Brain death - clinical criteria

Clinical criteria for brain death

At first glance, diagnosing brain death does not present any great difficulties: it is necessary to show that the brain has ceased functioning and its restoration is impossible. However, the extraordinary importance of making such a diagnosis determines the need for absolute accuracy in the final determination of this condition, which is why most studies concerning brain death are devoted to diagnostic issues. Conventionally, two types of diagnostic criteria can be distinguished - clinical signs and interpretation of paraclinical data. They are closely interrelated and can only be considered together. Clinical criteria are generally recognized and are practically the same throughout the world. Their study was based on the works of the authors who first described brain death. At that time, the signs were called neurological criteria of human death:

• persistent bilateral mydriasis;
• complete lack of response to any stimuli (areactivity);
• absence of spontaneous breathing when disconnected from the ventilator for 5 minutes;
• mandatory use of vasopressors to maintain blood pressure;
• absence of bioelectrical activity in the brain for several hours.

Further research that would improve the accuracy of diagnosis was mainly related to observations of cases of pathological conditions that mimic brain death and aimed at eliminating them. In 1995, the latest standards for diagnosing brain death were issued in the United States. They are only advisory in nature, and the actions of doctors depend on state laws.

Thus, to establish a diagnosis of brain death, the following clinical signs are currently required.

• The reason for the development of this condition must be precisely known.
• Intoxication, including drug intoxication, primary hypothermia, hypovolemic shock, metabolic endocrine coma, as well as the use of narcotic drugs and muscle relaxants, must be excluded.
• During clinical examination of the patient, the rectal temperature should be consistently above 32°C, systolic blood pressure should not be lower than 90 mm Hg (if the pressure is lower, it should be increased by intravenous administration of vasopressor drugs). In case of intoxication established as a result of toxicological examination, the diagnosis of brain death is not considered until its signs disappear.
• The following complex of clinical signs must be present:
  • complete and persistent absence of consciousness (coma);
  • atony of all muscles;
  • lack of response to strong pain stimuli in the area of the trigeminal points and any other reflexes that close above the cervical spinal cord;
  • absence of pupillary reaction to direct bright light. It should be known that no drugs that dilate the pupils were used. The eyeballs are motionless;
  • absence of corneal reflexes;
  • absence of oculocephalic reflexes. These reflexes are not examined in the presence of traumatic damage to the cervical spine or suspicion of it;
  • absence of oculovestibular reflexes. To study these reflexes, a bilateral caloric test is performed. Before performing it, it is necessary to ensure that there is no perforation of the eardrums;
  • absence of pharyngeal and tracheal reflexes, determined by movement of the endotracheal tube in the trachea and upper respiratory tract, as well as when advancing a catheter in the bronchi to aspirate secretions;
  • lack of spontaneous breathing.

The last point should be discussed in more detail. It is unacceptable to register the absence of breathing by simply disconnecting from the ventilator, since the hypoxia that develops in this case has a harmful effect on the body, primarily on the brain and heart, so the apneic oxygenation test is used. It is carried out after the results of the clinical examination are obtained.

• To monitor blood gas composition (pA _O2 and pA _CO2 ) _{, one of the arteriesof} the limb must be cannulated.
• _{Before disconnecting the ventilator,} it is necessary to carry out mechanical ventilation for 10-15 minutes in a mode that ensures normocapnia (p _a CO2 = 35-45 mm Hg) and hyperoxia (p _a O2 >200 mm Hg); FiO2 _- 1.0 (i.e. 100% oxygen), adequately selected minute ventilation of the lungs, optimal positive pressure at the end of expiration.
• After this, the ventilator is switched off, and humidified 100% oxygen is supplied to the endotracheal or tracheostomy tube at a rate of 6 l/min. The stages of blood gas monitoring are as follows:
  • before the start of the test under mechanical ventilation conditions;
  • 10-15 minutes after the start of mechanical ventilation with 100% oxygen;
  • immediately after disconnection from the ventilator, then every 10 minutes until the CO2 level _reaches 60 _mm Hg.
• If, at these or higher values of pCO2, _spontaneous respiratory movements are not restored, the apneic oxygenation test indicates that the respiratory center of the brainstem is not functioning. When minimal respiratory movements appear, mechanical ventilation is immediately resumed _.

The attitude towards the apnea test remains ambiguous. As is known, the apneic oxygenation test is carried out after the fact of loss of brain functions is established. There is no registered case of survival or transition to a vegetative state of a patient with an established complete loss of brain functions, but respiratory movements that appeared during the apneic oxygenation test. Thus, the outcome of the condition is already predetermined and there is no need to subject a patient in a terminal state to a difficult procedure. In addition, it is known that the apneic oxygenation test can provoke the development of arterial hypotension and hypoxemia. In this regard, damage to organs suitable for transplantation is possible. Finally, there is an opinion that the apneic oxygenation test can cause the death of potentially viable neurons. According to a number of authors, complications of the test develop in more than 60% of cases (acute arterial hypotension - 12%, acidosis - 68%, hypoxemia - 23%, etc.). On the other hand, the apnea test is the only clinical way to check the functioning of the medulla oblongata, and with proper observance of all resuscitation measures preceding the test, it is quite safe.

Thus, the medical community has not yet developed a clear opinion on the necessity and safety of the apneic oxygenation test. Most researchers are inclined to conduct the apneic oxygenation test after a neurological examination, at the end of the observation period and a set of paraclinical methods confirming the diagnosis of "brain death". In the USA and many Western European countries, it is legally established that if complications develop during the apneic oxygenation test, it can be replaced by one of the diagnostic tests confirming the diagnosis of "brain death".

Difficulties in establishing the diagnosis of "brain death" can sometimes be associated with incorrect interpretation of the presence and form of spinal automatisms. They are perceived especially dramatically by middle and junior medical personnel working in intensive care units. It has been shown that the presence of not only tendon reflexes, but also complex motor automatisms does not exclude the diagnosis of "brain death". The prevalence of this phenomenon is 25-39%, and the most dramatic is the so-called Lazarus sign - bending the body by 40-60 °, imitating standing up.

Spinal automatisms and reflexes in brain-dead patients

Body part	Common signs
Cervical spine	Tonic neck reflexes: spastic contracture of the neck muscles, flexion at the hip joint in response to turning the head, flexion at the elbow joint in response to turning the head, lowering of the shoulder in response to turning the head, spontaneous turning of the head to the side
Upper limbs	Unilateral extension - pronation. Isolated twitching of fingers. Shoulder flexion and elevation, a case with hand joining is described
Torso	Asymmetrical opisthotonic body position. Bending of the trunk at the waist, imitating a sitting position. Abdominal reflexes
Lower limbs	Flexion of the fingers in response to tapping. Triple flexion phenomenon. Babinski's sign

Some authors believe that the triple flexion phenomenon can be regarded as a complex undifferentiated response to stimulation. Such a reaction may be a symptom of ongoing terminal herniation of the brainstem, excluding the diagnosis of "brain death".

Clinical conditions that mimic brain death

Currently, conditions have been described whose clinical picture can imitate brain death. These include severe hypothermia (heart temperature below 28 °C), acute poisoning, including drug poisoning, as well as acute metabolic encephalopathies associated with dysfunction of any organ. Drug intoxications are of greatest interest. Differential diagnostics with them are constantly carried out in the context of clinical diagnosis of "brain death".

Drugs that can make it difficult to diagnose brain death

Preparation	Half-life, h	Breadth of therapeutic action
Amitriptyline	10-24	75-200 ng/ml
Valproic acid	15-20	40-100 mmol/ml
Diazepam	40	0.2-0.8 mmol/ml
Carbamazepine	10-60	2-10 mmol/ml
Ketamine	2-4	No data
Clonazepam	20-30	10-50 ng/ml
Codeine	3	200-350 ng/ml
Cocaine	1	150-300 ng/ml
Lorazepam	10-20	0.1-0.3 mmol/ml
Midazolam	2-5	50-150 ng/ml
Morphine	2-3	70-450 mmol/ml
Alcohol	10*	800-1500 mg/l
Thiopental sodium	10	6-35 mmol/ml
Phenobarbital	100	10-20 mmol/ml
Fentanyl	18-60	No data

* The excretion rate is given in milliliters per hour.

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