Brain death was first described in 1959 by P. Mollaret and M. Goulon. They traced the cessation of all brain functions under conditions of prolonged artificial ventilation and called this condition an extreme coma. Subsequently, such terms as “dissociated death”, “state of deanimation”, “cardiopulmonary drug”, “artificially prolonged agony”, etc. were proposed. Pathologists also use the term “respiratory brain”.
Reliable morphological feature brain death is necrosis of the cerebral hemispheres, cerebellum, brain stem, C I-II segments spinal cord, not accompanied by a glial reaction and ending in lysis of brain tissue. In conditions of continued cardiac activity and continuous artificial ventilation of the lungs, cerebral edema initially increases. At the same time, its weight increases, the tissue becomes flabby, and subarachnoid hemorrhages appear. Parts of the brain that are strangulated due to edema, such as the cerebellar tonsils and the uncines of the parahippocampal gyri, undergo decay and autolysis. Necrosis of neurons, impregnation of brain tissue with plasma, and disintegration of vessel walls are observed everywhere. In the subarachnoid space of the spinal cord, detached particles of necrotic cerebellar cortex are found, which are sometimes displaced with the flow of cerebrospinal fluid to the cauda equina. Necrosis of C I-II segments occurs as a result of cessation of blood flow in vertebral arteries, the branches of which provide blood supply to these segments. Sometimes in these segments of the spinal cord a picture of hemorrhagic infarction is observed.
Clinically, the picture is characterized by a stable and complete shutdown of all functions of the central nervous system. In this case, there is no consciousness and own breathing, all motor reactions to external irritations, tendon, periosteal, and skin reflexes disappear, muscle atony is noted, there is no reaction of the pupils to strong direct light (the pupils retain the same diameter, exceeding 5 mm), corneal, peri-vestibular reflexes - no caloric nystagmus is observed, no movements are detected in response to irritation of the muscles of the eyes, face, tongue, innervated by the cranial (cranial) nerves. Strong advancement of the endotracheal tube in the trachea, advancement of the catheter in the bronchi when suctioning mucus does not cause a pharyngeal reflex, reflexes from the mucous membrane of the nasopharynx and coughing movements. Strong pressure on eyeballs is not accompanied by bradycardia, the atropine test is negative (after intravenous administration 2 ml of 0.1% atropine sulfate solution does not increase heart rate). There is also no spontaneous or evoked electrical activity in the brain. At the moment of brain death and the functions of the brain stem are turned off, along with the cessation of one’s own breathing, collapse develops with a fall blood pressure to zero. Stopped own breathing in conditions of brain death is never restored, but blood pressure can be maintained at normal level under the influence of pressor amines. In rare cases, spontaneous restoration of blood pressure occurs at low levels (80⁄50 mm Hg), which is explained by the preservation of spinal regulation of hemodynamics.
6-48 hours after death, the brain recovers reflex activity spinal cord, which persists until cardiac arrest. In this case, monosynaptic stretch reflexes of the tendons of the triceps, biceps, Achilles and knee reflexes appear. With streak irritation of the skin of the anterior surface chest and abdomen, global contractions of the muscles of the trunk and sometimes the limbs are observed with the inclusion of muscles that are opposite in function. Characterized by widespread contraction of the abdominal muscles with streak irritation of the abdominal skin. After restoration of the autonomic functions of the spinal cord, blood pressure and body temperature increase slightly, which is due to their partial regulation at the spinal level.
Most countries do not have a legal definition of death and practice published codes of practice(for example, the “Code of Rules for the Diagnosis of Death” by the Royal Academy medical college, 2008). Laws may vary in other states and you should review them carefully before using the information below.
Death implies the irreversible loss of the most important characteristics necessary for the existence of a living person. The concept of death includes the irreversible loss of the ability to maintain:
consciousness
independent breathing.
Irreversible termination brain stem functions is equivalent to the above definition, and thus the death of the trunk implies the death of the person.
Brain stem death or complete brain death
In some countries(USA, Australia, Canada, Netherlands) use the term “complete brain death” either as an analogue of brainstem death, or when attempting to define the irreversible cessation of all brain functions, including brainstem function, that has occurred before death is declared. This may require the use of additional monitoring tests to assess brain electrical activity (eg, EEG) and/or cerebral blood flow (eg, angiography or TCD) and/or sensory or motor pathways (evoked potentials).
In practice, many countries, who use the term "complete brain death" still only perform clinical brain stem testing and by this mean complete brain death. Additional follow-up tests take time and require significant local expertise, but without clinical brainstem testing, misdiagnosis is possible.
Persistent vegetative state. In a patient in a chronic vegetative state, brain stem death does not occur, since spontaneous breathing and other functions of the brain stem are preserved.
Ascertainment of brain stem death in most countries:
The procedure involves two doctors, one conducts research, the other observes.
- Both doctors must have a license to practice medicine for at least five years.
- Both must be skilled in performing examinations and interpreting brainstem functions.
- There should be no conflict of interest (for example, a transplant surgeon cannot participate in the examination).
- One of the doctors must be a consultant physician.
In total, two complete series of tests are performed:
- Allow a short amount of time between tests for the blood gases to return to normal and for the blood glucose level to be retested.
- The time between test series is not limited.
The time of death is established after confirmation of the first series of tests.
Prerequisites for brain stem death
Cause of death:
Irreversible brain damage of known etiology is consistent with the resulting brainstem death.
Lack of consciousness:
Rule out other causes of lack of consciousness, including:
- medicinal
- narcotic
- hypothermia (temperature should be >34°C)
- circulatory, metabolic and endocrine (blood glucose between 3 and 20 mmol/l).
Concentration may need to be checked sedatives in plasma (for example, midazolam plasma levels should be<10 мкг/л) и/или назначение их антагонистов.
Ventilation:
Absence (or perceived absence) of spontaneous breathing.
No drugs (muscle relaxants) that cause apnea were administered.
Diagnosis of brain stem death
All the above prerequisites must be present and the absence all brain stem reflexes:
Fixed pupils, no reaction to light.
Corneal reflexes are absent.
The vestibular-ocular reflex is absent
- There is no reaction of the eyeball to the injection of 50 ml of ice water through a syringe onto each eardrum, while the head is bent 30 degrees. Normally, nystagmus occurs, with a fast component away from the ear being tested.
There is no motor response (of the limbs or facial muscles) to a painful stimulus in the area of innervation of the cranial nerves.
There are no pharyngeal and cough reflexes.
There is no response to aspiration of bronchial contents or stimulation of the pharynx.
Apnea test:
- After preoxygenation of 100% O2, minute ventilation is adjusted to achieve PaCO2 >6 kPa and pH<7,40.
- Disconnect the patient from the ventilator and observe him for five minutes. Supplemental oxygen support is often required, and the test should be stopped if hypoxia, hypotension, or arrhythmia occur.
- Spontaneous breathing should not be observed. Make sure PaCO2 has increased by at least 0.5 kPa.
- After making a conclusion on the first apnea test, you need to continue ventilation to normalize the parameters.
Auxiliary tests, which are not required in many countries around the world:
Oculocephalic reflex (doll eyes symptom).
- When turning the head, the eyeballs remain motionless.
Electrical activity of the brain
- Lack of EEG activity is a necessary condition in some countries. When performed in intensive care units, false-positive results are often observed.
Cerebral blood flow/metabolism
Angiography with contrast, Tc-I isotope scan IMPAO1), TCD or PEG to determine the cessation of blood flow and metabolism.
Brain evoked potentials (sensory and motor evoked potentials).
Difficult situations of establishing a vegetative state
Spinal reflexes. Spinal reflexes may persist after brain death. Reflex movements of the limbs and trunk can occur in response to peripheral stimulation (=as a reaction to peripheral stimulation). This should be explained to family members before testing.
Children. In children less than 37 weeks of gestation + at least two months, additional research is usually required (for example, cerebral angiography).
Apnea test:
In case of chronic obstructive pulmonary diseases, in which chronic hypercapnia is observed, consultation with a pulmonologist is necessary.
If the patient develops hypoxia during the apnea test, a positive continuous airway pressure (CPAP) maneuver is required to allow the test to continue.
Facial/eye trauma preventing complete examination of cranial nerves:
In such unusual situations, the senior specialist may decide to make a diagnosis or refuse testing.
If there is a bilateral injury or illness, additional tests may be performed.
Correction of the physiological consequences of brainstem death
Patients with brain stem death often experience complications.
Cardiovascular consequences of brainstem death:
The flare of hypertension often seen during herniation is usually followed by a period of hypotension and arrhythmia due to loss of sympathetic tone. This can lead to subendocardial ischemia.
Therapy aimed at supporting organ function includes fluid therapy (CVP 4-10 mmHg), norepinephrine (target SBP 60-80 mmHg) vasopressin (agripressin bolus 1 IU, then infusion 1-5 IU/hour ).
Respiratory consequences of brainstem death. A common consequence of trunk death is neurogenic pulmonary edema, requiring inhalation of high concentrations of O2 and positive end-expiratory pressure.
Endocrine consequences of brainstem death:
Dysfunction of the anterior and posterior pituitary glands may require replacement therapy with thyroid hormones (liothyronine bolus 4 mcg/hour, then 3 mcg/hour), hydrocortisone (50 mg every 6 hours) and vasopressin.
Decreased insulin secretion leads to hyperglycemia.
Thermal consequences of brainstem death. The patient develops poikilothermia and his temperature approaches room temperature (active warming is required).
Long-term effects of brain stem death. Even with full cardiovascular and endocrine support, asystole occurs after a few days or weeks. None of the patients with brain stem death "woke up."
If the patient's immediate family has consented to organ donation, intensive therapy aimed at supporting organ function is necessary to remove as much material as possible and ensure better organ function after transplantation. Many transplant departments have developed their own donor support protocols, which include three-component hormonal support of the donor (corticosteroids, T3/G4 and vasopressin) and maintenance of target values of SBP and oxygenation.
Brain death(synonym for respiratory brain) is a condition characterized by the irreversible cessation of all brain functions, including brain stem functions (all brain stem reflexes and breathing, in particular), while maintaining cardiac activity and systemic blood pressure. Systemic blood pressure is usually maintained with the help of drugs (pressor amines, hormones), and gas exchange is carried out thanks to artificial ventilation, because there is no spontaneous breathing. S. m. develops against the background of a decreasing and ultimately stopping blood supply to the brain as a result of increasing edema (see. Brain swelling), increased intracranial pressure (see. Intracranial hypertension) and equalizing it with decreasing systemic blood pressure.
The diagnosis of brain death is established only when there is a documented history of terminal state and with qualified observation of the patient in a hospital with the participation of a neurologist. Must be established for at least 6-12 h complete and stable absence of consciousness, all reflexes, incl. pupillary to strong light (the pupils remain dilated, the eyeballs are fixed in the middle position), oculocephalic and oculovestibular (when performing a caloric test with ice water), reaction to strong irritation of the larynx and trachea during suction of mucus with a catheter and movement of the endotracheal tube. There is atony of all muscles and a decrease in rectal temperature. It is necessary to take into account the possibility of reflex activity of the spinal cord (stretch reflexes, global contractions of the muscles of the trunk and limbs), due to the preservation of blood circulation in it and the manifestation of automatism. Once a clinical diagnosis of brain death has been made, the death of respiratory center structures should be confirmed using an apneic oxygenation test. To do this, the artificial respiration apparatus is temporarily turned off, and oxygen is supplied to the endotracheal tube at a speed of 6-8 l/min, which ensures normal PO 2. If, with a gradual (determined every 5 min) increasing RSO 2 to 60 mmHg.st. (7-8 kPa) and higher and natural stimulation of the respiratory center by carbon dioxide does not restore independent respiratory movements, the diagnosis of brain death is confirmed. If at least minimal independent respiratory movements appear, artificial respiration and previously started treatment are resumed.
Brain death is accompanied by a complete, stable absence of spontaneous and evoked electrical activity of the brain, which must be recorded from at least 10 electrodes using maximum gain. Absence of cerebral circulation can be documented by serial angiography of the great vessels of the head.
A diagnosis of brain death is valid only in the absence of previous hypothermia, endo- and exogenous intoxications, exposure to narcotic and sedatives, and muscle relaxants. The diagnosis of brain death is established by a commission of doctors, which solves the main moral and ethical problem of declaring a person dead with a beating heart and gas exchange in the lungs provided by the apparatus. Timely reliable establishment of S. m is an urgent problem for transplant surgery.
Bibliography: Popova L.M. and etc. Brain death for neurological diseases, Anest. and resuscitation, No. 5, p. 24, 1980; Walker A.E. Brain Death, trans. from English, M., 1988.
Brain death means a complete and irreversible cessation of its vital activity, when the heart continues to beat and breathing is maintained through artificial ventilation (ALV).
Unfortunately, the number of patients who have irreversible events in the brain is large. Their treatment is carried out by resuscitation specialists, ensuring the maintenance of the main life support systems - breathing and blood circulation. From a medical and ethical point of view, it is always difficult to establish the fact of irreversibility of brain death, because this means declaring a person dead, although his heart continues to contract.
The brain lives after a person’s death for about five minutes, that is, after cardiac arrest, it is still able to maintain its activity for some time. During this period, it is very important to have time to carry out resuscitation, then there will be a chance for a full life. Otherwise, irreversible neuronal death will be fatal.
For relatives and friends, the issue of recognizing a sick relative as non-viable due to brain death is very difficult: many believe that a miracle will happen, others believe that doctors are not making enough efforts to “revive” the patient.
There are frequent cases of litigation and disputes when relatives consider the disconnection of the ventilator to be premature or erroneous. All these circumstances force us to objectify the data of symptoms, neurological and other types of examinations, so that an error is excluded, and the doctor who turned off the ventilator does not act as an executioner.
In Russia and most other countries, brain death is identified with the death of the whole organism, when maintaining the vital functions of other organs through medication and hardware treatment is impractical, which distinguishes brain death from a vegetative state and coma.
As already mentioned, under normal conditions, brain death occurs 5 minutes after breathing and heartbeat stop, but at low temperatures and various diseases this period can be lengthened or shortened. In addition, resuscitation measures and treatment make it possible to restore cardiac activity and provide ventilation of the lungs, however, brain function cannot always be returned to its original state - comas, a vegetative state, or irreversible death of nervous tissue are possible, requiring different approaches from specialists.
Brain death established through clear criteria is the only reason when a doctor has the right to turn off all life support devices without the risk of being held legally liable. It is clear that such a formulation of the question requires compliance with all diagnostic algorithms for this condition, and an error is unacceptable.
Stages of diagnosing brain death
To accurately determine whether the brain is alive or whether irreversible and incompatible changes have already occurred in it, clear recommendations have been developed that should be followed by every specialist who encounters a patient in serious condition.
Diagnosis of brain death includes several stages:
- Accurate determination of the cause of the pathology.
- Exclusion of other brain changes that are clinically similar to his death, but under certain conditions can be reversible.
- Establishing the fact of cessation of activity of the entire brain, and not just its individual structures.
- Accurate determination of irreversibility of brain damage.
Based on clinical data, a doctor has the right to make a diagnosis of brain death without using additional instrumental diagnostic methods, since the developed criteria make it possible to determine the pathology with absolute accuracy. However, in our time, when the conclusion about any disease is based on a variety of objective results, instrumental and laboratory tests are involved in the diagnostic process.
brain perfusion on MRI is normal (left), with brain death (center), with a vegetative state (right)
Additional examinations are not excluded from diagnostic algorithms for brain death, but are not strictly required. Their purpose is to speed up the establishment of the fact of brain death, especially in clinically complex cases, although it is quite possible to do without them. In Russia, only electroencephalography and angiography of the carotid and vertebral arteries are allowed as the only reliable ones in determining signs of irreversibility of brain disorders.
Features and criteria for declaring brain death
In medicine, the concepts of clinical and biological death refer to the entire body, implying the reversibility or irreversibility of changes occurring. Applying this parameter to nervous tissue, we can speak of clinical brain death in the first 5 minutes after breathing stops, although the death of cortical neurons begins already in the third minute. Biological death characterizes a total disorder of brain activity that cannot be reversed by any resuscitation or treatment.
The need to assess the state of the brain usually arises in comatose and similar conditions, when the patient is unconscious, contact with him is impossible, hemodynamics and heart function may be unstable, breathing is usually supported by a device, the pelvic organs are not controlled, there is no movement and sensitivity, reflexes and muscle tone fades away.
Assessment of causes of brain death
A doctor has the right to begin diagnosing biological brain death only when the causative factors and mechanisms of changes in nervous tissue are precisely known. The causes of irreversible brain disorders can be primary, caused by direct damage to the organ, and secondary.
Primary brain damage leading to brain death is provoked by:
- Heavy ;
- , both traumatic and spontaneous;
- any nature (atherosclerosis, thromboembolism);
- Oncological diseases;
- Acute, ;
- Previous surgical operations inside the skull.
Secondary irreversible damage occurs due to pathology of other organs and systems - cardiac arrest, shock, severe hypoxia against the background of systemic circulatory disorders, severe infectious processes, etc.
An important diagnostic step is the exclusion of all other pathological conditions that could manifest symptoms similar to brain death, but which, nevertheless, are potentially reversible with proper treatment. Thus, the diagnosis of brain death should not even be assumed until a specialist makes sure that there are no influences such as:
- Intoxication, drug poisoning;
- Hypothermia;
- Hypovolemic shock due to dehydration;
- Coma of any origin;
- The effect of muscle relaxants, anesthetics.
In other words, an indispensable condition when diagnosing brain death will be the search for evidence that the symptoms are not caused by drugs that depress the nervous tissue, poisoning, metabolic disorders, or infections. In case of intoxication, appropriate treatment is carried out, but until its signs are eliminated, a conclusion about brain death is not considered. If all possible causes for the lack of brain functioning are excluded, then the question of its death will be raised.
When monitoring patients with brain disorders potentially associated with other causes, the rectal temperature is determined, which should not be less than 32 C, the systolic blood pressure is not less than 90 mm Hg. Art., and if it is lower, vasopressors are administered intravenously to maintain hemodynamics.
Clinical data analysis
The next stage in diagnosing brain death, which begins after establishing the causes and excluding other pathologies, will be the assessment of clinical data - coma, absence of brain stem reflexes, inability to spontaneously breathe (apnea).
Coma is a complete lack of consciousness. According to modern concepts, it is always accompanied by total atony of the muscular system. In a coma, the patient does not react to external stimuli, does not feel pain, changes in the temperature of surrounding objects, or touch.
Brainstem reflexes are determined in all patients without exception with probable brain death, At the same time, to verify the diagnosis, the following signs are always taken into account:
- There is no response to sufficiently intense pain effects in the areas of exit of the branches of the trigeminal nerve or the absence of other reflexes, the arcs of which close above the cervical part of the spinal cord;
- The eyes do not move, the pupils do not react to a light stimulus (when it is clearly established that there is no effect of medications that dilate them);
- Corneal, oculovestibular, tracheal, pharyngeal and oculocephalic reflexes are not detected.
Absence oculocephalic reflexes determined by turning the patient's head to the sides with raised eyelids: if the eyes remain motionless, then there are no reflexes. This symptom is not assessed for cervical spine injuries.
checking oculocephalic reflexes
connection of oculocephalic and oculovestibular reflexes with brain stem vitality
For determining oculovestibular reflexes The patient's head is raised, and cold water is pumped into the ear canals using a thin catheter. If the brain stem is active, the eyeballs will deviate to the sides. This symptom is not indicative of injury to the eardrums with a violation of their integrity. Pharyngeal and tracheal reflexes are checked by displacing the endotracheal tube or inserting a bronchial suction catheter.
One of the most important diagnostic criteria for brain death is considered inability to breathe independently (apnea). This indicator is the final one at the stage of clinical assessment of brain functioning and can be determined only after checking all of the above parameters.
To determine whether a patient is able to breathe on his own or not, it is unacceptable to simply disconnect him from the ventilator equipment, since sudden hypoxia will have a detrimental effect on the already suffering brain and myocardium. Disconnection from the equipment is carried out on the basis apneic oxygenation test.
An apneic test involves monitoring the gas composition of the blood (the concentration of oxygen and carbon dioxide in it), for which a catheter is installed in the peripheral arteries. Before disconnecting the ventilator, ventilation of the lungs is carried out for a quarter of an hour under conditions of normal CO2 content and high oxygen pressure. After these two rules are observed, the ventilator is turned off, and humidified 100% oxygen is supplied to the trachea through the endotracheal tube.
If spontaneous breathing is possible, then an increase in the level of carbon dioxide in the blood will lead to activation of the stem nerve centers and the appearance of spontaneous respiratory movements. The presence of even minimal breathing serves as a reason to exclude brain death and immediate return to mechanical ventilation. A positive test result, that is, absence of breathing, will indicate irreversible death of the brain stem structures.
Observation and proof of irreversibility of pathology
In the absence of breathing, we can talk about the loss of vital activity of the entire brain; the doctor can only establish the fact that this process is completely irreversible. The irreversibility of brain disorders can be judged after a certain period of observation, depending on the cause of the pathology that caused the death of the nervous tissue.
If primary brain damage has occurred, then to establish brain death, the duration of observation must be at least 6 hours from the moment when the symptoms of the pathology were first recorded. After this period, a repeat neurological examination is performed, and the apnea test is no longer necessary.
Previously, it was recommended to observe the patient for a minimum of 12 hours, but now in most countries of the world the time has been reduced to 6 hours, since this time interval is considered sufficient to diagnose brain death. In addition, reducing observation time plays an important role when planning organ transplantation from a brain-dead patient.
In case of secondary damage to the nervous tissue, a longer observation is required to make a diagnosis of brain death - at least a day from the moment of the initial symptoms of the pathology. If there is reason to suspect poisoning, the time is increased to 72 hours, during which neurological monitoring is carried out every 2 hours. If the results are negative, brain death is declared after 72 hours.
Based on the stated diagnostic criteria, during observation of the patient, undoubted signs of brain death are recorded - the absence of reflex and brainstem activity, a positive apneic test. These parameters are considered absolutely indicative and reliable, not requiring additional examination, and therefore are used by doctors all over the world.
Additional examinations
Of the additional examinations that may affect the diagnosis, and are allowed. EEG is indicated for those patients for whom it is difficult to determine reflexes - with injuries and suspected injuries of the cervical spine, ruptured eardrums. An EEG is performed after all tests, including apnea. In brain death, it shows the absence of any electrical activity in the nerve tissue. If the indicators are questionable, the study can be repeated or using stimuli (light, pain).
non-collapsed cerebral vessels are normal on angiography
If EEG is indicated in clinically complex cases and does not affect the duration of general observation, then panangiography of the carotid and vertebral arteries is designed to shorten this time as much as possible. It is carried out at the final diagnostic stage and confirms the irreversibility of the cessation of brain activity.
For example, in case of possible intoxication, the patient should be observed for at least three days, but brain death can be determined early if, immediately after the appearance of signs of loss of its functions, the main arteries of the brain are examined twice with an interval of at least half an hour. In the absence of contrasting of the arteries, we can talk about a total and irreversible stop of cerebral blood flow, and further observation becomes impractical.
Video: example of an EEG to confirm brain death
Clinical diagnosis of biological brain death is labor-intensive, requires constant monitoring and maintenance of vital functions, so for many years the search has been underway for another method that would allow us to establish a reliable diagnosis with no less accuracy than the clinic. However, no matter how hard the experts try, none of the proposed methods is comparable in accuracy and reliability to a clinical assessment of the state of the brain. Moreover, other techniques are more complex, less accessible, invasive or not specific enough, and the result is greatly influenced by the experience and knowledge of the doctor.
The desire to speed up the process of ascertaining brain death is largely due to the rapid development of a new branch of medicine - transplantology. Considering the diagnosis of brain death from this position, we can say that the price of a conclusion about brain death may be not one, but several lives - both of the potential donor and of other people in need of organ transplants, therefore haste or non-compliance with the observation algorithm is unacceptable.
When deciding to declare brain death, the doctor must remember the ethical side of the issue and the fact that the life of any person is priceless, therefore strict compliance of his actions with the established rules and instructions is mandatory. A possible mistake increases the already high degree of responsibility, forcing you to repeatedly play it safe and doubt, double-check and weigh every step.
The diagnosis of brain death is established jointly by a resuscitation specialist and a neurologist, and each of them must have at least five years of work experience. If additional examination is necessary, specialists of other profiles are involved. Transplantologists and other persons involved in the collection and transplantation of organs cannot and should not participate in or influence the process of diagnosing brain death.
After diagnosis...
Once brain death has been confirmed by all clinical data, doctors have three options. In the first case, they can invite transplantologists to decide on the issue of organ collection for transplantation (this mechanism is regulated by the legislation of a particular country). In the second, talk to your family, explain the essence of the pathology and the irreversibility of brain damage, and then stop artificial ventilation. The third option - the most economically unprofitable and impractical - continues to maintain the functioning of the heart and lungs until they decompensate and the patient dies.
The problem of brain death with intact cardiac activity is not only of a medical nature. It has a significant moral, ethical and legal aspect. Society as a whole knows that brain death is identical to the death of the patient, but doctors have to make serious efforts, tact and patience when talking with relatives, deciding on transplantation issues and determining the final option of their actions after making a diagnosis.
Unfortunately, cases of distrust in doctors, unjustified suspicions of unwillingness to continue treatment, and accusations of negligence in their duties are still common. Many people still think that with a superficial assessment of the patient’s condition, the doctor will simply turn off the ventilator without making sure that the pathology is irreversible. At the same time, delving into the diagnostic algorithms, one can imagine how long and difficult the path to the final diagnosis is.
Video: presentation-lecture on brain death
Pathophysiological mechanisms of brain death
Severe mechanical damage to the brain most often occurs as a result of trauma caused by sharp acceleration with an oppositely directed 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, during which direct destruction of parts of the brain occurs. Critical non-traumatic brain injuries most often occur as a result of hemorrhage either into the substance of the brain or under the meninges. Such severe forms of hemorrhage as parenchymal or subarachnoid, accompanied by the outpouring of large amounts of blood into the cranial cavity, trigger mechanisms of brain damage similar to traumatic brain injury. 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 for a specified period of time.
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 tissue as a result of its swelling and edema.
There are several physiological systems involved in maintaining intracranial content volume balance. Currently, it is believed that the volume of the cranial cavity is a function of the following quantities:
Vtot = Vblood + Vlq + Vbrain + Vwater + Vx
where V total is the volume of the contents of the skull at the present time; V blood - the volume of blood located in the intracerebral vessels and venous sinuses; V lkv - volume of cerebrospinal fluid; V brain - volume of brain tissue; V water - volume of free and bound water; V x - pathological additional volume (tumor, hematoma, etc.), normally absent in the cranial cavity.
In a normal state, all these components, which form the volume of the contents of the skull, are in constant dynamic equilibrium and create an 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 lqv change their volume most quickly, 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.
The cerebrospinal fluid is formed by the choroid plexuses at a rate of 0.3-0.4 ml/min; the entire volume of cerebrospinal fluid is completely replaced within 8 hours, that is, 3 times a day. The formation of cerebrospinal fluid is practically independent of the value of intracranial pressure and decreases with a decrease in blood flow through the choroid plexuses. At the same time, the absorption of cerebrospinal fluid 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 system of formation/absorption of cerebrospinal fluid and intracranial pressure is nonlinear. Thus, gradually increasing changes in the volume and pressure of the cerebrospinal fluid may not manifest themselves clinically, and after reaching an individually determined 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 increased intracranial pressure, is also described. While a large amount of cerebrospinal fluid was absorbed against the background of obstructed 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.
Disruption 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 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. Compensatory mechanisms that allow water to be extracted from brain tissue are also damaged when the barrier is disrupted. Acute changes in blood flow, oxygen, or glucose have a damaging effect directly on both neurons and components of the blood-brain barrier. At the same time, changes occur very quickly. An unconscious state 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.
If we summarize all of the above, the mechanisms leading to brain death can be presented as follows.
It has been established that when cerebral blood flow ceases and necrotic changes in brain tissue begin, the rate of irreversible death of different parts of the brain is different. Thus, the most sensitive to a lack of blood supply are neurons of the hippocampus, piriform neurons (Purkinje cells), neurons of the dentate nucleus of the cerebellum, large neurons of the neocortex and basal ganglia. 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 blood absolutely does not enter the cranial cavity within 30 minutes, this leads to complete and irreversible destruction of the structural integrity of the main parts of the central nervous system.
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 whose cerebral blood flow has stopped, the brain gradually becomes necrotic, and 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 an extreme coma. In this regard, in most English-language and Russian-language publications this condition is designated by the term “respiratory brain”. According to some researchers, this term does not adequately reflect the connection of necrotic changes specifically with mechanical ventilation, while the main role is assigned to the cessation of cerebral blood flow, however, this term has gained worldwide recognition and is widely used to define necrotic changes in the brain of patients whose condition meets the criteria for brain death more than 12 hours
In Russia, extensive research work to identify the correlation between the degree of brain autolysis and the duration of mechanical ventilation in patients meeting the criteria for brain death was carried out by L.M. Popova. 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 specifically of the “respiratory brain,” were identified. The picture was complemented by necrosis of the 2 upper segments of the spinal cord (obligate sign).
- In stage I, which corresponds to a duration of extreme coma of 1-5 hours, classical morphological signs of brain necrosis are not noted. However, already at this time, characteristic lipids and blue-green fine-grained pigment are detected in the cytoplasm. Necrotic changes are noted in the inferior olives of the medulla oblongata and the dentate nuclei of the cerebellum. Circulatory disorders develop in the pituitary gland and its funnel.
- In stage II (12-23 hours of extreme coma), signs of necrosis are detected in all parts of the brain and segments I-II 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, and initial signs of disintegration of the periventricular sections and hypothalamic region appear. After isolation, the brain is spread out on the table, the structure of the brain hemispheres is preserved, while ischemic changes in neurons are 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 (extreme coma 24-112 hours) is characterized by increasing widespread autolysis of necrotic brain substance and pronounced signs of demarcation of necrosis in the spinal cord and pituitary gland. The brain is flabby and does not hold its shape well. The affected areas - the hypothalamic region, the uncinates of the hippocampal gyri, the cerebellar tonsils and periventricular areas, as well as the brain stem - are in the stage of decay. Most neurons in the brainstem are missing. In place of the inferior olives there are multiple hemorrhages from necrotic vessels, repeating their shape. The arteries and veins of the surface of the brain are dilated and filled with hemolyzed red blood cells, which indicates a cessation of blood flow in them. In a generalized version, 5 pathological signs of brain death can be distinguished:
- necrosis of all parts of the brain with 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 lobe of the pituitary gland and at the level of the III and IV cervical segments of the spinal cord;
- stopping blood flow in all vessels of the brain;
- signs of edema and increased intracranial pressure.
Very typical in the subarachnoid and subdural spaces of the spinal cord are microparticles of necrotic cerebellar tissue, carried with the cerebrospinal fluid flow to the distal segments.
