Brain death

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Brain death
Other namesBrain stem death
A brain-dead patient. The patient can also be seen here executing the Lazarus sign.
Specialty Neurology, neurosurgery, palliative care, critical care medicine
Complications Total organ failure
Causes Cardiac arrest, myocardial infarction, stroke, blood clot
Diagnostic method Stimulation testing, EEG, pupil reactivity test
TreatmentArtificial life support
Prognosis None; brain death is irreversible
FrequencyRare
Deaths15,000 to 20,000

Brain death is the permanent, irreversible, and complete loss of brain function, which may include cessation of involuntary activity necessary to sustain life. [1] [2] [3] [4] It differs from persistent vegetative state, in which the person is alive and some autonomic functions remain. [5] It is also distinct from comas as long as some brain and bodily activity and function remain, and it is also not the same as the condition locked-in syndrome. A differential diagnosis can medically distinguish these differing conditions.

Contents

Brain death is used as an indicator of legal death in many jurisdictions, [6] but it is defined inconsistently and often confused by the public. [7] Various parts of the brain may keep functioning when others do not anymore, and the term "brain death" has been used to refer to various combinations. For example, although one major medical dictionary considers "brain death" to be synonymous with "cerebral death" (death of the cerebrum), [8] the US National Library of Medicine Medical Subject Headings (MeSH) system defines brain death as including the brainstem. The distinctions are medically significant because, for example, in someone with a dead cerebrum but a living brainstem, spontaneous breathing may continue unaided, whereas in whole-brain death (which includes brainstem death), only life support equipment would maintain ventilation. In certain countries, patients classified as brain-dead may legally have their organs surgically removed for organ donation.[ citation needed ]

Medicolegal history

Differences in operational definitions of death have obvious medicolegal implications (in medical jurisprudence and medical law). Traditionally, both the legal and medical communities determined death through the permanent end of certain bodily functions in clinical death, especially respiration and heartbeat. With the increasing ability of the medical community to resuscitate people with no respiration, heartbeat, or other external signs of life, the need for another definition of death occurred, raising questions of legal death. This gained greater urgency with the widespread use of life support equipment and the rising capabilities and demand for organ transplantation.

Since the 1960s, laws governing the determination of death have been implemented in all countries that have active organ transplantation programs. The first European country to adopt brain death as a legal definition (or indicator) of death was Finland in 1971, while in the United States, the state of Kansas had enacted a similar law earlier. [9]

An ad hoc committee at Harvard Medical School published a pivotal 1968 report to define irreversible coma. [10] [11] The Harvard criteria gradually gained consensus toward what is now known as brain death. In the wake of the 1976 Karen Ann Quinlan case, state legislatures in the United States moved to accept brain death as an acceptable indication of death. In 1981, a presidential commission issued a landmark report entitled Defining Death: Medical, Legal, and Ethical Issues in the Determination of Death, [12] which rejected the "higher-brain" approach to death in favor of a "whole-brain" definition. This report formed the basis for the Uniform Determination of Death Act, since enacted in 39 states. [13] Today, both the legal and medical communities in the US use "brain death" as a legal definition of death, allowing a person to be declared legally dead even if life support equipment maintains the body's metabolic processes. [14]

In the UK, the Royal College of Physicians reported in 1995, abandoning the 1979 claim that the tests published in 1976 sufficed for the diagnosis of brain death, and suggesting a new definition of death based on the irreversible loss of brain-stem function alone. [15] This new definition, the irreversible loss of the capacity for consciousness and for spontaneous breathing, and the essentially unchanged 1976 tests held to establish that state, have been adopted as a basis of death certification for organ transplant purposes in subsequent Codes of Practice. [16] [17] The Australia and New Zealand Intensive Care Society (ANZICS) states that the "determination of brain death requires that there is unresponsive coma, the absence of brain-stem reflexes and the absence of respiratory centre function, in the clinical setting in which these findings are irreversible. In particular, there must be definite clinical or neuro-imaging evidence of acute brain pathology (e.g. traumatic brain injury, intracranial haemorrhage, hypoxic encephalopathy) consistent with the irreversible loss of neurological function." [18] In Brazil, the Federal Council of Medicine revised its regulations in 2017, including "a requirement for the patient to meet specific physiological prerequisites and for the physician to provide optimized care to the patient before starting the procedures for diagnosing brain death and to perform complementary tests, as well as the need for specific training for physicians who make this diagnosis." [19]

In 2020, an international panel of experts, the World Brain Death Project, published a guideline that: [20]

provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria (BD/DNC) in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.

Medical criteria

Natural movements also known as the Lazarus sign or Lazarus reflex can occur on a brain-dead person whose organs have been kept functioning by life support. The living cells that can cause these movements are not living cells from the brain or brain stem; these cells come from the spinal cord. Sometimes these body movements can cause false hope for family members.

A brain-dead individual has no clinical evidence of brain function upon physical examination. This includes no response to pain and no cranial nerve reflexes. Reflexes include pupillary response (fixed pupils), oculocephalic reflex, corneal reflex, no response to the caloric reflex test, and no spontaneous respirations.

Brain death can sometimes be difficult to differentiate from other medical states such as barbiturate overdose, acute alcohol poisoning, sedative overdose, hypothermia, hypoglycemia, coma, and chronic vegetative states. Some comatose patients can recover to pre-coma or near pre-coma level of functioning, and some patients with severe irreversible neurological dysfunction will nonetheless retain some lower brain functions, such as spontaneous respiration, despite the losses of both cortex and brain stem functionality. Such is the case with anencephaly.

Brain electrical activity can stop completely, or drop to such a low level as to be undetectable with most equipment. An EEG will therefore be flat, though this is sometimes also observed during deep anesthesia or cardiac arrest. [21] Although in the United States a flat EEG test is not required to certify death, it is considered to have confirmatory value. In the UK it is not considered to be of value because any continuing activity it might reveal in parts of the brain above the brain stem is held to be irrelevant to the diagnosis of death on the Code of Practice criteria. [22]

The diagnosis of brain death is often required to be highly rigorous, in order to be certain that the condition is irreversible. Legal criteria vary, but in general require neurological examinations by two independent physicians. The exams must show complete and irreversible absence of brain function (brain stem function in UK), [23] and may include two isoelectric (flat-line) EEGs 24 hours apart (less in other countries where it is accepted that if the cause of the dysfunction is a clear physical trauma there is no need to wait that long to establish irreversibility). The patient should have a normal temperature and be free of drugs that can suppress brain activity if the diagnosis is to be made on EEG criteria.

Radionuclide scan: No intracranial blood flow. The "hot-nose" sign is shown. Radionuclide Cerebral Blood Flow Scan.png
Radionuclide scan: No intracranial blood flow. The "hot-nose" sign is shown.

Also, a radionuclide cerebral blood flow scan that shows complete absence of intracranial blood flow must be considered with other exams – temporary swelling of the brain, particularly within the first 72 hours, can lead to a false positive test on a patient that may recover with more time. [24]

CT angiography is neither required nor sufficient test to make the diagnosis. [25]

Confirmatory testing is only needed under the age of 1. [2] For children and adults, testing is optional. Other situations possibly requiring confirmatory testing include severe facial trauma where determination of brainstem reflexes will be difficult, pre-existing pupillary abnormalities, and patients with severe sleep apnea and/or pulmonary disease. [2] Confirmatory tests include: cerebral angiography, electroencephalography, transcranial Doppler ultrasonography, and cerebral scintigraphy (technetium Tc 99m exametazime). Cerebral angiography is considered the most sensitive confirmatory test in the determination of brain death. [2]

Organ donation

While the diagnosis of brain death has become accepted as a basis for the certification of death for legal purposes, it is a very different state from biological death – the state universally recognized and understood as death. [26] The continuing function of vital organs in the bodies of those diagnosed brain dead, if mechanical ventilation and other life-support measures are continued, provides optimal opportunities for their transplantation.

When mechanical ventilation is used to support the body of a brain dead organ donor pending a transplant into an organ recipient, the donor's date of death is listed as the date that brain death was diagnosed. [27]

In some countries (for instance, Spain, [28] Finland, the United Kingdom [29] , Portugal, France, and by 2026 Switzerland), everyone is automatically an organ donor after diagnosis of death on legally accepted criteria, although some jurisdictions (such as Singapore, Spain, the United Kingdom, France, Czech Republic, Poland and Portugal) allow opting out of the system. Elsewhere, consent from family members or next-of-kin may be required for organ donation. In New Zealand, Australia and most states in the United States, drivers are asked upon application if they wish to be registered as an organ donor. [30]

In the United States, if the patient is at or near death, the hospital must notify a designated Organ Procurement Organization (OPO) of the details, and maintain the patient while the patient is being evaluated for suitability as a donor. [31] The OPO searches to see if the deceased is registered as a donor, which serves as legal consent; if the deceased has not registered or otherwise noted consent (e.g., on a driver's license), the OPO will ask the next of kin for authorization. [32] The patient is kept on ventilator support until the organs have been surgically removed. If the patient has indicated in an advance health care directive that they do not wish to receive mechanical ventilation or has specified a do-not-resuscitate (DNR) order and the patient has also indicated that they wish to donate their organs, some vital organs such as the heart and lungs may not be able to be recovered. [33]

Demographics

United States

Brain death is responsible for 2% of all adult and 5% of pediatric in-hospital deaths in the United States. [34] In a nationwide survey of pediatric intensive care units (PICU) in the United States in 2019; there were more than 3,000 pediatric brain deaths out of a total of more than 15,344 children who died in PICUs. According to a national study, "brain death evaluations are performed infrequently, even in large PICUs." [35]

See also

Related Research Articles

<span class="mw-page-title-main">Coma</span> State of unconsciousness

A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. The person may experience respiratory and circulatory problems due to the body's inability to maintain normal bodily functions. People in a coma often require extensive medical care to maintain their health and prevent complications such as pneumonia or blood clots. Coma patients exhibit a complete absence of wakefulness and are unable to consciously feel, speak or move. Comas can be the result of natural causes, or can be medically induced.

<span class="mw-page-title-main">Neurology</span> Medical specialty dealing with disorders of the nervous system

Neurology is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the spinal cord and the peripheral nerves. Neurological practice relies heavily on the field of neuroscience, the scientific study of the nervous system.

<span class="mw-page-title-main">Locked-in syndrome</span> Condition in which a patient is aware but completely paralysed

Locked-in syndrome (LIS), also known as pseudocoma, is a condition in which a patient is aware but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for vertical eye movements and blinking. The individual is conscious and sufficiently intact cognitively to be able to communicate with eye movements. Electroencephalography results are normal in locked-in syndrome. Total locked-in syndrome, or completely locked-in state (CLIS), is a version of locked-in syndrome wherein the eyes are paralyzed as well. Fred Plum and Jerome B. Posner coined the term for this disorder in 1966.

<span class="mw-page-title-main">Anencephaly</span> Neural tube defect involving absence of much of the brain, skull and scalp

Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception. Strictly speaking, the Greek term translates as "without a brain", but it is accepted that children born with this disorder usually only lack a telencephalon, the largest part of the brain consisting mainly of the cerebral hemispheres, including the neocortex, which is responsible for cognition. The remaining structure is usually covered only by a thin layer of membrane—skin, bone, meninges, etc., are all lacking. With very few exceptions, infants with this disorder do not survive longer than a few hours or days after birth.

A vegetative state (VS) or post-coma unresponsiveness (PCU) is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. After four weeks in a vegetative state, the patient is classified as being in a persistent vegetative state (PVS). This diagnosis is classified as a permanent vegetative state some months after a non-traumatic brain injury or one year after a traumatic injury. The term unresponsive wakefulness syndrome may be used alternatively, as "vegetative state" has some negative connotations among the public.

Encephalopathy means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome has many possible organic and inorganic causes.

Prior to the introduction of brain death into law in the mid to late 1970s, all organ transplants from cadaveric donors came from non-heart-beating donors (NHBDs).

A flatline is an electrical time sequence measurement that shows no activity and therefore, when represented, shows a flat line instead of a moving one. It almost always refers to either a flatlined electrocardiogram, where the heart shows no electrical activity (asystole), or to a flat electroencephalogram, in which the brain shows no electrical activity. Both of these specific cases are involved in various definitions of death.

Epilepsy surgery involves a neurosurgical procedure where an area of the brain involved in seizures is either resected, ablated, disconnected or stimulated. The goal is to eliminate seizures or significantly reduce seizure burden. Approximately 60% of all people with epilepsy have focal epilepsy syndromes. In 15% to 20% of these patients, the condition is not adequately controlled with anticonvulsive drugs. Such patients are potential candidates for surgical epilepsy treatment.

Certain fundamental Jewish law questions arise in issues of organ donation. Donation of an organ from a living person to save another's life, where the donor's health will not appreciably suffer, is permitted and encouraged in Jewish law. Donation of an organ from a dead person is equally permitted for the same purpose: to save a life. This simple statement of the issue belies, however, the complexity of defining death in Jewish law. Thus, although there are side issues regarding mutilation of the body etc., the primary issue that prevents organ donation from the dead amongst Jews, in many cases, is the definition of death, simply because to take a life-sustaining organ from a person who was still alive would be murder.

<span class="mw-page-title-main">Lazarus sign</span> Reflex movement in brain-dead or brainstem failure patients

The Lazarus sign or Lazarus reflex is a reflex movement in brain-dead or brainstem failure patients, which causes them to briefly raise their arms and drop them crossed on their chests. The phenomenon is named after the Biblical figure Lazarus of Bethany, whom Jesus raised from the dead according to the Gospel of John.

<span class="mw-page-title-main">Steven Laureys</span> Belgian neurologist (born 1968)

Steven Laureys is a Belgian neurologist. He is principally known as a clinician and researcher in the field of neurology of consciousness.

Many different major religious groups and denominations have varying views on organ donation of a deceased and live bodies, depending on their ideologies. Differing opinions can arise depending on if the death is categorized as brain death or cease of the heartbeat. It is important for doctors and health care providers to be knowledgeable about differentiating theological and cultural views on death and organ donations as nations are becoming more multicultural.

A beating heart cadaver is a body that is pronounced dead in all medical and legal definitions, connected to a medical ventilator, and retains cardio-pulmonary functions. This keeps the organs of the body, including the heart, functioning and alive. As a result, the period of time in which the organs may be used for transplantation is extended. The heart contains pacemaker cells that will cause it to continue beating even when a patient is brain-dead. Other organs in the body do not have this capability and need the brain to be functioning to send signals to the organs to carry out their functions. A beating heart cadaver requires a ventilator to provide oxygen to its blood, but the heart will continue to beat on its own even in the absence of brain activity. This allows organs to be preserved for a longer period of time in the case of a transplant or donation. A small number of cases in recent years indicate that it can also be implemented for a brain-dead pregnant woman to reach the full term of her pregnancy. There is an advantage to beating heart cadaver organ donation because doctors are able to see the vitals of the organs and tell if they are stable and functioning before transplanting to an ailing patient.

Brainstem death is a clinical syndrome defined by the absence of reflexes with pathways through the brainstem – the "stalk" of the brain, which connects the spinal cord to the mid-brain, cerebellum and cerebral hemispheres – in a deeply comatose, ventilator-dependent patient. Identification of this state carries a very grave prognosis for survival; cessation of heartbeat often occurs within a few days, although it may continue for weeks if intensive support is maintained.

Bickerstaff brainstem encephalitis is a rare inflammatory disorder of the central nervous system, first described by Edwin Bickerstaff in 1951. It may also affect the peripheral nervous system, and has features in common with both Miller Fisher syndrome and Guillain–Barré syndrome.

Disorders of consciousness are medical conditions that inhibit consciousness. Some define disorders of consciousness as any change from complete self-awareness to inhibited or absent self-awareness and arousal. This category generally includes minimally conscious state and persistent vegetative state, but sometimes also includes the less severe locked-in syndrome and more severe but rare chronic coma. Differential diagnosis of these disorders is an active area of biomedical research. Finally, brain death results in an irreversible disruption of consciousness. While other conditions may cause a moderate deterioration or transient interruption of consciousness, they are not included in this category.

Clinical Electrophysiological Testing is based on techniques derived from electrophysiology used for the clinical diagnosis of patients. There are many processes that occur in the body which produce electrical signals that can be detected. Depending on the location and the source of these signals, distinct methods and techniques have been developed to properly target them.

Legal death is the recognition under the law of a particular jurisdiction that a person is no longer alive. In most cases, a doctor's declaration of death or the identification of a corpse is a legal requirement for such recognition. A person who has been missing for a sufficiently long period of time may be presumed or declared legally dead, usually by a court. When a death has been registered in a civil registry, a death certificate may be issued. Such death certificate may be required in a number of legal situations, such as applying for probate, claiming some benefits, or making an insurance claim.

The stages of death of a human being have medical, biochemical and legal aspects. The term taphonomy from palaeontology applies to the fate of all kinds of remains of organisms. Forensic taphonomy is concerned with remains of the.

References

  1. ↑ "Brain death". Encyclopedia of Death and Dying. Retrieved 25 March 2014.
  2. 1 2 3 4 Young, G Bryan. "Diagnosis of brain death". UpToDate. Retrieved 25 March 2014.
  3. ↑ Goila, A.; Pawar, M. (2009). "The diagnosis of brain death". Indian Journal of Critical Care Medicine. 13 (1): 7–11. doi: 10.4103/0972-5229.53108 . PMC   2772257 . PMID   19881172.
  4. ↑ Machado, C. (2010). "Diagnosis of brain death". Neurology International. 2 (1): 2. doi:10.4081/ni.2010.e2. PMC   3093212 . PMID   21577338.
  5. ↑ Multi-Society Task Force on PVS (May 1994). "Medical aspects of the persistent vegetative state (1)". N. Engl. J. Med. 330 (21): 1499–508. doi: 10.1056/NEJM199405263302107 . PMID   7818633.
  6. ↑ "Brain death". 20 October 2017.
  7. ↑ Jones AH, Dizon ZB, October TW (August 2018). "Investigation of Public Perception of Brain Death Using the Internet". Chest. 154 (2): 286–292. doi:10.1016/j.chest.2018.01.021. PMC   7339235 . PMID   29382473.
  8. ↑ Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier, archived from the original on 11 January 2014, retrieved 20 July 2015.
  9. ↑ (Randell T. (2004). "Medical and legal considerations of brain death". Acta Anaesthesiologica Scandinavica. 48 (2): 139–44. doi:10.1111/j.0001-5172.2004.00304.x. PMID   14995934. S2CID   38019096.
  10. ↑ "A definition of irreversible coma: report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death". JAMA. 205 (6): 337–40. 1968. doi:10.1001/jama.1968.03140320031009. PMID   5694976.
  11. ↑ Life-sustaining technologies and the elderly. Diane Publishing. 1987. ISBN   978-1-4289-2281-5 – via Google Books.
  12. ↑ Defining death: a report on the medical, legal and ethical issues in the determination of death. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. July 1981. hdl: 1805/707 .
  13. ↑ "Legislative Fact Sheet – Determination of Death Act". Uniform Law Commission. Retrieved 8 May 2012.[ dead link ]
  14. ↑ "Uniform Determination of Death Act" (PDF). National Conference of Commissioners on Uniform State Laws. Archived from the original (PDF) on 4 March 2016. Retrieved 26 March 2014.
  15. ↑ "Criteria for the diagnosis of brain stem death. Review by a working group convened by the Royal College of Physicians and endorsed by the Conference of Medical Royal Colleges and their Faculties in the United Kingdom". J R Coll Physicians Lond. 29 (5): 381–82. 1995. PMC   5401215 . PMID   8847677.
  16. ↑ "A Code of Practice for the Diagnosis and Confirmation of Death." Academy of Medical Royal Colleges, London, 2008
  17. ↑ American Academy of Neurology. (2000, January 13).Spontaneous Movements Often Occur After Brain Death. Science Daily.
  18. ↑ The ANZICS Statement on Death and Organ Donation (PDF) (3.2 ed.). Melbourne: Australian and New Zealand Intensive Care Society. 2013. p. 17. ISBN   978-1-876980-21-4. Archived from the original (PDF) on 19 March 2018.
  19. ↑ Westphal, Glauco Adrieno; Veiga, Viviane Cordeiro; Franke, Cristiano Augusto (July–September 2019). "Diagnosis of brain death in Brazil". Revista Brasileira de terapia intensiva. 31 (3): 403–09. doi:10.5935/0103-507X.20190050. PMC   7005965 . PMID   31618361.
  20. ↑ Greer, DM; Shemie, SD; Lewis, A; Torrance, S; Varelas, P; Goldenberg, FD; et al. (15 September 2020). "Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project". JAMA. 324 (11): 1078–97. doi:10.1001/jama.2020.11586. PMID   32761206. S2CID   221038198.
  21. ↑ Karasawa, H; et al. (January 2001). "Intracranial electroencephalographic changes in deep anesthesia". Clin Neurophysiol. 112 (1): 25–30. doi:10.1016/s1388-2457(00)00510-1. PMID   11137657. S2CID   30912230.
  22. ↑ "A Code of Practice for the Diagnosis of Death". Academy of Medical Royal Colleges, London, 2008
  23. ↑ Waters, C. E.; French, G.; Burt, M. (2004). "Difficulty in brainstem death testing in the presence of high spinal cord injury". British Journal of Anaesthesia. 92 (5): 760–64. doi: 10.1093/bja/aeh117 . PMID   15113764.
  24. ↑ "Brain Dead – NeuroLogica Blog". theness.com. 8 April 2008.
  25. ↑ Taylor, T; Dineen, RA; Gardiner, DC; Buss, CH; Howatson, A; Pace, NL (31 March 2014). "Computed tomography (CT) angiography for confirmation of the clinical diagnosis of brain death". The Cochrane Database of Systematic Reviews. 3 (3): CD009694. doi:10.1002/14651858.CD009694.pub2. PMC   6517290 . PMID   24683063.
  26. ↑ Truog RD, Miller FG. The meaning of brain death. JAMA Internal Medicine 2014, Publ online June 9, 2014 : doi : 10.1001/jamainternmed.2014.2272
  27. ↑ "Understanding Brain Death". 29 September 2011. What is the legal time of death for a brain dead patient? The legal time of death is the date and time that doctors determine that all brain activity has ceased. This is the time that is noted on the patient's death certificate.
  28. ↑ "Donación". Organización Nacional de Trasplantes (in Spanish). Archived from the original on 4 July 2017. Retrieved 1 April 2021.
  29. ↑ "UK laws".
  30. ↑ "National Donate Life America Donor Designation State Report Card 2013" (PDF). pp. 6 & 7. Archived from the original (PDF) on 22 March 2014. 2012 State Comparisons
  31. ↑ "State and Federal Law on Organ Procurement". Archived from the original on 6 March 2014. Unless the individual expressed contrary intent, a hospital must take measures to ensure the medical suitability of an individual at or near death while a procurement organization examines the patient for suitability as a donor.
  32. ↑ "The Deceased Donation Process". Organdonor.gov. Retrieved 1 April 2021.
  33. ↑ "Frequently Asked Questions About Donation". DNR will be honored. You can still be a tissue donor.
  34. ↑ Greer, David M. (30 December 2021). "Determination of Brain Death". New England Journal of Medicine. 385 (27): 2554–2561. doi:10.1056/NEJMcp2025326. PMID   34965339. S2CID   245566906.
  35. ↑ Kirschen, Matthew P.; Francoeur, Conall; Murphy, Marie; Traynor, Danielle; Zhang, Bingqing; Mensinger, Janell L.; Ichord, Rebecca; Topjian, Alexis; Berg, Robert A.; Nishisaki, Akira; Morrison, Wynne (May 2019). "Epidemiology of Brain Death in Pediatric Intensive Care Units in the United States". JAMA Pediatr. 173 (5): 469–476. doi:10.1001/jamapediatrics.2019.0249. ISSN   2168-6203. OCLC   8553840562. PMC   6503509 . PMID   30882855.
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