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 »  Abstract
 »  Evolution of Con...
 »  Criteria to Dete...
 »  History of Brain...
 »  Clinical Evaluat...
 » The Evaluation Team
 » Evaluation Criteria
 »  Criteria for Dia...
 » Mandatory Tests
 »  Are “ Conf...
 »  Incidence of Bra...
 »  Pathophysiology ...
 »  Concerns in Diag...
 »  Ethical Issues i...
 »  Medico-Legal Imp...
 »  Brain Stem Death...
 »  Need for Declara...
 » Conclusions
 »  References

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Table of Contents    
GUEST COMMENTARY
Year : 2018  |  Volume : 66  |  Issue : 2  |  Page : 308-315

Brain death revisited


Department of Neurosurgery, Apollo Main Hospital, Chennai, Tamil Nadu, India

Date of Web Publication15-Mar-2018

Correspondence Address:
Dr. K Ganapathy
Neurosurgeon Apollo Main Hospital, 21 Greames lane, Chennai - 600 006, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.227287

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 » Abstract 

Until six decades ago, death was considered to be a specific point in time, referring to the moment at which life ends. With the availability of ventilators, even determining when death has occurred is becoming difficult, as cessation of life functions is often not simultaneous across organ systems. With increasing accessibility to intensive care units (ICUs) even in Tier II and Tier III cities, and the government making it mandatory to notify brain death to facilitate cadaveric organ transplants, it behooves the neurosurgeon and neurologist to totally understand the minutiae of brain death. The author reflects on his personal experience in certifying brain death, over two decades, in a quaternary care hospital. Knowing the pathophysiology of brain stem dysfunction will help the clinician better understand the rationale of the mandatory clinical tests prescribed. The necessity for an early diagnosis and the pitfalls in the clinical diagnosis of brain death, the limitations of the so-called confirmatory tests, and the concerns and ethical issues will be highlighted. Review of the world literature demonstrates that there is no international consensus even on what constitutes brain death. An individual could be considered legally dead in one country but not in another!


Keywords: Brain death, brain death in India, Brain death reviewed
Key Message: Most countries agree that the clinical diagnosis of brain stem death is sufficient for certification of death in adults. In spite of the existing guidelines, variations and inconsistencies necessitate the requirement for an international consensus to define when a person can be declared brain dead. The ′clinical evaluation′ criteria must be strictly adhered to and the limitations of so-called confirmatory tests recognized.


How to cite this article:
Ganapathy K. Brain death revisited. Neurol India 2018;66:308-15

How to cite this URL:
Ganapathy K. Brain death revisited. Neurol India [serial online] 2018 [cited 2019 Apr 23];66:308-15. Available from: http://www.neurologyindia.com/text.asp?2018/66/2/308/227287




Thanatology, the science dealing with the study of death, has been in existence for centuries. Legal and medical quandaries regarding the definition of death are not new. In his 'Historia Naturalis', the Roman author, Pliny the Elder, wrote that “so uncertain is men's judgment that they cannot determine, even death itself”. Perceptions of death have been reflected in poetry, literature, legends and pictorial art. Most ancient civilizations accepted death as an easily determined empirical fact, not requiring further elaboration.


 » Evolution of Concept of Brain Death Top


Before 1960, death was defined as the complete and irreversible cessation of spontaneous cardiac and respiratory functions.[1],[2],[3] Brain death was first described by two French physicians, Mollart and Goulon [4] and termed 'coma depasse' (a state beyond coma). They differentiated 'coma depasse' from 'coma prolonged', the latter being the condition, which is now termed as the persistent vegetative state. In 1968, the Ad Hoc Committee of the Harvard Medical School [5] defined brain death as a state of irreversible coma, with the patient being totally unreceptive and unresponsive, with absent reflexes and no spontaneous respiratory effort during a 3-minute period of disconnection from the ventilator. The report unambiguously proposed that this clinical state should be accepted as death. However Joseph Verheijde and colleagues,[6] argued against the validity of the Harvard criteria for equating brain death with human death. They contended that brain death does not disrupt somatic integrative unity and coordinated biological functioning of a living organism. A few years later, Mohandas and Chou [7] suggested that patients should have known but irreparable intracranial lesions as well as irreversible damage to the brain stem, and that the diagnosis of brain death should be a purely clinical diagnosis. In 1995, the American Academy of Neurology (AAN) published the practice parameters for the diagnosis of brain death.[8] Before the advent of support systems, death was assumed to have taken place when the heart irreversibly stopped.[9] Transplantation programs with the need for viable organs necessitated re-evaluation of the concept of death.[10],[11] Today, brain death is considered equivalent to death of the individual, and death of the brain stem is accepted as death of the brain. Prior to availability of mechanical ventilation, patients without a respiratory drive would become anoxic and die.[12] Today patients with severe, irreversible and nearly total brain dysfunction, can be maintained on a ventilator nearly indefinitely. A fundamental philosophical and scientific question must be addressed- are these unfortunate patients alive or dead ?

Most nations have their own guidelines for determination of brain-death.[13] Age-specific pediatric criteria are also variable in different guidelines. A memorandum issued by the Conference of Royal Medical Colleges (1976)[14] emphasized that permanent functional death of the brain stem constitutes brain death. A second memorandum issued in 1979[15] equated brain stem death with death itself. Within the brain, not all cells die at the same time. In a severe vegetative state, the cerebral cortex, the center of cognitive functions including consciousness and intelligence, may be dead while the brain stem controlling basic life support functions is still functioning.


 » Criteria to Determine Brain Death: Geographical Variability Top


The White Paper on “Controversies in the Determination of Death” published by the President's Council on Bioethics [16],[17] still believes in whole-brain-death. USA, therefore, does not agree to brain stem death alone. Most countries agree that the clinical diagnosis of brain death or brain stem death is sufficient for determination of death in adults. Diagnosis of brain stem death does not require confirmation that all brain functions have ceased. Persisting functions should not indicate any form of consciousness. Supplementary tests are advocated only in the presence of confounding factors. Patients with preserved cortical electrical activity or intracranial blood flow can be considered dead in jurisdictions that utilize a brain stem approach, but not in those that apply a whole brain concept. The biological death of the whole human organism cannot (and is not required to) be proven during the diagnosis of brain death. While there is unanimity that confirmation of absence of brain stem reflexes is fundamental to the clinical determination of brain death, there are wide variations in the requirements for the conduct of the apnea test. Fewer than 60% of jurisdictions include induced hypercarbia to a specified target (and confirmation with arterial blood gas analysis) in their guidance. Others only stipulate disconnection from the ventilator for a defined period or provide no guidance for the conduct of the apnea test.[18] This is of concern because confirmation of apnea is fundamental to the determination of brain death (whole brain or brain stem) and this can only be assured if the degree of acute hypercarbia is sufficient to stimulate the respiratory centre. Whatever standard is used to determine brain death, 'irreversibility' is usually not defined, relying on repeated assessment over time. Seventy countries now endorse the practice of determining death by the neurological criteria. Although guidelines are available for the diagnosis of brain-death, variations and inconsistencies necessitate the requirement for an international consensus and the passing of uniform guidelines.


 » History of Brain Death Recognition in India Top


Immediately after the Transplantation of Human Organs Bill was passed, the author wrote an article “Viewing the critically ill, head trauma patient as an organ donor”[19] advocating that neurosurgeons should take a proactive role in recognizing brain death, to facilitate availability of organs for transplantation. This was not well received. Most neurosurgeons opined then that they would be perceived by the public as “organ procurers”. On December 25th 1995, the author [20] facilitated South Asia's first multi-organ transplant after certifying brain death in a head trauma patient. Subsequently, for many years, the author personally facilitated a large number of transplants, proactively certifying brain death at a time when it was not mandatory by law.


 » Clinical Evaluation of Brain Stem Death Top


Brain stem death is a clinical diagnosis in most countries. The accuracy, reliability, reproducibility and ease in carrying out clinical tests make the process of clinical evaluation sufficient for establishing the diagnosis. Brain stem death is a nonfunctional state of the brain stem, where all signs of brain stem activity are absent. Neurophysiological and imaging studies are not generally essential to confirm brain death. A repeat clinical evaluation 6 hours later is advised, but this time is variable.[21] Clinicians should make it clear to the relatives that ventilation is not being withdrawn to let the patient die (as the patient is already dead) but because continuing ventilation is indicated only for survival of individual organs.


 » The Evaluation Team Top


In India, according to the Transplantation of Human Organs (THO) Act, 1994 (Sub section 6 of Section 3),[22] 'brain stem death' refers to the stage at which all functions of the brain stem have permanently and irreversibly ceased. This is to be certified by a 'Board of Medical Experts' consisting of (1) The medical superintendent (MS)/In-Charge of the hospital in which 'brain stem' death has occurred, (2) a specialist, (3) a neurologist or a neurosurgeon nominated by the MS, from a panel approved by the Appropriate Authority, and the doctor under whose care the 'brain- stem' death has occurred. Amendments in the THO Act 2011 have allowed selection of a surgeon/physician and an anesthetist, if an approved neurosurgeon or neurologist is unavailable.


 » Evaluation Criteria Top


Criteria of brain death vary in different countries depending on the principal definition of brain-death,[13] which could either be the death of all central neurological tissue with the complete loss of cerebral function; or, the irreversible loss of integrated neurological function, e.g., consciousness and the ability to breathe.[23] In India, brain stem death was legalized in 1994, when The Transplantation of Human Organs (THO) Act was passed. The UK criteria for brain stem death is followed in our country. Brains of children younger than 5 years of age allow some functions to recover despite their clinical states, that would in adults be accepted as irreversible.[21] It may be reasonable to declare brain death in children older than 3 months if a single electroencephalogram has demonstrated electro-cerebral silence.[24],[25]

Brain death should not even be thought of, until the following reversible causes of coma have been excluded.[26] Intoxication (alcohol), drugs including muscle relaxants which depress the central nervous system (CNS), primary hypothermia, hypovolemic shock, as well as metabolic and endocrinal disorders should be ruled out. Hypernatremia and diabetes insipidus are more often the effects rather than the causes of brain death. The clinical diagnosis of brain death should be performed in three steps:[27] (1) Establishing the etiology; (2) excluding potentially reversible syndromes that may produce signs similar to brain death; and, (3) demonstrating clinical signs of brain death including coma, brain stem areflexia and apnea.

For certifying brain death, the following need to be evaluated: Presence of irreversible coma; and, the cessation of spontaneous respiration confirmed with apnea tests, absence of pupillary light reflexes, corneal reflexes, doll's eye movements, gag reflex, cough reflex (tracheal), eye movements on caloric testing bilaterally, motor response in any cranial nerve distribution, and motor response on stimulation of face/limb/trunk,


 » Criteria for Diagnosing Brain Death in Infants and Children Top


As children are more resilient than adults, a longer time between assessments, of greater than 6 hours, has been advocated.[26] This varies according to the patient's age: Term to 2 months old: 48 hours, >2 months to 1 year:24 hours, >1 year to <18 years: 12 hours, >18 year: As in adults. The diagnosis of brain death cannot be made in preterm infants of gestational age of less than 37 weeks. Hypotension, hypothermia, and metabolic disturbances should be treated and corrected prior to any evaluation. Assessments in neonates and infants should be performed by pediatric specialists with critical care training. Apnea testing is positive if there is presence of arterial PaCO2 ≥20 mm Hg above the baseline, and ≥60 mm Hg with no respiratory effort, during the testing period. If the apnea test cannot be safely completed, an ancillary study should be performed. Ancillary studies are deployed only when components of the examination or apnea testing cannot be completed safely, or there is uncertainty about the results.


 » Mandatory Tests Top


Apnea test

Apnea testing is essential for confirmation of brain stem death. This should be carried out only when all prerequisites have been met with and all other brain stem reflexes are absent. An associated high cervical cord injury, which may have abolished phrenic nerve function is a contraindication. Important changes in vital signs (such as, marked hypotension or severe cardiac arrhythmias) during the apnea test, may be related to inadequate precautions, or due to increasing acidosis. Prerequisites suggested [28] include a core temperature of ≥36.5 degree Celsius, a systolic blood pressure of ≥90 mm Hg, presence of euvolaemia (preferably a positive fluid balance in the previous 6 hours, and eucapnea (arterial pCO2 ≥40 mm Hg). An useful method of raising the pCO2 in an overventilated hypocapnic patient is to connect an oxygen filled bag to the endotracheal tube and rebreathe pure oxygen for 10 minutes without CO2 exhaustion. Patients may have a normal blood pressure despite fulfilling the clinical criteria of brain death.[29] The components of the apnea test include absence of spontaneous respiratory efforts during a period of disconnection (10 minutes) from the mechanical ventilator, with the arterial carbon dioxide reaching a critical point (≥60 mm Hg) without the presence of hypoxemia during this period. The steps in testing include: a) Disconnecting the ventilator; b) delivering 100% oxygen at 6 L/min by placing a cannula at the level of the carnia; c) observing closely for respiratory movements. Respiration is defined as abdominal or chest excursions that produce adequate tidal volumes. Respiration like movements can occur at the end of the apnea test, when oxygenation may become marginal. However, these do not produce adequate tidal volumes. When the test is in doubt, a spirometer can be connected to the patient to confirm the absence of tidal volumes; and, d) measuring arterial pO2, pCO2, and pH after 10 minutes and then reconnecting the ventilator. If the respiratory movements are absent and the arterial pCO2 is ≥60 mmHg (or a 20mmHg increase in the pCO2 over the baseline value), the apnea test is positive, i.e., it supports the diagnosis of brain death. Target arterial PCO2 levels are derived from a small number of patients who had respiratory efforts after induction of hypercarbia but who otherwise fulfilled the criteria for the clinical diagnosis of brain death.[30] If respiratory movements are observed, the apnea test is negative (i.e., it does not support the clinical diagnosis of brain death), and the test should be repeated. If during the apnea test, the systolic blood pressure becomes ≤90 mmHg, the pulse oximeter indicates marked desaturation, and cardiac arrhythmias occur, one should draw a blood sample immediately, reconnect the ventilator and analyze arterial blood gases. The apnea test is positive if the arterial pCO2 is ≥60 mmHg. If the pCO2 is <60 mmHg, the result is indeterminate and needs a repeat testing at a later stage. Contraindications to the apnea testing include the presence of arterial hypotension (systolic blood pressure <90 mmHg), hypoxemia (pO2 <90 mmHg) and severe acidosis (pH < 7.20). If present, these abnormalities should be corrected before performing the test.

Motor response to pain

There should be no motor response in the distribution of any cranial nerve. Such a response would be grimacing (facial nerve motor response) in response to thumb pressure over the supraorbital groove (trigeminal nerve sensation). Similarly, there should be no response to painful stimuli of the trunk suggesting absence of sensory nerve conduction across the foramen magnum. Neuromuscular blocking agents can produce prolonged weakness.[31] If neuromuscular blocking agents have recently been administered, examination with a bedside peripheral nerve stimulator is needed.[32]

Pupillary response to light

The response to bright light should be absent in both the eyes. The pupil should be observed closely for one minute to allow time for a slow response to become evident. Both widely dilated as well as mid-positioned fixed pupils are seen in brain dead patients. The presence of widely dilated pupils is not a necessary criterion for brain death but fixed pupils with no response to light is a mandatory requirement for its diagnosis. The size may vary from 4-9 mm. Dilated pupils are compatible with brain death because intact sympathetic cervical pathways connected with the radially arranged fibers of the dilator muscle may remain intact.[33],[34]

Corneal reflex

This should be absent. Repeated corneal stimulation is unnecessary and should be avoided. Corneal abrasions are undesirable if the patient is a potential corneal donor.

Oculocephalic reflex (doll's eye phenomenon)

This test must not be performed in patients with an unstable cervical spine. The head is turned from the starting position to a new steady position, and then briskly turned towards the opposite side. The eyes move to the contralateral side denoting the integrity of the medial longitudinal fasciculus in the brain stem.

Oculovestibular reflex

Ocular movements are absent after head-turning and caloric testing with ice water. Before testing, both the ears must be inspected with an auroscope to confirm that the tympanic membranes are intact and that the external auditory canal is not obstructed. If the eardrum is perforated, the test can be performed using cold air as the stimulus. A fracture of the base of skull resulting in blood, cerebrospinal fluid or brain tissue in the external auditory canal is a contraindication to performing this test on that ear. The patient's head is placed in the center and lifted 30 degree from the supine position. A soft catheter is introduced into the external auditory canal and slow irrigation with at least 5 ml of ice-cold water is performed while the eyes are held open by an assistant. The eyes should be observed for one minute after the irrigation is completed before repeating the test on the other side. An intact oculovestibular reflex causes tonic deviation of the eyes opposite to that of the irrigated ear. Any movement of one or both eyes, whether conjugate or not, excludes the diagnosis of brain death. In a brain-dead patient, the eyes remain fixed. A combined ice-cold water caloric stimulation and head rotation testing has been suggested as the most profound stimulation for deeply unconscious patients.

Gag reflex

This should be absent. A tongue depressor is used to stimulate each side of the oropharynx and the patient observed for any pharyngeal or palatal movement. Evaluation of the gag reflex may be difficult in an intubated patient and should not be performed if extubation is required to conduct the test.

Cough reflex

A suction catheter is introduced into the endotracheal or tracheostomy tube to deliberately stimulate the carina. The patient is closely observed for any cough response or movements of the chest or diaphragm.

Pitfalls in clinical evaluation

The following conditions may interfere with the clinical diagnosis of brain death. Confirmatory tests are recommended. These conditions include severe facial trauma, preexisting pupillary abnormalities, toxic levels of sedative drugs, aminoglycosides, tricyclic antidepressants, anticholinergics, antiepileptics, chemotherapeutic agents, neuromuscular blocking agents, sleep apnea or severe pulmonary disease resulting in chronic retention of CO2. The following clinical observations, if present, though compatible with the diagnosis of brain death, may be a source of confusion. Motor responses (“Lazarus sign”)[35] may occur spontaneously during apnea testing, often during the hypoxic or hypotensive episodes, and are of spinal origin. They include spontaneous movements of limbs other than pathologic flexion or extension response and respiratory-like movements (shoulder elevation and adduction, back arching, intercostal expansion without significant tidal volumes) and should not be misinterpreted as evidence of brain stem function. Sweating, blushing, tachycardia, normal blood pressure without pharmacologic support or sudden increases in blood pressure, absence of diabetes insipidus, occasional presence of deep tendon reflexes, superficial abdominal reflexes, triple flexion response and Babinski response may also sometimes be present.


 » Are “ Confirmatory” Tests Really Confirmatory Top


Confirmatory tests are optional in most guidelines and reserved for the situation when clinical diagnosis cannot be completed or is doubtful. Cerebral angiography, particularly a four-vessel angiogram, that demonstrates an absent cerebral circulation remains the gold-standard supplementary test for the diagnosis of brain-death. Computed tomographic (CT) angiography, CT perfusion and magnetic resonance (MR) angiography have not been validated or recommended. Radionuclide imaging techniques, like the technetium-99 m scan, have been widely performed. There is no uptake of isotope in the brain parenchyma (“hollow skull phenomenon”) in brain-dead patients. The use of multimodal evoked potentials in the diagnosis of brain-death has been described. A combination of median nerve somatosensory, brain-stem auditory and visual evoked potentials was used in the evaluation of brain-death. The plethora of gadgetry ultimately only gives answers of dubious reliability to the wrong questions! None are superior to clinical assessment. Most of these tests have been validated against the gold standard of bedside diagnosis and are not 100% specific or sensitive.[36],[37],[38],[39],[40] They may have a place in patients in whom the results of specific components of clinical testing cannot be reliably evaluated [28] These techniques currently do not form part of the mandatory diagnostic requirements in most countries, including India.

The other confirmatory tests include:

Electroencephalogram

Loss of bioelectric brain activity for at least 30 minutes of recording, as measured by a 16 or 18-channel EEG, is a reliable confirmatory test for the diagnosis of brain death.[41],[42],[43],[28] The disadvantage of EEG is that devices in the intensive care unit (ICU) may cause artifacts, leading to spurious results.[26] EEG may also not show electrical activity in barbiturate coma. EEG continues to be the most commonly applied supplementary test for diagnosing brain-death worldwide and was mandatory in a number of European countries in the mid 1990s. The EEG is significantly affected by hypothermia, drug administration and metabolic disturbances, thus diminishing its clinical utility.

Sensory evoked potentials

In studies [44],[45],[46],[28],[47] of patients with brain death, most patients have no responses to tests for somatosensory and brain stem auditory evoked potentials. This test is, therefore, useful in distinguishing isolated brain stem death from high cervical transverse cord lesions and focal bilateral lemniscal lesions.

Conventional angiography

In brain death, there is no intracerebral filling at the level of the carotid bifurcation or circle of Willis.[28] The external carotid circulation is patent, and filling of the superior longitudinal sinus may be delayed. Recently, clinicians have used MR or CT angiograms in lieu of the more invasive traditional angiography.[48],[49],[50] The author [51] demonstrated a carotid stop with no dye entering the intracranial region beyond the base of the skull, while the external carotid vessels were clearly visualized. This was following injection in the right common carotid artery to investigate the possibility of a vascular etiology in a critically ill patient. As the angiogram was being done, the patient developed new clinical features suggestive of brain death.

Transcranial doppler ultrasonography

The Assessment Subcommittee of the American Academy of Neurology has accepted transcranial Doppler ultrasonography as a reliable procedure for confirmation of brain death.[52] Transcranial Doppler is subject to technical problems.[37] Ten percent of patients may not have temporal insonation windows. Therefore, the initial absence of Doppler signals cannot be interpreted as a finding consistent with brain death. Small systolic peaks in the early systole without a diastolic flow or reverberating flow, indicate a very high vascular resistance associated with greatly increased intracranial pressure. Transcranial Doppler (TCD) is a noninvasive technique and was found to be highly sensitive in determining absent cerebral perfusion, as reported by Ducrocq.[37]


 » Incidence of Brain Death Top


The exact incidence of brain death is not known. According to Shiogai, it constitutes approximately 1% of all deaths.[53] Jennett et al.,[54] reported an incidence of about 4000 cases a year in Britain. Many authors report a diagnosis of 'brain death' 25-30 times a year in large referral centers.[26],[29],[54],[55],[56],[57] Brain death is usually a result of severe head injury, aneurysmal subarachnoid hemorrhage, and intracerebral hemorrhage.[33],[58],[59],[60] Head injury due to road traffic accidents can account for almost 50% of brain deaths. Large ischemic strokes associated with brain swelling and herniation, hypoxic-ischemic encephalopathy after prolonged cardiac resuscitation or asphyxia, and massive brain edema in patients with fulminant hepatic necrosis are other causes leading to brain death.[30],[61],[62] Variability in documentation of brain death has been reported. A retrospective study of 76 adults compared the preclinical testing, neurological examination, apnea tests, ancillary tests and also accurately documented the time of death. Strict adherence to the American Association of Neurology (AAN) guidelines for brain death was maintained. The preclinical requisites were fulfilled in 53.9% patients and complete neurological examinations were documented in 76.3% patients. The apnea test was completed in 39.5% patients. Ancillary tests were completed in 29.8% of them. Accurate documentation of the time of death occurred in 59.2% patients. Overall, strict adherence to the current AAN guidelines for the diagnosis of death by neurological criteria was correctly documented in only 38.2% of the subjects enrolled in the study. The study revealed a wide variability in diagnosing brain death.[63]


 » Pathophysiology of Brain Death Top


Severe damage to neuronal tissue leads to edema and increase in intracranial pressure (ICP). Elevated ICP reduces cerebral perfusion pressure and cerebral blood flow. A vicious cycle is established in which decreasing cerebral perfusion and increasing ICP reinforce one another until blood no longer enters the cranial cavity and transtentorial herniation and coning at the foramen magnum occurs. This herniation crushes the brain-stem leading to permanent dysfunction. Late neuronal injury is explained by reperfusion associated with hypoxic-ischemic brain injury. Death is a continuous ongoing process, not an isolated event. Total loss of neurophysiological functions of the brain for more than 8 minutes confirms total and irreversible loss of brain function.[64],[65] Complete cardiovascular and autonomic uncoupling has been shown after brain stem death.[66] Diffuse metabolic cellular injury due to lack of hypothalamic control, producing generalized metabolic and hypoxic lesions in all tissues also occurs.[67] Hypernatremia and diabetes insipidus are more often the effect rather than the cause of brain death. Even with maximal support, cardio-respiratory deterioration leading to somatic death will occur within days,[18],[68] although persistence of the cardio-respiratory drive for prolonged periods, even over 100 days, has been reported.[69] The medullary reticular formation (RF) contains the vital centers controlling heartbeat, breathing and circulation. The pontine RF contains centers for coordination of acoustic, vestibular, respiratory and cardiovascular processes. The midbrain RF contains centers for visuospatial orientation and eating behavior. As brain-stem is structurally and functionally very compact, even small lesions can destroy vital cardiac and respiratory centers, disconnect the cerebral cortex from the brain-stem, and damage sensory fibers from higher centers of consciousness, perception and cognition. Damage to the RF may lead to loss of cognition, persistent unconsciousness and coma. The brain stem, which includes the midbrain, pons and medulla, contains the nuclei of the last ten cranial nerves and ascending and descending tracts. The reticular activating system provides the anatomical and physiological basis for wakeful consciousness.


 » Concerns in Diagnosing Brain Death Top


Clinical guidelines for determining brain death are not consistently validated by the presence of irreversible brain stem ischemic injury or necrosis at autopsy.[7] They do not, therefore, completely exclude the reversible loss of integrated neurological functions in those certified as potential donors. Several critical brain structures remain viable and continue integrated neurological functioning after clinically determined brain (stem) death occurs. These include electroencephalogram activity, and hypothalamic functions. A recent review of the clinical literature,[70] found evidence that suggested preservation of the hypothalamic function in a substantial proportion of patients declared dead by the neurologic criteria. Approximately half of the patients reported in the literature showed evidence suggesting the presence of osmoregulation via the regulated secretion of vasopressin (anti-diuretic hormone). A substantial proportion of patients were also secreting hypophysiotropic hormones originating in the hypothalamus. Patients with preserved cortical electrical activity or intracranial blood flow are considered to be dead in countries that utilize a brain stem criteria, but not dead in those where a whole-brain criteria is applied. Brain stem death has a lower burden of proof than whole-brain death.[71] The latter can be viewed as an 'approximation' because the irreversible loss of all intracranial neurological functions is not confirmed during its clinical determination, Clinical observations indicate that heart-beating organ donors may occasionally have residual brain functions, including hormonal and neural responses to nociception and pain during the procurement process.[72] Surgical procurement, which is performed on donors without general anesthesia [73] induces hemodynamic responses in donors [50] Wijdicks and Pfeifer [74] studied 41 brain dead patients, mostly young donors declared brain dead by clinical examination, within 24 hours of blunt-force traumatic brain injury. Although neuronal ischemic changes were frequently profound, a respirator brain with extensive ischemic neuronal loss and tissue fragmentation was not observed. They concluded that the neuropathologic examination is not diagnostic of brain-death.


 » Ethical Issues in Declaring Brain Death Top


The DDR (Dead Donor Rule)[75] is the formalization of the widely held belief that it is wrong to kill one person to save the life of another, leading to the conclusion that people should already be dead before vital organs are removed, an act that would certainly kill them. The DDR is neither a law nor a regulation — it is a description of an ethical norm: an organ donor must be dead before vital organs are removed.


 » Medico-Legal Implications in Certifying Brain Death Top


To a large extent the medico-legal implications of certifying brain death depends on the statuettes prevailing in individual states and its interpretation on a case-by-case basis. In one instance in Texas,[76] the husband of a brain dead patient asked that she be removed from physiological support, but the hospital refused, as the patient was 14 weeks pregnant at the time. The Texas Advance Directives Act, like similar laws in several other states, includes a provision prohibiting the withdrawal of life-sustaining treatment from a pregnant patient. The hospital interpreted this law as applying to the patient and thus refused to discontinue treatment. The husband filed a lawsuit, and the court ruled that the Texas Advance Directives Act did not apply because the patient had been determined to be legally dead. Thus, mechanical support could not be considered life-sustaining, and the court ordered the hospital to discontinue physiologic support, with which the hospital complied, though by that time two months had passed since her initial admission. In another instance, the parents of a 13-year old child refused to accept the hospital's decision to discontinue mechanical ventilation following brain death as the heart was still beating. They argued that the California statute recognising brain death, violated their religious beliefs. The court upheld the caregivers contention. 15 months later, the patient was residing in an apartment with home ventilator care in New Jersey. Autonomy, properly understood, is the right to avoid unwanted intrusions rather than a right to have any medical treatment, however futile or cost ineffective. The process implies that once a person is brain dead, it is unethical to continue treatment.[76]


 » Brain Stem Death: The Indian Law Top


India enacted a law in 1994[78] to legalize the recognition of brain-stem death. Maharashtra [77] has recently mandated the notification of brain dead cases. The Government Resolution underlines the responsibilities of hospitals registered under the Transplantation of Human Organs (THO) Act 1994, that is, they are authorized transplant centers. As a large number of brain-deaths occur in hospitals not authorized to do transplants, the appropriate authority (Director of Health Services) has registered all hospitals in the state that have an operation theatre and ICU as NonTransplant Organ Retrieval Centers (NTORCs). These hospitals are permitted to certify brain-death as per the prescribed procedure and then conduct organ retrieval for therapeutic purposes; however, they are not permitted to perform an actual transplantation. Thus, it is mandatory now for all NTORCs and authorized transplant centers in the state to certify and notify the brain-death cases to the Zonal Transplantation Co-ordination committee. This is a strong step to streamline the procedure for cadaveric organ retrieval and transplantation. In India, there is no legal definition of death. Section 46 of the Indian Penal Code states, “the word 'death', denotes death of a human being unless the contrary appears from the context”. India follows the UK practice and considers death as equivalent to brain stem death. Medically and legally, the patient is dead, if brain stem death (brain death is used as a synonym for the latter) has been certified. The doctors involved in the diagnosis should in no way be connected with the transplant surgeries concerning the 'brain-stem dead' cadavers. The certification should be done on the laid out forms (Form No. 8) as per the Transplantation of Human Organs Act.[78] The declaration of brain death must be recorded in the medical notes with the date and time. The legal time of death is the time at which the second prescribed clinical tests are carried out. Comprehensive reviews of brain stem death and brain death from an Indian perspective have also been documented.[78],[79],[80]


 » Need for Declaration of Brain Death Top


Once an unequivocal diagnosis of brain death has been made, most medical and legal authorities agree that continuing treatment is not in the interest of the patient or is ethically permissible. This is not related to withdrawing support to allow a patient to die, but rather to ceasing a futile intervention in a patient who is already dead. Acceptance of this approach would reduce human distress, lead to the rational use of the limited ICU facilities, and increase the availability of organs. Solid organs can be donated only after confirmation of brain death. Unless medical personnel provide family members with information that all cognitive and life support functions have irreversibly stopped, the family may harbor false hopes for the loved one's recovery.

Further care

Brain death has created a new class of dead people that does not conform to the society's expectations of normal death and dying. Brain death also causes great stress for the family and friends. Many families may benefit if a short time is provided to adjust to the sudden tragedy and hopelessness of the situation. This helps them develop trust in their physician and in the diagnosis. An effective communication with the family members, as well as caring and providing support for them is crucial before the request for organ donation is made. The only rational reason for continuing treatment after confirming brain death is for organ donation. Once the permission from family members is obtained, the transplant team takes over further care. Law in India is still not clear if the support system can be withdrawn once the family refuses organ donation.[81]


 » Conclusions Top


With the increasing availability of intensive care units even in Tier II and Tier III cities in India, a number of seriously ill patients are now being revived. While many recover, a significant number end up being brain dead. It is imperative that all neurosurgeons and neurologists fully understand the intricacies of brain death so that they can discuss in detail with the family, the implications of continuing treatment and its repercussions. If there is no transplant coordinator or grief counsellor in the hospital, the neurosurgeon should also discuss with the family the option of the patient being an organ donor.

Acknowledgments

I am thankful to my wife, Mrs. Vijayalakshmi, for assisting me in compiling this manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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