What does brain death mean? Pathophysiological mechanisms of brain death. The concept of clinical and biological death

Brain death (respiratory brain) is a state of irreversible loss of brain function while maintaining blood circulation and respiration, which can be artificially maintained for a long time.

The problem of death, which is the opposite side of human existence (the problem of life), is one of the cornerstones of philosophy, religion, natural science, including medicine. Ascertaining the death of a person as a task has taken place at all times, but it has become especially important in the era of the development of resuscitation and transplantology. Ethical, religious, legal and medical issues play an important role in the problem of ascertaining the moment of death.

Since the 16th century, many cases of erroneous diagnosis of death and even the burial of supposedly dead people have been described in the medical and legal literature. In medicine, the reliability of traditional signs of death has been discussed more than once: - cessation of breathing and heartbeat, - insensitivity to electrical impulses, - stiffness of muscles, - pallor and cyanosis, - hypostasis, - cadaveric spots, etc. Despite the development of medical science and practice, today day the question of the criteria for death remains debatable. This is indicated by at least a considerable number of international conferences and symposiums on the problem of criteria for human death.

The surge of interest in the problem of death criteria is associated with the rapid development of resuscitation and transplantation, with an urgent need for donor organs. A dilemma arises: if earlier the moment of death was judged by the cessation of vital functions (pulse, heartbeat, respiration, reflexes), now technologies such as artificial lung ventilation, electrical stimulation, artificial circulation make it possible, in the absence of these signs, to artificially maintain the functioning of the human body, i. e. death can be made a manageable process.

But is it always advisable from the point of view of ethics, medicine, religion, law? Resuscitation raises acute questions: - whether to use resuscitation in obviously incurable patients; - how long should artificial life support be continued in case of an injury incompatible with life; - what is still considered an objective criterion for the death of a person?

Today, the laws of many countries legally equate the terms "brain death" and "human death". In the 1970s and 1980s, numerous medical organizations around the world developed specific criteria for the diagnosis of brain death. Such criteria have appeared in the UK, Canada, USA, Sweden, Japan and some Asian countries. All these standards essentially agreed on three clinical findings: - coma, - absence of respiration (loss of spontaneous respiration), - absence of brainstem reflexes. An organism in a state of brain death is doomed to death in the traditional sense (cardiac arrest) within the next few days or (rarely) two weeks, very rarely - for a longer time.

Brain death as a synonym for ascertaining the death of the whole organism was first described in the medical literature in 1959. On the way to developing acceptable criteria for brain death, the following were accepted and rejected: transcendental coma, irreversible coma, apallic state, death of the neocortex, etc.

Eventually, by 1994, there were two legal positions on what it meant to be dead in terms of brain functions: - "brain death" - the irreversible loss of all brain functions, including the brain stem, a "permanent vegetative state"; - irreversible loss of higher brain functions, the brainstem is largely intact. However, the latter position has no legal status.

Brain death must be distinguished from a permanent vegetative state. A permanent vegetative state (PVS) occurs as a result of damage to the cerebral cortex, which controls cognitive functions. However, the body is not dead, and spontaneous breathing and heartbeats may still occur. But there is no conscious interaction with the environment. The diagnosis of PVS can be confirmed with a follow-up of 3 to 6 months. People in this state require compassion and respect, to be free from pain and discomfort, but they do not need technological support or treatment that will bring no improvement to their status. In connection with this condition, there are serious problems with the allocation of resources for their maintenance, nutrition, hydration.

In the USSR, the relevant documents were approved by the USSR Ministry of Health in 1984 (temporary instruction) and in 1987 (permanent instruction), and in the Russian Federation - in 1993. (Instructions for ascertaining the death of a person based on the diagnosis of brain death. Order of the Ministry of Health of the Russian Federation No. 100/30 of 04/02/2001). The statement of the onset of death is carried out by a commission of doctors, which includes an resuscitator-anaesthesiologist with at least 5 years of experience, a neurologist, and specialists in additional research methods. The commission cannot include specialists involved in organ retrieval and transplantation. The Instruction does not apply to the establishment of brain death in children.

When discussing the ethical, legal, religious and medical aspects of the criterion of "brain death" the question of the reliability of this criterion is important. The world's 40-year experience shows that the diagnosis of brain death, if performed without violating instructions, is absolutely reliable. Not a single patient in the world in this condition survived more than the specified period, all such patients are doomed to cardiac arrest.

Diagnosis of brain death must necessarily include the following conditions: - active personnel who have undergone special training; - the whole procedure is strictly documented; - the decision to terminate life-supporting measures is taken collectively; - informing relatives is not necessary, because it is important for relatives to know that all measures were taken to save life and cure the patient, but they turned out to be ineffective. An important ethical problem is the attitude of the whole society to the criterion of "brain death". Indeed, for many people, death is marked by cardiac arrest. This once again indicates that bioethical culture is a highly demanded task.

Giving the appearance of life.

In a state of brain death, a person is dead. We can say that the death of the brain is the death of the whole organism. Currently, “brain death” is understood as a pathological condition associated with total necrosis of the brain, as well as the first cervical segments of the spinal cord, while maintaining cardiac activity and gas exchange, provided by continuous mechanical ventilation. Brain death is caused by the cessation of blood circulation in the brain, which occurs with a sharp increase in intracranial pressure and equalizing it with systolic blood pressure. Necrosis of the first cervical segments is due to the cessation of blood circulation through the system of vertebral arteries. The actual synonym for brain death is the concept of "transcendental coma", the treatment of which is meaningless. A patient who has been diagnosed with brain death is a living corpse, as they say, the drug "heart - lungs". In the practice of pathologists, the term "respiratory brain" is sometimes used.

Criteria for brain death

• A. Lack of brain stem function:
  • 1. Ophthalmological examination (ocular examination)
    • "fixed" ("fixed") pupils: no pupillary reaction to light (Features of assessment after resuscitation, see below)
    • Absence of corneal reflexes
    • Absence of an oculocephalic reflex
    • Absence of the oculovestibular reflex (calloric test with ice water). The external auditory canal of one ear is washed with 60-100 ml of ice water (not performed if the eardrum is damaged) with the head position raised 30 ° above the horizontal plane of the bed. Brain death is ruled out if, in response to rinsing with ice-cold water, the eyeballs turn towards the irrigated ear. The procedure is repeated on the other side at least 5 minutes after the previous examination.
    • Apnea test (Apnea test): the absence of spontaneous respiratory movements when the patient is disconnected from the ventilator (to determine the function of the medulla oblongata. An increase in CO 2 in arterial blood leads to an increase in intracranial pressure, which, in turn, can cause cerebral herniation and vasomotor instability, so this test should be done last when the cause of brain death is obvious.
    • PaCO2 should be above 60mmHg, and the absence of breathing confirms the diagnosis of Brain Death (If there is no breathing at this level of PaCO2, then there will be no breathing at higher rates). The test is not conclusive in patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF).
    • Hypoxemia during the test should be excluded (because of the risk of developing cardiac arrhythmia and myocardial infarction). For this:
      • before the procedure, the lungs are ventilated with 100% oxygen for 15 minutes.
      • Before the test, the patient is transferred to artificial lung ventilation, maintaining PaCO2 > 40mmHg (this shortens the time of the test and makes it possible to avoid hypoxemia with greater certainty.)
      • During the test, passive oxygen inhalation at a rate of 6 L/min should be performed through a No: 14French tracheostomy suction catheter (which is fixed to the side of the inhalation/tracheostomy tube - with the side port covered - adhesive tape), the end of which is located at the level of Carina.
    • It starts with normocapnia, the average time to reach the level of PaCO2 = 60mmHg is 6 minutes (which corresponds to the classical rise rate of −3.7 +/-2.3), sometimes it is necessary to wait up to 12 minutes. The test must be aborted if:
      • the patient is breathing (does not meet the definition of death)
      • severe arterial hypotension develops
      • Oxygen saturation (pulse oximeter) drops below 80%
      • Severe cardiac arrhythmia develops
    • If the patient is not breathing, arterial blood is sent for blood gas determination at the usual intervals, regardless of the reason for stopping the test. If PaCO2 > 60mmHg and the patient is not breathing, the test is considered positive. If the patient's condition is stable, the determination of blood gases takes a few minutes, and PaCO2<60mmHg. Тест может быть продолжен.
  • 2. Absence of the oropharyngeal reflex. (gag reflex)

• b. Lack of motor response to severe, deep central pain (deep central pain)
  • 1. The presence of decortication or decerebrate postures, as well as convulsions, exclude the diagnosis of Brain Death.
  • 2. The presence of spinal reflexes (flexor reflex of the foot - flexor plantar reflexes, flexor withdrawal, muscle stretch reflexes and even abdominal and cremaster reflexes can be observed with brain death. Sometimes complex complex movements can be observed - bringing one or both hands to the face or an attempt sit-Lazarus sign-symptom- (especially in hypoxemia. These movements are probably associated with stimulation of intact motor neurons of the upper spinal cord. If the patient has such complex movements, other confirmatory tests should be performed before establishing the diagnosis.

• C. Absence of conditions complicating the diagnosis and simulating brain death.
  • 1. Hypothermia: Core temp must be > 32C (90F)
  • 2. Data on potentially reversible endogenous and exogenous intoxications, including drug and metabolic origin. (Barbiturates, benzodiazepines, meprobamate, methaqualone, trichlorethylene, paralyzing drugs, hepatic encephalopathy, hyperosmolar coma). .
  • 3. Shock (Mean arterial pressure must be >90mmHg) and anoxia.
  • 4. Immediately after resuscitation (fixed and dilated pupils may be the result of atropine)
  • 5. Patients after barbituric (the content should not exceed 10 microg / ml)
  • 6. Confirmation of the diagnosis of brain death (EEG, Cerebral angiography, Cerebral isotope angiography (CRAG), Auditory evoked potentials of the brainstem (BSAER) are not produced, but may be considered appropriate, by a consulting therapist.

• D. Follow-up of the patient should continue until the diagnosis of Brain Death is established and after the tests have been carried out for a certain period of time.
  • 1. For extensive brain damage due to irreversible pathological processes (massive cerebral hemorrhage, etc.), some experts may establish a diagnosis of brain death based on a single examination and confirmation by clinical confirmatory tests.
  • 2. With undoubted irreversible, clinically established conditions and the use of clinical confirmatory tests after 6 hours.
  • 3. With undoubted irreversible, clinically established conditions and in the absence of clinical confirmatory tests after 12 hours.
  • 4. With an inaccurate clinical diagnosis and in the absence of clinical confirmatory tests - 12-24 hours.
  • 5. With anoxic brain damage as the cause of Brain Death - 24 hours, but the observation period can be reduced when determining the cessation of cerebral blood flow.

(President's Commission for Study of Ethical Problems in Medicine; Guidelines for the Determination of Death. "JAMA" 246:2184-6,1981.)

Necessary Criteria for Determining Brain Death

for patients older than 1 year.

1. Every effort has been made to identify the next of kin or other people close to the sick person.
2. The causes of coma are known and sufficient to consider the impairment of brain function to be irreversible.
3. Drugs that depress the function of the central nervous system, hypothermia (<32C) и гипотония (среднее артериальное давление <55ммHg) исключены, а также не обнаружено признаков применения препаратов,вызывающих нейромышечную блокаду.
4. The observed movements are related to the function of the spinal cord.
5. No cough and/or pharyngeal reflexes
6. Corneal and pupillary reflexes absent
7. There is no reaction to a caloric test with cold, ice-cold water (irrigation of the external auditory canal with an intact tympanic membrane).
8. Absence of respiratory movements during the apnea test (apnea test) for at least 8 minutes with a documented increase in PaCO2> 20 mmHg from the initial level.
   1. This test must be performed with extreme care to avoid the risk of hypoxia or hypotension. If a drop in blood pressure is observed during the test, the test should be terminated and the arterial blood sample sent for PaCO2 analysis, where if 55 mmHg or 20 mmHg above baseline is exceeded, the test can be considered confirming brain death.
9. At least one of the 4 criteria listed below must be taken into account.
   1. Items 2-8 must be confirmed by two independent researchers within at least 6 hours.
   2. Items 2-8 must be confirmed. EEG determines the absence of bioelectrical activity. The second study was conducted within 2 hours to confirm points 2-8.
   3. Items 2-8 are confirmed. Cerebral angiography does not determine cerebral blood flow. The second study is carried out within 2 hours to confirm points 2-8.
   4. If items 2-8 cannot be determined due to an injury or condition preventing examination (Example: a facial injury prevents a calorie test) The following criteria must be met:
      1. No cerebral blood flow detected
      2. The possible scope of the examination was repeated 6 hours after the first

Clinical confirmatory studies

Cerebral angiography

It is now rarely used due to high cost, the need for transportation to the radiology department, the involvement of highly skilled workers, the waste of time, and the potential danger of damage to organs intended for transplantation. Visualization of the absence of cerebral blood flow incompatible with brain life on angiography of 4 cerebral vessels is the gold standard of brain death.

Electroencephalography-EEG

Can be carried out on a bed. Requires the participation of a qualified specialist - an interpreter. Does not detect brain stem activity. Electrocerebral silence (ECS) does not exclude the possibility of reversible coma. It is necessary to continue monitoring the patient for at least 6 hours after determining the ECS. EEG can be used to clarify the diagnosis of brain death in patients who have been reliably excluded: drug intoxication, hypothermia or shock. The definition of electrocerebral silence on the EEG is based on the absence of electrical activity >2 microvolts under the following conditions:

• The recording electrodes from the scalp and the neutral (referential) electrodes must be located at a distance of more than 10 cm
• The recording was made with 8 electrodes on the scalp and one on the ear
• Resistance between electrodes less than 10,000 ohms (or impedance less than 6,000 ohms) but more than 100 ohms
• Sensitivity 2 microvolts/mm
• Time constants for part of recording 0.3-0.4 sec(time constants for part of recording)
• Lack of response to stimuli (pain, noise, light)
• Recording over 30 minutes
• Re-examination in doubtful cases
• Qualified technician and electroencephalographer with experience in intensive care units
• EEG transmission by telephone is not allowed.

Cerebral Radioisotope Angiography-Cerebral Radionuclid Angiogram-CRAG

Can be done in bed using a conventional scintillation chamber with a low energy collimator. It may not be effective in the presence of minimal cerebral blood flow, especially in the brain stem, so it is recommended to continue observation for 6 hours if there are no clear signs of massive brain damage (trauma, hemorrhage) and other complications. The examination is carried out by an experienced interpreter.

Can be used to diagnose brain death in the following conditions:

• In the presence of conditions complicating the diagnosis - hypothermia, drug intoxication (patients withdrawn from a barbituric coma), metabolic disorders.
• In patients with massive facial trauma, when ophthalmic examination is difficult or doubtful.
• In patients with severe chronic obstructive pulmonary disease (COPD) or with chronic heart failure (CHF) where an apnea test cannot be considered reliable. To shorten the observation period, especially when there is a question about organ transplantation.

Technique.

• The scintillation chamber is placed with the head and neck in an anterior-posterior projection.
• 20-30mCi 99m Tc labeled albumin or pertechnetate is injected in a volume of 0.5-1.5 ml into a peripheral or central vein, followed by the introduction of 30 ml of saline.
• A series of dynamic shots is taken with a 2-second interval for 60 seconds.
• Then statistical analysis of images is carried out for 400,000 counts in the anterior-posterior and then in the lateral projection.
• If the examination needs to be repeated for reasons of doubtful results or inconsistency with the diagnosis of brain death, this is possible after a 12-hour interval, necessary to remove the isotope from the circulating blood.

The study confirms Brain Death if it demonstrates the absence of blood flow in the carotid arteries at the base of the skull, the absence of filling of the basins of the middle and anterior cerebral arteries (delayed and true visualization of the sinuses of the dura mater may be observed in brain death). The absence of the "candelabra effect" indicates the absence of cerebral blood flow over the base of the brain.

• Absence:
  • consciousness, any speech activity;
  • purposeful reaction to a hail, speech directed to the patient, to painful irritation (for example, a pinch on the skin in the neck);
  • purposeful movements of the eyeballs: in this case, the eyes can open spontaneously, while the gaze is not fixed on anything, the eyes make “floating” random movements.
• Urinary and fecal incontinence.
• Respiratory failure: irregular breathing movements, rare breathing. This forces the use of artificial lung ventilation - a method of replacing the respiratory function.
• Instability of arterial (blood) pressure: too low level or sharp fluctuations in pressure. Medications (hypertensive drugs) are used to compensate for blood pressure.
• Rare contractions of the heart: medications are used to correct the heart rhythm (accelerating heart contractions).

Causes

• Brain death develops under the influence of extreme conditions on the brain, primarily on its trunk (brain area responsible for maintaining a normal breathing rhythm and arterial (blood) pressure):
  • severe traumatic brain injury;
  • acute violation of cerebral circulation (ischemic or hemorrhagic stroke);
  • severe poisoning;
  • brain tumors.

• These diseases can damage the brain stem primarily (for example, traumatic brain injury with a fracture of the base of the skull and dysfunction of the stem) and secondarily (by developing cerebral edema and the occurrence of stem dislocation syndrome (swelling brain tissue protrudes through the foramen magnum and strongly compresses the stem, which leads to tissue death.

Diagnostics

• Analysis of complaints and anamnesis of the disease:
  • how long ago such a condition developed (lack of speech and motor activity, lack of consciousness);
  • what event preceded the onset of this condition (head injury, diagnosis of cerebrovascular accident or brain tumor).

• Neurological examination.
  • Assessment of the level of consciousness.
  • Checking reflexes, for the implementation of which the brain stem is responsible (the area of ​​\u200b\u200bthe brain in which the life support centers are located - respiratory, vasomotor).
  • Exclusion of factors that can cause a clinical picture that mimics brain death:
    • toxicological analysis: looking for toxins, including drugs, in the blood that can mimic brain death;
    • measurement of body temperature: to diagnose brain death, it must be above 32.2 ° C (low body temperature can cause a false picture of brain death);
    • blood test: glucose level, protein metabolism products (creatinine, urea), as well as determination of the level of adrenal hormones (cortisol), thyroid gland (thyroxine, triiodothyronine). Exclusion of metabolic disorders necessary for the diagnosis of brain death.
• Apnea test: The purpose of this test is to assess the ability of the respiratory center to work independently, provoking spontaneous respiratory movements. To do this, the human body is saturated with oxygen in synchronization with the artificial lung ventilation apparatus, and then the apparatus is turned off. If, upon reaching a critical level of carbon dioxide in the blood, spontaneous breathing does not appear, this is interpreted as an irreversible dysfunction of the respiratory center in the brain stem.
• EEG (electroencephalography): the method evaluates the electrical activity of different parts of the brain, which can change with various diseases. When the brain is dead, there is no organized activity (bioelectric silence).
• Angiography of the brain: the method evaluates the patency of the arteries of the brain and the activity of blood flow through them. With brain death, there is a lack of blood flow through the intracranial arteries.

Pathophysiological mechanisms of brain death

Severe mechanical damage to the brain most often occurs as a result of an injury caused by a sharp acceleration with an opposite vector. Such injuries most often occur in car accidents, falls from great heights, etc. Traumatic brain injury in these cases is caused by a sharp antiphase movement of the brain in the cranial cavity, in which there is a direct destruction of brain regions. Critical non-traumatic brain lesions often result from hemorrhage either into the substance of the brain or under the meninges. Such severe forms of hemorrhages as parenchymal or subarachnoid, accompanied by the outpouring of a large amount of blood into the cranial cavity, trigger mechanisms of brain damage similar to craniocerebral trauma. Anoxia, which occurs as a result of a temporary cessation of cardiac activity, also leads to fatal brain damage.

It has been shown that if blood completely stops flowing into the cranial cavity within 30 minutes, this causes irreversible damage to neurons, the restoration of which becomes impossible. This situation occurs in 2 cases: with a sharp increase in intracranial pressure to the level of systolic blood pressure, with cardiac arrest and inadequate chest compressions during the specified period of time.

In order to fully understand the mechanism of development of brain death as a result of secondary damage in the case of transient anoxia, it is necessary to dwell in more detail on the process of formation and maintenance of intracranial pressure and the mechanisms leading to fatal damage to brain tissues as a result of its swelling and edema.

There are several physiological systems involved in maintaining the balance of the volume of intracranial contents. It is currently believed that the volume of the cranial cavity is a function of the following quantities:

Vtotal \u003d Vblood + Vlkv + Vbrain + Vwater + Vx

where V total - the volume of the contents of the skull at the present time; V blood - the volume of blood in the intracerebral vessels and venous sinuses; V lkv - the volume of cerebrospinal fluid; V of the brain - the volume of brain tissue; V water - the volume of free and bound water; V x - pathological additional volume (tumor, hematoma, etc.), which is normally absent in the cranial cavity.

In the normal state, all these components that form the volume of the contents of the skull are in constant dynamic equilibrium and create intracranial pressure of 8-10 mm Hg. Any increase in one of the parameters in the right half of the formula leads to an inevitable decrease in the others. Of the normal components, V of water and V lkv change their volume most rapidly, and to a lesser extent, V of blood. Let us dwell in more detail on the main mechanisms leading to an increase in these indicators.

CSF is formed by vascular (choroid) plexuses at a rate of 0.3-0.4 ml / min, the entire volume of CSF is completely replaced in 8 hours, that is, 3 times a day. The formation of cerebrospinal fluid practically does not depend on the magnitude of intracranial pressure and decreases with a decrease in blood flow through the choroid plexuses. At the same time, CSF absorption is directly related to intracranial pressure: when it increases, it increases, and when it decreases, it decreases. It has been established that the relationship between the CSF formation/absorption system and intracranial pressure is non-linear. Thus, gradually increasing changes in the volume and pressure of CSF may not be clinically manifested, and after reaching an individually defined critical value, clinical decompensation and a sharp increase in intracranial pressure occur. The mechanism for the development of dislocation syndrome, which occurs as a result of the absorption of a large volume of cerebrospinal fluid with an increase in intracranial pressure, is also described. While a large amount of CSF was absorbed against the background of obstruction of venous outflow, the evacuation of fluid from the cranial cavity may slow down, which leads to the development of dislocation. At the same time, preclinical manifestations of increasing intracranial hypertension can be successfully determined using EchoES.

Violation of the blood-brain barrier and cytotoxic cerebral edema play an important role in the development of fatal brain damage. It has been established that the intercellular space in the brain tissue is extremely small, and the tension of intracellular water is maintained due to the functioning of the blood-brain barrier, the destruction of any of the components of which leads to the penetration of water and various plasma substances into the brain tissue, causing its edema. The compensatory mechanisms that allow the extraction of water from the brain tissue are also damaged when the barrier is breached. Abrupt changes in blood flow, oxygen content or glucose have a damaging effect directly on neurons and on the components of the blood-brain barrier. At the same time, changes occur very quickly. Unconsciousness develops within 10 seconds after the blood supply to the brain completely stops. Thus, any unconscious state is accompanied by damage to the blood-brain barrier, which leads to the release of water and plasma components into the extracellular space, causing vasogenic edema. In turn, the presence of these substances in the intercellular space leads to metabolic damage to neurons and the development of intracellular cytotoxic edema. Together, these 2 components play a major role in increasing intracranial volume and leading to increased intracranial pressure.

To summarize all of the above, the mechanisms leading to brain death can be represented as follows.

It has been established that when cerebral blood flow ceases and necrotic changes in the brain tissue begin, the rate of irreversible death of different parts of the brain is different. Thus, neurons of the hippocampus, pear-shaped neurons (Purkinje cells), neurons of the dentate nucleus of the cerebellum, large neurons of the new cortex and basal ganglia are most sensitive to a lack of blood supply. At the same time, cells of the spinal cord, small neurons of the cerebral cortex, and the main part of the thalamus are much less sensitive to anoxia. However, if the blood does not enter the cranial cavity within 30 minutes, this leads to a complete and irreversible destruction of the structural integrity of the main parts of the CNS.

So, brain death occurs when arterial blood stops flowing into the cranial cavity. As soon as the supply of nutrients to the brain tissue stops, the processes of necrosis and apoptosis begin. Autolysis develops most rapidly in the diencephalon and cerebellum. As mechanical ventilation is carried out in a patient with stopped cerebral blood flow, the brain gradually becomes necrotic, characteristic changes appear that directly depend on the duration of respiratory support. Such transformations were first identified and described in patients who were on mechanical ventilation for more than 12 hours in transcendental coma. In this regard, in most English-language and Russian-language publications, this condition is referred to as the "respiratory brain". According to some researchers, this term does not quite adequately reflect the relationship of necrotic changes with mechanical ventilation, while the main role is assigned to the cessation of cerebral blood flow, however, this term has received worldwide recognition and is widely used to determine necrotic changes in the brain of patients whose condition meets the criteria for brain death. more than 12 hours

In Russia, L.M. Popov. The duration of mechanical ventilation until the development of extrasystole ranged from 5 to 113 hours. According to the duration of stay in this state, 3 stages of morphological changes in the brain, characteristic of the "respiratory brain", were distinguished. The picture was supplemented by necrosis of the 2 upper segments of the spinal cord (an obligate sign).

• In stage I, corresponding to the duration of the transcendental coma of 1-5 hours, classical morphological signs of brain necrosis are not noted. However, already at this time, characteristic lipids and a blue-green fine-grained pigment are detected in the cytoplasm. In the lower olives of the medulla oblongata and dentate nuclei of the cerebellum, necrotic changes are noted. In the pituitary gland and its funnel, circulatory disorders develop.
• In stage II (12-23 hours of transcendental coma), signs of necrosis are detected in all parts of the brain and I-II segments of the spinal cord, but without pronounced decay and only with initial signs of reactive changes in the spinal cord. The brain becomes more flabby, there are initial signs of the collapse of the periventricular sections and the hypothalamic region. After isolation, the brain is flattened on the table, the pattern of the structure of the cerebral hemispheres is preserved, while the ischemic change in neurons is combined with fatty degeneration, granular decay, and karyocytolysis. In the pituitary gland and its funnel, circulatory disorders increase with small foci of necrosis in the adenohypophysis.
• Stage III (exorbitant coma 24-112 hours) is characterized by an increasing widespread autolysis of the necrotic substance of the brain and pronounced signs of demarcation of necrosis in the spinal cord and pituitary gland. The brain is flabby, does not hold its shape well. The affected areas - the hypothalamic region, the hooks of the hippocampal gyri, the cerebellar tonsils and periventricular regions, as well as the brain stem - are in the process of decay. Most of the neurons in the brain stem are missing. In place of the lower olives, there are multiple hemorrhages from necrotic vessels, repeating their forms. The arteries and veins of the brain surface are dilated and filled with hemolyzed erythrocytes, which indicates the cessation of blood flow in them. In a generalized version, 5 pathoanatomical signs of brain death can be distinguished:
  • necrosis of all parts of the brain with the death of all elements of the medulla:
  • necrosis of the I and II cervical segments of the spinal cord;
  • the presence of a demarcation zone in the anterior pituitary gland and at the level of III and IV cervical segments of the spinal cord;
  • stop blood flow in all vessels of the brain;
  • signs of edema and increased intracranial pressure.

Quite characteristic in the subarachnoid and subdural spaces of the spinal cord are microparticles of necrotic cerebellar tissue, carried with a current of liquor to the distal segments.