between examinations. Worldwide, there is wide variability in the number and type of specialist personnel required for certification, with Issue Theme Brain Death; Guest Editor, Eelco F.M. Wijdicks, MD, PhD 44% of countries requiring one doctor, 34% requiring two, and 16% requiring three or more.2 The use of confirmatory tests is also another area of inconsistent practice, with some coun­ tries requiring at least one confirmatory test and others leaving it to the certifying doctors to decide. Asia is the largest and most populous continent in the world with 4.4 billion people of multiple ethnicity, cultures, and religious beliefs, located in 48 countries over a vast geographical expanse. The last review of brain death guide­ lines in Asia was published in 2001, as part of a worldwide survey of brain death criteria and practices.2 In Asian socie­ ties, life and death practices and beliefs are often influenced by and intertwined with those of local cultures and customs. Although the concept of brain death has been accepted in many Asian countries, its implementation and practice have so far been quite varied. Over the past decade, many Asian countries have experi­ enced rapid urbanization and socioeconomic development, giving rise to marked improvements in the educational level, Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. DOI http://dx.doi.org/ 10.1055/s-0035-1547539. ISSN 0271-8235. Brain Death: The Asian Perspective affluence, and health care services provided. In this article, we review and update the brain death certification guidelines and practices in Asian countries and compare them against those practised in the rest of the world. For this review, we obtained published guidelines from professional societies or any documents resulting from gov­ ernment legislations on brain death from Asian countries. In addition, a survey with questions about brain death practices and guidelines was sent to as many countries as we were able to contact. We sought to have the survey questions answered by the president or an official of the relevant professional society in each country (e.g., the critical care medicine society or neurological medicine society.) The Asian Perspective We were able to gather information or receive survey replies from 14 countries (out of 48) or approximately 29%of the 48 countries in Asia. Nonetheless, the total population of these 14 countries amounts to 3.37 billion or 77% of Asia’s total population. We will present the guidelines for each country separately (-T a b le 1). China China is the largest country in East Asia and the most populous country in Asia and the world with 1.35 billion people. In 2013, the Brain Injury Evaluation Quality Control Centre of the National Health and Family Planning Commis­ sion published the country’s criteria and practical guidance for determination of brain death in adults.4,5 Brain death in China is defined as death of the whole brain, including the brainstem. The certification of brain death in China requires fulfillment of clinical testing criteria and completion of confirmatory tests. To date, these guidelines have not been legislated into law. Certification begins with establishing that the patient is in a deep coma with absent brainstem reflexes and no sponta­ neous respiration. The apnea test is required and should show no respiratory efforts at a PaC02 > 60 mm Hg or 20 mm Hg above baseline. The accepted confirmatory tests are somato­ sensory evoked potentials (SSEPs), electroencephalogram (EEC), and transcranial Doppler (TCD) examinations, with a requirement that any two of these three tests yield results consistent with brain death. These clinical and confirmatory tests will need to be repeated 12 hours later, for brain death to be certified. Performance of each test requires the attendance of at least two doctors, with both having completed at least 5 years of clinical practice. Organ donation is allowed to proceed after brain death has been certified if the patient has previously indicated a desire to donate his/her organs upon death. The age of consent for organ donation in China is 18 years. If the patient has not previously made a decision on organ donation, the next of kin can be approached for consent and organ donation can proceed if they agree. Organs that may be donated include the heart, lungs, kidneys, liver, pancreas, and small intestine. Chua et al. Japan In 1997, Japan passed an Act on Organ Transplantation legalizing the determination of brain death only when organs are to be recovered from the deceased patient for donation.6 This Act is only applicable to patients who have previously consented to organ donation and where the next of kin have not objected. This Act was further amended in 2009, allowing the determination of brain death and the recovery of organs when the family has consented to donation even when the deceased had not previously consented to organ donation.7' 9 This change has made possible the donation of organs by children less than 15 years of age with parental consent, except for infants less than 12 weeks old and children less than 18 years old who may be victims of child abuse. Japan follows the “whole-brain” concept of brain death and requires demonstration on clinical neurologic examina­ tion of irreversible coma with absent brainstem reflexes, and the apnea test threshold set at PaC02 > 60 mm Hg. An EEG examination showing isoelectric activity is mandatory. Both the clinical examination and the EEG must be repeated, at a time interval dependent on the age of the patient, for confirmation of brain death. For patients > 6 years old, the required time interval is > 6 hours; for those < 6 years old, the time interval has to be > 24 hours. During each test, there must be at least two doctors in attendance, with only special­ ists in neurology, neurosurgery, anesthesiology, emergency medicine, intensive care, or pediatrics allowed to certify brain death. Doctors trained in other disciplines cannot certify brain death unless they are also accredited in one of the listed specialties. Organs that may be donated include the heart, lungs, liver, kidneys, pancreas, small intestines, and eye. South Korea The Korean Organ Transplantation Act, which was first passed in February 2000 and revised in May 2010, provides the legal basis for determination of brain death and promotion of organ transplantation.10 Under this Act, brain death refers to a person whose whole-brain function is determined to have irreversibly ceased, and is only restrictively recognized for the purpose of allowing organ donation. Certification of brain death requires clinical determination of irreversible coma with loss of all brainstem reflexes, including the apnea test. The clinical examination must be repeated at a time interval dependent on the patient’s age: For patients > 6 years of age, it is 6 hours; for those between 1 to 6 years of age, it is 24 hours; and for patients between 2 months and < 1 year of age, the time interval is 48 hours.10' 12 There is a requirement for four to six staff to be in attendance, with a minimum of two specialist medical staff, one of whom must be a neurologist or a neurosurgeon, and at least one nonmedical staff. The diagnosis of brain death is decided by the majority of those present at the two clinical examinations and following an EEG examination showing isoelectric activity. The reasons cited for requiring such a large group to certify brain death are—to avoid public scepti­ cism of the diagnosis and distrust of doctors, eliminate the Seminars in Neurology Vol. 35 No. 2/2015 153 Whole brain Whole brain Brainstem Brainstem Whole Brain Whole brain Whole Brain Whole brain Whole brain Brainstem Whole brain Brainstem Whole brain Japan South Korea Taiwan Hong Kong Philippines Vietnam Thailand Myanmar Malaysia Singapore Indonesia India Sri Lanka Yes Yes > 60 / |2 0 above baseline At least 2 At least 2 6 h Yes Yes > 60 / |2 0 above baseline Not specified > 60 / T20 above baseline Not specified > 6 0 / f2 0 above baseline > 50/ |2 0 above baseline > 60 / T20 above baseline fN ro fN rsi r\i ro Not specified 25 m in -2 4 h No >60 and pH < 7.3 fN Yes Yes Yes Yes Yes Yes Yes 12 h Not applicable Depends on age; range o f 6 -48 h Not specified 6 h Not specified 2 h Any tim e after 1st examination Depends on age; range of 4 -2 4 h Not specified fN Yes Not specified Depends on age; range o f 6 -48 h Depends on age; range of 6 -2 4 h 12 h Time interval to repeat examina­ tion 4 to 6 Yes Is repeat clinical testing required? Apnea Test PaC02 threshold (mm Hg) Number of personnel needed for certification fN Yes Yes Yes Yes Yes No Yes No Yes Yes Yes Yes Yes Yes Available brain death certification guidelines? No No No No 2 EECs required for children < 1 year old No No No No No No Yes Yes Yes Are ancillary tests required? Opt-in Opt-in Opt-in Opt-in and opt-out Opt-in Opt-in Opt-in Opt-in Opt-in Opt-in Opt-in Opt-in Opt-in Opt-in Consent for organ donation Brain Death: The Asian Perspective Vol. 35 No. 2/2015 Abbreviations: EEG, electroencephalogram. Whole brain China Seminars in Neurology 09 < Brain death concept 09 < Table 1 Characteristics of brain death certification in different Asian countries 154 Chua et al. rsi Brain Death: The Asian Perspective possibility of diagnostic errors, and allow swift decision making through consensus of the group. Organ donation can only proceed if there is prior consent from the patient and no objections from the next of kin. Patients < 16 years of age can donate their organs with parental consent. Organs that may be donated include the kidneys, liver, heart, lungs, pancreas, and small intestines. Taiwan In Taiwan, the Human Organ Transplantation Act was passed in 1987, and in the same year, guidelines for brain death determination were also established. Brain death is defined as death of the brainstem, which is diagnosed via two clinical assessments at separate time intervals by two doctors showing absent brainstem reflexes. The patient needs to have been on a ventilator for at least 12 hours before the first brain death examination can be performed.13 For patients more than 3 years old, the time interval between examinations must be at least 4 hours. For children 1 to 3 years old, the time interval must be least 12 hours. For children less than 1 year old but at least a full-term baby, the time interval must be least 24 hours. No mandatory confirma­ tory test is required. Only two groups of doctors are allowed to certify brain death. The first group consists of specialists in neurology, neurosurgery, or pediatric neurology. The second group comprises specialists in surgery, medicine, general pediatrics, anesthesiology, emergency medicine, or intensive care. Doctors in the second group are required to complete an 8-hour brain death course before they are allowed to be certifiers. Each pair of doctors certifying brain death will usually comprise one doctor from each group. Individuals who wish to register as organ donors must be at least 18 years of age. When a deceased patient has indicated prior consent to donate his/her organs, consent from the next of kin is still required before organ recovery can proceed. If the deceased has not previously registered as a donor, the next of kin can be approached for consent. Organs that may be donated include the heart, lungs, liver, kidneys, pancreas, and small intestines. Hong Kong In Hong Kong, brain death is based on the concept of “brainstem" death, which is likely a legacy of its previous colonial status under the United Kingdom (UK). This requires demonstration of irreversible cessation of brainstem function using guidelines established by the Hong Kong Society of Critical Care Medicine in 1992 and later revised in Septem­ ber 2009.14 These criteria are valid for patients 2 years of age or older. Two separate clinical neurologic examinations per­ formed by two doctors are required, with the first examina­ tion occurring after at least 4 hours of observation of the patient in a deep coma (Glasgow Coma Score of 3). The second examination can occur any time after the first, providing at least 4 hours of observed deep coma before brain death is certified. This duration is extended to 24 hours for brain death certified in patients following cardiorespiratory arrest. The doll’s eye or oculocephalic reflex is not included among the brainstem tests required for certification. For Chua et al. the apnea test, the required PaC02 target is > 60 mm Hg and a pH < 7.30. There is no mandatory requirement for a confirmatory test, which is only required if the preconditions for clinical testing are not met. Examples of such conditions include metabolic disorders, residual drug levels, pre-existing cranial neuropathies, and inability to tolerate the apnea test. The accepted confirmatory tests are the cerebral angiogram and the radionuclide scan. For the two doctors performing the certification, one of them has to be an intensivist, neurologist, or neurosurgeon. The other doctor should preferably have the same qualifica­ tions, but can be any doctor with at least 6 years of clinical practice and the appropriate knowledge and skills. Signed consent from the patient or the next of kin is required for organ donation. The organs that may be donated include the kidneys, heart, lungs, and liver. Philippines In the Philippines, the Organ Donation Act was passed in 1991, which permits an individual to donate all or part of his body by way of legacy or will.15This was followed in the same year by the legal recognition of brain death. The Philippines Neurological Association spearheaded a multidisciplinary consultation that led eventually to a consensus agreement on the clinical criteria for certification of brain death. These criteria were last updated in February 2012. Under these criteria, brain death is defined as irreversible coma with permanent cessation of whole-brain function, including the brainstem. The diagnosis is made from clinical neurologic examination showing absent brainstem reflexes, including the apnea test. Confirmatory tests are not required except in situations where the preconditions for clinical testing are not fully met, in which case an EEG or TCD examination would be required. A repeat clinical examination is required and must be performed at least 2 hours after the first examination.16 Each assessment requires the attendance of two doctors compris­ ing the attending doctor and another who should preferably be a neurologist, neurosurgeon, anesthesiologist, or internist. The time of death is the time when the patient was initially diagnosed to be brain dead. Their criteria also advise caution when diagnosing brain death in children less than 5 years of age. The Philippines Network for Organ Sharing was estab­ lished by the Department of Health to develop a national system for promoting organ donation from deceased donors and to ensure equitable allocation of organs. Those who wish to donate their organs upon death can register their consent and be issued an organ donor card. For those who have not made a choice, consent can be sought from the next of kin of the deceased. Vietnam In Vietnam, the law-governing organ and tissue transplanta­ tion was passed and implemented in 2007. Brain death is defined as death of the whole brain including the brainstem. There are no national guidelines for certification of brain death, with the diagnosis made on clinical neurologic Seminars in Neurology Vol. 35 No. 2/2015 155 156 Brain Death: The Asian Perspective Chua et al. examination with absence of brainstem reflexes by two doctors. Repeat examination is required, although there is no mandated minimum time interval between the two examinations. No confirmatory test is required. Consent for organ donation is obtained from the next of kin. Thailand Thailand has well established brain death certification crite­ ria endorsed by the General Medical Council of Thailand since 1989. Certification of brain death requires two clinical assessments showing absent brainstem reflexes, performed at least 6 hours apart. No mandatory confirmatory test is required.17'18 Three doctors are required for brain death certification comprising the attending doctor, a neurologist, or neuro­ surgeon, and the director of the hospital or his representative. Deceased donation of organs is possible with either prior signed consent by the deceased or consent from the next of kin. Potential donors must be less than 60 years of age. Myanmar In Myanmar, brain death was legally recognized in 2009 and is defined as death of the whole brain, including the brain­ stem. However, there are no national criteria or guidelines for certification. Brain death is diagnosed by clinical neurologic testing demonstrating absence of brainstem function. Repeat clinical testing is required, although there is no mandated time interval between examinations. No confirmatory test is required. Two certifying doctors are required, one of whom needs to be a neurologist and the other a neurosurgeon if organ donation is being considered. When organ donation is not being considered, certification can be performed by an inter­ nist and an intensivist. Consent for organ donation is obtained from the next of kin. Malaysia In Malaysia, brain death is defined as the irreversible loss of brain function as a whole, including that of the brainstem. The patient must be in a deep coma, apneic, and been on mechanical ventilation for at least 24 hours. A consensus statement on brain death was written by an expert committee in 2003 and endorsed by the Malaysian Medical Council in 2006.19,20 These guidelines have been adopted by the Minis­ try of Health, although it has not been legislated into law by the Malaysian Parliament. In adults, brain death is diagnosed through clinical neurologic testing of brainstem reflexes, including the apnea test. Two examinations must be per­ formed by two specialists at least 6 hours apart. No confir­ matory test is required. For children, the interval between examinations will vary depending on the age: For those aged between 7 days to 2 months, it is 48 hours; for those aged 2 months to 1 year, it is 24 hours; and for those older than 1 year, it is 12 hours. In addition, for those less than 1 year old, an EEG examination is required to accompany each clinical examination to complete the certification.19 When hypoxic ischemic encephalopathy is the cause of brain death, the interval between examinations will need to be at least 24 Seminars in Neurology Vol. 35 No. 2/2015 hours, unless the EEG shows isoelectric silence or the radio­ nuclide scan shows absence of intracranial blood flow. Specialists performing brain death certification must have at least 3 years of postgraduate experience and be trained in brain death certification. They should preferably be anes­ thesiologists, intensivists, internists, neurologists, or neurosurgeons. The legal age for consent for organ donation is 18 years. For those below this age, consent from the parents must be sought. The organs that may be donated include the heart, lungs, liver, and kidneys. Singapore In 1987, parliament passed the Human Organ Transplant Act, which allowed the certification of brain death from traumatic causes when the deceased had not opted-out of donating his/ her organs upon death. In 1998, the Interpretation Act of Section 2A was passed, which legally recognized brain death from all causes, even in the absence of planned organ dona­ tion.21 Brain death is defined as the irreversible loss of brainstem function, which is diagnosed through bedside testing of seven brainstem reflexes, including the apnea test. The PaC02 target for apnea testing is 50 mm Hg or an increase of > 20 mm Hg above baseline. Certification must be performed by two independent doctors iforgan donation by the deceased is being considered. If organ donation is not being considered, only one indepen­ dent doctor is required and the other doctor can be the attending neurologist, neurosurgeon, or intensivist. The two certifying doctors may perform the clinical testing together or separately. Although there is no mandatory need to repeat the brainstem tests, this is often performed as part of the workflow for certification of brain death in the intensive care unit (ICU). The certifying doctors must be specialists from surgery, medicine, anesthesia, or pediatrics and have completed a half-day brain death certification course co-organized by the Ministry of Health. Confirmatory tests are not routinely required and are only employed when the preconditions for clinical testing are not met or when the observed responses to the clinical brainstem testing are ambiguous. The only two legally recognized confirmatory tests are the cerebral angiogram and the radio­ nuclide scan. Singapore has both opt-in and opt-out consent laws for organ donation, which were passed in 1972 and 1987, respectively.21 The opt-in law allows for donation of any specified organ while the Human Organ Transplant Act or opt-out law only allows for donation of the heart, liver, kidneys, and cornea for purpose of transplantation. When the deceased has consented to organ donation, no further consent is required from the next of kin, nor are they able to object to donation. Indonesia The Indonesian criteria for brain death certification were issued by the Indonesian Medical Association in 1988 and defined brain death as the irreversible cessation of all func­ tions of the entire brain, including the brainstem.22,23 The Brain Death: The Asian Perspective most common reason for certification of brain death in Indonesia is to facilitate end-of-life care and termination of organ support. The diagnosis involves an examination dem­ onstrating irreversible coma from a structural brain injury and absent brainstem function, including the apnea test with the PaC02 threshold at > 60 mm Hg. Repeat testing is re­ quired and can be performed anytime w ithin an interval ranging from 25 minutes to 24 hours. No routine confirmato­ ry testing is required. Three doctors are required to certify brain death and they should be specialists in anesthesiology, intensive care medicine, or neurology. India India is the largest country in South Asia and the second most populous country in the world w ith 1.2 billion people. The Transplantation of Human Organ Act was passed in 1994 and regulates the removal, storage, and transplantation of human organs.24,25 In India, brain death is defined as death of the brainstem, which requires two clinical assessments, per­ formed at least 6 hours apart, showing absence of brainstem function. The apnea test requires a PaC02 > 60 mm Hg or a rise o f > 20 mm Hg above the baseline. No confirmatory test is required. A panel of four doctors is required, comprising a registered medical practitioner, a neurologist, or neurosurgeon from a notified panel, a registered medical practitioner in charge of the institution, and a registered medical practitioner treating the patient. If a neurosurgeon or neurologist is not available, the doctor in charge of the hospital may nominate an inde­ pendent doctor who can be a surgeon, internist, anesthesiol­ ogist, or intensivist.24-26 If the intent of the patient regarding organ donation is unknown, doctors may approach the next of kin for consent. Organs that may be donated include the heart, lungs, liver, and kidneys. Sri Lanka In Sri Lanka, the 1987 Transplantation of Human Tissues Act provides for the donation of human bodies and tissues for therapeutic, scientific, educational, and research purposes, and for the removal of such tissues and their use on living persons.27 Under this Act, death is defined as the irreversible cessation of all functions of the entire brain, which is deter­ mined by prolonged absence of spontaneous circulatory and respiratory function. When the patient is mechanically ven­ tilated, irreversible cessation of brain function shall be deter­ mined by prevailing best medical practice. The Act does not stipulate what the exact criteria should be.28 Currently, brain death is certified when repeated clinical examinations by two doctors 12 hours apart show absence of brainstem function. The PaC02 threshold for the apnea test is not specified. No confirmatory tests are needed. Potential organ donors must be at least 21 years old. If the deceased had not given prior consent, consent may be obtained from the next of kin. Organs that may be donated include the kidneys and liver. Organ donation is coordinated by the Sri Lanka Association of Nephrology and Transplantation.29 Chua et al. Discussion A summary of the main characteristics of brain death certifi­ cation of each country is shown in -T a b le 1 . We found that in the majority of countries in Asia that we surveyed, guidelines and criteria for certification of brain death exist. These guide­ lines often stipulated the tests to be performed, the expected findings in brain death, the need for repeat testing, the time interval between testing, and the number and type of medical personnel needed for certification. Most Asian countries have adopted the whole-brain concept definition of brain death, while most countries w ith past colonial links to the UK have adopted brainstem death as the definition of brain death. Despite this distinction, not all countries having the wholebrain concept of brain death mandate a whole-brain test to confirm brain death. The Philippines, Thailand, Indonesia, Malaysia, Sri Lanka, Myanmar, and Vietnam only require clinical neurologic evidence of irreversible coma and absence of brainstem reflexes, including the apnea test. These are largely the same criteria employed by countries having the brainstem death concept of brain death. The preconditions to brain death certification are fairly similar throughout Asia and the rest of the world. These involve first establishing an anatomical cause of extensive irreversible brain damage, usually w ith CT imaging. Second, other reversible causes of coma, such as severe hypothermia (core temperature < 32°C), severe electrolyte, acid-base or endocrine disturbances, drug intoxications, severe hepatic or renal dysfunction, must be excluded through clinical exami­ nation and laboratory testing.30 Third, residual neuromuscu­ lar blockade should be ruled out w ith a peripheral nerve stimulator for patients who have received neuromuscular blocking agents in the preceding 4 hours. The clinician should only proceed to perform the bedside brainstem tests after the three preceding steps have been performed. Though guidelines for brainstem testing are avail­ able in most Asian countries, these guidelines recommend practices that vary widely from country to country. These differences likely reflect the lack of evidence to support a standard way of certifying brain death. There are seven main brainstem tests that are often employed for brain death certification. They are fixed pupils in a mid-dilated position (4-6 mm in diameter) w ith no response to light, absent corneal reflex, absent oculocephalic (doll’s eye) reflex to rapid turning of the head, absent oculovestibular (caloric) reflex to instillation of cold saline into each ear canal, absent pharyn­ geal (gag) and laryngeal (cough) reflexes, absent facial move­ ments to pressure on the supraorbital nerve, and apnea to a maximal PaC02 stimulus.30 There is consensus that the brainstem reflexes need to be absent; however, not all countries require testing of all seven brainstem tests. Further­ more, the PaC02 threshold required for apnea testing varies, w ith most countries adopting a threshold of > 60 mm Hg or an increase o f > 20 mm Hg above the baseline. Some coun­ tries do not have a specified threshold, leaving it to certifying doctors to decide. Almost all the Asian countries surveyed reported require­ ment of a repeat neurologic examination to confirm irrevers­ ibility of lost brain function. However, the minimum time Seminars in Neurology Vol. 35 No. 2/2015 157 158 Brain Death: The Asian Perspective Chua et al. interval between examinations again varies widely, ranging from not specified to between 6 and 48 hours. This variability may again be a reflection of the lack of evidence to guide practice. To date, there is no evidence that performing a second examination improves the accuracy of the brain death diagnosis. A recent retrospective study of 100 New York hospitals involving 1,229 adult and 82 pediatric brain death certifications did not find a single second examination that showed a reversal of previously absent brainstem re­ flexes.31 The study concluded that a single neurologic examination would suffice for patients older than 1 year of age. While not adding value, dual examinations have also been found to increase costs, cause unnecessary delays in confirming death and may adversely affect organ donation potential.31,32 All Asian countries require two or more doctors to certify brain death, with India requiring as many as four doctors. Although it is reasonable and appro­ priate to have at least two certifying doctors, especially when only one of them is required to be a neurologist, neurosurgeon, intensivist, or anesthesiologist, requiring more would seem unnecessary and cause delays in certify­ ing brain death. This would not be ideal if ICU beds are in short supply or when organ donation is being considered. Most Asian countries require that one or both certifying doctors be a neurologist, neurosurgeon, or intensivist. In some countries, nonspecialist doctors who have received special training in brain death certification are also allowed to be certifiers. This concession may reflect the logistic difficulty of limiting certification to only a small pool of specialists, especially for large countries with many smaller city hospitals. Common to all countries, doctors involved in the organ transplant process or subsequent care of the transplant recipient cannot be part of the team certifying brain death for the organ donor. The need for confirmatory tests also varies widely across Asia. There are broadly two groups of confirmatory tests: The first group measures brain electrophysiology and include tests such as EEG and SSEPs; the second group measures intracranial blood flow and includes tests such as cerebral angiography, CT angiography, MR angiography, radionuclide scan, and TCD. The countries that require routine confirmatory testing are China, South Korea, and Japan. All the other countries only require confirmatory tests when preconditions for clinical testing cannot be fulfilled or if there are ambiguous findings observed during clinical testing. The type and choice of confirmatory tests also varies from country to country, deter­ mined by factors such as round-the-clock availability, infra­ structure limitations, availability of specialized manpower, and costs. It has recently been argued that confirmatory tests are not really necessary in certification of brain death in adults.33 Such tests are usually ordered as safeguards in the diagnosis of brain death; yet, they are not really confirmatory, with each test having false-positive and false-negative results.33 South Korea requires an EEG examination after two clinical neurologic examinations to confirm brain death. Japan re­ Seminars in Neurology Vol. 35 No. 2/2015 quires the EEG examination to follow each clinical examina­ tion and for both to be repeated. China has by far the most onerous requirement, needing two out of the three accepted confirmatory tests (SSEPs, EEG, and TCD) to be repeated after each clinical examination. This level of testing is probably unnecessary and may reflect distrust of the public in their health care providers. In addition to adding unnecessary costs, it will also delay certification and hence the viability of transplantable organs. It has been reported that confirmatory tests that measure intracranial blood flow, such as cerebral angiography and radionuclide scans, are more reliable and therefore preferred to the EEG and SSEPs, which are more susceptible to con­ founding by hypothermia and drugs.34 It would seem more logical and cost effective to depend on a single reliable confirmatory test than to do multiple unreliable tests. In Asia, the policies and laws on certification of brain death are often intricately interwoven with those governing de­ ceased organ donations. Most Asian countries have adopted an opt-in approach to obtaining consent for organ donation, whereby potential deceased organ donors need to have previously signed a pledge to be an organ donor or have consent signed by a willing next of kin. The deceased organ donation rates in many Asian coun­ tries are not published, but are believed to be generally very low compared with those reported in Europe and North America. The deceased donor rate for Asia was reported to be 1.1 per million population (pmp) compared with Europe and the United States at 15 to 20 pmp in Year 2000.35 There are many reasons for this low rate: wide disparity in pre­ hospital emergency services, underdeveloped health care and ICU facilities, lack of support for treatment of neurologic injuries leading to premature deaths, and the lack of a national organ procurement agency to coordinate identifica­ tion and recruitment of donors.36 Although there are laws allowing organ donation, many Asian societies have ethnic, cultural, and religious beliefs that influence their views of death and the physical body, and remain barriers to their buy-in for organ donation after death.36This is especially so in Japan, where deceased organ donation is not generally accepted despite brain death being widely accepted as equiva­ lent to death from cardiorespiratory arrest. Past improprieties by the medical community in deter­ mining brain death may have contributed to this.37 In 1968, a cardiac surgeon from Sapporo removed the heart from a donor who was not yet brain dead. The condition of the recipient was also reportedly noncritical and did not warrant a transplant. As a result, great public distrust of organ transplant developed, particularly of transplants involving brain dead donors. This low buy-in for organ donation in Asia has resulted in a small and limited supply of transplantable organs from deceased donors. The rising incidence of chronic diseases among Asian societies has resulted in a corresponding rise in the incidence of organ failures and demand for organ transplantation. These trends have resulted in a widening gap between the demand and supply of transplantable organs. Brain Death: The Asian Perspective The Influence of Religion on Brain Death and Organ Donation In Asian societies, brain death and organ donation are affect­ ed by religious concerns. We highlight the major religions below. Buddhism Buddhism has a large following in Asia. The basic teachings of Buddhism are the Four Noble Truths and the 8-fold Path.38' 41 The Four Noble Truths teach that all existence is suffering (dukha). To bring an end to suffering, insatiable human desires must be illuminated and this can be achieved by following the 8-fold Path. The central theme of Buddhism is eternal release from suffering and entering the blessed state of nirvana. Followers view life on earth as transitory and transplanting organs to keep life going as foolishness. If life is nothing but suffering, why receive an organ to prolong suffering? Individuals should let go because letting go is the end of suffering. Buddhism does not accept death as the absence of brain function, heartbeat, or breathing. Followers believe that after breathing stops, the soul remains in the body. Death is defined at the moment of departure of the soul from the body. The body must not be disturbed so that the soul can have a peaceful migration to a new destiny. Rituals are performed to complete the dying process. These customs hamper early organ retrieval. In favor of organ donation, a fundamental tenet of Buddhism is that there is virtue in eliminating suffering. This position lends itself to acts of altruism toward those in need, and suggests that donating one’s organs is to be encouraged. Confucianism Confucianism is a philosophical and quasi-religious system that emphasizes filial piety.38 Confucianism teaches that one is born with a complete body and should die the same way. Family members desire the deceased to depart to another world with an intact body rather than with missing parts. Through the concept of Ren, or benevolence/kindness, modern scholars expound the virtues of organ donation. Taoism Taoism emphasizes naturalness, peace, vitality, and “follow­ ing the flow of nature.’’38 If dying is a natural process, attempts to abort it are unnatural. Upon death, the body must be preserved to provide the soul with a resting place to ensure immortality. Elaborate rituals are performed to chan­ nel life-enhancing spirits into the body. Followers believe that death is another form of life where food, drink, clothing, money, and so on, are needed. Any damage to the body will affect the dead life’s completeness. In support of organ donation, modern scholars argue that the body is only a shelter that does not have any substantive meaning. Flence donating organs to sustain another life should not be opposed. Chua et al. Shintoism Shintoism is the indigenous religion of Japan.42 The three goals of Shintoism are the preservation of life, promotion of good health, and harmonization with nature. To pronounce death in a heart-beating deceased brain dead patient is unnatural. Interfering with the dead body is believed to bring bad luck and damage the relationship between the deceased and family. The practice of allowing a waiting time after death to ensure the soul does not return to the body is another hurdle to organ donation. The typical Japanese household adopts a combination of Shintoism, Taoism, Buddhism, and Confucianism. This com­ bination of factors affects organ donation adversely. Hinduism Hinduism, often described as a way of life, embraces a diversity of traditions and beliefs.41-43-44 This life is believed to be a transition between the previous life and the next. An important tenet of Hinduism is to help those who are suffer­ ing and Daan, or selfless giving, ranks third among its Niyamas (virtuous acts). There are many references that support the concept of organ donation in Hinduism. The physical integrity of the dead body is not seen as crucial to the reincarnation of the soul. Scientific and medical treatises (Charaka and Sushruta Samhita) form an important part of the Vedas. Sage Sushruta includes features of organ and limb transplants and is supportive of organ donation. Islam The majority opinion of Muslim jurists and scholars is that organ donation is permissible in Islam. This ruling is made by international fiqh councils and prominent scholars, such as the Islamic Fiqh Academy, the Highest Council of Scholars in Riyadh, the former Mufti of Egypt Dr. Muhammad Syed Tantawi, the Fatwa Council of Kuwait, the prominent Muslim scholar Dr. Yusuf Al-Qaradhawi, the National Scholar’s Coun­ cil of Malaysia, and the Fatwa Committee of the Islamic Religious Council of Singapore.45 The arguments in favor of organ donation are as follows. First, Islam calls for the seeking of cure and treatment for illnesses. Currently, the most effective treatment for those who suffer from organ failure is to receive a new organ in place of the failed one. Second, the objectives (maqasid) of the Syariah clearly state the importance of protecting and saving human lives. This is mentioned in the Holy Quran, “whoever saves one life, it is as though he has saved the whole of humanity” (Quran 5:32). Third, the Syariah is built upon values such as care and compassion. The Syariah thus calls for mankind to help one another and to alleviate human suffering and pain. Traditions attributed to the Prophet Muhammad also encourage Muslims to help their fellow human beings: “Whoever helps another will be granted help from Allah in the Hereafter." Fourth, donating one’s organs is an act of amal jariyah (continuous charitable deed) in which the rewards accrue even after one’s death.45’46 The arguments against organ donation are as follows. First, Islam places a great emphasis on respect and sanctity of the human body. Violating the human body, whether living or Seminars in Neurology Vol. 35 No. 2/2015 159 160 Brain Death: The Asian Perspective Chua et al. dead, is forbidden in Islam. It could be argued that organ donation, for example, kidney transplantation, may not be an absolute necessity in view of the availability of dialysis (though the quality of life is suboptimal). Second, there is the conflict between free will and predetermination: If God has foreordained the failure of an organ, what right do humans have to replace the function of that organ by trans­ plantation? Third, Muslims have a perception that they are not owners of their own body or organs and have no right to give their organs away. Fourth, Muslims believe that on the Day of Judgement their bodily parts and organs will testify before God the good and bad deeds they had done in life. How can such testimony occur if an organ had been donated away in life or after death? Fifth, brain death is not considered death from an Islamic perspective.41,45,46 Death in Islam is an active process, a transition for the soul from the physical to the spiritual world. As regards end-of-life rituals, a person is not considered dead until the body has become cold and rigor mortis has set in. The family should be allowed to stay with the patient and continue with end-of-life rituals until cardiopulmonary arrest has occurred. Given this set of beliefs linked to Islamic theology, the reluctance of family members to allow physicians to incise the breathing body of their loved one sustained by life support is under­ standable. This belief is not easily reversed.41 Worldwide, most Islamic scholars endorse organ donation, with a dissenting voice from the minority. Christianity Most Christians, Roman Catholics, and Protestants do not have theological objections to brain death or organ dona­ tion.41 Christians are taught to “love your neighbor" (Mat­ thew 5:43) and because organ donation has the potential to save lives and help others, its teachings favor organ donation. Conclusions Asia is the contingent with the largest land mass and popula­ tion in the world. Many countries in Asia have experienced massive urbanization and socioeconomic development in the past decade. This has brought rising affluence and demands for high-quality health care. Most Asian countries today have recognized brain death, adopting the whole-brain concept of brain death, defined as the irreversible loss of all brain functions including those of the brainstem. Although many countries have brain death certification guidelines, the criteria applied are not always uniform, especially for the apnea test. There are also differ­ ences in the need for repeat neurologic examinations, the minimum interval between examinations, and the number and type of personnel needed for certification. Most countries do not require the routine use of a confirmatory test for certification. Organ donation is a complicated issue influenced not only by medical decisions, but also by religion, traditions, and ethics. The buy-in for deceased organ donation is still very low in Asia despite the acceptance of brain death. Coupled with a rising incidence of chronic diseases and organ failures, Seminars in Neurology Vol. 35 No. 2/2015 this has resulted in a widening gap between the demand and supply for transplantable solid organs. It may be an oppor­ tune time for governments and health care organizations in Asia to work together to improve this situation. Acknowledgments The authors thank the following specialists (neurologists, neurosurgeons, anesthesiologists, and others) who gave of their precious time to complete the survey and answer questions on the policies and laws in their respective countries: Daiquan Gao, Feng Gang (China); Hirofumi Morihara, Nonaka Sinseh, Masahiro Sonoo, Miyaji, Shozo Tobimatsu (Japan); Dong Chan Kim, Cheol Woong Jung, Benjamin Youchan Shin (South Korea); Lung Chan, ShanJin Ryu (Taiwan); So Hing Yu (Hong Kong); Jose Navarro, Paul Matthew Pasco, Jose Emmanuel Palo, Antonio Mangubat (Philippines); Huy Thang Nguyen (Vietnam); Sombat Muengtaweepongsa (Thailand); Win Min Thit (Myanmar); Lim Wee Leong, Goh Khean Jin (Malaysia); Sandhi Christanto (Indonesia); Hari Har Dash, Man Mohan Mehndiratta, Parampreet Kharbanda (India); Thashi Chang (Sri Lanka). References Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. A definition of irreversible coma. JAMA 1968;205(6):337-340 2 Wijdicks EF. Brain death worldwide: accepted fact but no global consensus in diagnostic criteria. Neurology 2002;58(l):20-25 3 Wijdicks EF. The clinical criteria of brain death throughout the world: why has it come to this? Can J Anaesth 2006:53(6): 540-543 4 Brain Injury Evaluation Quality Control Centre of National Health and Family Planning Commission. Criteria and practical guidance for determination of brain death in adults (BQCC version). Chin Med J (Engl) 2013;126(24):4786-4790. Available at: http://www. cmj.org/ch/reader/create_pdf.aspx?file_no=20132199&flag=l&year_id=2013&quarter_id=24. Accessed December 2, 2014 5 Su Y, Yang Q Liu G, et al. Diagnosis of brain death: confirmatory tests after clinical test. Chin MedJ (Engl) 2014; 127(7): 1272—1277 6 Japan Organ Transplant Network Homepage. Available at: http:// www.jotnw.or.jp/english/index.html. Accessed December 2, 2014 7 Natori Y. Legal determination of brain death. JMAJ 2011 ;54(6): 363-367 8 Enforcement of Amended Organ Transplantation Law. June 2011. Office for Organ Transplantation Health Service Bureau Ministry of Health, Labor and Welfare. Available at: http://www.mhlw.go.jp/ english/policy/health-medical/health/dl/enforcement.pdf. Ac­ cessed December 2, 2014 9 Aruga T. Revised Organ Transplant Act and critical care physicians. JMAJ 2011;54(6):368-374 10 Joo HN. The organ transplantation act and recent trends in Korea. Asia PacJ Public Health 2013;25(2):209-213 Available at: http:// aph.sagepub.com/content/25/2/209. December 2, 2014 n JooJ. Management of brain-dead donors in Korea. J Korean Med Assoc 2014;57(2): 137—142 12 Lee SD, Kim JH. Changes in the organ procurement system in South Korea: effects on brain-dead donor numbers. Transplant Proc 2009;41(9):3551-3555 13 Brain death guidelines inTaiwan. Available at: http://law.moj.gov. tw/LawClass/LawAll.aspx?PCode=L0020079. December 2, 2014 1 Brain Death: The Asian Perspective Hong Kong Society of Critical Care Medicine Position Statement. Guidelines on certification of brain death. Available at: http:// www.hksccm.org/index.php?option=com_content&view=artide&id=l 118:2009-sep-14-guidelines-on-certification-of-deathfollowing-the-irreversible-cessation-of-brainstem-function&catid=91&ltemid=69&lang=en. Accessed December 2,2014 15 Organ Donation Act of 1991. Republic of the Philippines. Available at: http://www.hksccm.org/index.php?option=com_content%view=article%id=l 118%lang=en. Accessed December 2, 2014 16 Establishment of a national program for sharing of organs from deceased donors. Administrative order no 2010-0019. Republic of the Philippines. Department of Health. Available at: http://wwwl. umn.edu/humanrts/research/Philippines/D0H%20Adm.%200rder %202010-0019%20on%200rgan%20Trafficking.pdf. Accessed De­ cember 2, 2014 17 Brain death and organ donation, Thailand. Available at: http:// www.med.cmu.ac.th/secret/meded/Mede7/%B5%E9%B9%A9%BA% Dl%BA/MEDE07PDF/Chapter03%20MEDE07.pdf. Accessed De­ cember 2, 2014 18 Tungsiripat R, Tangcharoensathien V. Regulation of organ trans­ plantation in Thailand. Does it work? Available at: http://r4d.dfid. gov.uk/pdf/outputs/healthecfinj<p/wp04_03.pdf. Accessed De­ cember 2, 2014 19 Consensus statement on Brain Death. 2003. Ministry of Health Malaysia. Available at: http://www.moh.gov.my/images/gallery/ orga/Consensus%20statement%20on%20brain%20death%202003. pdf. Accessed December 2, 2014 20 Guideline of the Malaysian Medical Council. 2006. MMC Guideline 08/2006. Available at: http://www.moh.gov.my/images/gallery/ orga/Brain%20Death%20-%20Malaysian%20Medical%20Council. pdf. Accessed December 2, 2014 21 Manual on Organ Donation and Transplantation. Singapore: Min­ istry of Health Singapore; 2013 22 Brain death diagnosis and clinical application. Indonesia. Avail­ able at: http://www.academia.edu/6887735/Brain_Death_Diagnosis_and_Clinical„Application. Accessed December 2,2014 23 Brain death and organ donation in Indonesia. Available at: http:// www.hukor.depkes.go.id/up_prod_permenkes/PMK%20No.% 2037%20Th%202014%20ttg%20Penentuan%20Mati%20dan%20Pemanfaatan%200rgan%20Donor.pdf. Accessed December 2, 2014 24 Agarwai SK, Srivastava RK, Gupta S, Tripathi S. Evolution of the transplantation of human organ act and law in India. Transplan­ tation 2012;94(2): 110—113 25 The Transplantation of Human Organs (Amendment) Bill. 2009. Available at: http://www.prsindia.org/uploads/media/Organ% 20transplantation/Legislative%20Brief%20-%20Transplantation% 20of%20human%20organs%20Bill%202009.pdf. Accessed Decem­ ber 2, 2014 26 Sethi NK, Sethi PK. Brainstem death: implications in India. J Assoc Physicians India 2003;51:910-911 14 Chua et al. 27 Sri Lanka. In: World Health Organization, Legislative Responses to Organ Transplantation. Leiden, The Netherlands: Martinus Nijhoff Publishers; 1994:349-352 28 Rohan RP. A brain death: concepts and confusion among medical experts, legal authorities and general public in Sri Lanka. Galle Med J 2008;13(1 ):48— 50 29 Walallawita LD. Brainstem death and organ donation. Sri Lankan J Anaesthesiology 2009;17(2):95-98 30 Wijdicks EF. The diagnosis of brain death. N Engl J Med 2001; 344( 16):1215—1221 31 Lustbader D, O’Hara D, Wijdicks EF, et al. Second brain death examination may negatively affect organ donation. Neurology 2011 ;76(2):119—124 32 Varelas PN, Rehman M, Abdelhak T, et al. Single brain death examination is equivalent to dual brain death examinations. Neurocrit Care 2011; 15(3):547-553 33 Wijdicks EF. The case against confirmatory tests for determining brain death in adults. Neurology 2010;75(1 ):77— 83 34 Young GB, Shemie SD, Doig CJ, Teitelbaum j. Brief review: the role of ancillary tests in the neurological determination of death. Can J Anaesth 2006;53(6):620-627 35 World Health Organization. WHO Report - Ethics, Access and Safety in Tissue and Organ Transplantation: Issues of Global Concern. Geneva, Switzerland: WHO; 2003 36 Vathsala A. Improving cadaveric organ donation rates in kidney and liver transplantation in Asia. Transplant Proc 2004;36(7):1873-1875 37 Wada issue. Available at: https://www.jstage.jst.go.jp/article/ ihjl960/36/1 /36_l_13/_pdf. Accessed December 2, 2014 38 Tai MC. An Asian perspective on organ transplantation. Wien Med Wochenschr 2009; 159(17-18):452-456 39 Keown D. Buddhism, brain death and organ transplantation. J Buddh Ethics 2010;17:1-36 40 Metz W. The Enlightened One: Buddhism. In: Beaver RP, Bergman J, Langley MS, eds.The World's Religions. Oxford: Lion; 1982:222-244 41 Bresnahan MJ, Mahler K. Ethical debate over organ donation in the context of brain death. Bioethics 2010;24(2):54-60 42 Hardacre H. Response of Buddhism and Shinto to the issue of brain death and organ transplant. Camb Q. Healthc Ethics 1994;3(4): 585-601 43 Firth S. End-of-life: a Hindu view. Lancet 2005:366(9486): 682-686 44 Hinduism and Organ Donation. Available at: http://www.organdonation.nhs.uk/how_to_become_a_donor/religious_perspectives/leaflets/hindu_dharma_and_organ_donation.asp. Accessed December 19, 2014 45 Organ transplant in Islam. Available at: http://www.muis.gov.sg/ cms/uploadedFiles/MuisGovSG/Religious/OOM/Resources/Muis% 201<idney%20book%20ENG.pdf. Accessed December 2, 2014 46 Sharif A. Organ donation and Islam-challenges and opportunities. Transplantation 2012;94(5):442-446 Seminars in Neurology Vol. 35 No. 2/2015 161 Copyright of Seminars in Neurology is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
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